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WHO Drug Information Vol 21, No. 2, 2007
World Health Organization
WHO Drug Information

Contents
Safety and Efficacy Issues
Entecavir: not for use in HIV/HBV co-infection Deferasirox: acute renal failure and cytopenias Safety of oseltamivir Fluticasone: reports of behavioural changes Quetiapine: pancreatitis and thrombocytopenia Aprotinin: hypersensitivity reactions and renal dysfunction Metoclopramide in children: extrapyramidal symptoms Drug-eluting stents: to be used with caution Darbepoetin alfa and epoetin alfa: update for non-myeloid malignancies Ayurvedic and Chinese medicines: heavy metals ADHD drugs: cardiovascular and psychiatric events Clozapine can impair motility of the entire GI tract 87 87 87 88 88 89 90 90 91 91 92 93 Eculizumab approved for paroxysmal nocturnal haemoglobinuria 115
Access to Medicines
Neglected tropical diseases Open access database for neglected medicines development 116 116
Consultation Document
International Pharmacopoeia
Artemether and lumefantrine capsules Magnesium sulfate injection Zinc sulfate Paediatric zinc sulfate tablets Paediatric zinc sulfate oral solution 118 123 124 125 127
Recent Publications, Information and Events

Informed consent for research in resourcepoor settings 129 Lessons learned in home management of malaria 129 Developing drug information centres in India 130 First-in-man clinical trials for high risk products 130 Pakistan Pharmacists Society discussion forum 130 New quality assurance compendium 130 Pharmacological management of human H5N1 infection 131
Essential Medicines
15th Model List of Essential Medicines Model List of Essential Medicines, 15th Edition, revised March 2007 94 95
Regulatory Action and News

Tegaserod: marketing suspension 112 Pergolide: voluntary withdrawal of products 112 Aliskiren approved for hypertension 113 Lapatinib approved for breast cancer 114 Adalimumab approved for Crohn disease114 Rapid test for meningitis cleared for marketing 114
Proposed International Nonproprietary Names: List 97
133
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World Health Organization
Announcement
The 13th International Conference of Drug Regulatory Authorities (ICDRA) will be hosted by the Swiss Agency for Therapeutic Products (Swissmedic) in collaboration with the World Health Organization The ICDRA will take place in Berne, Switzerland from 16 to 19 September 2008
Updated information will be provided regularly at: http://www.icdra.ch or http://www.who.int/medicines/icdra/en/index/html
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Entecavir : not for use in HIV/HBV co-infection
European Union The Committee for Medicinal Products for Human Use (CHMP) reminds healthcare professionals that entecavir (Baraclude) has not been evaluated for the treatment of patients with chronic hepatitis B virus (HBV) infection who are co-infected with the human immunodeficiency virus (HIV) and are not receiving highly active antiretroviral therapy (HAART). Based on new data, the EMEA advises healthcare professionals that: Baraclude has not been evaluated in HIV/HBV co-infected patients not simultaneously receiving effective HIV treatment. When considering therapy with entecavir in an HIV/HBV co-infected patient not receiving HAART, there appears to be a risk of developing HIV resistance. Until reassuring data become available, Baraclude should only be considered in this setting under exceptional circumstances.
Reference: European Medicines Agency, Public Statement, EMEA/79902/20075. March 2007.
Deferasirox is indicated in the management of chronic iron overload in patients with transfusion-dependent anaemias aged 6 years or older. It is also indicated in the management of chronic iron overload in patients with transfusion-dependent anaemias aged two to five who cannot be adequately treated with deferoxamine. Therapy should be initiated and maintained by physicians experienced in the treatment of chronic iron overload due to blood transfusions. Cases of acute renal failure (some with fatal outcome) have been reported following the post-marketing use of deferasirox. For the fatal cases, it is impossible to completely exclude a contributory role of deferasirox to the renal impairment The fact that there was an improvement after stopping the treatment in most of the cases with nonfatal acute renal failure is suggestive of a contributory role. Deferasirox has not been studied in patients with renal impairment.
Reference: Communication from Novartis Pharmaceuticals Canada Inc. on Medeffect at http://www.hc-sc.gc.ca
Safety of oseltamivir
European Union The European Medicines Agency (EMEA) has documented new reports of neuropsychiatric adverse events occurring with the use of oseltamivir (Tamiflu) originating from Japan. These cases have been detected through routine safety monitoring.
Deferasirox: acute renal failure and cytopenias

Canada The manufacturer of deferasirox (Exjade) has updated the safety information regarding reports of acute renal failure and peripheral blood cytopenias.
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The Agencys Committee for Medicinal Products for Human Use (CHMP) has monitored closely all adverse drug reactions reported in connection with the use of oseltamivir since it was introduced in the European Union in 2003. The CHMP recommended an update of the product information on neuropsychiatric side effects: Convulsion, depressed level of consciousness, abnormal behaviour, hallucinations and delirium have been reported during Tamiflu administration, leading in rare cases to accidental injury. Patients, especially children and adolescents should be closely monitored and their healthcare professional should be contacted immediately if the patient shows any signs of unusual behaviour. The EMEA and CHMP will continue to closely monitor any emerging safety information on Tamiflu, including neuropsychiatric disorders. If any concerns emerge, further action will be taken. With these measures in place, the CHMP maintains its opinion that the benefits of Tamiflu outweigh its risks when the product is used according to the adopted recommendations.
Reference: EMEA Press Release, 23 March 2007. Doc. Ref. EMEA/134566/2007. http:// www.emea.europa.eu
the reporter did not see a causal relationship between the adverse drug reaction and salbutamol. Psychiatric effects have also been reported in association with the use of oral corticosteroids and inhaled budesonide, which raises the possibility of a group effect.
Reference: Fluticasone inhalation and behavioural changes in children. Lareb, Netherlands Pharmacovigilance Centre, January 2007 (www.lareb.nl).
Quetiapine: pancreatitis and thrombocytopenia

Canada Quetiapine (Seroquel) is an atypical antipsychotic drug indicated for the management of symptoms of schizophrenia and the acute management of manic episodes associated with bipolar disorder (1). In Canada, quetiapine has been marketed since December 1997. From 1997 to 2006, Health Canada has received 615 domestic reports of adverse reactions suspected of being associated with the use of quetiapine. Nine reports involved cases of pancreatitis and 11 involved cases of thrombocytopenia. Neither of these ARs is mentioned in the Canadian product monograph (1). Pancreatitis The 9 reported cases of pancreatitis involved patients aged 2471 years. In 5 cases, quetiapine was the only suspect drug; in the other cases, reported cosuspect drugs included medications that have been associated with pancreatitis: clozapine, divalproex sodium, fenofibrate and minocycline (2, 3). Acute pancreatitis typically presents as an acute inflammation of the pancreas that may or may not involve the surrounding tissues (2). Gallstones and heavy alcohol use are the most common causes (2). The severity of drug-induced pancreatitis is variable; the majority of pa-
Fluticasone: reports of behavioural changes

Netherlands The Netherlands Pharmacovigilance Centre, Lareb, has received 17 reports of behavioural changes in children associated with the use of inhaled fluticasone propionate or salmeterol/fluticasone propionate (4). In 11 cases, symptoms disappeared when fluticasone propionate was withdrawn. A positive rechallenge was observed in one case. Six patients who had received fluticasone propionate also received salbutamol. However, in all but one case,
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tients recover without any long-term morbidity, but 5% 15% of patients experience life-threatening complications (4). People at risk of drug-induced pancreatitis include elderly patients taking multiple medications, patients who are HIV positive, patients who have cancer and patients receiving immunomodulatory agents (5). Thrombocytopenia The 11 reported cases of thrombocytopenia involved patients aged 2884 years. In 6 cases, quetiapine was the only suspect drug. In 5 cases, reported cosuspect drugs included medications that have been associated with thrombocytopenia: citalopram, clozapine, olanzapine, pantoprazole, rofecoxib and zuclopenthixol (612). Thrombocytopenia is usually defined as a platelet count of less than 150 x 109/L or a 50% decrease in the platelet count from baseline (6). Some reports define druginduced thrombocytopenia as a platelet count of less than 100 x 109/L (6). Although relatively rare, drug-induced thrombocytopenia may be associated with risks of morbidity and mortality (6). Perhaps because of its low incidence and idiosyncratic nature, drug-induced thrombocytopenia has often gone unrecognized during early clinical trials of drugs and was first reported after marketing (6).
Extracted from Canadian Adverse Reaction Newsletter, Volume 17, Number 2, 2007
References 1. Seroquel (quetiapine fumarate tablets) [product monograph]. Mississauga (ON): AstraZeneca Canada Inc.; 2006. 2. Eltookhy A, Pearson NL. Drug-induced pancreatitis. Can Pharmacists J, 2006;139(6): 5860. 3. Gropper D, Jackson CW. Pancreatitis associated with quetiapine use. J Clin Psychopharmacol, 2004;24(3):3435.
4. Kale-Pradhan PB, Conroy JL. Pancreatitis. In: Drug-induced diseases: prevention, detection, and management. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; 2005. p. 53747. 5. Adverse Drug Reactions Advisory Committee (ADRAC). Drug induced pancreatitis. Aust Adv Drug Reactions Bull, 2006;25(6):22. 6. Skirvin JA. Thrombocytopenia. In: Tisdale JE, Miller DA, editors. Drug-induced diseases:
prevention, detection, and management.

Bethesda (MD): American Society of HealthSystem Pharmacists, Inc.; 2005. p. 64959. 7. Kentos A, Robin V, Lambermont M, et al. Probable rofecoxib-induced thrombocytopenia. Rheumatology, 2003;42(5):699700. 8. Hirshberg B, Gural A, Caraco Y. Zuclopenthixol-associated neutropenia and thrombocytopenia. Ann Pharmacother, 2000;34(6): 7402. 9. Huynh M, Chee K, Lau DH. Thrombotic thrombocytopenic purpura associated with quetiapine. Ann Pharmacother, 2005;39(7 8):1346-8. 10. Watson TD, Stark JE, Vesta KS. Pantoprazole-induced thrombocytopenia. Ann Pharmacother, 2006;40(4):75861. 11. Celexa (citalopram hydrobromide tablets) [product monograph]. Montreal: Lundbeck Canada Inc.; 2006. 12. Clozaril (clozapine tablets) [product monograph]. Dorval (QC): Novartis Pharmaceuticals Canada Inc.; 2006.
Aprotinin: hypersensitivity reactions and renal dysfunction

Canada Health Canada has informed hospitals and pharmacies of an association of aprotinin (Trasylol) with hypersensitivity reactions and renal dysfunction. Aprotinin is indicated for prophylactic use to reduce perioperative blood loss and the need for blood transfusion in
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those patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft (CABG) surgery who are at increased risk for blood loss and blood transfusion requirement. The authorized indication for Trasylol is restricted to those patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft (CABG) surgery who are at increased risk for blood loss and blood transfusion. Trasylol administration may cause fatal and nonfatal anaphylactic or anaphylactoid reactions. Fatal reactions have occurred with an initial (test) dose as well as with any of the components of the dose regimen. Fatal reactions have also occurred in situations where the initial (test) dose was tolerated. As a result, Trasylol should only be administered in operative settings where cardiopulmonary bypass can be rapidly initiated. The risk for anaphylactic or anaphylactoid reactions is increased among patients with prior aprotinin exposure, and a history of any prior aprotinin exposure must be sought prior to Trasylol administration. The risk for a fatal reaction appears to be greater upon re-exposure. As a result, administration of Trasylol to patients with a known or suspected previous aprotinin exposure during the last 12 months is contraindicated. Trasylol administration increases the risk of renal dysfunction and may increase the need for dialysis in the perioperative period. This risk may be especially increased for patients with preexisting renal impairment or those who receive aminoglycoside antibiotics or drugs that alter renal function.
Reference: Information Update 2007-36, 31 March 2007: Communication from Bayer Inc. on http://.www.hc-sc.gc.ca
Metoclopramide in children: extrapyramidal symptoms

Netherlands Following an increase in the number of registered cases of extrapyramidal symptoms in children receiving metoclopramide, the Medicines Evaluation Board has restricted the use of metoclopramide in this population to treatment of severe nausea and vomiting of known origin, and only if treatment with other products is ineffective or is not possible. The MEB considers there are better alternatives to metoclopramide. For example, domperidone is a better choice in treating post-operative nausea in children. Domperidone is also the drug of choice in treating migraine in children because the risk of extrapyramidal effects is lower than with metoclopramide. Similarly, 5-HT3 receptor antagonists (e.g. ondansetron) are the drugs of choice in nausea due to strongly emetogenic chemotherapy because of better efficacy and fewer adverse events.
Reference: News and Publications. The Medicines Evaluation Board, the Netherlands, 21 February 2007. http://www.cbg-meb.nl/uk/ nieuws
Drug-eluting stents: to be used with caution

Sweden The Swedish Medical Products Agency (MPA), in conjunction with the National Board of Health and Welfare and the Swedish Society of Cardiology, has recommended utmost restraint in the use of drug-eluting stents. The recommendation was based on the results of clinical studies, including the Swedish Coronary and Angioplasty Registry (SCAAR) study that showed increased risk of thrombosis associated with the use of drug-eluting stents. The results of the SCAAR study and four other randomized studies showed that drug-eluting stents
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have no advantages in terms of myocardial infarction or mortality, compared with bare-metal stents; in addition, the SCAAR study data indicated a small, long-term increased risk of these events. According to the MPA, drug-eluting stents must only be used in patients for whom no other treatment alternative exists or in patients who are at greatly increased risk of restenosis and for whom the effect of restenosis is expected to be severe.
Reference: Swedish Medical Products Agency, 13 February 2007. http://www.lakemedelesverket.se.
mia is due to the disease itself. Therefore, none of the ESAs are indicated in this patient population. Recent clinical studies have provided new safety information regarding the use of ESAs, including risks of tumour progression and serious cardiovascular events. ESAs increased the risk of death and of serious cardiovascular adverse events in patients with cancer or renal failure, when treated to a target haemoglobin level of greater than 120 g/L. An increased risk of death was seen in cancer patients with active malignant disease, who were not being treated with either radiation or chemotherapy and who were treated with ESAs to a target haemoglobin level of 120 g/L. ESAs are not indicated in this patient population. ESAs shortened the time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy; in addition, ESAs decreased overall survival and increased deaths at 4 months, attributed to disease progression in patients with metastatic breast cancer receiving chemotherapy, when these groups of patients were treated to a target haemoglobin level of greater than 120 g/L.
Reference: Communication from Amgen Canada, Inc. 16 April 2007 on http://www.hcsc.gc.ca
Darbepoetin alfa and epoetin alfa: update for non-myeloid malignancies

Canada The manufacturers of the erythropoiesis-stimulating agents (ESAs), have updated safety information based on completed or ongoing clinical studies regarding treatment with darbepoetin alfa (Aranesp) and epoetin alfa (Eprex). Darbepoetin alfa is indicated for the treatment of anaemia associated with chronic renal failure, and for the treatment of anaemia in patients with non-myeloid malignancies, where anaemia is due to the effect of concomitantly administered chemotherapy. Epoetin alfa (Eprex) is indicated for the treatment of anaemia associated with chronic renal failure, the treatment of anaemia in patients with non-myeloid malignancies, where anaemia is due to the effect of concomitantly administered chemotherapy, the treatment of anaemia in zidovudine-treated/HIV-infected patients, and for the treatment of patients undergoing major elective surgery to facilitate autologous blood collection, and to reduce allogeneic blood exposure. Epoetin alfa is no longer indicated in the treatment of anaemia in patients with non-myeloid malignancies, where anae-
Ayurvedic and Chinese medicines: heavy metals

Australia The Therapeutic Goods Administration (TGA) has released a statement about the safety of Ayurvedic medicines in Australia, in response to recent research into the toxic content of heavy metals found in some Ayurvedic medicines (1). There are several possible explanations for the presence of heavy metals in traditional herbal remedies (2). Salts of
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heavy metals (for example those of lead, mercury and arsenic) are used as principal ingredients in some traditional Indian and (to a lesser extent) Chinese herbal remedies (4). In addition, cross-contamination of ingredients can occur between these types of products and products not intended to contain metal salts if manufacturing conditions are not controlled. The possibility of contamination and adulteration should be considered for any herb or herbal medicine purchased overseas or imported for personal use, or obtained over the internet.
Extracted from Australian Adverse Drug Reactions Bulletin, Volume 26, Number 1, 2007
References 1. Safety of Ayurvedic medicine in Australia. www.tga.gov.au/cm/ayurvedic.htm 2. Ernst E. Contamination of herbal medicines. The Pharmaceutical Journal 2005; 275; 167 3. Pharmacopoeia of the Peoples Republic of China. Beijing, China: Peoples Medical Publishing House 2005.
Another FDA review of ADHD medicines revealed a slight increased risk (about 1 per 1000) for drug-related psychiatric adverse events, such as hearing voices, becoming suspicious for no reason, or becoming manic, even in patients who did not have previous psychiatric problems. The medicines that are the focus of the revised labelling and new Patient Medication Guides include the following:
Adderall (mixed salts of a single entity amphetamine product) Tablets Adderall XR (mixed salts of a single entity amphetamine product) Extended-Release Capsules Concerta (methylphenidate hydrochloride) Extended-Release Tablets Daytrana (methylphenidate) Transdermal System Desoxyn (methamphetamine HCl) Tablets Dexedrine (dextroamphetamine sulfate) Spansule Capsules and Tablets Focalin (dexmethylphenidate hydrochloride) Tablets Focalin XR (dexmethylphenidate hydrochloride) Extended-Release Capsules Metadate CD (methylphenidate hydrochloride) Extended-Release Capsules Methylin (methylphenidate hydrochloride) Oral Solution Methylin (methylphenidate hydrochloride) Chewable Tablets Ritalin (methylphenidate hydrochloride) Tablets Ritalin SR (methylphenidate hydrochloride) Sustained-Release Tablets
ADHD drugs: cardiovascular and psychiatric events

United States of America The Food and Drug Administration (FDA) has directed the manufacturers of all drug products approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) to develop Patient Medication Guides concerning risks of possible cardiovascular and psychiatric events. An FDA review of reports of serious cardiovascular adverse events in patients taking usual doses of ADHD products revealed reports of sudden death in patients with underlying serious heart problems or defects, and reports of stroke and heart attack in adults with certain risk factors.
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Ritalin LA (methylphenidate hydrochloride) Extended-Release Capsules Strattera (atomoxetine HCl) Capsules Reference: FDA News, P07-26, 21 February 2007 with draft Patient Medication Guides for each product at http://www.fda.gov/cder/drug/ infopage/ADHD/default.htm.
tion may be associated with serious effects such as intestinal obstruction, bowel perforation and toxic megacolon. In addition to reports of constipation associated with clozapine, there have been three reports of paralytic ileus and a further three reports of oesophageal dysmotility. These case reports suggest that clozapine may reduce GI motility throughout the gut, resulting in complications higher in the GI tract. Many anticholinergic drugs can cause GI dysmotility, but clozapine has a much more potent effect through its interaction with multiple receptors (including anticholinergic and serotonergic receptors) affecting GI activity. This action is exacerbated by co-prescription of anticholinergic agents such as benztropine and tricyclic antidepressants.
References 1. Alvir JMJ, Lieberman JA, Safferman AZ, et al. Clozapine-induced agranulocytosis. New England Journal of Medicine 1993;329:162167 2. PM Ellis. Clozapine: Fatal constipation more common than fatal agranulocytosis. Prescriber Update. March 2007. http:// www.medsafe.govt.nz
Clozapine can impair motility of the entire GI tract

New Zealand Clozapine (Clozaril, Clopine) is an atypical antipsychotic that is effective for treatment-resistant schizophrenia. It causes agranulocytosis in up to 1% of patients (1) and regular monitoring of neutrophil counts is mandatory throughout treatment. In New Zealand one death from agranulocytosis has been reported. In contrast, four deaths from complications of severe constipation have been reported to the Intensive Medicines Monitoring Programme. Health professionals are reminded that the gastrointestinal (GI) effects of clozapine are potentially serious. Constipation is often regarded as a frequent, minor side effect of clozapine. However, review of New Zealand reports shows that clozapine-induced constipa-
Spontaneous monitoring systems are useful in detecting signals of relatively rare, serious and unexpected adverse drug reactions. A signal is defined as "reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously. Usually, more than a single report is required to generate a signal, depending upon the seriousness of the event and the quality of the information". All signals must be validated before any regulatory decision can be made.
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Essential Medicines
15th Model List
of Essential Medicines
Model List updated The WHO Model List of Essential Medicines allows countries to select medicines of public health priority, address problems of cost and availability and provides guidance to pharmaceutical manufacturers on medicine needs. During its 2007 meeting in Geneva, the WHO Expert Committee on Essential Medicines made a number of important updates to the Model List of Essential Medicines (set out on the following pages). These included the addition of five fixed-dose-combinations to treat HIV/ AIDS in adults, two of which are available in generic form, and antimalarials recommended by WHO. Five oral liquid formulations were included for children three for epilepsy, one for children born prematurely, and one new medicine for HIV/AIDS. Three other epilepsy medicines were included in the form of chewable, dispersable tablets which are also effective in children. A medicines list for children Following recommendations from the Expert Committee, work will begin to create a list if essential medicines specifically tailored to childrens needs. A group of experts will meet in July 2007 to begin work on a list of medicines to address diseases of high mortality and morbidity in children. Children suffer from the same illnesses as adults but they are more seriously affected by certain conditions such as respiratory tract infections, malaria and diarrhoeal diseases particularly in developing countries. An estimated 10.6 million children under five die every year, many from treatable conditions. In 2005, 2.3 million children under 15 years were HIV positive. In spite of the huge need, there are few formulations appropriate for children or that can be easily consumed by a child. At present, children must often take crushed adult tablets, with little evidence to guide the efficacy and safety of the dose. When medicines do exist in the right dosage they are usually in syrup form, which may pose supply, storage and pricing problems in developing countries. The challenge for children becomes more acute when they are affected by a condition requiring combination therapy, such as HIV/AIDS and malaria. In these cases, fixed dose combination tablets are required. While production of adult fixeddose-combinations is increasing, these are lacking for children. In addition, antiretrovirals for children are currently three times more expensive than the adult versions. WHO will also work with partners to advocate innovation and research into childrens medicines, manufacture of new dosage forms and new formulas, and mechanisms to relay information about childrens medicines to countries quickly and effectively.
Reference: WHO News Release. WHO/17. 13 April 2007 http://www.who.int
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WHO Model List of Essential Medicines

15th Edition, revised March 2007
Explanatory Notes
The core list presents a list of minimum medicine needs for a basic health care system, listing the most efficacious, safe and cost-effective medicines for priority conditions. Priority conditions are selected on the basis of current and estimated future public health relevance, and potential for safe and cost-effective treatment. The complementary list presents essential medicines for priority diseases, for which specialized diagnostic or monitoring facilities, and/or specialist medical care, and/or specialist training are needed. In case of doubt medicines may also be listed as complementary on the basis of consistent higher costs or less attractive cost-effectiveness in a variety of settings. The square box symbol ( ) is primarily intended to indicate similar clinical performance within a pharmacological class. The listed medicine should be the example of the class for which there is the best evidence for effectiveness and safety. In some cases, this may be the first medicine that is licensed for marketing; in other instances, subsequently licensed compounds may be safer or more effective. Where there is no difference in terms of efficacy and safety data, the listed medicine should be the one that is generally available at the lowest price, based on international drug price information sources. Therapeutic equivalence is only indicated on the basis of reviews of efficacy and safety and when consistent with WHO clinical guidelines. National lists should not use a similar symbol and should be specific in their final selection, which would depend on local availability and price. Medicines are listed in alphabetical order, within sections. The presence of an entry on the Essential Medicines List carries no assurance as to pharmaceutical quality. It is the responsibility of each local regulatory authority to ensure that each brand is of appropriate pharmaceutical quality (including stability) and that, when relevant, different brands are interchangeable. Dosage forms of medicines are listed in alphabetical order and there is no implication of preference for one form over another. Standard treatment guidelines should be consulted for information on appropriate dosage forms. Entries of the type oral liquid are intended to permit any solution, suspension or other form of liquid. Granules for reconstitution as an oral liquid may substitute for oral liquids, and typically carry benefits in the form of better stability and lower transport costs. If more than one type of oral liquid is available on the same market (e.g. solution, suspension, granules for reconstitution), they may be interchanged and in such cases should be bioequivalent. It is preferable that oral liquids do not contain sugar, and that solutions for children do not contain alcohol. Entries of the type tablet are intended to allow various forms of immediate-release tablet such as uncoated, film-coated, crushable, chewable, dispersible etc. Enteric coating, on the other hand, modifies drug release, and enteric-coated products are a modified release dosage form. Crushable, chewable and dispersible tablets may be easier to administer to paediatric populations and to the elderly.
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15th Model List of Essential Medicines
1. Anaesthetics
1.1 General anaesthetics and oxygen
halothane
inhalation injection: 50 mg (as hydrochloride)/ ml in 10-ml vial inhalation inhalation (medicinal gas) powder for injection: 0.5 g, 1.0 g (sodium salt) in ampoule
ketamine
2. Analgesics, antipyretics, nonsteroidal anti-inflammatory medicines (NSAIMs), medicines used to treat gout and disease modifying agents in rheumatoid disorders (DMARDs)
2.1 Nonopioids and nonsteroidal antiinflammatory medicines (NSAIMs)
acetylsalicylic acid Suppository: 50150 mg Tablet: 100500 mg
nitrous oxide oxygen

thiopental
1.2 Local anaesthetics

bupivacaine
Injection: 0.25%; 0.5% (hydrochloride) in via.
ibuprofen paracetamol*
Tablet: 200 mg; 400 mg Oral liquid: 125 mg/5 m Suppository: 100 mg Tablet: 100500 mg
Injection for spinal anaesthesia: 0.5% (hydrochloride) in 4-ml ampoule to be mixed with 7.5% glucose solution
lidocaine
Injection: 1%; 2% (hydrochloride) in vial Injection for spinal anaesthesia: 5% (hydrochloride) in 2-ml ampoule to be mixed with 7.5% glucose solution Topical forms: 24% (hydrochloride)
* Not recommended for anti-inflammatory use due to lack of proven benefit to that effect.
2.2 Opioid analgesics

codeine morphine Tablet: 30 mg (phosphate) Injection: 10 mg (morphine hydrochloride or morphine sulfate) in 1-ml ampoule Oral liquid: 10 mg (morphine hydrochloride or morphine sulfate)/5 ml Tablet: 10 mg (morphine sulfate) Tablet (prolonged release): 10 mg; 30 mg; 60 mg (morphine sulfate)
lidocaine + epinephrine (adrenaline)
Dental cartridge: 2% (hydrochloride) + epinephrine 1:80 000
Injection: 1%; 2% (hydrochloride) + epinephrine 1:200 000 in vial
Complementary List
ephedrine
Injection: 30 mg (hydrochloride)/ml in 1-ml ampoule (For use in spinal anaesthesia during delivery, to prevent hypotension)
2.3 Medicines used to treat gout

allopurinol Tablet: 100 mg
1.3 Preoperative medication and sedation for short-term procedures

atropine
diazepam
2.4 Disease modifying agents used in rheumatoid disorders (DMARDs)

chloroquine Tablet: 100 mg; 150 mg (as phosphate or sulfate).
Injection: 1 mg (sulfate) in 1-ml ampoule Injection: 5 mg/ml in 2-ml ampoule Tablet: 5 mg
Complementary List
azathioprine methotrexate penicillamine sulfasalazine
Tablet: 50 mg Tablet: 2.5 mg (as sodium salt) Capsule or tablet: 250 mg Tablet: 500 mg
morphine promethazine
Injection: 10 mg (sulfate or hydrochloride) in 1-ml ampoule Oral liquid: 5 mg (hydrochloride)/5 ml
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3. Antiallergics and medicines used in anaphylaxis

chlorphenamine
sodium nitrite sodium thiosulfate
Injection: 30 mg/ml in 10-ml ampoule Injection: 250 mg/ml in 50-ml ampoule
Injection: 10 mg (hydrogen maleate) in 1-ml ampoule Tablet: 4 mg (hydrogen maleate)
dexamethasone
Injection: 4 mg dexamethasone phosphate (as disodium salt) in 1-ml ampoule Injection: 1 mg (as hydrochloride or hydrogen tartrate) in 1-ml ampoule
5. Anticonvulsants/antiepileptics
carbamazepine Oral liquid: 100 mg/5 ml Tablet (chewable): 100 mg; 200 mg Tablet (scored): 100 mg; 200 mg
diazepam
epinephrine (adrenaline)
hydrocortisone
prednisolone*
Powder for injection: 100 mg (as sodium succinate) in vial Tablet: 5 mg; 25 mg
Injection: 5 mg/ml in 2-ml ampoule (intravenous or rectal) Injection: 500 mg/ml in 2-ml ampoule; 500 mg/ml in 10-ml ampoule
magnesium sulfate*
* There is no evidence for complete clinical similarity between prednisolone and dexamethasone at high doses.
* For use in eclampsia and severe pre-eclampsia and not for other convulsant disorders.
phenobarbital Injection: 200 mg/ml (phenobarbital sodium)
4. Antidotes and other substancess used in poisonings

4.1 Non-specific
charcoal, activated Powder
Oral liquid: 15 mg/5 ml (phenobarbital) or 5 ml (phenobarbital sodium) Tablet: 15-100 mg (phenobarbital)
4.2 Specific
acetylcysteine atropine calcium gluconate deferoxamine dimercaprol DL-methionine methylthioninium chloride (methylene blue) naloxone penicillamine Injection: 200 mg/ml in 10-ml ampoule Injection: 1 mg (sulfate) in 1-ml ampoule Injection: 100 mg/ml in 10-ml ampoule Powder for injection: 500 mg (mesilate) in vial Injection in oil: 50 mg/ml in 2-ml ampoule Tablet: 250 mg Injection: 10 mg/ml in 10-ml ampoule phenytoin
Capsule: 25 mg; 50 mg;

100 mg (sodium salt)
Injection: 50 mg/ml in 5-ml vial (sodium salt) Oral liquid: 25-30 mg/5 ml.* Tablet: 25 mg; 50 mg; 100 mg (sodium salt) Tablet (chewable): 50 mg
* The presence of both 25 mg/5 ml and 30 mg/5 ml strengths on the same market would cause confusion in prescribing and dispensing and should be avoided.
valproic acid Oral liquid: 200 mg/5 ml Tablet (crushable): 100 mg Tablet (enteric-coated): 200 mg; 500 mg (sodium valproate)
Injection: 400 micrograms (hydrochloride) in 1-ml ampoule Capsule or tablet: 250 mg Powder for oral administration
Complementary List
potassium ferric hexacyanoferrate(II) -2H20 (Prussian blue) sodium calcium edetate
ethosuximide
Capsule: 250 mg Oral liquid: 250 mg/5 ml
Injection: 200 mg/ml in 5-ml ampoule
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6. Anti-infective medicines
6.1 Anthelminthics
6.1.1 Intestinal anthelminthics albendazole levamisole
mebendazole
ampicillin
Powder for injection: 500 mg; 1 g (as sodium salt) in vial Powder for injection: 1.44 g benzylpenicillin (=2.4 million IU) in 5-ml vial
benzathine benzylpenicillin
Tablet (chewable): 400 mg Tablet: 50 mg; 150 mg (as hydrochloride) Tablet (chewable): 100 mg; 500 mg Tablet (chewable): 500 mg
benzylpenicillin
Powder for injection: 600 mg (= 1 million IU); 3 g (= 5 million IU) (sodium or potassium salt) in vial Powder for injection: 1 g (as sodium salt) in vial
cefazolin*
niclosamide*
* For surgical prophylaxis.

cefixime* Capsule: 400 mg
* Niclosamide is listed for use when praziquantel treatment fails.

praziquantel pyrantel Tablet: 150 mg; 600 mg Oral liquid: 50 mg (as embonate)/ml Tablet (chewable): 250 mg (as embonate) 6.1.2 Antifilarials ivermectin Tablet (scored): 3 mg; 6 mg
* Only listed for single-dose treatment of uncomplicated ano-genital gonorrhoea.

cloxacillin
Powder for injection: 500 mg (as sodium salt) in vial Capsule: 500 mg; 1 g (as sodium salt) Powder for oral liquid: 125 mg (as sodium salt)/5 ml
Complementary List
phenoxymethylpenicillin Powder for oral liquid: 250 mg (as potassium salt)/5 ml
diethylcarbamazine suramin sodium
Tablet: 50 mg; 100 mg (dihydrogen citrate) Powder for injection: 1 g in vial
Tablet: 250 mg (as potassium salt) procaine benzylpenicillin Powder for injection: 1 g (=1 million IU); 3 g (=3 million IU) in vial
6.1.3 Antischistosomals and antitrematode medicine praziquantel triclabendazole Tablet: 600 mg Tablet: 250 mg
Complementary List
ceftazidime
Powder for injection: 250 mg (as pentahydrate) in vial Powder for injection: 250 mg, 1 g (as sodium salt) in vial Powder for injection: 250 mg (as monohydrate) + 250 mg (as sodium salt); 500 mg (as monohydrate) + 500 mg (as sodium salt) in vial
ceftriaxone
Complementary List
oxamniquine* Capsule: 250 mg Oral liquid: 250 mg/5 ml
imipenem* + cilastatin *
* Oxamniquine is listed for use when praziquantel treatment fails.
6.2 Antibacterials
6.2.1 Beta Lactam medicines amoxicillin Capsule or tablet: 250 mg; 500 mg (anhydrous) Powder for oral liquid: 125 mg (anhydrous)/5 ml amoxicillin + clavulanic acid Tablet: 500 mg + 125 mg
* Only listed for the treatment of life-threatening hospital-based infection due to suspected or proven multidrug-resistant infection.
6.2.2 Other antibacterials azithromycin* Capsule: 250 mg or 500 mg Oral liquid: 200 mg/5 ml
* Only listed for single-dose treatment of genital Chlamydia trachomatis and of trachoma.
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chloramphenicol
Capsule: 250 mg Oily suspension for injection: 0.5 g (as sodium succinate)/ml in 2-ml ampoule
sulfadiazine
Injection: 250 mg (sodium salt) in 4-ml ampoule Tablet: 500 mg
vancomycin
Oral liquid: 150 mg (as palmitate)/5 ml Powder for injection: 1 g (sodium succinate) in vial
ciprofloxacin*
Powder for injection: 250 mg (as hydrochloride) in vial
Tablet: 250 mg (as hydrochloride)
* Final selection depends on indication for use.

doxycycline* Capsule or tablet: 100 mg (hydrochloride)
6.2.3 Antileprosy medicines Medicines used in the treatment of leprosy should never be used except in combination. Combination therapy is essential to prevent the emergence of drug resistance. Colour coded blister packs (MDT blister packs) containing standard two medicine (paucibacillary leprosy) or three medicine (multibacillary leprosy) combinations for adult and childhood leprosy should be used. MDT blister packs can be supplied free of charge through WHO. clofazimine Capsule: 50 mg; 100 mg Tablet: 25 mg; 50 mg; 100 mg Capsule or tablet: 150 mg; 300 mg

erythromycin
Capsule or tablet: 250 mg (as stearate or ethyl succinate) Powder for injection: 500 mg (as lactobionate) in vial Powder for oral liquid: 125 mg (as stearate or ethyl succinate)
dapsone rifampicin
6.2.4 Antituberculosis medicines ethambutol isoniazid Tablet: 100400 mg (hydrochloride) Tablet: 100300 mg Tablet (scored): 50 mg isoniazid + ethambutol pyrazinamide Tablet: 150 mg + 400 mg Tablet: 400 mg Tablet (dispersible): 150 mg Tablet (scored): 150 mg rifampicin Capsule or tablet: 150 mg; 300 mg
gentamicin*
Injection: 10 mg; 40 mg (as sulfate)/ml in 2-ml vial

metronidazole
Injection: 500 mg in 100-ml vial
Oral liquid: 200 mg (as benzoate)/5 ml Suppository: 500 mg; 1 g Tablet: 200-500 mg nitrofurantoin spectinomycin sulfamethoxazole + trimethoprim Tablet: 100 mg Powder for injection: 2 g (as hydrochloride) in vial Injection: 80 mg + 16 mg/ml in 5-ml and 10-ml ampoules
rifampicin + isoniazid Tablet: 60 mg + 30 mg; 150 mg + 75 mg; 300 mg + 150 mg 60 mg + 60 mg (For intermittent use three times weekly) 150 mg + 150 mg (For intermittent use three times weekly) rifampicin + isoniazid + ethambutol rifampicin + isoniazid + pyrazinamide Tablet: 150 mg + 75 mg + 275 mg Tablet: 60 mg + 30 mg + 150 mg; 150 mg + 75 mg + 400 mg
Oral liquid: 200 mg + 40 mg/5 ml Tablet: 100 mg + 20 mg; 400 mg + 80 mg trimethoprim Tablet: 100 mg; 200 mg
Complementary List
clindamycin
Capsule: 150 mg Injection: 150 mg (as phosphate)/ml
150 mg + 150 mg + 500 mg (For intermittent use three times weekly) rifampicin + isoniazid + Tablet: 150 mg + 75 mg + pyrazinamide + ethambutol 400 mg + 275 mg
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streptomycin
Powder for injection: 1 g (as sulfate) in vial
6.4.2 Antiretrovirals Based on current evidence and experience of use, medicines in the following three classes of antiretrovirals are included as essential medicines for treatment and prevention of HIV (prevention of motherto-child transmission and post exposure prophylaxis). The Committee emphasizes the importance of using these products in accordance with global and national guidelines. The Committee recommends and endorses the use of fixed-dose combinations and the development of appropriate new fixed-dose combinations, including modified dosage forms, non-refrigerated products and paediatric dosage forms with assured pharmaceutical quality.
Complementary List
Reserve second-line drugs for the treatment of multidrug-resistant tuberculosis (MDR-TB) should be used in specialized centres adhering to WHO standards for TB control. amikacin Powder for injection: 1000 mg in vial Granules: 4 g in sachet Tablet: 500 mg capreomycin Powder for injection: 1000 mg in vial cycloserine ethionamide kanamycin ofloxacin* Capsule or tablet: 250 mg Tablet: 125 mg; 250 mg Powder for injection: 1000 mg in vial Tablet: 200 mg; 400 mg
-aminosalicylic acid
6.4.2.1 Nucleoside/nucleotide reverse transcriptase inhibitors

abacavir (ABC) Oral liquid: 100 mg (as sulfate)/5 m Tablet: 300 mg (as sulfate) didanosine (ddI) Buffered powder for oral liquid: 100 mg; 167 mg; 250 mg packets
* Levofloxacin may be an alternative based on availability and programme considerations.
6.3 Antifungal medicines

clotrimazole Vaginal cream: 1%; 10% Vaginal tablet: 100 mg; 500 mg
fluconazole
Capsule (unbuffered enteric-coated): 125 mg; 200 mg; 250 mg; 400 mg Tablet (buffered chewable, dispersible): 25 mg; 50 mg; 100 mg; 150 mg; 200 mg emtricitabine (FTC)* Capsule: 200 mg Oral liquid: 10 mg/ml
Capsule: 50 mg Injection: 2 mg/ml in vial Oral liquid: 50 mg/5 ml
griseofulvin nystatin
Capsule or tablet: 125 mg; 250 mg Lozenge: 100 000 IU Pessary: 100 000 IU Tablet: 100 000 IU; 500 000 IU
* 3TC is an acceptable alternative to FTC, based on knowledge of the pharmacology, the resistance patterns and clinical trials of antiretrovirals.
lamivudine (3TC) Tablet: 150 mg Oral liquid: 50 mg/5 ml stavudine (d4T) Capsule: 15 mg; 20 mg; 30 mg; 40 mg*
Complementary List amphotericin B flucytosine Powder for injection: 50 mg in vial Capsule: 250 mg Infusion: 2.5 g in 250 ml potassium iodide Saturated solution
* The Committee expects this dosage form to be reviewed for possible deletion at the next meeting.
Powder for oral liquid: 5 mg/5 ml tenofovir Capsule: 300 mg (tenofovir disoproxil fumarate equivalent to 245 mg tenofovir disoproxil) Capsule: 100 mg; 250 mg Oral liquid: 50 mg/5 ml Solution for IV infusion injection: 10 mg/ml in 20-ml vial Tablet: 300 mg
6.4 Antiviral medicines

6.4.1 Antiherpes medicines
aciclovir
zidovudine (ZDV or AZT)
Powder for injection: 250 mg (as sodium salt) in vial Tablet: 200 mg
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6.4.2.2 Non-nucleoside reverse transcriptase inhibitors

efavirenz (EFV or EFZ) Capsule: 50 mg; 100 mg; 200 mg Oral liquid: 150 mg/5 ml Tablet: 600 mg nevirapine (NVP) Oral liquid: 50 mg/5 ml Tablet: 200 mg
zidovudine + lamivudine + nevirapine 6.4.3 Other antivirals ribavirin
Tablet: 300 mg + 150 mg + 200 mg
Injection for intravenous administration: 1000 mg and 800 mg in 10-ml phosphate buffer solution Oral solid dosage forms: 200 mg; 400 mg; 600 mg
6.5 Antiprotozoal medicines

6.5.1 Antiamoebic and antigiardiasis medicines diloxanide
metronidazole
6.4.2.3 Protease inhibitors Selection of protease inhibitor(s) from the Model List will need to be determined by each country after consideration of international and national treatment guidelines and experience. Ritonavir is recommended for use in combination as a pharmacological booster, and not as an antiretroviral in its own right.
This section will be reviewed by the Committee as a priority at its next meeting. It is expected that application for a heat stable tablet formulation containing 200/50 mg lopinavir + ritonavir will be submitted for the next meeting. indinavir (IDV) Capsule: 200 mg; 333 mg; 400 mg (as sulfate).
Tablet: 500 mg (furoate) Injection: 500 mg in 100-ml vial
Oral liquid: 200 mg (as benzoate)/5 ml Tablet: 200-500 mg 6.5.2 Antileishmaniasis medicines
meglumine antimoniate
Injection, 30%, equivalent to approximately 8.1% antimony in 5-ml ampoule
lopinavir + Capsule: 133.3 mg + 33.3 mg ritonavir (LPV/r) Oral liquid: 400 mg + 100 mg/5 ml nelfinavir (NFV) Oral powder: 50 mg/g Tablet: 250 mg (as mesilate) ritonavir Oral liquid: 400 mg/5 ml Oral solid dosage form: 100 mg saquinavir (SQV) FIXED-DOSE COMBINATIONS efavirenz + emtricitabine* + tenofovir Tablet: 600 mg + 200 mg + 300 mg Capsule: 200 mg
paromomycin Solution for intramuscular injection: 750 mg/2 ml (as sulfate)
Complementary List
amphotericin B pentamidine
Powder for injection: 50 mg in vial Powder for injection: 200 mg; 300 mg (isetionate) in vial
6.5.3 Antimalarial medicines
6.5.3.1 For curative treatment

Medicines for the treatment of P. falciparum malaria cases should be used in combination. The list currently recommends combinations according to treatment guidelines. The Committee recognizes that not all of these FDCs exist and encourages their development and rigorous testing. The Committee also encourages development and testing of rectal dosage formulations. amodiaquine* Tablet: 153 mg or 200 mg (as hydrochloride)
emtricitabine* + tenofovir Tablet: 200 mg + 300 mg
stavudine + lamivudine + nevirapine Tablet: 30 mg + 150 mg + 200 mg
* To be used (a) in combination with artesunate 50 mg OR (b) may be used alone for the treatment of Plasmodium vivax, P.ovale and P.malariae infections.
artemether Oily injection: 80 mg/ml in 1-ml ampoule
zidovudine + lamivudine Tablet: 300 mg + 150 mg
For use in the management of severe malaria.
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artemether + lumefantrine*
Tablet: 20 mg + 120 mg
mefloquine proguanil*
Tablet: 250 mg (as hydrochloride) Tablet: 100 mg (hydrochloride)
* Not recommended in the first trimester of pregnancy or in children below 5 kg.

artesunate* Injection: ampoules, containing 60 mg anhydrous artesunic acid with a separate ampoule of 5% sodium bicarbonate solution
* For use only in combination with chloroquine.

6.5.4 Antipneumocystosis and antitoxoplasmosis medicines pyrimethamine sulfamethoxazole + trimethoprim Tablet: 25 mg Injection: 80 mg + 16 mg/ml in 5-ml ampoule; 80 mg + 16 mg/ml in 10-ml ampoule
For use in the management of severe malaria. Tablet: 50 mg
* To be used in combination with either amodiaquine, mefloquine or sulfadoxine + pyrimethamine.

chloroquine Oral liquid: 50 mg (as phosphate or sulfate)/5 ml Tablet: 100 mg; 150 mg (as phosphate or sulfate) doxycycline* Capsule: 100 mg (as hydrochloride) Tablet (dispersible): 100 mg (as monohydrate)
Complementary List
pentamidine
Tablet: 200 mg; 300 mg
6.5.5 Antitrypanosomal medicines
6.5.5.1 African trypanosomiasis

Medicines for the treatment of 1st stage African trypanosomiasis pentamidine* Powder for injection: 200 mg (pentamidine isetionate) in vial
* For use only in combination with quinine.

mefloquine* Tablet: 250 mg (as hydrochloride)
* To be used for the treatment of Trypansoma brucei gambiense infection.

suramin sodium* Powder for injection: 1 g in vial.
* To be used in combination with artesunate 50 mg

primaquine* Tablet: 7.5 mg; 15 mg (as diphosphate)
* To be used exclusively for the treatment of the initial phase of T. brucei rhodesiense infection.
Medicines for the treatment of 2nd stage African trypanosomiasis eflornithine melarsoprol Injection: 200 mg (hydrochloride)/ml in 100-ml bottle Injection: 3.6% solution, 5-ml ampoules (180 mg of active compound)
* Only for use to achieve radical cure of P.vivax and P.ovale infections, given for 14 days.
quinine* Injection: 300 mg quinine hydrochloride/ml in 2-ml ampoule Tablet: 300 mg (quinine sulfate) or 300 mg (quinine bisulfate)
* For use only in the management of severe malaria, and should be used in combination with doxycycline.
sulfadoxine + * pyrimethamine Tablet: 500 mg + 25 mg
6.5.5.2 American trypanosomiasis

benznidazole nifurtimox Tablet: 100 mg Tablet: 30 mg; 120 mg; 250 mg
* Only in combination with artesunate 50 mg

6.5.3.2 For prophylaxis
chloroquine* Oral liquid: 50 mg (as phosphate or sulfate)/5 ml Tablet: 150 mg (as phosphate or sulfate)
7. Antimigraine medicines
7.1 For treatment of acute attack
acetylsalicylic acid paracetamol Tablet: 300-500 mg Tablet: 300-500 mg
* For use only in central American regions for P.vivax.

doxycycline Capsule or tablet: 100 mg ( hydrochloride)
7.2 For prophylaxis

propranolol
Tablet: 20 mg; 40 mg (hydrochloride)
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8. Antineoplastic, immunosuppressives and medicines used in palliative care

8.1 Immunosuppressive medicines
Complementary List azathioprine Powder for injection: 100 mg (as sodium salt) in vial Tablet: 50 mg ciclosporin Capsule: 25 mg Concentrate for injection: 50 mg/ml in 1-ml ampoule for organ transplantation
mercaptopurine methotrexate
Tablet: 50 mg Powder for injection: 50 mg (as sodium salt) in vial Tablet: 2.5 mg (as sodium salt)
procarbazine vinblastine vincristine
Capsule: 50 mg (as hydrochloride) Powder for injection: 10 mg (sulfate) in vial Powder for injection: 1 mg; 5 mg (sulfate) in vial
8.3 Hormones and antihormones

Complementary List
dexamethasone
8.2 Cytotoxic medicines

This section is expected to be reviewed at the next meeting.
Injection: 4 mg dexamethasone phosphate (as disodium salt) in 1-ml ampoule Powder for injection: 100 mg (as sodium succinate) in vial Tablet: 5 mg; 25 mg
hydrocortisone
Complementary List
prednisolone*
asparaginase bleomycin calcium folinate
Powder for injection: 10 000 IU in vial Powder for injection: 15 mg (as sulfate) in vial Injection: 3 mg/ml in 10-ml ampoule Tablet: 15 mg
* There is no evidence for complete clinical similarity between prednisolone and dexamethasone at high doses. tamoxifen Tablet: 10 mg; 20 mg (as citrate)
8.4 Medicines used in palliative care

The WHO Expert Committee recognizes the importance of listing specific medicines in the Palliative Care Section. Some medicines currently used in palliative care are included in the relevant sections of the Model List, according to their therapeutic use, e.g. analgesics. The Guidelines for Palliative Care that were referenced in the previous list are in need of update. The Committee expects applications for medicines needed for palliative care to be submitted for the next meeting.
chlorambucil cisplatin cyclophosphamide
Tablet: 2 mg Powder for injection: 10 mg; 50 mg in vial Powder for injection: 500 mg in vial Tablet: 25 mg
cytarabine dacarbazine dactinomycin daunorubicin doxorubicin etoposide
Powder for injection: 100 mg in vial Powder for injection: 100 mg in vial Powder for injection: 500 micrograms in vial Powder for injection: 50 mg (as hydrochloride) Powder for injection: 10 mg; 50 mg (hydrochloride) in vial Capsule: 100 mg Injection: 20 mg/ml in 5-ml ampoule
9. Antiparkinsonism medicines
biperiden Injection: 5 mg (lactate) in 1-ml ampoule Tablet: 2 mg (hydrochloride) levodopa + carbidopa Tablet: 100 mg + 10 mg; 250 mg + 25 mg
10. Medicinces affecting the blood

10.1 Antianaemia medicines
ferrous salt Oral liquid: equivalent to 25 mg iron (as sulfate)/ml
fluorouracil
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Tablet: equivalent to 60 mg iron ferrous salt + Tablet equivalent to 60 mg iron + folic acid 400 micrograms folic acid (Nutritional supplement for use during pregnancy) folic acid hydroxocobalamin Tablet: 1 mg; 5 mg Injection: 1 mg in 1-ml ampoule
glyceryl trinitrate
isosorbide dinitrate
Tablet (sublingual): 500 micrograms Tablet (sublingual): 5 mg Tablet: 40 mg; 80 mg (hydrochloride)
verapamil
12.2 Antiarrhythmic medicines

This subsection will be reviewed at the next meeting of the Expert Committee.
atenolol
10.2 Medicines affecting coagulation

heparin sodium Injection: 1000 IU/ml; 5000 IU/ml; 20,000 IU/ml in 1-ml ampoule Injection: 10 mg/ml in 5-ml ampoule Tablet: 10 mg protamine sulfate
warfarin
Tablet: 50 mg; 100 mg Injection: 250 micrograms/ ml in 2-ml ampoule Oral liquid: 50 micrograms/ml Tablet: 62.5 micrograms; 250 micrograms
digoxin
phytomenadione
epinephrine (adrenaline) lidocaine verapamil
Tablet: 1 mg; 2 mg; 5 mg (sodium salt)
Injection: 100 micrograms/ml (as acid tartrate or hydrochloride) in 10-ml ampoule Injection: 20 mg (hydrochloride)/ ml in 5-ml ampoule Injection: 2.5 mg (hydrochloride)/ ml in 2-ml ampoule Tablet: 40 mg; 80 mg (hydrochloride)
11. Blood products and plasma substitutes

11.1 Plasma substitutes
dextran 70*
Injectable solution: 6%
* Polygeline, injectable solution, 3.5% is considered as equivalent
Complementary List
procainamide quinidine
11.2 Plasma fractions for specific use

All plasma fractions should comply with the WHO Requirements for the Collection, Processing and Quality Control of Blood, Blood Components and Plasma Derivatives (Revised 1992). (WHO Technical Report Series, No. 840, 1994, Annex 2).
Injection: 100 mg (hydrochloride)/ml in 10-ml ampoule. Tablet: 200 mg (sulfate)
12.3 Antihypertensive medicines

amlodipine atenolol enalapril
Tablet: 5 mg Tablet: 50 mg; 100 mg Tablet: 2.5 mg Powder for injection: 20 mg (hydrochloride) in ampoule Tablet: 25 mg, 50 mg (hydrochloride)
Complementary List
human normal immunoglobulin
Intravenous administration: 5%, 10% protein solution Intramuscular administration: 16% protein solution
hydralazine*
factor VIII concentrate factor IX complex (coagulation factors, II, VII, IX, X) concentrate
Dried Dried
* Hydralazine is listed for use in the acute management of severe pregnancy-induced hypertension only. Its use in the treatment of essential hypertension is not recommended in view of the availability of more evidence of efficacy and safety of other medicines.
hydrochlorothiazide
12. Cardiovascular medicines

12.1 Antianginal medicines
atenolol
Tablet (scored): 25 mg Tablet: 250 mg
methyldopa*
Tablet: 50 mg; 100 mg
* Methyldopa is listed for use in the management of pregnancy-induced hypertension only. Its use in the
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treatment of essential hypertension is not recommended in view of the availability of more evidence of efficacy and safety of other medicines.
Complementary List
selenium sulfide
Detergent-based suspension: 2%
Complementary List
13.2 Anti-infective medicines

Powder for infusion: 50 mg in ampoule
methylrosanilinium
sodium nitroprusside
Aqueous solution: 0.5% Tincture: 0.5%
chloride (gentian violet) neomycin sulfate + bacitracin Ointment: 5 mg neomycin sulfate + 250 IU bacitracin zinc/g Aqueous solution: 1:10 000
12.4 Medicines used in heart failure

This subsection will be reviewed at the next meeting of the Expert Committee. digoxin Injection: 250 micrograms/ ml in 2-ml ampoule Oral liquid: 50 micrograms/ml Tablet: 62.5 micrograms; 250 micrograms
enalapril furosemide
potassium permanganate silver sulfadiazine
Cream: 1%, in 500-g container
Tablet: 2.5 mg Injection: 10 mg/ml in 2-ml ampoule Tablet: 40 mg
13.3 Anti-inflammatory and antipruritic medicines

betamethasone
Ointment or cream: 0.1% (as valerate) Lotion Ointment or cream: 1% (acetate)
calamine lotion hydrocortisone
hydrochlorothiazide
Tablet (scored): 25 mg
Complementary List
13.4 Astringent medicines

aluminium diacetate Solution: 5%
dopamine
Injection: 40 mg (hydrochloride) in 5-ml vial
12.5 Antithrombotic medicines

acetylsalicylic acid Tablet: 100 mg
13.5 Medicines affecting skin differentiation and proliferation

benzoyl peroxide Lotion or cream: 5% Solution: 5% Ointment: 0.1%-2% Ointment: 5% Solution: 10-25% Solution: 5% Ointment or cream: 10% coal tar dithranol fluorouracil
podophyllum resin
Complementary List
streptokinase
Powder for injection: 1.5 million IU in vial
12.6 Lipid-lowering agents

simvastatin*
Tablet: 5 mg; 10 mg; 20 mg; 40 mg
salicylic acid urea
* For use in high-risk patients.
13. Dermatological medicines (topical)

13.1 Antifungal medicines
benzoic acid + salicylic acid
miconazole
13.6 Scabicides and pediculicides

benzyl benzoate
Lotion: 25% Cream: 5% Lotion: 1%
permethrin
Ointment or cream: 6% + 3% Ointment or cream: 2% (nitrate) Solution: 15%
14. Diagnostic agents

14.1 Ophthalmic medicines
fluorescein Eye drops: 1% (sodium salt)
sodium thiosulfate
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tropicamide
Eye drops: 0.5%
Oral liquid: 75 mg/5 ml Tablet: 150 mg (as hydrochloride) magnesium hydroxide Oral liquid: equivalent to 550 mg magnesium oxide/10 ml
14.2 Radiocontrast media

amidotrizoate
Injection: 140-420 mg iodine (as sodium or meglumine salt)/ ml in 20-ml ampoule Aqueous suspension Injection: 140-350 mg iodine/ ml in 5-ml; 10-ml; 20-ml ampoule
17.2 Antiemetic medicines

metoclopramide Injection: 5 mg (hydrochloride)/ ml in 2-ml ampoule Tablet: 10 mg (hydrochloride) promethazine Injection: 25 mg (hydrochloride)/ ml in 2-ml ampoule Oral liquid: 5 mg (hydrochloride)/5 ml Tablet: 10 mg; 25 mg (hydrochloride)
barium sulfate
iohexol
Complementary List
meglumine iotroxate
Solution: 5-8 g iodine in 100-250 ml
15. Disinfectants and antiseptics

15.1 Antiseptics
chlorhexidine
17.3 Anti-inflammatory medicines

Solution: 5% (digluconate) for dilution Solution: 70% (denatured) Solution: 10%
sulfasalazine
Retention enema Suppository: 500 mg Tablet: 500 mg
ethanol polyvidone iodine
Complementary List
15.2 Disinfectants
chlorine base
hydrocortisone
Retention enema Suppository: 25 mg (acetate)
compound
chloroxylenol
Powder: (0.1% available chlorine) for solution Solution: 4.8% Solution: 2%
( only applies to hydrocortisone retention enema). 17.4 Laxatives

senna
glutaral
16. Diuretics
amiloride
furosemide
Tablet: 7.5 mg (sennosides) (or traditional dosage forms)
Tablet: 5 mg (hydrochloride) Injection: 10 mg/ml in 2-ml ampoule Tablet: 40 mg
17.5 Medicines used in diarrhoea

17.5.1 Oral rehydration oral rehydration salts* glucose: sodium: chloride: potassium: citrate: osmolarity: glucose: sodium chloride: potassium chloride: trisodium citrate dihydrate+: 75 mEq 75 mEq or mmol/l 65 mEq or mmol/l 20 mEq or mmol/l 10 mmol/l 245 mOsm/l 13.5 g/l 2.6 g/l 1.5 g/l 2.9 g/l
hydrochlorothiazide
Tablet (scored): 25 mg
mannitol spironolactone
Injectable solution: 10%; 20% Tablet: 25 mg
17. Gastrointestinal medicines

17.1 Antacids and other antiulcer medicines
aluminium hydroxide Oral liquid: 320 mg/5 ml Tablet: 500 mg
ranitidine
+ trisodium citrate dihydrate may be replaced by sodium hydrogen carbonate (sodium bicarbonate) 2.5 g/l. However, as the stability of this latter formulation is very poor under tropical conditions, it is only recommended when manufactured for immediate use.
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* In cases of cholera, a higher concentration of sodium may be required.

17.5.2 Medicines for diarrhoea in children zinc sulfate* Oral liquid: in 10 mg per unit dosage forms Tablet: in 10 mg per unit dosage forms * In acute diarrhoea zinc sulfate should be used as an adjunct to oral rehydration salts. 17.5.3 Antidiarrhoeal (symptomatic) medicines in adults codeine* Tablet: 30 mg (phosphate)
18.3.3 Intrauterine devices copper-containing device 18.3.4 Barrier methods condoms diaphragms 18.3.5 Implantable contraceptives levonorgestrel-releasing implant Two-rod levonorgestrelreleasing implant, each rod containing 75 mg of levonorgestrel (150 mg total)
18.4 Estrogens
ethinylestradiol*
* The role of this item has been questioned and its continued inclusion on the list will be reviewed at the next meeting of the Expert Committee.
Tablet: 10 micrograms; 50 micrograms
18. Hormones, other endocrine medicines and contraceptives

18.1 Adrenal hormones and synthetic substitutes
Addisons disease is a rare condition; adrenal hormones are already included in section 3.
* The public health relevance and/or comparative efficacy and/or safety of this item has been questioned and its continued inclusion on the list will be reviewed at the next meeting of the Expert Committee.
18.5 Insulins and other antidiabetic agents

glibenclamide insulin injection (soluble) intermediate-acting insulin Tablet: 2.5 mg; 5 mg Injection: 40 IU/ml in 10-ml vial; 100 IU/ml in 10-ml vial Injection: 40 IU/ml in 10-ml vial; 100 IU/ml in 10-ml vial (as compound insulin zinc suspension or isophane insulin) Tablet: 500 mg (hydrochloride)
18.2 Androgens
Complementary List
testosterone
Injection: 200 mg (enantate) in 1-ml ampoule
metformin
18.3 Contraceptives
18.3.1 Oral hormonal contraceptives
ethinylestradiol + levonorgestrel ethinylestradiol + norethisterone
18.6 Ovulation inducers

Complementary List
Tablet: 30 micrograms + 150 micrograms Tablet: 35 micrograms + 1.0 mg
clomifene
Tablet: 50 mg (citrate)
18.7 Progestogens
norethisterone* Tablet: 5 mg * The public health relevance and/or comparative efficacy and/or safety of this item has been questioned and its continued inclusion on the list will be reviewed at the next meeting of the Expert Committee.
levonorgestrel
Tablet: 30 micrograms; 750 micrograms (pack of two); 1.5 mg
18.3.2 Injectable hormonal contraceptives medroxyprogesterone acetate Depot injection: 150 mg/ml in 1-ml vial Injection: 25 mg + 5 mg
Complementary List
medroxyprogesterone acetate*
Tablet: 5 mg
medroxyprogesterone acetate + estradiol cypionate norethisterone enantate
Oily solution: 200 mg/ml in 1-ml ampoule
* The public health relevance and/or comparative efficacy and/or safety of this item has been questioned and its continued inclusion on the list will be reviewed at the next meeting of the Expert Committee.
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18.8 Thyroid hormones and antithyroid medicines

levothyroxine potassium iodide
propylthiouracil
All vaccines should comply with the WHO Requirements for Biological Substances. BCG vaccine cholera vaccine diphtheria vaccine hepatitis A vaccine hepatitis B vaccine
Tablet: 50 micrograms; 100 micrograms (sodium salt) Tablet: 60 mg Tablet: 50 mg
19. Immunologicals
19.1 Diagnostic agents
All tuberculins should comply with the WHO Requirements for Tuberculins (Revised 1985). WHO Expert Committee on Biological Standardization. Thirty-sixth report. (WHO Technical Report Series, No. 745, 1987, Annex 1). tuberculin, purified protein derivative (PPD) Injection
Haemophilus influenzae type b vaccine

influenza vaccine Japanese encephalitis vaccine measles vaccine meningococcal meningitis vaccine mumps vaccine pertussis vaccine pneumococcal vaccine poliomyelitis vaccine rabies vaccine rotavirus vaccine rubella vaccine tetanus vaccine typhoid vaccine varicella vaccine yellow fever vaccine
19.2 Sera and immunoglobulins

All plasma fractions should comply with the WHO Requirements for the Collection, Processing and Quality Control of Blood, Blood Components and Plasma Derivatives (Revised 1992). WHO Expert Committee on Biological Standardization. Forty-third report. (WHO Technical Report Series, No. 840, 1994, Annex 2). anti-D immunoglobulin (human) Injection: 250 micrograms in single-dose vial Injection: 500 IU in vial Injection
antitetanus immunoglobulin (human) antivenom immunoglobulin* * Exact type to be defined locally. diphtheria antitoxin
rabies immunoglobulin
Injection: 10 000 IU; 20 000 IU in vial Injection: 150 IU/ ml in vial
20. Muscle relaxants (peripherally acting) and cholinesterase inhibitors

alcuronium
19.3 Vaccines
Selection of vaccines from the Model List will need to be determined by each country after consideration of international recommendations, epidemiology and national priorities. The list below details the vaccines for which there is either a recommendation from the Strategic Advisory Group of Experts on Immunization (SAGE) (http://www.who.int/immunization/ sage_conclusions/en/index.html) and/or a WHO position paper (http://www.who.int/immunization/documents/positionpapers/en/index.html). This site will be updated as new position papers are published and contains the most recent information and recommendations.
Injection: 5 mg (chloride)/ ml in 2-ml ampoule Injection: 500 micrograms in 1-ml ampoule; 2.5 mg (metilsulfate) in 1-ml ampoule Tablet: 15 mg (bromide)
neostigmine
suxamethonium
Injection: 50 mg (chloride)/ ml in 2-ml ampoule
Powder for injection (chloride), in vial
Complementary List
pyridostigmine
Injection: 1 mg in 1-ml ampoule
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Tablet: 60 mg (bromide)
vecuronium
Powder for injection: 10 mg (bromide) in vial
mifepristone* misoprostol *
Tablet 200 mg tablet 200 micrograms
* Requires close medical supervision. Where permitted under national law and where culturally acceptable.
21. Ophthalmological preparations

This section will be reviewed at the next meeting of the Expert Committee.
22.2 Antioxytocics (tocolytics)

nifedipine Immediate release capsule: 10 mg
21.1 Anti-infective agents

aciclovir Ointment: 3% W/W
gentamicin* Solution (eye drops): 0.3% (sulfate)
23. Peritoneal dialysis solution

Complementary List

tetracycline
intraperitoneal dialysis solution (of appropriate composition)
Parenteral solution
Eye ointment: 1% (hydrochloride)
21.2 Anti-inflammatory agents

prednisolone
24. Psychotherapeutic medicines

24.1 Medicines used in psychotic disorders
chlorpromazine
Solution (eye drops): 0.5% (sodium phosphate)
21.3 Local anaesthetics

tetracaine
Solution (eye drops): 0.5% (hydrochloride)
Injection: 25 mg (hydro chloride)/ml in 2-ml ampoule
Oral liquid: 25 mg (hydrochloride)/5 ml Tablet: 100 mg (hydrochloride)

fluphenazine
21.4 Miotics and antiglaucoma medicines

acetazolamide
pilocarpine
Tablet: 250 mg Solution (eye drops): 2%; 4% (hydrochloride or nitrate) Solution (eye drops): 0.25%; 0.5% (as maleate)
Injection: 25 mg (decanoate or enantate) in 1-ml ampoule Injection: 5 mg in 1-ml ampoule Tablet: 2 mg; 5 mg
haloperidol
timolol
21.5 Mydriatics
atropine Solution (eye drops): 0.1%; 0.5%, 1% (sulfate)
24.2 Medicines used in mood disorders

24.2.1 Medicines used in depressive disorders
amitriptyline
Tablet: 25 mg (hydrochloride) Capsule or tablet: 20 mg (present as hydrochloride)
Complementary List
fluoxetine
Solution (eye drops): 2% (as hydrochloride)
24.2.2 Medicines used in bipolar disorders carbamazepine lithium carbonate valproic acid Tablet (scored): 100 mg; 200 mg Capsule or tablet: 300 mg Tablet (enteric-coated): 200 mg; 500 mg (sodium valproate)
22. Oxytocics and antioxytocics

22.1 Oxytocics
ergometrine
Injection: 200 micrograms (hydrogen maleate) in 1-ml ampoule Injection: 10 IU in 1-ml ampoule
oxytocin
Complementary List
24.3 Medicines used in generalized anxiety and sleep disorders

diazepam
misoprostol
Vaginal tablet: 25 micrograms
Tablet (scored): 2 mg; 5 mg
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24.4 Medicines used for obsessive compulsive disorders and panic attacks
clomipramine Capsule: 10 mg; 25 mg (hydrochloride)
26. Solutions correcting water, electrolyte and acid-base disturbances

26.1 Oral
oral rehydration salts potassium chloride See section 17.5.1 Powder for solution
24.5 Medicines used in substance dependence programmes

Complementary List
methadone*
Concentrate for oral liquid: 5 mg/ml; 10 mg/ml (hydrochloride) Oral liquid: 5 mg/5 ml; 10 mg/5 ml
26.2 Parenteral
glucose Injectable solution: 5%; 10% isotonic; 50% hypertonic
* The square box is added to include buprenorphine. The medicines should only be used within an established support programme.
glucose with Injectable solution: 4% glucose, sodium chloride 0.18% sodium chloride (equivalent to Na+ 30 mmol/l, Cl- 30 mmol/l) potassium chloride Solution: 11.2% in 20-ml ampoule (equivalent to K+ 1.5 mmol/ml, Cl- 1.5 mmol/ml)
25. Medicines acting on the respiratory tract

25.1 Antiasthmatic and medicines for chronic obstructive pulmonary disease
beclometasone
Inhalation (aerosol): 50 micrograms per dose (dipropionate); 250 micrograms (dipropionate) per dose Injection: 1 mg (as hydrochloride or hydrogen tartrate) in 1-ml ampoule Inhalation (aerosol): 20 micrograms/metered dose
sodium chloride Injectable solution: 0.9% isotonic (equivalent to Na+ 154 mmol/l, Cl- 154 mmol/l sodium hydrogen Injectable solution: carbonate 1.4% isotonic (equivalent to Na+ 167 mmol/l, HCO3- 167 mmol/l) Solution: 8.4% in 10-ml ampoule (equivalent to Na 1000 mmol/l, HCO3-1000 mmol/l)
+
ipratropium bromide
salbutamol
sodium lactate,
Injectable solution
Inhalation (aerosol): 100 micrograms (as sulfate) per dose Injection: 50 micrograms (as sulfate)/ml in 5-ml ampoule Oral liquid: 2 mg/5 ml
compound solution
26.3 Miscellaneous
water for injection 2-ml; 5-ml; 10-ml ampoules
27. Vitamins and minerals

ascorbic acid
ergocalciferol
Respirator solution for use in nebulizers: 5 mg (as sulfate)/ml Tablet: 2 mg; 4 mg (as sulfate)
Tablet: 50 mg Capsule or tablet: 1.25 mg (50 000 IU) Oral liquid: 250 micrograms/ ml (10 000 IU/ml)
25.2 Other medicines acting on the respiratory tract

caffeine citrate Injection: 20 mg/ml (equivalent to 10 mg caffeine base/ml) Oral liquid: 20 mg/ml (equivalent to 10 mg caffeine base/ml) iodine
Capsule: 200 mg Iodized oil: 1 ml (480 mg iodine); 0.5 ml (240 mg iodine) in ampoule (oral or injectable); 0.57 ml (308 mg iodine) in dispenser bottle
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nicotinamide
Tablet: 50 mg Tablet: 25 mg (hydrochloride) Capsule: 50 000 IU; 100 000 IU; 200 000 IU (as palmitate)
riboflavin sodium fluoride thiamine
Tablet: 5 mg In any appropriate topical formulation Tablet: 50 mg (hydrochloride)
pyridoxine retinol
Oral oily solution: 100 000 IU (as palmitate)/ml in multidose dispenser Tablet (sugar-coated): 10 000 IU (as palmitate) Water-miscible injection: 100 000 IU (as palmitate) in 2-ml ampoule
Complementary List
calcium gluconate
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Tegaserod: marketing suspension
Canada Marketing and sales of tegaserod hydrogen maleate (Zelnorm) tablets have been suspended in Canada to permit further evaluation of important safety information. Zelnorm is a serotonin 5-HT4 receptor partial agonist indicated for the symptomatic treatment of irritable bowel syndrome with constipation in female patients whose main symptoms are constipation and abdominal pain and/or discomfort and for the treatment of chronic idiopathic constipation in patients under 65 years of age. A recent retrospective analysis of pooled clinical trial data showed that the incidence of cardiovascular ischemic events (1) in patients taking Zelnorm was higher than in those taking placebo: Canadian pharmacists and distributors have been requested to return the product to the company. Patients should discontinue treatment and contact their physician for advice about alternative therapies.
Reference: Communication from Novartis Pharmaceuticals Canada Inc. 30 March 2007 posted by Medeffect at http://www.hc-sc.gc.ca
placebo. Zelnorm is a prescription medication approved for short term treatment of women with irritable bowel syndrome with constipation and for patients younger than 65 years with chronic constipation. Patients should contact their physician to discuss alternative treatments for their condition. Physicians should work with their patients and transition them to other therapies as appropriate to their symptoms and need. Thirteen patients treated with Zelnorm (0.1%) had serious and life-threatening cardiovascular side effects; among these, four patients had a heart attack (one died), six had a type of severe heart chest pain which can quickly turn into a heart attack, and three had a stroke. The FDA has indicated a willingness to consider limited re-introduction of Zelnorm at a later date if a population of patients can be identified in whom the benefits of the drug outweigh the risks. However, before FDA makes a decision about limited re-introduction, any proposed plan would be discussed at a public advisory committee meeting.
Reference: FDA Public Health Advisory, 30 March 2007
Pergolide: voluntary withdrawal of products

United States of America The Food and Drug Administration (FDA) has announced that manufacturers of pergolide drug products, used to treat Parkinson disease, will voluntarily remove these drugs from the market because of the risk of serious damage to patients heart valves. The products being with-
United States of America The Food and Drug Administration (FDA) has informed patients and health care professionals that tegaserod maleate (Zelnorm) will no longer be marketed. A new safety analysis has found a higher chance of heart attack, stroke, and worsening heart chest pain in patients treated with tegaserod compared to
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drawn are Permax, the trade name for pergolide, and two generic versions Two new studies showed that patients with Parkinson disease who were treated with pergolide had an increased chance of serious damage to their heart valves when compared to patients who did not receive the drug. Pergolide is a dopamine agonist used with levodopa and carbidopa to manage the signs and symptoms of Parkinson disease. Healthcare professionals who prescribe pergolide should consider the following: If continued treatment is necessary, another dopamine agonist should be substituted for pergolide. There are other dopamine agonists approved for the treatment of Parkinson disease that are not associated with heart valve damage. Published transition regimens describe the conversion from one DA to another. If treatment with a dopamine agonist is to be discontinued, pergolide should not be stopped abruptly, because rapid discontinuation of all dopamine agonist therapies can be dangerous. Instead, gradually decrease the dose of pergolide. Patients who will be taken off pergolide should be told that other effective options for treatment exist, including three other dopamine agonists that are not associated with damage to heart valves. One of the drugs included in the recent studies showing increased chance of heart valve problems is cabergoline (Dostinex), another dopamine agonist. This drug is approved in the US for the treatment of hyperproteinaemia disorders. Dostinex is not approved in the US for the treatment of Parkinson disease. For
hyperproteinaemia disorders, a considerably lower dose of Dostinex is used.

Reference: FDA News, P07-54 and Public Health Advisory, 29 March 2007 at http:// www.fda.gov
Aliskiren approved for hypertension

United States of America The Food and Drug Administration (FDA) has announced the approval of aliskiren (Tekturna) tablets for the treatment of hypertension. Aliskiren acts by inhibiting renin. Effectiveness was demonstrated in six placebo-controlled eight-week clinical trials, which studied over 2000 patients with mild to moderate hypertension. The effect was maintained for up to one year. When used in combination with hydrochlorothiazide, further reductions in blood pressure were achieved. Aliskiren was effective across all demographic subgroups, but African American patients tended to have smaller reductions in blood pressure than Caucasians and Asians, as is generally true for drugs that affect the renin-angiotensin system. Side effects were usually mild and brief. Diarrhoea was reported by approximately 2 percent of patients on the higher of the two approved doses, compared with approximately 1 percent on placebo. Rarely, patients developed an allergic reaction with swelling of the face, lips or tongue and difficulty breathing. This has been seen with other drugs for high blood pressure that act directly on the reninangiotensin system. Aliskiren and other drugs that act directly on the renin-angiotensin system should not be used during pregnancy.
Reference: FDA News, P07-38. 6 March 2007 at http://www.fda.gov
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Lapatinib approved for advanced breast cancer

United States of America The Food and Drug Administration (FDA) has approved lapatinib (Tykerb ), a targeted anti-cancer treatment to be used in combination with capectabine (Xeloda) for patients with advanced, metastatic breast cancer that is HER2 positive. The combination treatment is indicated for women who have received prior therapy with other cancer drugs, including an anthracycline, a taxane, and trastuzumab. According to the American Cancer Society, about 180 000 new cases of breast cancer are diagnosed each year. Lapatinib is a kinase inhibitor unlike, for example, trastuzumab a monoclonal antibody, which is a large protein molecule that targets the part of the HER2 protein on the outside of the cell. Because of this difference in mechanism of action, Tykerb works in some HER2 positive breast cancers that are no longer benefiting from trastuzumab. Commonly reported side effects included diarrhoea, nausea, vomiting, rash and hand-foot syndrome which may include numbness, tingling, redness, swelling and discomfort of hands and feet. Generally reversible decreases in heart function have also been reported in a small percentage of patients.
Reference: FDA News, P07-44, 13 March 2007 at http://www.fda.gov
levels of human tumour necrosis factor alpha, which plays an important role in abnormal inflammatory and immune responses. The labelling includes a boxed warning about potential serious adverse events. Adalimumab has been studied in 1478 patients with Crohn disease in four clinical trials comparing the drug to a placebo and two longer term extension studies. Use of this product has been associated with serious, sometimes fatal, infections, including cases of tuberculosis, opportunistic infections, and sepsis. Before initiating adalimumab treatment, patients should be evaluated for tuberculosis risk factors and tested for latent tuberculosis infection. Other serious adverse events reported by adalimumab users include lymphoma. The most frequent adverse events included upper respiratory infections, sinusitis, and nausea. Humira was previously approved for the treatment of three autoimmune diseases: rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
Reference: FDA News, P07-30. 27 February 2007 at http://www.fda.gov
Rapid test for meningitis cleared for marketing

United States of America The Food and Drug Administration (FDA) has cleared for marketing a test that uses molecular biology to quickly detect the presence of viral meningitis. The Xpert EV test, when used in combination with other laboratory tests, will help physicians distinguish between viral and bacterial meningitis. Meningitis is diagnosed by testing the fluid obtained from a patient during a spinal tap. Typically, diagnostic tests for meningitis can take up to a week to get
Adalimumab approved for Crohn disease

United States of America The Food and Drug Administration (FDA) has approved adalimumab (Humira) to treat adult patients with moderate to severe Crohn disease. Adalimumab is a humanderived, genetically-engineered monoclonal antibody to reduce excessive
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results. But results from the Xpert EV test are available in two and one-half hours. The accuracy of the Xpert EV test was confirmed in a multi-site study at six institutions. A total of 255 patient samples were tested and demonstrated that 96 percent of patients who tested positive did have viral meningitis, and that 97 percent of patients who tested negative did not have viral meningitis.
designed to destroy bacteria and other infection-causing organisms break these cells down. This leads to abnormally darkened urine and, more importantly, causes anaemia. Depending upon the severity of the disorder, patients with PNH may have pain, fatigue and debilitating weakness, the need for frequent blood transfusions, blood clots, and life-threatening or fatal strokes, heart attacks and intestinal disease. Eculizumab does not cure PNH, but treats the breakdown of red blood cells, the most common characteristic of PNH. Eculizumab blockade of the bodys natural immune system increases the patients susceptibility to certain serious infections, particularly meningococcal infections. Serious meningococcal infection was the most important adverse reaction experienced by patients in clinical studies. Because of the high risk for serious meningococcal infections, all 196 PNH patients in the clinical studies were vaccinated with a meningococcal vaccine; two of them developed meningococcal sepsis.
Eculizumab approved for paroxysmal nocturnal haemoglobinuria

United States of America The Food and Drug Administration (FDA) has approved eculizumab (Soliris), the first product for the treatment of paroxysmal nocturnal haemoglobinuria (PNH), a rare type of blood disorder that can lead to disability and premature death. PNH, which usually develops in adults, is a disease characterized by red blood cells that develop abnormally. Once the abnormal cells are present in the bloodstream, naturally occurring proteins
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Access to Medicines
Neglected tropical diseases
One sixth of the worlds population suffer from one or more neglected tropical diseases such as Buruli ulcer, cholera, cysticercosis, dracunculiasis (guineaworm disease), foodborne trematode infections, such as fascioliasis, hydatidosis, leishmaniasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soiltransmitted helminthiasis, trachoma and trypanosomiasis, although there are other estimates that suggest the number could be much higher. Several of these diseases are vectorborne. Populations most affected are often the poorest and most vulnerable and are in tropical and subtropical areas of the world. Some diseases affect individuals throughout their lives, causing a high degree of morbidity and physical disability and, in certain cases, gross disfigurement. Others are acute infections, with transient, severe and sometimes fatal outcomes. For a large group of these diseases mainly helminthic infections effective, inexpensive or donated drugs are available for their prevention and control. However, there is second group which requires systematic case-finding and management at an early stage. Simple diagnostic tools and safe and effective treatment regimens still need to be developed for some of these diseases. For others, vector control is available, as in the case of Chagas disease. Increased awareness and advocacy are needed to draw attention to the realistic prospect of reducing the negative impact of neglected tropical diseases on the health and social and economic wellbeing of affected communities.
Reference: WHO Department of Control of Neglected Tropical Diseases at http:// www.who.int/neglected_diseases/en/ index.html
Open access database for neglected medicines development

An international network of researchers has announced the release of a new web-based resource designed to facilitate the development of medicines to fight infectious diseases afflicting the developing world. The Drug Target Prioritization Database is available at http://TDRtargets.org. The database is described as a comprehensive set of information pertinent to drug target discovery, for a diverse array of parasitic and bacterial diseases. The Drug Target Prioritization Network was established in 2005 by the Special Programme for Research and Training in Tropical diseases (TDR) of WHO and includes a global team of academic laboratories, research centres and industry scientists, focusing on the pathogens responsible for malaria, tuberculosis, African sleeping sickness, leishmaniasis, Chagas disease and worm infections such as schistosomiasis and filariasis all of which are in desperate need of new treatments. Together, these diseases are responsible for billions of infections in the developing world and more than six million deaths per year.
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Access to Medicines
New avenues for drug discovery The database is unique in that it allows any researcher in both developed and developing countries to have access to information on the complete genome sequences for organisms responsible for five tropical diseases, with more anticipated for the parasitic worms known as helminths. Pharmaceutical firms have extensive libraries of chemicals that might act against the disease pathogens. The missing step, which this initiative takes, is to make available a list of proposed and validated drug targets, in addition to allowing users to define their own search criteria. This resource should expedite the time-consuming and high-risk early stages of drug development. The TDRtargets.org web site combines available genomic and bioinformatic data for each priority organism with automatically extracted and manually curated information from the research
literature and other databases relevant to each putative drug target. The network has invested substantial effort in annotation to assist scientists in the identification of high-value drug targets. The database also permits comments from experts in the field. User-defined weightings permit potential drug targets to be ranked according to their desirability, providing prioritized, customized lists. While this network was developed to facilitate drug target identification, it is also useful for the identification of vaccine and diagnostic targets as well, and could spur fundamental research into areas such as target validation, assay development, biomarkers and drug resistance.
Reference: Special Programme for Research and Training in Tropical diseases (TDR) at http://TDRtargets.org
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Consultation Document
Artemether and lumefantrine capsules
Draft proposal for the International Pharmacopoeia (March 2007). Please address any comments to Quality Assurance and Safety: Medicines, Medicines Policy and Standards, World Health Organization, 1211 Geneva 27, Switzerland. Fax: ++41 22 791 4730 or e-mail to rabhouansm@who.int
Category. Antimalarial. Storage. Artemether and Lumefantrine capsules should be kept in a well-closed container, protected from light. Additional information. Strength in the current WHO Model List of Essential Medicines: 20 mg Artemether and 120 mg Lumefantrine.
[Note from the Secretariat: Artemether and Lumefantrine capsules are not included in the current WHO Model list of essential medicines, only tablets of above strength.]
REQUIREMENTS Complies with the monograph for Capsules. Artemether and Lumefantrine capsules contain Artemether and Lumefantrine. They contain not less than 90.0% and not more than 110.0% of the amounts of artemether (C16H26O5) and lumefantrine (C30H32Cl3NO) stated on the label. Identity tests A Carry out test A.1 or, where UV detection is not available, test A.2. A.1. Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R6 as the coating substance and a mixture of 40 volumes of light petroleum R1, 10 volumes of ethyl acetate R and 5 volumes of glacial acetic acid R as the mobile phase. Apply separately to the plate 10 l of each of the following 2 solutions in acetone R. For solution (A) shake a quantity of the contents of the capsules equivalent to about 10 mg Artemether (about 60 mg Lumefantrine) for 5 minutes with 10 ml, filter, and use the clear filtrate. For solution (B) use 1 mg artemether RS and 6 mg lumefantrine RS per ml. After removing the plate from the chromatographic chamber, allow it to dry exhaustively in air or in a current of cool air.
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(i)
Examine the chromatogram in ultraviolet light (254 nm). The principal spot obtained with solution A corresponds in position, appearance, and intensity to that obtained with solution B (identifying Lumefantrine).
(ii)
Spray the plate with sulfuric acid/methanol TS. Heat the plate for 10 minutes at 140 C. Examine the chromatogram in daylight. The principal spot obtained with solution A corresponds in position, appearance, and intensity to that obtained with solution B (identifying Artemether).
A.2. Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R5 as the coating substance and a mixture of 40 volumes of light petroleum R1, 10 volumes of ethyl acetate R and 5 volumes of glacial acetic acid R as the mobile phase. Apply separately to the plate 10 l of each of the following 2 solutions in acetone R. For solution (A) shake a quantity of the contents of the capsules equivalent to about 10 mg Artemether (about 60 mg Lumefantrine) for 5 minutes with 10 ml, filter, and use the clear filtrate. For solution (B) use 1 mg artemether RS and 6 mg lumefantrine RS per ml. After removing the plate from the chromatographic chamber, allow it to dry exhaustively in air or in a current of cool air. Spray with sulfuric acid/methanol TS. Heat the plate for 10 minutes at 140C, allow it to cool and expose to iodine vapours for 20 minutes. Examine the chromatogram immediately in daylight. The principal spots obtained with solution A corresponds in position, appearance, and intensity to those obtained with solution B. B. See the test described below under Assay. The retention times of the two principal peaks in the chromatogram obtained with solution (1) are similar to those in the chromatogram obtained with solution (2). Artemether-related substances. Protect samples from light, also during chromatography. Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R5 as the coating substance and a mixture of 40 volumes of light petroleum R1, 10 volumes of ethyl acetate R and 5 volumes of glacial acetic acid R as the mobile phase. Prepare the following solutions in the solvent consisting of 1 volume of purified water and 1 volume of acetonitrile R. For solution (1), weigh and mix the contents of 20 capsules. To a quantity of the powder containing 100 mg of artemether add 20 ml of the solvent, sonicate for 15 minutes and centrifuge. Filter a portion of the supernatant through a 0.45 m filter, discarding the first few ml of the filtered solution. For solution (2) dissolve 2 mg of each of artemether RS, dihydroartemisinin (artenimol RS) and artemether RS in 20 ml of the solvent. For solution (3) dilute 2.0 ml of solution (2) to 20 ml with the solvent. For solution (4) dilute 3.0 ml of solution (2) to 20 ml with the solvent. For solution (5) dilute 5.0 ml of solution (2) to 20 ml with the solvent. For solution (6) dilute 1.0 ml of solution (2) to 2 ml with the solvent. For solution (7) dilute 3.0 ml of solution (2) to 4 ml with the solvent.
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Apply separately to the plate 20 l of each of the solution (1), (3), (4), (5), (6) and (7). After application allow the spots to dry for 15 minutes in a current of cool air. Develop over a path of 12 cm. After removing the plate from the chromatographic chamber, allow it to dry exhaustively in air or in a current of cool air. Dip the plate in sulfuric acid/ methanol TS. Heat the plate for 10 minutes at 140 C. Examine the chromatogram in daylight. Artemether and related substances have the following Rf values: impurity A about 0.25; dihydroartemisinin about 0.3; impurity B about 0.35; -artemether about 0.4; artemether about 0.55. In the chromatogram obtained with solution (1): any spot corresponding in Rf value to impurity A is not more intense than the spot corresponding to artemether obtained with solution (7) (1.5%); any spot corresponding in Rf value to dihydroartemisinin is not more intense than the spot corresponding to dihydroartemisinin obtained with solution (6) (1.0%); any spot corresponding in Rf value to impurity B is not more intense than the spot corresponding to artemether obtained with solution (5) (0.5%); any spot corresponding in Rf value to -artemether is not more intense than the spot corresponding to -artemether obtained with solution (4) (0.3%); the spot of any other impurity is not more intense than the spot corresponding to artemether obtained with solution (3) (0.2%). Disregard any spot remaining at the point of application. Assay. Carry out the test as described under 1.14.4 High-performance liquid chromatography, using a stainless steel column (15 cm x 3.9 mm) packed with particles of silica gel, the surface of which has been modified with chemically bonded octadecylsilyl groups (5 m) (1 Symmetry is suitable.) Use the following conditions for gradient elution: Mobile phase A: 700 volumes of ion pair reagent and 300 volumes of acetonitrile R. Mobile phase B: 300 volumes of ion pair reagent and 700 volumes of acetonitrile R. Prepare the ion pair reagent by dissolving 5.65 g of sodium hexanesulfonate R and 2.75 g of sodium dihydrogen phosphate R in about 900 ml of purified water. Adjust the pH to 2.3 using phosphoric acid (~105 g/l) TS, dilute to 1000 ml and filter through a 0.45 m filter.
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Time (min) 028 2829 2945 4546 4655
Mobile phase A (% v/v) 60 60 to 0 0 0 to 60 60
Mobile phase B (% v/v) 40 40 to 100 100 100 to 40 40
Comments Isocratic Linear gradient Isocratic Linear gradient Isocratic re-equilibration
Prepare the following solutions in the solvent which is obtained by mixing 200 ml of ion pair reagent, 60 ml of purified water and 200 ml of 1-propanol R and diluting to 1000 ml with acetonitrile R. For solution (1), weigh and mix the contents of 20 capsules. Transfer a quantity of the powder containing about 20 mg of artemether (about 120 mg of lumefantrine), accurately weighed, to a 100 ml volumetric flask. Add approximately 85 ml of the solvent, sonicate for 20 minutes, allow to cool to room temperature and dilute to volume with the solvent. Filter through a 0.45 m filter, discarding the first few ml of the filtered solution. For solution (2), accurately weigh 20 mg artemether RS and 120 mg lumefantrine RS in a 100 ml volumetric flask. Add approximately 85 ml of solvent, sonicate until dissolved, allow to cool to room temperature and dilute to volume. Operate with a flow rate of 1.3 ml per minute. As a detector use an ultraviolet spectrophotometer set at a wavelength of about 210 nm for the first 28 minutes and then switch to about 380 nm. Inject alternately 20 l each of solutions (1) and (2). (The peak for artemether is eluted at a retention time of approximately 19 minutes, and that for lumefantrine at a retention time of approximately 34 minutes.) Measure the areas of the peak responses obtained in the chromatograms from solutions (1) and (2), and calculate the content of artemether (C16H26O5) and lumefantrine (C30H32Cl3NO). Impurities (artemether-related) Dihydroartemisinin 284.4 C15H24O5
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-artemether 298.4
C16H26O5
B. 298.4
C16H26O5
A. 238.3
C14H22O3
[Names to be provided for A and B]
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Magnesi sulfatis injectio Magnesium sulfate Injection

Note from the Secretariat: Inclusion of a monograph for magnesium sulfate injection is considered advisable in view of the potential for errors in dosage due to confusion concerning the strength of this injection since Magnesium sulfate is the heptahydrate (mol wt 246.5 compared with 120 for anhydrous substance). This injection is included in the WHO Model List of Essential Medicines and within the Making Pregnancy Safer programme of the Family and Community Health cluster of WHO.
Description. A clear, colourless solution. Category. Used in the prevention of seizures in eclampsia and pre-eclampsia. Labelling. The designation of the container of Magnesium sulfate injection should indicate the quantity in terms of the amount of magnesium sulfate heptahydrate and as the approximate concentration of magnesium ions (Mg2+) in millimoles per ml. Additional information. Strength in the current WHO Model list of essential medicines: 500 mg of magnesium heptahydrate /ml; the concentration of magnesium ions (Mg2+) is approximately 2 millimoles per ml (2 mmolMg2+/ml). REQUIREMENTS Complies with the monograph for Parenteral Preparations. Definition. Magnesium sulfate injection is a sterile solution of Magnesium Sulfate Heptahydrate in water for injections. The solution is sterilized by Heating in an Autoclave or by another suitable method (see 5.8 Methods of Sterilization). Magnesium sulfate injection contains not less than 90.0% and not more than 110.0% of the amount of MgSO4,7H2O stated on the label. Identity tests A. Dilute the injection to give a solution containing 5 mg of magnesium sulfate heptahydrate per ml. To 2 ml of this solution, add 1 ml of ammonia (100g/l) TS; a white precipitate is produced which redissolves after adding 1 ml of ammonium chloride (100g/l) TS. Add 1 ml of disodium hydrogen phosphate (40g/l) TS; a white, fine crystalline precipitate is formed. B. Dilute the injection to give a solution containing 20 mg of magnesium sulfate heptahydrate per ml; yields reaction A described under 2.1 General identification tests as characteristic of sulfates.
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pH value. (1.13) pH of the injection, diluted if necessary to contain 500 mg of magnesium sulfate heptahydrate /ml: 5.5 - 7.0. Assay. Dilute an accurately measured volume of the injection containing about 0.50 g of magnesium sulfate heptahydrate to 100 ml with water R and proceed with the titration as described under 2.5 Complexometric titrations for magnesium. Each ml of disodium edetate (0.05 mol/l) VS is equivalent to 12.32 mg of MGSO4, 7H2O
Zinci sulfas Zinc sulfate

Zinc sulfate monohydrate Zinc sulfate heptahydrate
Note from the Secretariat: Preparation of the zinc monographs was initiated because zinc supplementation is included in the revised the WHO/UNICEF recommendations for the management of diarrhoea as an adjunct to oral rehydration therapy.]
ZnSO4,H2O (monohydrate); ZnSO4,7H2O (heptahydrate) Relative molecular mass. 179.5 (monohydrate); 287.5 (heptahydrate). Chemical name. Zinc sulfate monohydrate; CAS Reg. No. 7446-19-7 (monohydrate). Zinc sulfate heptahydrate; CAS Reg. No. 7446-20-0 (heptahydrate). Description. A white or almost white, crystalline powder, or colourless, transparent crystals. Solubility. Very soluble in water, practically insoluble in ethanol (~750 g/l) TS. Category. Adjunct to oral rehydration salts in( prevention and) treatment of dehydration due to diarrhoea; astringent. Storage. Zinc sulfate should be kept in a well-closed non-metallic container. REQUIREMENTS Definition. Zinc sulfate monohydrate contains not less than 99.0% and not more than 101.0% of ZnSO4,H2O. Zinc sulfate heptahydrate contains not less than 99.0% and not more than 104.0% of ZnSO4,7H2O.
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Identity tests A. Dissolve 0.25 g in 5 ml of water R and add 0.2 ml of sodium hydroxide (400 g/l) TS. A white precipitate is formed. Add a further 2 ml of sodium hydroxide (400 g/l) TS. The precipitate dissolves. Add 10 ml of ammonium chloride (100 g/l) TS. The solution remains clear. Add 0.1 ml of sodium sulfite TS. A flocculent white precipitate is formed. B. A 50 mg/ml solution yields the reactions described under 2.1 General identification tests as characteristic of sulfates. C. The test substance complies with the limits of the assay. pH value. (1.13) pH of a 50 mg/ml solution in carbon-dioxide-free water R, 4.4-5.6. Chlorides. Use 0.83 g in 20 ml for the preparation of the test solution as described under 2.2.1 Limit test for chlorides; not more than 300 g/g. Iron. Use 0.40 g for the preparation of the test solution as described under 2.2.4 Limit test for iron; not more than 100 g/g. Assay
For the monohydrate Dissolve about 80 mg, accurately weighed, in 5 ml of acetic acid (~120 g/l) TS and proceed with the titration as described under 2.5 Complexometric titrations for zinc. Each ml of disodium edetate (0.05 mol/l) VS is equivalent to 8.975 mg of ZnSO4,H2O. For the heptahydrate Dissolve about 0.13 g, accurately weighed, in 5 ml of acetic acid (~120 g/l) TS and proceed with the titration as described under 2.5 Complexometric titrations for zinc. Each ml of disodium edetate (0.05 mol/l) VS is equivalent to 1.438 g of ZnSO4,7H2O.
Paediatric zinc sulfate tablets

Note from the Secretariat: The term paediatric has been used in the title of this monograph since these tablets are included in the WHO Model List of Essential Medicines (revised March 2005) under medicines for diarrhoea in children (section17.5.2).
Preparation of the zinc monographs was initiated because zinc supplementation is included in the revised the WHO/UNICEF recommendations for the management of diarrhoea as an adjunct to oral rehydration therapy.
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Category. Adjunct to oral rehydration salts in (prevention and) treatment of dehydration due to diarrhoea. Storage. Paediatric zinc sulfate tablets should be kept in a well-closed container. Labelling. The designation of the container of Paediatric zinc sulfate tablets should state that the active ingredient is in the monohydrate form and indicate the quantity in terms of the equivalent amount of elemental zinc. Additional information. Strength in the current WHO Model list of essential medicines: 10 mg of elemental zinc (as zinc sulfate monohydrate). REQUIREMENTS Comply with the monograph for Tablets. Definition. Paediatric zinc sulfate tablets contain Zinc Sulfate as the monohydrate in a suitable dispersible basis that may contain suitable flavouring agents. They contain not less than 90.0% and not more than 110.0% of the amount of zinc stated on the label. Manufacture. The formulation of the tablets and the manufacturing process are designed and controlled so as to ensure that the metallic taste of the zinc salt is adequately masked. Identity tests. For solution (A) shake a quantity of the powdered tablets containing the equivalent of 100 mg of zinc with 20 ml, filter, and use the clear filtrate. A. To 5 ml of solution (A) add 0.2 ml of sodium hydroxide (400 g/l) TS. A white precipitate is formed. Add a further 2 ml of sodium hydroxide (400 g/l) TS. The precipitate dissolves. Add 10 ml of ammonium chloride (100 g/l) TS. The solution remains clear. Add 0.1 ml of sodium sulfite TS. A flocculent white precipitate is formed. B. Five ml of solution (A) yields reaction A described under 2.1 General identification tests as characteristic of sulfates. Disintegration. Comply with 5.4 Disintegration test for tablets and capsules, operating the apparatus for 60 seconds. Assay. Weigh and powder 20 tablets. To a quantity of the powder equivalent to about 29 mg of zinc, accurately weighed, add 5 ml of acetic acid (~120 g/l), sonicate for 15 minutes and add about 50 ml water R. Proceed with the titration as described under 2.5 Complexometric titrations for zinc. Each ml of disodium edetate (0.05 mol/l) VS is equivalent to 3.27 mg of zinc.
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Paediatric zinc sulfate oral solution

Note from the Secretariat: The term paediatric has been used in the title of this monograph since these tablets are included in the WHO Model List of Essential Medicines (revised March 2005) under medicines for diarrhoea in children (section17.5.2).
Preparation of the zinc monographs was initiated because zinc supplementation is included in the revised the WHO/UNICEF recommendations for the management of diarrhoea as an adjunct to oral rehydration therapy. Category. Adjunct to oral rehydration salts in (prevention and) treatment of dehydration due to diarrhoea. Storage. Paediatric zinc sulfate oral solution should be kept in a well-closed container. Labelling. The designation of the container of Paediatric zinc sulfate oral solution should indicate the quantity in terms of the equivalent amount of elemental zinc. Additional information. Strength in the current WHO Model list of essential medicines: 10 mg of zinc (as zinc sulfate) per 5 ml. REQUIREMENTS Complies with the monograph for Liquids for Oral Use. Definition. Paediatric zinc sulfate oral solution is a solution of Zinc Sulfate as the monohydrate or heptahydrate in a suitable flavoured vehicle. It contains not less than 90.0% and not more than 110.0% of the amount of zinc stated on the label. Manufacture. The formulation of the oral solution and the manufacturing process are designed and controlled so as to ensure that the metallic taste of the zinc salt is adequately masked. Identity tests A. To 5 ml add 0.2 ml of sodium hydroxide (400 g/l) TS. A white precipitate is formed. Add a further 2 ml of sodium hydroxide (400 g/l) TS. The precipitate dissolves. Add 10 ml of ammonium chloride (100 g/l) TS. The solution remains clear. Add 0.1 ml of sodium sulfite TS. A flocculent white precipitate is formed. B. Five ml yields reaction A described under 2.1 General identification tests as characteristic of sulfates.
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pH value. (1.13) pH of the oral solution: 2.54.5. Relative density
Note from the Secretariat: Comment is invited as to whether inclusion of a requirement for relative density is advisable and, if so, what limits would be considered suitable using method 1.3 of Ph. Int. (20 C).
Assay. To a quantity of the oral solution equivalent to about 10 mg of zinc, accurately measured, add 50 ml of purified water and 5 ml of ammonia buffer TS and titrate with disodium edetate (0.01 mol/l) VS using Mordant Black 11 indicator mixture R as indicator. Each ml of disodium edetate (0.01 mol/l) VS is equivalent to 0.6539 mg of zinc.
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Informed consent for research Technological and financial resources are also necessary to build capacity for local in resource-poor settings
Ethical challenges in study design and informed consent for health research in resource-poor settings considers ethical
challenges to research design and informed consent in biomedical and behavioural studies conducted in resource-poor settings. A review of the literature explores relevant social, cultural, and ethical issues in the conduct of biomedical and social health research in developing countries. Ten case vignettes illustrate ethical challenges that arise in international research with culturally diverse populations. Professional and public debates concerning the application of guidelines for ethical conduct in studies carried out in developing countries are likely to continue as new information becomes available. Researchers in biomedicine, public health, and the social and behavioural sciences confront the challenging task of adhering to national and international regulations in social and cultural environments in which ethical guidelines may not be easily translated or applied. Increased awareness of ethical concerns associated with study design and informed consent among researchers working in resourcepoor settings is needed. But strengthening professional knowledge about international research ethics is not enough. Investigators also require practical advice on the best methods or models for articulating ethical guidelines in the field. Empirical research on a wide range of issues relevant to the application of ethical guidelines is needed, including studies of macro social and economic developments that drive the globalization of the biomedical research enterprise. collaborators and communities to ensure that results of research are integrated into existing health systems. This requires collaborative efforts and engaged commitment on the part of investigators, funding agencies, policy-makers, governmental institutions, and industry.
Reference: Ethical challenges in study design and informed consent for health research in resource-poor settings http:// www.who.int/ tdr/publications/ publications/ seb_topic5.htm UNDP/WorldBank/ WHO-TDR http:// www.who.int/tdr/ topmenu/news/
Lessons learned in home management of malaria

Implementation research in four African countries Studies on treatment-seeking behaviour have shown that most malaria episodes are first treated at home using shopbought drugs. Part of the reason for this is poor access to formal health services. These treatments may be incorrect or suboptimal. Since the majority of children who die from malaria do so within 48 hours of onset of illness, the early use of effective antimalaria medicines close to the home can help to reduce the burden of the disease in sub-Saharan Africa and minimize the life-threatening consequences of treatment delays.
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This guide focuses in particular on four countries Burkina Faso, Ghana, Nigeria and Uganda where country teams have completed community based studies in home management of malaria.
Reference: World Health Organization. Lessons learned in Home Management of Malaria. Implementation research in four African countries, 2007
Reference: FIP pharmacy information section newsletter. March 2007 www.fip.org
First-in-man clinical trials for high risk products

European Union The Committee for Medicinal Products for Human Use (CHMP) has adapted a draft guideline for first-in-man clinical trials for potential high-risk medicinal products. This guideline has been prepared as one of the measures for minimizing the risk of serious adverse reactions of the nature that occurred during the first-in-man clinical trials of TGN1412 (gene therapy). It gives guidance on managing the transition from non-clinical studies to first tests in humans for high-risk medicinal products. The draft guideline has been released for a two-month public consultation.
Reference: Press Release. EMEA, 26 March 2007. http://www.emea.europa.eu
Developing drug information centres in India

A unique training workshop was organized in Bangalore in December 2006. Participants from India were provided with an introduction to drug information practice and rational drug use. The course was a part of a programme to expand the influence of the drug information centres and clinical pharmacy training programmes which have developed in the south of India over the last ten years. The current programme is being coordinated by the Karnataka State Pharmacy Council (KSPC) and is funded by WHO (India Office). KSPC established a drug information centre in 1997 and also works with hospital-based clinical pharmacy training programs in Bangalore. Other departments of pharmacy practice in south India include drug information training in their clinical programs and offer independent information to clinicians within their institutions. The centres will provide information to healthcare professionals and the public, and will collect reports of suspected adverse drug reactions. Limited funding will be provided to purchase information resources but long-term support will be required at the state level.
Pakistan Pharmacists Society
discussion forum
The Pakistan Pharmacists Society promotes and expands the profession of pharmacy and the role of pharmacists. In order to improve drug use and pharmacy practice in the country, the Society has launched a website to serve as an online source of news, pharmacy jobs, and to provde an opportunity for pharmacists to link up, share ideas and develop activities of interest.
Reference: Pakistan Pharmacists Society (PPS) http:// www.pharmacist.pk and http:// www. pharmacy.org.pk
New quality assurance compendium

Over the years, WHOs Expert Committee on Specifications for Pharmaceutical Preparations has made numerous recommendations to establish standards
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and guidelines and to promote the effective functioning of national regulatory and control systems and implementation of internationally agreed standards. Many of the relevant documents endorsed by the Expert Committee are reproduced in a recently published compendium of guidelines and related materials Quality Assurance of Pharmaceuticals. Second Edition aiming to provide information covering all aspects of WHO good manufacturing practices and inspection. The compendium includes. 1. WHO good manufacturing practices: main principles for pharmaceutical products Quality management in the drug industry: philosophy and essential elements Heating Ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms Validation Water for pharmaceutical use 2. WHO good manufacturing practices: starting materials Active pharmaceutical ingredients (bulk drug substances) Pharmaceutical excipients 3. WHO good manufacturing practices: specific pharmaceutical products Sterile pharmaceutical products Biological products Investigational pharmaceutical products for clinical trials in humans The manufacture of herbal medicines Radiopharmaceutical products
4. Inspection Pre-approval inspections Inspection of pharmaceutical manufacturers Inspection of drug distribution channels Quality systems requirements for national good manufacturingbpractice inspectorates Guidance on good manufacturing practices: inspection report Model certificate of good manufacturing practices 5. Hazard and risk analysis in pharmaceutical products Application of hazard analysis and critical control point (HACCP) methodology to pharmaceuticals 6. Sampling operations Sampling of pharmaceutical products and related materials
Reference: Quality Assurance of Pharmaceuticals. Second Edition. http://www.who.int/ bookorders
Pharmacological management of human H5N1 infection

The recent geographical spread of highly pathogenic avian influenza A virus in poultry and wild waterfowl has increased opportunities for transmission of the H5N1 virus to humans. Outbreaks in poultry have now been accompanied by human cases in nine countries. To date, human cases have remained rare and sporadic, but the disease is very severe and the case fatality is high. With the H5N1 virus now confirmed in birds in more than 50 countries, additional sporadic human cases should be anticipated.
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Although international experts agree that antiviral drugs should be considered for treatment of H5N1 patients and also for chemoprophylaxis, the efficacy and effectiveness of these management options have not been systematically assessed. Guidance on their use is needed worldwide. In March 2006, the World Health Organization (WHO) convened an international panel of clinicians experienced in the treatment of H5N1 patients, infectious disease experts, public health officers and methodologists to develop rapid advice for the pharmacological management of patients with H5N1 infection. To develop evidence-based guidelines, the panel used a transparent methodological guideline process, based on the GRADE approach, that included evaluation of existing systematic reviews, literature searches and expert consultation. The resulting guidelines separate strong from weak recommendations for or against a specific action and assign four categories of quality of evidence (high, moderate, low and very low). The panel considered several different specific patient and exposure groups and made a number of strong recommendations for or against specific actions regarding the treatment and chemoprophylaxis of H5N1 virus infection. All recommendations are specific to the
current pre-pandemic situation. Recommendations were based on careful consideration of the benefits, harms, burdens and cost of interventions. Risk categorizations for exposure were developed to assist countries in prioritizing the use of antiviral drugs where their availability is limited. Overall, the quality of the underlying evidence for all recommendations was very low. No data from controlled clinical trials of H5N1 infection are available. The existing evidence is based on small observational case series of H5N1 patients, results from in vitro and animal model studies of H5N1, or the extrapolation of data from high quality studies conducted to evaluate the treatment and chemoprophylaxis of normal, or seasonal, influenza. These shortcomings highlight the need for further research. While the quality of the evidence for some of the critical outcomes was moderate or low, the overall quality of evidence on which to base a summary assessment was very low for all antiviral drugs. Differences exist in the quality of evidence for individual critical outcomes among the various antiviral drugs (annex 3 sets out the gradings and ratings).
Reference: World Health Organization. WHO Rapid Advice Guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus. WHO/PSM/PAR/ 2006 at http://www.who.int/medicines
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WHO Drug Information, Vol. 21, No. 2, 2007
Proposed INN: List 97
International Nonproprietary Names for Pharmaceutical Substances (INN)

Notice is hereby given that, in accordance with article 3 of the Procedure for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances, the names given in the list on the following pages are under consideration by the World Health Organization as Proposed International Nonproprietary Names. The inclusion of a name in the lists of Proposed International Nonproprietary Names does not imply any recommendation of the use of the substance in medicine or pharmacy. Lists of Proposed (196) and Recommended (157) International Nonproprietary Names can be found in Cumulative List No. 12, 2007 (available in CD-ROM only). The statements indicating action and use are based largely on information supplied by the manufacturer. This information is merely meant to provide an indication of the potential use of new substances at the time they are accorded Proposed International Nonproprietary Names. WHO is not in a position either to uphold these statements or to comment on the efficacy of the action claimed. Because of their provisional nature, these descriptors will neither be revised nor included in the Cumulative Lists of INNs.
Dnominations communes internationales des Substances pharmaceutiques (DCI)

Il est notifi que, conformment aux dispositions de l'article 3 de la Procdure suivre en vue du choix de Dnominations communes internationales recommandes pour les Substances pharmaceutiques les dnominations ci-dessous sont mises l'tude par l'Organisation mondiale de la Sant en tant que dnominations communes internationales proposes. L'inclusion d'une dnomination dans les listes de DCI proposes n'implique aucune recommandation en vue de l'utilisation de la substance correspondante en mdecine ou en pharmacie. On trouvera d'autres listes de Dnominations communes internationales proposes (196) et recommandes (157) dans la Liste rcapitulative No. 12, 2007 (disponible sur CD-ROM seulement). Les mentions indiquant les proprits et les indications des substances sont fondes sur les renseignements communiqus par le fabricant. Elles ne visent qu' donner une ide de l'utilisation potentielle des nouvelles substances au moment o elles sont l'objet de propositions de DCI. L'OMS n'est pas en mesure de confirmer ces dclarations ni de faire de commentaires sur l'efficacit du mode d'action ainsi dcrit. En raison de leur caractre provisoire, ces informations ne figureront pas dans les listes rcapitulatives de DCI.
Denominaciones Comunes Internacionales para las Sustancias Farmacuticas (DCI)

De conformidad con lo que dispone el prrafo 3 del "Procedimiento de Seleccin de Denominaciones Comunes Internacionales Recomendadas para las Sustancias Farmacuticas", se comunica por el presente anuncio que las denominaciones detalladas en las pginas siguientes estn sometidas a estudio por la Organizacin Mundial de La Salud como Denominaciones Comunes Internacionales Propuestas. La inclusin de una denominacin en las listas de las DCI Propuestas no supone recomendacin alguna en favor del empleo de la sustancia respectiva en medicina o en farmacia. Las listas de Denominaciones Comunes Internacionales Propuestas (196) y Recomendadas (157) se encuentran reunidas en Cumulative List No. 12, 2007 (disponible slo en CD-ROM). Las indicaciones sobre accin y uso que aparecen se basan principalmente en la informacin facilitada por los fabricantes. Esta informacin tiene por objeto dar una idea nicamente de las posibilidades de aplicacin de las nuevas sustancias a las que se asigna una DCI Propuesta. La OMS no est facultada para respaldar esas indicaciones ni para formular comentarios sobre la eficacia de la accin que se atribuye al producto. Debido a su carcter provisional, esos datos descriptivos no deben incluirse en las listas recapitulativas de DCI.
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Proposed International Nonproprietary Names: List 97

Comments on, or formal objections to, the proposed names may be forwarded by any person to the INN Programme of the World Health Organization within four months of the date of their publication in WHO Drug Information, i.e., for List 97 st Proposed INN not later than 31 of October 2007. th Publication date: 25 of June 2007
Dnominations communes internationales proposes: Liste 97

Des observations ou des objections formelles l'gard des dnominations proposes peuvent tre adresses par toute personne au Programme des Dnominations communes internationales de l'Organisation mondiale de la Sant dans un dlai de quatre mois compter de la date de leur publication dans WHO Drug Information, c'est dire pour la Liste 97 de DCI Proposes le 31 octobre 2007 au plus tard. Date de Publication: 25 juin 2007
Denominaciones Comunes Internacionales Propuestas: Lista 97

Cualquier persona puede dirigir observaciones u objeciones respecto de las denominaciones propuestas, al Programa de Denominaciones Comunes Internacionales de la Organizacin Mundial de la Salud, en un plazo de cuatro meses, contados desde la fecha de su publicacin en WHO Drug Information, es decir, para la Lista 97 de DCI Propuestas el 31 de Octubre de 2007 a ms tardar. Fecha de publicacin: el 25 de Juno de 2007. Proposed INN (Latin, English, French, Spanish) DCI Propose DCI Propuesta Chemical name or description: Action and use: Molecular formula Chemical Abstracts Service (CAS) registry number: Graphic formula Nom chimique ou description: Proprits et indications: Formule brute Numro dans le registre du CAS: Formule dveloppe Nombre qumico o descripcin: Accin y uso: Frmula molecular Nmero de registro del CAS: Frmula desarrollada
alaninati brivanibum brivanib alaninate
(2R)-1-({4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo [2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-yl L-alaninate angiogenesis inhibitor

L-alaninate de (2R)-1-({4-[(4-fluoro-2-mthyl-1H-indol-5-yl)oxy]5-mthylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-yle inhibiteur de l'angiognse L-alaninato de (2R)-1-({4-[(4-fluoro-2-metil-1H-indol-5-il)oxi]5-metilpirrolo[2,1-f][1,2,4]triazin-6-il}oxi)propan-2-ilo inhibidor de la angiognesis
alaninate de brivanib
alaninato de brivanib
C22H24FN5O4
N H H2N O CH3 O H CH3 O CH3 F N N O
649735-63-7
NH CH3
134
albiglutidum* albiglutide
([8-glycine]human glucagon-like peptide 1-(7-36)-peptidyl) ([8-glycine]human glucagon-like peptide 1-(7-36)-peptidyl)(human serum albumin (585 residues)) antidiabetic ([8-glycine]peptide 1 analogue au glucagon humain-(7-36)peptidyl)([8-glycine]peptide 1 analogue au glucagon humain-(7-36)peptidyl)(albumine srique humaine (585 aminoacides)) antidiabtique ([8-glicina]pptido1 anlogo al glucagn humano-(7-36)-peptidil) ([8-glicina]pptido 1 anlogo al glucagn humano-(7-36)peptidil)(albumina sria humana (585 aminocidos)) antidiabtico C3232H5032N864O979S41
HGEGTFTSDV EFIAWLVKGR KLVNEVTEFA CAKQEPERNE EIARRHPYFY ASSAKQRLKC VHTECCHGDL AEVENDEMPA YSVVLLLRLA NCELFEQLGE PEAKRMPCAE LEVDETYVPK KEQLKAVMDD SSYLEGQAAK DAHKSEVAHR KTCVADESAE CFLQHKDDNP APELLFFAKR ASLQKFGERA LECADDRADL DLPSLAADFV KTYETTLEKC YKFQNALLVR DYLSVVLNQL EFNAETFTFH FAAFVEKCCK EFIAWLVKGR FKDLGEENFK NCDKSLHTLF NLPRLVRPEV YKAAFTECCQ FKAWAVARLS AKYICENQDS ESKDVCKNYA CAAADPHECY YTKKVPQVST CVLHEKTPVS ADICTLSEKE ADDKETCFAE HGEGTFTSDV ALVLIAFAQY GDKLCTVATL DVMCTAFHDN AADKAACLLP QRFPKAEFAE ISSKLKECCE EAKDVFLGMF AKVFDEFKPL PTLVEVSRNL DRVTKCCTES RQIKKQTALV EGKKLVAASQ
albiglutide
albiglutida
782500-75-8
SSYLEGQAAK 50 LQQCPFEDHV 100 RETYGEMADC 150 EETFLKKYLY 200 KLDELRDEGK 250 VSKLVTDLTK 300 KPLLEKSHCI 350 LYEYARRHPD 400 VEEPQNLIKQ 450 GKVGSKCCKH 500 LVNRRPCFSA 550 ELVKHKPKAT 600 AALGL 645
Disulfide bridges location Position des ponts disulfure / Posiciones de los puentes disulfuro 113-122 376-421 135-151 420-429 150-161 452-498 184-229 497-508 228-237 521-537 260-306 536-547 305-313 574-619 325-339 618-627 338-349
albinterferonum alfa-2b* albinterferon alfa-2b
human serum albumin (585 residues) fusion protein with human interferon -2b (165 residues) antiviral protine de fusion entre lalbumine srique humaine (585 aminoacides) et l'interfron -2b humain (165 aminoacides) antiviral protena de fusin entre la albumina srica humana (585 aminocidos) y el interfern -2b humano (165 aminocidos) antiviral
albinterfron alfa-2b
albinterfern alfa 2b
135
C3796H5937N1015O1143S50
DAHKSEVAHR KTCVADESAE CFLQHKDDNP APELLFFAKR ASLQKFGERA LECADDRADL DLPSLAADFV KTYETTLEKC YKFQNALLVR DYLSVVLNQL EFNAETFTFH FAAFVEKCCK MLLAQMRRIS LFSTKDSSAA ILAVRKYFQR FKDLGEENFK NCDKSLHTLF NLPRLVRPEV YKAAFTECCQ FKAWAVARLS AKYICENQDS ESKDVCKNYA CAAADPHECY YTKKVPQVST CVLHEKTPVS ADICTLSEKE ADDKETCFAE LFSCLKDRHD WDETLLDKFY ITLYLKEKKY ALVLIAFAQY GDKLCTVATL DVMCTAFHDN AADKAACLLP QRFPKAEFAE ISSKLKECCE EAKDVFLGMF AKVFDEFKPL PTLVEVSRNL DRVTKCCTES RQIKKQTALV EGKKLVAASQ FGFPQEEFGN TELYQQLNDL SPCAWEVVRA
472960-22-8
LQQCPFEDHV RETYGEMADC EETFLKKYLY KLDELRDEGK VSKLVTDLTK KPLLEKSHCI LYEYARRHPD VEEPQNLIKQ GKVGSKCCKH LVNRRPCFSA ELVKHKPKAT AALGLCDLPQ QFQKAETIPV EACVIQGVGV EIMRSFSLST KLVNEVTEFA CAKQEPERNE EIARRHPYFY ASSAKQRLKC VHTECCHGDL AEVENDEMPA YSVVLLLRLA NCELFEQLGE PEAKRMPCAE LEVDETYVPK KEQLKAVMDD THSLGSRRTL LHEMIQQIFN TETPLMKEDS NLQESLRSKE 50 100 150 200 250 300 350 400 450 500 550 600 650 700 750
Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro
53-62 75-91 90-101 124-169 168-177 200-246 245-253 265-279 278-289 316-361 360-369 392-438 437-448 461-477 476-487 514-559 558-567 586-683 614-723
Glycosylation sites : N-318 T-691
anamorelinum anamorelin
(3R)-3-benzyl-N,N',N'-trimethyl-1-(2-methylalanyl-D-tryptophyl)= piperidine-3-carbohydrazide growth hormone-releasing factor (3R)-3-benzyl-N,N',N'-trimthyl-1-(2-mthylalanyl-D-tryptophyl)= pipridine-3-carbohydrazide facteur de libration de l'hormone de croissance (3R)-3-bencil-N,N',N'-trimetil-1-(2-metilalanil-D-triptofil)piperidina3-carbohidrazida factor estimulante de la liberacin de la hormona del crecimiento C31H42N6O3
H3C CH3 H2N O HN H N H O N O N CH3 N CH3
anamorline
anamorelina
249921-19-5
CH3
apremilastum apremilast
N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methanesulfonyl)ethyl]1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide antiasthmatic N-{2-[(1S)-1-(3-thoxy-4-mthoxyphnyl)-2-(mthanesulfonyl)thyl]1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}actamide antiasthmatique N-{2-[(1S)-1-(3-etoxy-4-metoxifenil)-2-(metansulfonil)etil]-1,3-dioxo2,3-dihidro-1H-isoindol-4-il}acetamida antiasmtico
aprmilast
apremilast
136
C22H24N2O7S
O N H3 C O NH O O O S CH3 H CH3 O OCH3
608141-41-9
arbaclofenum placarbilum arbaclofen placarbil
(3R)-3-(4-chlorophenyl)-4-[({(1S)-2-methyl-1-[(2-methylpropanoyl)= oxy]propoxy}carbonyl)amino]butanoic acid antispasmodic acide (3R)-3-(4-chlorophnyl)-4-[({(1S)-2-mthyl1-[(2-mthylpropanoyl)oxy]propoxy}carbonyl)amino]butanoque antispasmodique cido (3R)-3-(4-clorofenil)-4-[({(1S)-2-metil-1-[(2-metilpropanoil)oxi]= propoxi}carbonil)amino]butanoico antiespasmdico C19H26ClNO6
H3C O H3C CH3 O CH3 O H O N H CO2H H
arbaclofne placarbil
arbaclofeno placarbilo
847353-30-4
Cl
arterolanum arterolane
N-(2-amino-2-methylpropyl)-2-{cis-dispiro[adamantane2,3'-[1,2,4]trioxolane-5',1"-cyclohexan]-4"-yl}acetamide antimalarial N-(2-amino-2-methylpropyl)-2-{cis-dispiro[adamantane2,3'-[1,2,4]trioxolane-5',1"-cyclohexan]-4"-yl}actamide antipaludique N-(2-amino-2-metilpropil)-2-{cis-dispiro[adamantano2,3'-[1,2,4]trioxolano-5',1"-ciclohexan]-4"-il}acetamida antipaldico C22H36N2O4

O O O H O N H CH3 H2N CH3
artrolane
arterolano
664338-39-0
137
azilsartanum medoxomilum azilsartan medoxomil
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo4,5-dihydro-1,2,4-oxadiazol-3-yl)-1,1'-biphenyl-4-yl]methyl}1H-benzimidazol-7-carboxylate angiotensine II receptor antagonist 2-thoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)1,1'-biphnyl-4-yl]mthyl}-1H-benzimidazole-7-carboxylate de (5-mthyl-2-oxo-1,3-dioxol-4-yl)mthyle antagoniste du rcepteur de langiotensine II 2-etoxi-1-{[2'-(5-oxo-4,5-dihidro-1,2,4-oxadiazol-3-il)-1,1'-bifenil4-il]metil}-1H-benzoimidazol-7-carboxilato de (5-metil-2-oxo1,3-dioxol-4-il)metilo antagonista del receptor de la angiotensina II C30H24N4O8
O O H3C O O O N N O CH3
azilsartan mdoxomil
azilsartn medoxomilo
863031-24-7
O O HN N
azoximeri bromidum azoximer bromide
poly{[1-(carboxymethyl)piperazin-1-ium-1,4-diyl bromide]ethyleneco-[(piperazin-1,4-diyl 1-oxide)ethylene]} immunomodulator poly{[bromure de 1-(carboxymthyl)piprazin-1-ium1,4-diyl]thylne-co-[(1-oxyde de piprazine-1,4-diyl)thylne]} immunomodulateur poly{[bromuro de 1-(carboximetil)piperazin-1-io-1,4-diil]etilenoco-[(1-xido de piperazin-1,4-diil)etileno]} inmunomodulador [[C8H15BrN2O2]x[C6H12N2O]y]n
CO2H N+ Br N
x
bromure d'azixomre
bromuro de azoxmero
892497-01-7
N O
N
y n
138
begacestatum begacestat
5-chloro-N-[(2S)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan2-yl]thiophene-2-sulfonamide gamma secretase inhibitor 5-chloro-N-[(2S)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromthyl)butan2-yl]thiophne-2-sulfonamide inhibiteur de la secrtase gamma 5-cloro-N-[(2S)-4,4,4-trifluoro-1-hidroxi-3-(trifluorometil)butan2-il]tiofeno-2-sulfonamida inhibidor de la secretasa gamma C9H8ClF6NO3S2
O O H Cl S S N H OH CF3 CF3
bgacestat
begacestat
769169-27-9
belinostatum belinostat blinostat belinostat
N-hydroxy-3-[3-(N-phenylsulfamoyl)phenyl]prop-2-enamide antitumour agent, inhibitor of histone deacetylase N-hydroxy-3-[3-(phnylsulfamoyl)phnyl]prop-2-namide agent antitumoral, inhibiteur de la dactylase de l'histone N-hidroxi-3-{3-[(fenilsulfamoil]fenil}prop-2-enamida antitumoral, inhibidor de la desacetilasa de histona C15H14N2O4S
O H N S N H OH
414864-00-9
O O
boceprevirum boceprevir
(1R,2S,5S)-N-[(2)-4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)]3-{(2S)-2-[(tert-butylcarbamoyl)amino]-3,3-dimethylbutanoyl}6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide antiviral (1R,2S,5S)-N-[(2)-4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)]3-{(2S)-2-[(tert-butylcarbamoyl)amino]-3,3-dimthylbutanoyl}6,6-dimthyl-3-azabicyclo[3.1.0]hexane-2-carboxamide antiviral (1R,2S,5S)-N-[(2)-4-amino-1-ciclobutil-3,4-dioxobutan-2-il)]3-{(2S)-2-[(terc-butilcarbamoil)amino]-3,3-dimetilbutanoil}-6,6-dimetil3-azabiciclo[3.1.0]hexano-2-carboxamida antiviral
bocprvir
boceprevir
139
C27H45N5O5
H3C H3C H3C CH3 O N H N H CH3 H CH3 H O N H CH3 CH3 H HN O H O
394730-60-0
NH2 O
canakinumabum* canakinumab
immunoglobulin G1, anti-[Homo sapiens interleukin 1, beta (IL1B)] human monoclonal ACZ885; gamma1 heavy chain (Homo sapiens VH-IGHG1*03) (221-214)-disulfide with kappa light chain (Homo sapiens V-KAPPA-IGKC*01); (227-227:230-230)-bisdisulfide dimer immunomodulator immunoglobuline G1, anti-[Homo sapiens interleukine 1, beta (IL1B)] anticorps monoclonal humain ACZ885; chane lourde gamma1 (Homo sapiens VH-IGHG1*03) (221-214)-disulfure avec la chane lgre kappa (Homo sapiens V-KAPPA-IGKC*01); dimre (227-227:230-230)-bisdisulfure immunomodulateur inmunoglobulina G1, anticuerpo monoclonal humano ACZ885 anti-[ interleukina 1 de Homo sapiens, beta (IL1B)]; cadena pesada gamma1 (Homo sapiens VH-IGHG1*03) (221-214)-disulfuro con la cadena ligera kappa (Homo sapiens V-KAPPA-IGKC*01); dmero (227-227:230-230)-bisdisulfuro inmunomodulador C6452H9958N1722O2010S42
Light chain 402710-27-4 Heavy chain 402710-25-2
canakinumab
canakinumab
carfilzomibum carfilzomib
{(2S)-2-[(morpholin-4-yl)acetamido]-4-phenylbutanoyl}-L-leucylN1-{(2S)-1-[(2R)-2-methyloxiran-2-yl]-4-methyl-1-oxopentan-2-yl}L-phenylalaninamide antineoplastic
carfilzomib
{(2S)-2-[(morpholin-4-yl)actamido]-4-phnylbutanoyl}-L-leucylN1-{(2S)-1-[(2R)-2-mthyloxiran-2-yl]-4-mthyl-1-oxopentan-2-yl}L-phnylalaninamide
antinoplasique carfilzomib {(2S)-2-[(morfolin-4-il)acetamido]-4-fenilbutanoil}-L-leucilN1-{(2S)-1-[(2R)-2-metiloxiran-2-il]-4-metil-1-oxopentan-2-il}L-fenilalaninamida antineoplsico
140
C40H57N5O7
868540-17-4
O N
O N H
H N
O N H CH3
H N
O CH3 H O CH3
O H3C
O H 3C
ceftarolinum fosamilum ceftaroline fosamil
(6R,7R)-7-{(2Z)-2-(ethoxyimino)-2-[5-(phosphonoamino)1,2,4-thiadiazol-3-yl]acetamido}-3-{[4-(1-methylpyridin-1-ium-4-yl)1,3-thiazol-2-yl]sulfanyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene2-carboxylate antibiotic (6R,7R)-7-{(2Z)-2-(thoxyimino)-2-[5-(phosphonoamino)1,2,4-thiadiazol-3-yl]actamido}-3-{[4-(1-mthylpyridin-1-ium-4-yl)1,3-thiazol-2-yl]sulfanyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ne2-carboxylate antibiotique (6R,7R)-7-{(2Z)-2-(etoxiimino)-2-[5-(fosfonoamino)-1,2,4-tiadiazol3-il]acetamido}-3-{[4-(1-metilpiridin-1-io-4-il)-1,3-tiazol-2-il]sulfanil}8-oxo-5-tia-1-azabiciclo[4.2.0]oct-2-eno-2-carboxilato antibitico C22H21N8O8PS4

CH3 N N S HO HO P O NH N O O O H N H N H S CO2 S S N N+ CH3
cftaroline fosamil
ceftarolina fosamilo
229016-73-3
cenersenum cenersen
antisense oligonucleotide inhibitor of p53 expression 2'-deoxy-P-thiocytidylyl-(3'5')-2'-deoxy-P-thiocytidylyl-(3'5')2'-deoxy-P-thiocytidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-deoxyP-thioguanylyl-(3'5')-2'-deoxy-P-thiocytidylyl-(3'5')P-thiothymidylyl-(3'5')-2'-deoxy-P-thiocytidylyl-(3'5')-2'-deoxyP-thiocytidylyl-(3'5')-2'-deoxy-P-thiocytidylyl-(3'5')-2'-deoxyP-thiocytidylyl-(3'5')-2'-deoxy-P-thiocytidylyl-(3'5')-2'-deoxyP-thiocytidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-deoxyP-thioguanylyl-(3'5')-2'-deoxy-P-thioguanylyl-(3'5')-2'-deoxyP-thiocytidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-deoxyP-thiocytidylyl-(3'5')-2'-deoxycytidine antineoplastic
141
cnersen
oligonuclotide antisense inhibiteur de l'expression de p53 2'-doxy-P-thiocytidylyl-(3'5')-2'-doxy-P-thiocytidylyl-(3'5')2'-doxy-P-thiocytidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-doxyP-thioguanylyl-(3'5')-2'-doxy-P-thiocytidylyl-(3'5')P-thiothymidylyl-(3'5')-2'-doxy-P-thiocytidylyl-(3'5')-2'-doxyP-thiocytidylyl-(3'5')-2'-doxy-P-thiocytidylyl-(3'5')-2'-doxyP-thiocytidylyl-(3'5')-2'-doxy-P-thiocytidylyl-(3'5')-2'-doxyP-thiocytidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-doxyP-thioguanylyl-(3'5')-2'-doxy-P-thioguanylyl-(3'5')-2'-doxyP-thiocytidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-doxyP-thiocytidylyl-(3'5')-2'-doxycytidine antinoplasique oligonucletido antisentido inhibidor de la expresin de p53 2'-desoxi-P-tiocitidilil-(3'5')-2'-desoxi-P-tiocitidilil-(3'5')-2'-desoxiP-tiocitidilil-(3'5')-P-tiotimidilil-(3'5')-2'-desoxi-P-tioguanilil(3'5')-2'-desoxi-P-tiocitidilil-(3'5')-P-tiotimidilil-(3'5')-2'-desoxiP-tiocitidilil-(3'5')-2'-desoxi-P-tiocitidilil-(3'5')-2'-desoxiP-tiocitidilil-(3'5')-2'-desoxi-P-tiocitidilil-(3'5')-2'-desoxiP-tiocitidilil-(3'5')-2'-desoxi-P-tiocitidilil-(3'5')-P-tiotimidilil(3'5')-2'-desoxi-P-tioguanilil-(3'5')-2'-desoxi-P-tioguanilil(3'5')-2'-desoxi-P-tiocitidilil-(3'5')-P-tiotimidilil-(3'5')-2'-desoxiP-tiocitidilil-(3'5')-2'-desoxicitidina antineoplsico C187H226N62O103P19S19 872847-66-0
cenersn
cholini fenofibratum choline fenofibrate
2-hydroxy-N,N,N-trimethylethanaminium 2-[4-(4-chlorobenzoyl)= phenoxy]-2-methylpropanoate antihyperlipidaemic 2-[4-(4-chlorobenzoyl)phnoxy]-2-mthylpropanoate de 2-hydroxyN,N,N-trimthylthanaminium antihyperlipidmiant 2-[4-(4-clorobenzoil)fenoxi]-2-metilpropanoato de 2-hidroxiN,N,N-trimetiletanaminio antihiperlipmico C5H14NO .C17H14ClO4
H3C HO N+
+ -
fnofibrate de choline
fenofibrato de colina
856676-23-8
Cl O H3C O CO2CH3
CH3 CH3
142
cinaciguatum cinaciguat
4-({(4-carboxybutyl)[2-(2-{[4-(2-phenylethyl)phenyl]methoxy}phenyl)= ethyl]amino}methyl)benzoic acid guanylate cyclase activator acide 4-({(4-carboxybutyl)[2-(2-{[4-(2-phnylthyl)phnyl]mthoxy}= phnyl)thyl]amino}mthyl)benzoque activateur de la guanylate cyclase cido 4-({(4-carboxibutil)[2-(2-{[4-(2-feniletil)fenil]metoxi}fenil)= etil]amino}metil)benzoico activador de la guanilato ciclasa C36H39NO5 329773-35-5
CO2H O N CO2H
cinaciguat
cinaciguat
contusugenum ladenovecum* contusugene ladenovec
(Recombinant) replication restricted adenovirus (type 5) vector, E1 deleted, partial E3 deletion, containing/expressing a wild type p53 gene driven by a cytomegalovirus promoter induce cell growth arrest and apotopsis Vecteur adnovirus (type 5) recombinant dfectif, dlt de E1 et partiellement de E3, contenant le gne p53 sauvage sous le contrle du promoteur cytomgalovirus induit l'arrt de la croissance cellulaire et l'apoptose Vector adenovirus (tipo 5) recombinante defectivo, con delecin de E1 y parcialmente de E3, que contiene el gen p53 salvaje controlado por el promotor de cytomegalovirus induce la detencin del crecimiento celular y la apoptosis 600735-73-7
contusugne ladnovec
contusugn ladenovec
dapagliflozinum dapagliflozin
(1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}D-glucitol antidiabetic (1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-hoxyphnyl)mthyl]phnyl}D-glucitol antidiabtique (1S)-1,5-anhidro-1-C-{4-cloro-3-[(4-etoxifenil)metil]fenil}-D-glucitol hipoglucemiante
dapagliflozine
dapagliflozina
143
C21H25ClO6
O CH3
461432-26-8
Cl HO O OH HO OH
delimotecanum delimotecan
poly{[2-O-(carboxymethyl)--D-glucopyranosyl-(16)]-co-[2-O-(15{[(4S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl]oxy}-2,5,8,11tetraoxo-3,6,9,12-tetraazapentadecyl)--D-glucopyranosyl(16)]-co-[-D-glucopyranosyl-(16)]} antineoplastic poly{[2-O-(carboxymthyl)--D-glucopyranosyl-(16)]-co-[2-O-(15{[(4S)-4,11-dithyl-4-hydroxy-3,14-dioxo-3,4,12,14-ttrahydro1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl]oxy}-2,5,8,11ttraoxo-3,6,9,12-ttraazapentadcyl)--D-glucopyranosyl-(16)]co-[-D-glucopyranosyl-(16)]} antinoplasique poli{[2-O-(carboximetil)--D-glucopiranosil-(16)]-co-[2-O-(15-{[(4S)4,11-dietil-4-hidroxi-3,14-dioxo-3,4,12,14-tetrahidro1H-pirano[3',4':6,7]indolizino[1,2-b]quinolin-9-il]oxi}-2,5,8,11tetraoxo-3,6,9,12-tetraazapentadecil)--D-glucopiranosil-(16)]co-[-D-glucopiranosil-(16)]} antineoplsico
dlimotcan
delimotecn
144
[C39H46N6O14[C6H10O5]x[C8H12O7]y]n
HO
O OH
187852-63-7 (for Na salt)
HO
O O CH3 OH O N N H3C
O OH
x
O OH HO
O O
y
HO2C
O OH
HO
O O
H N O
O N H
H N O
N H
O
n
dovitinibum dovitinib
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazole2-yl]quinolin-2(1H)-one antineoplastic 4-amino-5-fluoro-3-[6-(4-mthylpiprazin-1-yl)-1H-benzimidazol2-yl]quinolin-2(1H)-one antinoplasique 4-amino-5-fluoro-3-[6-(4-metilpiperazin-1-il)-1H-benzoimidazol2-il]quinolin-2(1H)-ona antineoplsico C21H21FN6O

N N H NH2 F N CH3
dovitinib
dovitinib
405169-16-6
O HN
eldecalcitolum eldecalcitol
(5Z,7E)-2-(3-hydroxypropoxy)-9,10-secocholesta-5,7,10(19)-triene1,3,25-triol vitamin D analogue (5Z,7E)-2-(3-hydroxypropoxy)-9,10-scocholesta-5,7,10(19)-trine1,3,25-triol analogue de la vitamine D (5Z,7E)-2-(3-hidroxipropoxi)-9,10-secocolesta-5,7,10(19)-trieno1,3,25-triol anlogo de la vitamina D
eldcalcitol
eldecalcitol
145
C30H50O5
H3 C H CH3 H HO H CH2 HO HO H O H H OH CH3 CH3
104121-92-8
elvitegravirum elvitegravir
6-[(3-chloro-2-fluorophenyl)methyl]-1-[(2S)-1-hydroxy-3-methylbutan2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid antiviral acide 6-[(3-chloro-2-fluorophnyl)mthyl]-1-[(2S)-1-hydroxy3-mthylbutan-2-yl]-7-mthoxy-4-oxo-1,4-dihydroquinoline3-carboxylique antiviral cido 6-[(3-cloro-2-fluorofenil)metil]-1-[(2S)-1-hidroxi-3-metilbutan2-il]-7-metoxi-4-oxo-1,4-dihidroquinolina-3-carboxlico antiviral C23H23ClFNO5
HO CH3 O Cl F O H N CO2H CH3 CH3
elvitgravir
elvitegravir
697761-98-1
epetirimodum epetirimod ptirimod epetirimod
1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine immunomodulator 1-(2-mthylpropyl)-1H-imidazo[4,5-c][1,5]naphtyridin-4-amine immunomodulateur 1-(2-metilpropil)-1H-imidazo[4,5-c][1,5]naftiridin-4-amina inmunomodulador
146
C13H15N5
H3C H3C N N N N
227318-71-0
NH2
epoetinum kappa epoetin kappa potine kappa epoetina kappa
1-165-erythropoietin (human JR-013), glycoform antianaemic rythropotine (humaine JR-013)-(1-165), glycoforme antianmique 1-165-eritropoyetina (humana JR-013), glicoforma antianmico C809H1301N229O240S5 879555-13-2
eribulinum eribulin
(2R,3R,3aS,7R,8aS,9S,10aR,11S,12R,13aR,13bS,15S,18S,21S,24 S,26R,28R,29aS)-2-[(2S)-3-amino-2-hydroxypropyl]-3-methoxy26-methyl-20,27-dimethylidenehexacosahydro-11,15:18,21:24,28triepoxy-7,9-ethano-12,15-methano-9H,15H-furo[3,2-i]furo[2',3':5,6]= pyrano[4,3-b][1,4]dioxacyclopentacosin-5(4H)-one antineoplastic (2R,3R,3aS,7R,8aS,9S,10aR,11S,12R,13aR,13bS,15S,18S,21S,24 S,26R,28R,29aS)-2-[(2S)-3-amino-2-hydroxypropyl]-3-mthoxy26-mthyl-20,27-dimthylidnehexacosahydro-11,15:18,21:24,28tripoxy-7,9-thano-12,15-mthano-9H,15H-furo[3,2-i]furo[2',3':5,6]= pyrano[4,3-b][1,4]dioxacyclopentacosin-5(4H)-one antinoplasique (2R,3R,3aS,7R,8aS,9S,10aR,11S,12R,13aR,13bS,15S,18S,21S,24 S,26R,28R,29aS)-2-[(2S)-3-amino-2-hidroxipropil]-26-metil20,27-dimetilideno-3-metoxihexacosahidro-11,15:18,21:24,28triepoxi-7,9-etano-12,15-metano-9H,15H-furo[3,2-i]furo[2',3':5,6]= pirano[4,3-b][1,4]dioxaciclopentacosin-5(4H)-ona antineoplsico C40H59NO11
H3C H H2 N O H H HO H H O O H H H2C O H H CH2 H CH3 H O H O
ribuline
eribulina
253128-41-5
H H O O
H O H H H
147
faxeladolum faxeladol faxladol faxeladol
3-[(1R,2R)-2-(dimethylaminomethyl)cyclohexyl]phenol analgesic 3-{(1R,2R)-2-[(dimthylamino)mthyl]cyclohexyl}phenol analgsique 3-[(1R,2R)-2-(dimetilaminometil)ciclohexil]fenol analgsico C15H23NO

CH3 N H H CH3
433265-65-7
OH
ferricum carboxymaltosum ferric carboxymaltose
poly[D-glucopyranosyl(14)]-D-gluconic acid complex of hydrated iron(III) oxide haematinic complexe d'oxide de fer(III) et d'acide poly[D-glucopyranosyl(14)]D-gluconique hydrat hmatinique cido poli[D-glucopiranosil(14)]-D-glucnico complejo de xido de hierro(III) hidratado hematnico FeIIIw([C6H10O5]aC6H11O7)x(OH)yOz.nH2O 9007-72-1
carboxymaltose ferrique
carboximaltosa frrica
flovagatranum flovagatran
(1R)-1-{N-[(benzyloxy)carbonyl]-D-phenylalanyl-L-prolinamido}= butylboronic acid thrombin inhibitor acide (1R)-1-{N-[(benzyloxy)carbonyl]-D-phnylalanyl-L-prolinamido} butylboronique inhibiteur de la thrombine cido (1R)-1-{N-[(benciloxi)carbonil]-D-fenilalanil-L-prolinamido}= butilbornico inhibidor de la trombina
flovagatran
flovagatrn
148
C27H36BN3O7
871576-03-3
CH3 O O N H H O H N H B OH
O O
H N
OH
gantenerumabum* gantenerumab
immunoglobulin G1, anti-(human beta-amyloid peptides A42 and A40) human monoclonal antibody; gamma1 heavy chain (Homo sapiens VH-IGHG1) (229-215)-disulfide with kappa light chain (Homo sapiens V-KAPPA-IGKC); (235-235:238-238)-bisdisulfide oured immunomodulator immunoglobuline G1, anti-(peptides beta-amyloides A42 et A40 humains) anticorps monoclonal humain; chane lourde gamma1 (Homo sapiens VH-IGHG1) (229-215)-disulfure avec la chane lgre kappa (Homo sapiens V-KAPPA-IGKC); dimre (235-235:238-238)-bisdisulfure immunomodulateur inmunoglobulina G1, anticuerpo monoclonal humano anti-(pptidos beta-amiloides A42 et A40 humanos); cadena pesada gamma1 (Homo sapiens VH-IGHG1) (229-215)-disulfuro con la cadena ligera kappa (Homo sapiens V-KAPPA-IGKC); dimero (235-235:238238)-bisdisulfuro inmunomodulador 89957-37-9
1- heavy chain / Chane lourde 1 / Cadena pesada 1 QVELVESGGG INASGTRTYY GNTHKPYGYV LGCLVKDYFP SLGTQTYICN LFPPKPKDTL REEQYNSTYR QPREPQVYTL KTTPPVLDSD SLSPGK LVQPGGSLRL ADSVKGRFTI RYFDVWGQGT EPVTVSWNSG VNHKPSNTKV MISRTPEVTC VVSVLTVLHQ PPSRDELTKN GSFFLYSKLT SCAASGFTFS SRDNSKNTLY LVTVSSASTK ALTSGVHTFP DKKVEPKSCD VVVDVSHEDP DWLNGKEYKC QVSLTCLVKG VDKSRWQQGN SYAMSWVRQA LQMNSLRAED GPSVFPLAPS AVLQSSGLYS KTHTCPPCPA EVKFNWYVDG KVSNKALPAP FYPSDIAVEW VFSCSVMHEA PGKGLEWVSA TAVYYCARGK SKSTSGGTAA LSSVVTVPSS PELLGGPSVF VEVHNAKTKP IEKTISKAKG ESNGQPENNY LHNHYTQKSL 50 100 150 200 250 300 350 400 450 456
gantnrumab
gantenerumab
-light chain / Chane lgre / Cadena ligera DIVLTQSPAT GASSRATGVP QGTKVEIKRT VDNALQSGNS GLSSPVTKSF LSLSPGERAT ARFSGSGSGT VAAPSVFIFP QESVTEQDSK NRGEC LSCRASQSVS DFTLTISSLE PSDEQLKSGT DSTYSLSSTL SSYLAWYQQK PEDFATYYCL ASVVCLLNNF TLSKADYEKH PGQAPRLLIY QIYNMPITFG YPREAKVQWK KVYACEVTHQ 50 100 150 200 215
The position of cysteine (C) residues that form disulphide bridges and asparagine residues that are N-glycosylated are in bold.
149
golotimodum golotimod golotimod golotimod
D--glutamyl-L-tryptophan immonomudulator D--glutamyl-L-tryptophane immunomodulateur D--glutamil-L-triptfano inmunomodulador
C16H19N3O5
H NH2 HO2C O H N
229305-39-9
CO2H H
N H
ibalizumabum* ibalizumab
immunoglobulin G4, anti-(human CD4) humanized monoclonal antibody Hu5A8 (TNX-355); gamma4 heavy chain [humanized VH (Homo sapiens FR/Mus musculus CDR [8.8.15] from clone Mu5A8)Homo sapiens IGHG4*01] (136-219)-disulfide with kappa light chain [humanized V-KAPPA (Homo sapiens FR/Mus musculus CDR [12.3.8] from clone Mu5A8)-Homo sapiens IGKC*01] ; (228228:231-231)-bisdisulfide dimer antiviral immunoglobuline G4, anti-(CD4 humain) anticorps monoclonal humanis Hu5A8 (TNX-355); chane lourde gamma4 [VH humanis (Homo sapiens FR/Mus musculus CDR [8.8.15] du clone 5A8)-Homo sapiens IGHG4] (136-219)-disulfure avec la chane lgre kappa [VKAPPA humanis (Homo sapiens FR/Mus musculus CDR [12.3.8] du clone Mu5A8)-Homo sapiens IGKC*01]; dimre (228-228:231231)-bisdisulfure antiviral inmunoglobulina G4, anti-(CD4 humano) anticuerpo monoclonal humanizado Hu5A8 (TNX-355); cadena pesada gamma4 [VH humanizado (Homo sapiens FR/Mus musculus CDR [8.8.15] del clon 5A8)-Homo sapiens IGHG4] (136-219)-disulfuro con la cadena ligera kappa [V-KAPPA humanizada (Homo sapiens FR/Mus musculus CDR [12.3.8] del clon Mu5A8)-Homo sapiens IGKC*01]; dmero (228-228:231-231)-bisdisulfuro antiviral
ibalizumab
ibalizumab
150
680188-33-4
Ig 4-heavy chain / Chane lourde Ig 4 / Cadena pesada Ig 4 QVQLQQSGPE INPYNDGTDY DNYATGAWFA VKDYFPEPVT KTYTCNVDHK DTLMISRTPE TYRVVSVLTV YTLPPSQEEM DSDGSFFLYS VVKPGASVKM DEKFKGKATL YWGQGTLVTV VSWNSGALTS PSNTKVDKRV VTCVVVDVSQ LHQDWLNGKE TKNQVSLTCL RLTVDKSRWQ SCKASGYTFT TSDTSTSTAY SSASTKGPSV GVHTFPAVLQ ESKYGPPCPS EDPEVQFNWY YKCKVSNKGL VKGFYPSDIA EGNVFSCSVM SYVIHWVRQK MELSSLRSED FPLAPCSRST SSGLYSLSSV CPAPEFLGGP VDGVEVHNAK PSSIEKTISK VEWESNGQPE HEALHNHYTQ PGQGLDWIGY TAVYYCAREK SESTAALGCL VTVPSSSLGT SVFLFPPKPK TKPREEQFNS AKGQPREPQV NNYKTTPPVL KSLSLSLGK 50 100 150 200 250 300 350 400 449
Ig -light chain / Chane lgre Ig / Cadena ligera Ig DIVMTQSPDS KLLIYWASTR RTFGGGTKLE VQWKVDNALQ VTHQGLSSPV LAVSLGERVT ESGVPDRFSG IKRTVAAPSV SGNSQESVTE TKSFNRGEC MNCKSSQSLL SGSGTDFTLT FIFPPSDEQL QDSKDSTYSL YSTNQKNYLA ISSVQAEDVA KSGTASVVCL SSTLTLSKAD WYQQKPGQSP VYYCQQYYSY LNNFYPREAK YEKHKVYACE 50 100 150 200 219
idrabiotaparinuxum natricum idrabiotaparinux sodium
nonasodium methyl (2-deoxy-3,4-di-O-methyl-2-{6-[5-(2oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido]= hexanamido}-6-O-sulfo--D-glucopyranosyl)-(14)-(2,3-di-O-methyl-D-glucopyranosyluronate)-(14)-(2,3,6-tri-O-sulfo-D-glucopyranoside)-(14)-(2,3-di-O-methyl-L-idopyranosyluronate)-(14)-2,3,6-tri-O-sulfo-D-glucopyranoside antithrombotic 2-doxy-3,4-di-O-mthyl-2-{[6-({5-[(3aS,4S,6aR)-2-oxohexahydro1H-thino[3,4-d]imidazol-4-yl]pentanoyl}amino)hexanoyl]amino}6-O-sulfo--D-glucopyranosyl-(14)-2,3-di-O-mthyl-D-glucopyranuronosyl-(14)-2,3,6-tri-O-sulfo--D-glucopyranosyl(14)-2,3-di-O-mthyl--L-idopyranuronosyl-(14)-2,3,6-tri-O-sulfo-D-glucopyranoside de mthyle nonasodique antithrombotique 2-desoxy-3,4-di-O-metil-2-{[6-({5-[(3aS,4S,6aR)-2-oxohexahidro1H-tieno[3,4-d]imidazol-4-il]pentanoil}amino)hexanoil]amino}6-O-sulfo--D-glucopiranosil-(14)-2,3-di-O-metil-D-glucopiranuronosil-(14)-2,3,6-tri-O-sulfo--D-glucopiranosil(14)-2,3-di-O-metil--L-idopiranuronosil-(14)-2,3,6-tri-O-sulfo-D-glucopiranosido de metilo y nonasodico antitrombtico
idrabiotaparinux sodique
idrabiotaparinux sdico
151
C53H79N4Na9O51S8
405159-59-3
O O NaO3S O CO2Na OCH3 O O O O CH3 SO3Na O
SO3Na O
NaO3S SO3Na CO2Na O O O OCH3 O O
O O O
SO3Na
OCH3 H3CO HN
SO3Na S H
OCH3
OCH3 N H O H
H HN NH O
laropiprantum laropiprant
[(3R)-4-[(4-chlorophenyl)methyl]-7-fluoro-5-(methanesulfonyl)1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid prostanoid DP1 receptor antagonist acide [(3R)-4-[(4-chlorophnyl)mthyl]-7-fluoro-5-(mthanesulfonyl)1,2,3,4-ttrahydrocyclopenta[b]indol-3-yl]actique antagoniste du rcepteur DP1 des prostanodes cido [(3R)-4-[(4-clorofenil)metil]-7-fluoro-5-(metanosulfonil)1,2,3,4-tetrahidrociclopenta[b]indol-3-il]actico antagonista del receptor DP1 de prostanoides C21H19ClFNO4S
F N O O S CH3 H Cl CO2H
laropiprant
laropiprant
571170-77-9
levamlodipinum levamlodipine
3-ethyl 5-methyl (4S)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)6-methyl-1,4-dihydropyridine-3,5-dicarboxylate calcium channel blocker (4S)-2-[(2-aminothoxy)mthyl]-4-(2-chlorophnyl)-6-mthyl1,4-dihydropyridine-3,5-dicarboxylate de 3-thyle et de 5-mthyle antagoniste des canaux calciques (4S)-2-[(2-aminoetoxi)metil]-4-(2-clorofenil)-6-metil1,4-dihidropiridina-3,5-dicarboxilato de 3-etilo y 5-metilo antagonista de los canales del calcio
lvamlodipine
levamlodipino
152
C20H25ClN2O5
H3C H3C O O H O Cl H N NH2 CH3
103129-82-4
O O
lonaprisanum lonaprisan
11-(4-acetylphenyl)-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor17-pregna-5,9-dien-3-one progesterone receptor antagonist 11-(4-actylphnyl)-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor17-prgna-5,9-din-3-one antagoniste des rcepteurs de la progestrone 11-(4-acetilfenil)-20,20,21,21,21-pentafluoro-17-hidroxi-19-nor17-pregna-5,9-dien-3-ona antagonista de los receptores de progesterona C28H29F5O3
O H3C H H H O CH3 OH CF3 F F
lonaprisan
lonaprisn
211254-73-8
metenkefalinum metenkefalin
L-tyrosylglycylglycyl-L-phenylalanyl-L-methionine
-endorphin human-(1-5)-peptide and opioid receptors agonist mtenkefaline

L-tyrosylglycylglycyl-L-phnylalanyl-L-mthionine
-endorphine humaine-(1-5)-peptide agoniste des rcepteurs opiodes et metencefalina

L-tirosilglicilglicil-L-fenilalanil-L-metionina -endorfina humana-(1-5)-peptido agonista de los receptores y de opiceos
C27H35N5O7S
H L -Tyr Gly Gly
L -Phe L-Met
58569-55-4
OH
153
milveterolum milveterol
N-{2-hydroxy-5-[(1R)-1-hydroxy-2-{[2-(4-{[(2R)-2-hydroxy2-phenylethyl]amino}phenyl)ethyl]amino}ethyl]phenyl}formamide bronchodilator N-{2-hydroxy-5-[(1R)-1-hydroxy-2-{[2-(4-{[(2R)-2-hydroxy2-phnylthyl]amino}phnyl)thyl]amino}thyl]phnyl}formamide bronchodilatateur N-{2-hidroxi-5-[(1R)-1-hidroxi-2-{[2-(4-{[(2R)-2-hidroxi2-feniletil]amino}fenil)etil]amino}etil]fenil}formamida broncodilatador C25H29N3O4

H OH H N N H
milvtrol
milveterol
652990-07-3
HO HN O H
H OH
motesanibum motesanib
N-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-{[(pyridin-4-yl)methyl]= amino}pyridine-3-carboxamide antineoplastic N-(3,3-dimthyl-2,3-dihydro-1H-indol-6-yl)-2-{[(pyridin-4-yl)mthyl]= amino}pyridine-3-carboxamide antinoplasique N-(3,3-dimetil-2,3-dihidro-1H-indol-6-il)-2-{[(piridin-4-il)metil]= amino}piridina-3-carboxamida antineoplsico C22H23N5O
HN NH N N O N H CH3 CH3
motsanib
motesanib
453562-69-1
nepiderminum nepidermin npidermine
human epidermal growth factor, recombinant DNA origin epidermal growth factor facteur humain de croissance pidermique, origine ADN recombinant facteur de croissance pidermique factor de crecimiento epidrmico humano; origen: ADN recombinante factor de crecimiento epidrmico
nepidermina
154
C270H401N73O83S7
62253-63-8
10
H Asn Ser Asp Ser Glu Cys Pro Leu Ser His Asp Gly Tyr Cys Leu His Asp Gly Val Cys Met Tyr Ile Glu Ala Leu Asp Lys
20
Tyr Ala Cys Asn Cys Val Val Gly Tyr Ile Gly Glu
30 40
Arg Cys
Gln Tyr Arg Asp Leu Lys Trp Trp Glu Leu Arg
50
OH
neratinibum neratinib
(2E)-N-[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide antineoplastic (2E)-N-[4-({3-chloro-4-[(pyridin-2-yl)mthoxy]phnyl}amino)-3-cyano7-thoxyquinolin-6-yl]-4-(dimthylamino)but-2-namide antinoplasique (2E)-N-[4-({3-cloro-4-[(piridin-2-yi)metoxi]fenil}amino)-3-ciano7-etoxiquinolin-6-il]-4-(dimetilamino)but-2-enamida antineoplsico C30H29ClN6O3

H3 C CH3 H 3C N O HN O HN N CN Cl O N
nratinib
neratinib
698387-09-6
perampanelum perampanel prampanel perampanel
2-(6'-oxo-1'-phenyl-1',6'-dihydro[2,3'-bipyridin]-5'-yl)benzonitrile AMPA receptor antagonist 2-(6'-oxo-1'-phenyl-1',6'-dihydro[2,3'-bipyridin]-5'-yl)benzonitrile antagoniste des rcepteurs de l'AMPA 2-(1'-fenil-6'-oxo-1',6'-dihidro[2,3'-bipiridin]-5'-il)benzonitrilo antagonista de los receptores del AMPA C23H15N3O
O N CN N
380917-97-5
155
peretinoinum peretinoin
(2E,4E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,4,6,10,14pentaenoic acid retinoid derivative, antineoplastic acide (2E,4E,6E,10E)-3,7,11,15-ttramthylhexadca-2,4,6,10,14pentnoque rtinode, antinoplasique cido (2E,4E,6E,10E)-3,7,11,15-tetrametilhexadeca-2,4,6,10,14pentaenoico retinoide, antineoplsico C20H30O2
CH3 H 3C CH3 CH3
prtinoin
peretinona
81485-25-8
CH3 CO2H
pexacerfontum pexacerfont
N-[(2R)-butan-2-yl]-8-(6-methoxy-2-methylpyridin-3-yl)2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4-amine antidepressant N-[(2R)-butan-2-yl]-8-(6-mthoxy-2-mthylpyridin-3-yl)2,7-dimthylpyrazolo[1,5-a][1,3,5]triazin-4-amine antidpresseur N-[(2R)-butan-2-il]-8-(6-metoxi-2-metilpiridin-3-il)2,7-dimetilpirazolo[1,5-a][1,3,5]triazin-4-amina antidepresivo C18H24N6O

H3C H3C H H N N H3C N N N CH3
pexacerfont
pexacerfont
459856-18-9
H3C
OCH3
pimavanserinum pimavanserin
1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)3-{[4-(2-methylpropoxy)phenyl]methyl}urea serotonin receptor antagonist 1-[(4-fluorophnyl)mthyl]-1-(1-mthylpipridin-4-yl)3-{[4-(2-mthylpropoxy)phnyl]mthyl}ure antagoniste des rcepteurs de la srotonine 1-[(4-fluorofenil)metil]-1-(1-metilpiperidin-4-il)3-{[4-(2-metilpropoxi)fenil]metil}urea antagonista del receptor de la serotonina
pimavansrine
pimavanserina
156
C25H34FN3O2
CH3 N F N O H N O
706779-91-1
CH3 CH3
piragliatinum piragliatin
(2R)-2-[3-chloro-4-(methanesulfonyl)phenyl]3-[(1R)-3-oxocyclopentyl]-N-(pyrazin-2-yl)propanamide antidiabetic (2R)-2-[3-chloro-4-(mthanesulfonyl)phnyl]3-[(1R)-3-oxocyclopentyl]-N-(pyrazin-2-yl)propanamide antidiabtique (2R)-2-[3-cloro-4-(metanosulfonil)fenil]-3-[(1R)-3-oxociclopentil]N-(pirazin-2-il)propanamida hipoglucemiante C19H20ClN3O4S

O O S H3 C Cl H H
piragliatine
piragliatina
625114-41-2
O N H O
N N
pomalidomidum pomalidomide pomalidomide pomalidomida
4-amino-2-[(3RS)-2,6-dioxopiperidin-3-yl]-2H-isoindole-1,3-dione antineoplastic 4-amino-2-[(3RS)-2,6-dioxopipridin-3-yl]-2H-isoindole-1,3-dione antinoplasique 4-amino-2-[(3RS)-2,6-dioxopiperidin-3-il]-2H-isoindol-1,3-diona antineoplsico C13H11N3O4

O N H NH2 O O NH O and enantiomer et nantiomre y enantimero
19171-19-8
157
posaraprostum posaraprost
propan-2-yl (5Z)-7-{(1R,2S)-2-[(1E,3S)-3-hydroxy-5-phenylpent1-en-1-yl]-5-oxocyclopent-3-en-1-yl}hept-5-enoate anti-inflammatory (5Z)-7-{(1R,2S)-2-[(1E,3S)-3-hydroxy-5-phnylpent-1-n-1-yl]5-oxocyclopent-3-n-1-yl}hept-5-noate de propan-2-yle anti-inflammatoire (5Z)-7-{(1R,2S)-2-[(1E,3S)-3-hidroxi-5-fenilpent-1-en-1-il]5-oxociclopent-3-en-1-ilo}-hept-5-enoato de propan-2-ilo antiinflamatorio C26H34O4
O H O H H OH O CH3 CH3
posaraprost
posaraprost
172740-14-6
pyronaridinum pyronaridine
4-[(7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino]2,6-bis[(pyrrolidin-1-yl)methyl]phenol antimalarial 4-[(7-chloro-2-mthoxybenzo[b][1,5]naphthyridin-10-yl)amino]2,6-bis[(pyrrolidin-1-yl)mthyl]phnol antipaludique 4-[(7-cloro-2-metoxibenzo[b][1,5]naftiridin-10-il)amino]2,6-bis[(pirrolidin-1-il)metil]fenol antipaldico C29H32ClN5O2

N H3CO N HN OH N N Cl
pyronaridine
pironaridina
74847-35-1
158
rabeximod rabeximod
2-(9-chloro-2,3-dimethyl-6H-indolo[2,3-b]quinoxalin-6-yl)N-[2-(dimethylamino)ethyl]acetamide immunomodulator 2-(9-chloro-2,3-dimthyl-6H-indolo[2,3-b]quinoxalin-6-yl)N-[2-(dimthylamino)thyl]actamide immunomodulateur 2-(9-cloro-2,3-dimetil-6H-indolo[2,3-b]quinoxalin-6-il)N-[2-(dimetilamino)etil]acetamida inmunomodulador C22H24ClN5O

Cl CH3 N CH3 N N H N O N CH3
rabeximod
rabeximod
872178-65-9
CH3
raltegravirum raltegravir
N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-[2-(5-methyl1,3,4-oxadiazole-2-carboxamido)propan-2-yl]-6-oxo1,6-dihydropyrimidine-4-carboxamide antiviral N-[(4-fluorophnyl)mthyl]-5-hydroxy-1-mthyl-2-[2-(5-mthyl1,3,4-oxadiazole-2-carboxamido)propan-2-yl]-6-oxo1,6-dihydropyrimidine-4-carboxamide antiviral N-[(4-fluorofenil)metil]-5-hidroxi-1-metil-2-[2-(5-metil-1,3,4-oxadiazol2-carboxamido)propan-2-il]-6-oxo-1,6-dihidropirimidina4-carboxamida antiviral C20H21FN6O5

O H3 C H3 C O N N N H H3 C CH3 N N O OH O N H F
raltgravir
raltegravir
518048-05-0
regrelorum regrelor
N6-(N-ethylcarbamoyl)-2',3'-O-[(1S,2E)-3-phenylprop-2-ene-1,1-diyl]5'-adenylic acid platelet aggregation inhibitor
159
rgrlor
acide N6-(N-thylcarbamoyl)-2',3'-O-[(1S,2E)-3-phnylprop-2-ne1,1-diyl]-5'-adnylique antiagrgant plaquettaire cido N6-(N-etilcarbamoil)-2',3'-O-[(1S,2E)-3-fenilprop-2-eno1,1-diilo]-5'-adenlico inhibidor de la agregacion plaqueteria C22H25N6O8P
O H3C N H N O P O N O NH N N
regrelor
787548-03-2
HO OH O
O H
rolapitantum rolapitant
(5S,8S)-8-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}methyl)8-phenyl-1,7-diazaspiro[4.5]decan-2-one neurokinin NK1 receptor antagonist (5S,8S)-8-({(1R)-1-[3,5-bis(trifluoromthyl)phnyl]thoxy}mthyl)8-phnyl-1,7-diazaspiro[4.5]dcan-2-one antagoniste du rcepteur NK1 de la neurokinine (5S,8S)-8-({(1R)-1-[3,5-bis(trifluorometil)fenil]etoxi}metil)-8-fenil1,7-diazaspiro[4.5]decan-2-ona antagonista del receptor NK1 de neurokinina C25H26F6N2O2
O HN NH CF3
rolapitant
rolapitant
552292-08-7
O H CH3
CF3
160
romiplostimum* romiplostim
L-methionyl[human immunogloblin heavy constant gamma 1-(227 C-terminal residues)-peptide (Fc fragment)] fusion protein with 41 amino acids peptide, (7-7':10,10')-bisdisulfide dimer platelet stimulating factor (through Mpl receptor)
romiplostim
(7-7':10,10')-bisdisulfure du dimre de la protine de fusion entre le L-mthionyl[chaine constante gamma 1 de limmunoglobuline humaine-(227 aminoacides C-terminaux)-peptide (fragment Fc)] et un peptide de 41 aminoacides facteur de stimulation plaquettaire (par le rcepteur MpI) (7-7':10,10')-bisdisulfuro del dmero de la protena de fusin entre la L-metionil[cadena constante gamma 1 de la inmunoglobulina humana-(227 aminocidos C-terminales)-pptido (fragmento Fc)] y un pptido de 41 aminocidos factor estimulante de plaquetas (mediante el receptor Mpl) C2634H4086N722O790S18
Monomer / Monomre / Monmero MDKTHTCPPC DPEVKFNWYV KCKVSNKALP KGFYPSDIAV GNVFSCSVMH GGGGGIEGPT PAPELLGGPS DGVEVHNAKT APIEKTISKA EWESNGQPEN EALHNHYTQK LRQWLAARA VFLFPPKPKD KPREEQYNST KGQPREPQVY NYKTTPPVLD SLSLSPGKGG TLMISRTPEV YRVVSVLTVL TLPPSRDELT SDGSFFLYSK GGGIEGPTLR TCVVVDVSHE HQDWLNGKEY KNQVSLTCLV LTVDKSRWQQ QWLAARAGGG 50 100 150 200 250 269
romiplostim
267639-76-9
Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 7-7' 10-10' 42-102 42'-102' 148-206 148'-206'
ronacaleretum ronacaleret
3-{3-[(2R)-3-{[1-(2,3-dihydro-1H-inden-2-yl)-2-methylpropan2-yl]amino}-2-hydroxypropoxy]-4,5-difluorophenyl}propanoic acid antagonist of the G-protein coupled calcium sensing receptor acide 3-{3-[(2R)-3-{[1-(2,3-dihydro-1H-indn-2-yl)-2-mthylpropan2-yl]amino}-2-hydroxypropoxy]-4,5-difluorophnyl}propanoque antagoniste du rcepteur sensible au calcium coupl la protine G cido3-{3-[(2R)-3-{[1-(2,3-dihidro-1H-inden-2-il)-2-metilpropan2-il]amino}-2-hidroxipropoxi]-4,5-difluorofenil}propanoico antagonista del receptor sensible al calcio acoplado a protena G C25H31F2NO4
F H3C CH3 N H F O H OH CO2H
ronacalret
ronacaleret
753449-67-1
161
ropidoxuridinum ropidoxuridine ropidoxuridine ropidoxuridina
1-(2-deoxy--D-erythro-pentofuranosyl)-5-iodopyrimidin-2(1H)-one antineoplastic 1-(2-doxy--D-rythro-pentofuranosyl)-5-iodopyrimidin-2(1H)-one antinoplasique 1-(2-desoxi--D-eritro-pentofuranosil)-5-iodopirimidin-2(1H)-ona antineoplsico C9H11IN2O4

N HO O O N I
093265-81-7
OH
rosonabantum rosonabant
(5RS)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-(piperidin-1-yl)4,5-dihydro-1H-pyrazole-3-carboxamide cannabinoid receptor antagonist (5RS)-5-(4-chlorophnyl)-1-(2,4-dichlorophnyl)-N-(pipridin-1-yl)4,5-dihydro-1H-pyrazole-3-carboxamide antagoniste des rcepteurs cannabinodes (5RS)-5-(4-clorofenil)-1-(2,4-diclorofenil)-N-(piperidin-1-il)4,5-dihidro-1H-pirazol-3-carboxamida antagonista del receptor de cannabinoides C21H21Cl3N4O
Cl N Cl N O N H N and enantiomer et nantiomre y enantimero
rosonabant
rosonabant
861151-12-4
Cl
salirasibum salirasib
2-{[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl]sulfanyl}benzoic acid antineoplastic acide 2-{[(2E,6E)-3,7,11-trimthyldodca-2,6,10-trin-1-yl]sulfanyl}= benzoque antinoplasique cido 2-{[(2E,6E)-3,7,11-trimetildodeca-2,6,10-trien-1-il]sulfanil}= benzoico antineoplsico
salirasib
salirasib
162
C22H30O2S
CO2H S CH3 CH3
162520-00-5
CH3 CH3
sitimagenum ceradenovecum* sitimagene ceradenovec
(recombinant) replication restricted adenovirus (type 5) vector, E1 and E3 deleted, containing/expressing the Herpes simplex virus thymidine kinase (HSV-tk) gene antineoplastic Vecteur adnovirus (type 5 recombinant dfectif, dlt de E1 et E3, contenant le gne thymidine kinase du virus de lherps simplex (Herpes simplex virus - HSV-tk) antinoplasique Vector adenovirus (tipo 5 recombinante defectivo,con delecin de E1 y E3, que contiene el gen timidina kinasa del virus del herpes simplex (Herpes simplex virus - HSV-tk) antineoplsico 898830-54-1
sitimagne cradnovec
sitimagn ceradenovec
sotrastaurinum sotrastaurin
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]1H-pyrrole-2,5-dione protein kinase C inhibitor 3-(1H-indol-3-yl)-4-[2-(4-mthylpiprazin-1-yl)quinazolin-4-yl]1H-pyrrole-2,5-dione inhibiteur de la protine kinase C 3-(1H-indol-3-il)-4-[2-(4-metilpiperazin-1-il)quinazolin-4-il]-1H-pirrol2,5-diona inhibidor de la proteinquinasa C C25H22N6O2
O H N O
sotrastaurine
sotrastaurina
425637-18-9
N N N N CH3 N H
163
taranabantum taranabant
N-[(2S,3S)-4-(4-chlorophenyl)-3-(3-cyanophenyl)butan-2-yl}2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide cannabinoid receptor antagonist N-[(2S,3S)-4-(4-chlorophnyl)-3-(3-cyanophnyl)butan-2-yl}2-mthyl-2-{[5-(trifluoromthyl)pyridin-2-yl]oxy}propanamide antagoniste des rcepteurs cannabinodes N-[(2S,3S)-4-(4-clorofenil)-3-(3-cianofenil)butan-2-il}-2-metil2-{[5-(trifluorometil)piridin-2-il]oxi}propanamida antagonista de los receptores de cannabinoides C27H25ClF3N3O2
H3 C NC H H N H O O H3C CH3 N CF3
taranabant
taranabant
701977-09-5
Cl
tarenflurbilum tarenflurbil tarenflurbil tarenflurbilo
(2R)-2-(2-fluoro-[1,1'-biphenyl-4-yl])propanoic acid apoptosis regulator (2R)-2-(2-fluoro-[1,1'-biphnyl-4-yl])propanoic acid rgulateur de l'apoptose cido (2R)-2-(2-fluoro-[1,1'-bifenil-4-il])propanoico regulador de la apoptosis C15H13FO2
H F CH3 CO2H
051543-40-9
teplizumabum* teplizumab
immunoglobulin G1, anti-[human CD3 epsilon (CD3E)] humanized monoclonal antibody MGA031 [hOKT3gamma1(Ala-Ala)]; gamma1 heavy chain 236L>A, 337L>A [humanized VH (Homo sapiens FR/Mus musculus CDR from clone OKT3)-Homo sapiens IGHG1*01, 117L>A (CH2 1.3), 118L>A (CH2 1.2)] (222-213)-disulfide with kappa light chain [humanized V-KAPPA (Homo sapiens FR/Mus musculus CDR from clone OKT3)-Homo sapiens IGKC*01] ; (228228: 231-231)-bisdisulfide dimer immunomodulator
164
tplizumab
immunoglobuline G1, anti-[CD3 epsilon humain (CD3E)] anticorps monoclonal humanis MGA031 [hOKT3gamma1(Ala-Ala)]; chane lourde gamma1 [VH humanis (Homo sapiens FR/Mus musculus CDR du clone OKT3)-Homo sapiens IGHG1*01, 117L >A (CH2 1.3), 118L>A (CH2 1.2)] (222-213)-disulfure avec la chane lgre kappa [V-KAPPA humanis (Homo sapiens FR/Mus musculus CDR du clone OKT3)-Homo sapiens IGKC*01]; dimre (228-228: 231-231)bisdisulfure immunomodulateur inmunoglobulina G1, anti-[CD3 epsilon humano (CD3E)] anticuerpo monoclonal humanizado MGA031 [hOKT3gamma1(Ala-Ala)]; cadena pesada gamma1 [VH humanizada (Homo sapiens FR/Mus musculus CDR del clon OKT3)-Homo sapiens IGHG1*01, 117L >A (CH2 1.3) , 118L>A (CH2 1.2)] (222-213)-disulfuro con la cadena ligera kappa [V-KAPPA humanizada (Homo sapiens FR/Mus musculus CDR del clon OKT3)-Homo sapiens IGKC*01]; dmero (228-228: 231-231)-bisdisulfuro inmunomodulador C6462H9938N1738O2022S46
Heavy chain / Chane lourde / Cadena pesada QVQLVQSGGG VVQPGRSLRL SCKASGYTFT INPSRGYTNY NQKVKDRFTI SRDNSKNTAF DDHYCLDYWG QGTPVTVSSA STKGPSVFPL YFPEPVTVSW NSGALTSGVH TFPAVLQSSG ICNVNHKPSN TKVDKKVEPK SCDKTHTCPP DTLMISRTPE VTCVVVDVSH EDPEVKFNWY TYRVVSVLTV LHQDWLNGKE YKCKVSNKAL YTLPPSRDEL TKNQVSLTCL VKGFYPSDIA DSDGSFFLYS KLTVDKSRWQ QGNVFSCSVM Light chain / Chane lgre / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCSASSSVS SKLASGVPSR FSGSGSGTDY TFTISSLQPE TKLQITRTVA APSVFIFPPS DEQLKSGTAS NALQSGNSQE SVTEQDSKDS TYSLSSTLTL SSPVTKSFNR GEC
teplizumab
876387-05-2
RYTMHWVRQA LQMDSLRPED APSSKSTSGG LYSLSSVVTV CPAPEAAGGP VDGVEVHNAK PAPIEKTISK VEWESNGQPE HEALHNHYTQ YMNWYQQTPG DIATYYCQQW VVCLLNNFYP SKADYEKHKV PGKGLEWIGY TGVYFCARYY TAALGCLVKD PSSSLGTQTY SVFLFPPKPK TKPREEQYNS AKGQPREPQV NNYKTTPPVL KSLSLSPGK KAPKRWIYDT SSNPFTFGQG REAKVQWKVD YACEVTHQGL 50 100 150 200 250 300 350 400 449 50' 100' 150' 200' 213'
Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro
22-96 22''-96'' 23'-87' 23'''-87''' 133'-193' 133'''-193''' 146-202 146''-202'' 213'-222 213'''-222'' 228-228'' 231-231'' 263-323 263''-323'' 369-427 369''-427''
terameprocolum terameprocol trameprocol terameprocol
1,1'-[(2R,3S)-2,3-dimethylbutane-1,4-diyl]bis(3,4-dimethoxybenzene) antineoplastic 1,1'-[(2R,3S)-2,3-dimthylbutane-1,4-diyl]bis(3,4-dimthoxybenzne) antinoplasique 1,1'-[(2R,3S)-2,3-dimetilbutano-1,4-diil]bis(3,4-dimetoxibenceno) antineoplsico C22H30O4

H H3CO H3CO H3C H CH3 OCH3 OCH3
24150-24-1
165
thrombinum alfa* thrombin alfa thrombine alfa trombina alfa
human thrombin (recombinant, glycoform ) coagulation promoting agent thrombine humaine (recombinante, glycoforme ) facteur de promotion de la coagulation trombina humana (recombinante, glicoforma ) factor promotor de la coagulacin C1511H2342N418O436S15
Light chain / Chane lgre / Cadena ligera TFGSGEADCG LRPLFEKKSL EDKTERELLE Heavy chain / Chane lourde / Cadena pesada QVMLFRKSPQ KHSRTRYERN IHPVCLPDRE LPIVERPVCK FNNRWYQMGI ELLCGASLIS IEKISMLEKI TAASLLQAGY DSTRIRITDN VSWGEGCDRD DRWVLTAAHC YIHPRYNWRE KGRVTGWGNL MFCAGYKPDE GKYGFYTHVF IVEG LLYPPWDKNF NLDRDIALMK KETWTANVGK GKRGDACEGD RLKKWIQKVI SDAEIGMSPW TENDLLVRIG LKKPVAFSDY GQPSVLQVVN SGGPFVMKSP DQFGE
869858-13-9
SYIDGR 36 50 100 150 200 250 295
Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 9-155 64-80 209-223 237-267 Glycosylation site / Site de glycosylation / Posicin de glicosilacin Asn-89
tiliquinatinum tiliquinatine tiliquinatine tiliquinatina
(2R)-2-{4-[(7-bromoquinolin-2-yl)oxy]phenoxy}propanoic acid antineoplastic acide (2R)-2-{4-[(7-bromoquinolin-2-yl)oxy]phnoxy}propanoque antinoplasique cido (2R)-2-{4-[(7-bromoquinolin-2-il)oxi]fenoxi}propanoico antineoplsico C18H14BrNO4
Br N O H O CH3 CO2H
445041-75-8
totrombopagum totrombopag
(4Z)-2-(3,4-dimethylphenyl)-4-(2-{2-hydroxy-3'-(1H-tetrazol-5-yl) [1,1'-biphenyl-3-yl]}hydrazinylidene)-5-methyl-2,4-dihydro3H-pyrazol-3-one thrombopoietin receptor agonist (4Z)-2-(3,4-dimthylphnyl)-4-{2-[2-hydroxy-3'-(1H-ttrazol-5-yl) [1,1'-biphnyl-3-yl]]diazanylidne}-5-mthyl-2,4-dihydro-3H-pyrazol3-one agoniste du rcepteur de la thrombopotine (4Z)-2-(3,4-dimetilfenil)-4-{2-[2-hidroxi-3'-(1H-tetrazol-5-il)[1,1'-bifenil-3-il]]hidrazinilideno}-5-metil-2,4-dihidro-3H-pirazol-3-ona agonista de los receptores de trombopoyetina
totrombopag
totrombopag
166
C25H22N8O2
H3C N N N O N H HN N
376592-42-6
N N OH
H3 C
CH3
trabedersenum trabedersen
2'-deoxy-P-thiocytidylyl-(3'5')-2'-deoxy-P-thioguanylyl-(3'5')-2'deoxy-P-thioguanylyl-(3'5')-2'-deoxy-P-thiocytidylyl-(3'5')-2'deoxy-P-thioadenylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-deoxyP-thioguanylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-deoxyP-thiocytidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-deoxyP-thioadenylyl-(3'5')-P-thiothymidylyl-(3'5')-P-thiothymidylyl(3'5')-P-thiothymidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-deoxyP-thioguanylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-deoxyadenosine antineoplastic 2'-doxy-P-thiocytidylyl-(3'5')-2'-doxy-P-thioguanylyl-(3'5')-2'doxy-P-thioguanylyl-(3'5')-2'-doxy-P-thiocytidylyl-(3'5')-2'doxy-P-thioadnylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-doxyP-thioguanylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-doxyP-thiocytidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-doxyP-thioadnylyl-(3'5')-P-thiothymidylyl-(3'5')-P-thiothymidylyl(3'5')-P-thiothymidylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-doxyP-thioguanylyl-(3'5')-P-thiothymidylyl-(3'5')-2'-doxyadnosine antinoplasique 2'-desoxi-P-tiocitidilil-(3'5')-2'-desoxi-P-tioguanilil-(3'5')-2'-desoxiP-tioguanilil-(3'5')-2'-desoxi-P-tiocitidilil-(3'5')-2'-desoxiP-tioadenilil-(3'5')-P-tiotimidilil-(3'5')-2'-desoxi-P-tioguanilil(3'5')-P-tiotimidilil-(3'5')-2'-desoxi-P-tiocitidilil-(3'5')P-tiotimidilil-(3'5')-2'-desoxi-P-tioadenilil-(3'5')-P-tiotimidilil(3'5')-P-tiotimidilil-(3'5')-P-tiotimidilil-(3'5')-P-tiotimidilil-(3'5')2'-desoxi-P-tioguanilil-(3'5')-P-tiotimidilil-(3'5')-2'desoxiadenosina antineoplsico C177H225N60O94P17S17 925681-61-4
trabedersen
trabedersn
167
trelanserinum trelanserin
2-(7-fluoro-2-oxo-4-{2-[4-(thieno[3,2-c]pyridin-4-yl)piperazin1-yl]ethyl}-1,2-dihydroquinolin-1-yl)acetamide serotonin receptor antagonist 2-(7-fluoro-2-oxo-4-{2-[4-(thino[3,2-c]pyridin-4-yl)piprazin1-yl]thyl}-1,2-dihydroquinolein-1-yl)actamide antagoniste des rcepteurs de la srotonine 2-(7-fluoro-2-oxo-4-{2-[4-(tieno[3,2-c]piridin-4-il)piperazin-1-il]etil}1,2-dihidroquinolin-1-il)acetamida antagonista de los receptores de serotonina C24H24FN5O2S
O H2N O F N N N N
trlansrine
trelanserina
189003-92-7
tridecactidum* tridecactide
alpha-1-13-corticotropin, human L-seryl-L-tyrosyl-L-seryl-L-methionyl-L-glutamyl-L-histidylL-phenylalanyl-L-arginyl-L-tryptophylglycyl-L-lysyl-L-prolyl-L-valine corticotropin-like activity alpha-1-13-corticotropine, humaine L-sryl-L-tyrosyl-L-sryl-L-mthionyl-L-glutamyl-L-histidylL-phnylalanyl-L-arginyl-L-tryptophylglycyl-L-lysyl-L-prolyl-L-valine activit corticotrope alfa-1-13-corticotropina, humana L-seril-L-tirosil-L-seril-L-metionil-L-glutamil-L-histidil-L-fenilalanilL-arginil-L-triptofilglicil-L-lisil-L-prolil-L-valina actividad corticotropa C75H106N20O19S
H Ser Tyr Ser Met Glu His Phe
tridcactide
tridecactida
22006-64-0
Arg Trp Gly
10
Lys Pro Val OH
tropantiolum tropantiol
2-({[(1R,2R,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1] octan-2-yl]methyl}{2-[(2-sulfanylethyl)amino]ethyl}amino)ethanethiol chelating agent 2-({[(1R,2R,3S,5S)-3-(4-chlorophnyl)-8-mthyl-8-azabicyclo[3.2.1] octan-2-yl]mthyl}{2-[(2-sulfanylthyl)amino]thyl}amino)thanethiol chlateur 2-({[(1R,2R,3S,5S)-3-(4-clorofenil)- 8-azabiciclo[ 3.2.1]octan2-il]metil}{2-[(2-sulfaniletil)amino]etil}amino)etanotiol quelante
tropantiol
tropantiol
168
C21H34ClN3S2
Cl H N H H N H CH3
189950-11-6
H N
HS
SH
vatreptacogum alfa (activated)* vatreptacog alfa (activated)
[158-aspartic acid, 296-valine, 298-glutamine]human coagulation factor VII activated, recombinant DNA origin blood coagulation factor [158-acide aspartique, 296-valine, 298-glutamine]facteur de coagulation VII humain activ, origine ADN recombinant facteur de coagulation sanguine [158-cido asprtico, 296-valina, 298-glutamina]factor de coagulacin VII humano activado ; origen ADN recombinante factor de coagulacin sangunea C1981H3051N561O620S27 897936-89-9
vatreptacog alfa (activ)
vatreptacog alfa (activada)
Light chain / Chane lgre / Cadena ligera ANAFLEELRP GSLERECKEE QCSFEEAREI FKDAERTKLF WISYSDGDQC 50 ASSPCQNGGS CKDQLQSYIC FCLPAFEGRN CETHKDDQLI CVNENGGCEQ 100 YCSDHTGTKR SCRCHEGYSL LADGVSCTPT VEYPCGKIPI LEKRNASKPQ 150 GR 152 Heavy chain / Chane lourde / Cadena pesada IVGGKDCP KGECPWQVLL LVNGAQLCGG WRNLIAVLGE HDLSEHDGDE QSRRVAQVII PVVLTDHVVP LCLPERTFSE RTLAFVRFSL NVPRLMTQDC LQQSRKVGDS PNITEYMFCA HYRGTWYLTG IVSWGQGCAT VGHFGVYTRV LRAPFP TLINTIWVVS PSTYVPGTTN VSGWGQLLDR GYSDGSKDSC SQYIEWLQKL AAHCFDKIKN HDIALLRLHQ GATALVLQVL KGDSGGPHAT MRSEPRPGVL 200 250 300 350 400 406
H NH2 CO2H OH
Modified residues / Rsidus modifis / Residuos modificados E HO2C H NH2 6-7-14-16-19-20-25-26-29-35 4-carboxyGlu
HO2C
CO2H
D HO2C 63 3-hydroxyAsp
Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 50-61 55-70 72-81 91-102 98-112 17-22 114-127 135-262 159-164 178-194 310-329 340-368 Glycosylation sites / Sites de glycosylation / Posiciones de glicosilacin Ser-52 Ser-60 Asn-145 Asn-322
velimogenum aliplasmidum* velimogene aliplasmid
plasmid DNA vector, expressing HLA-B7 and beta-2 microglobulin, driven by a Rous sarcoma virus promoter stimulates destruction of melanoma cells vecteur ADN plasmidique, contenant les gnes HLA-B7 et beta2microglobuline, sous le contrle du promoteur virus de sarcome de Rous stimule la destruction des cellules mlaniques vector ADN de plsmdo, que contiene los genes HLA-B7 y beta2microglobulina, controlado por el promotor de virus del sarcoma de Rous estimula la destruccin de las clulas del melanoma 296251-72-4
vlimogne aliplasmide
velimogn aliplsmido
169
voclosporinum voclosporin
1,11-anhydro[L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucylN-methyl-L-valyl-[(2S,3R,4R,6E)-3-hydroxy-4-methyl2-(methylamino)nona-6,8-dienoyl][(2S)-2-aminobutanoyl]N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucine] immunosuppressant 1,11anhydro{L-alanyl-D-alanyl-N-mthyl-L-leucyl-N-mthyl-L-leucylN-mthyl-L-valyl-[(2S,3R,4R,6E)-3-hydroxy-4-mthyl2-(mthylamino)nona-6,8-dinoyl]-(2S)-2-aminobutanoylN-mthylglycyl-N-mthyl-L-leucyl-L-valyl-N-mthyl-L-leucyl] immunosuppresseur 1,11-anhidro[L-alanil-D-alanil-N-metil-L-leucil-N-metil-L-leucil-N-metilL-valil-[(2S,3R,4R,6E)-3-hidroxi-4-metil-2-(metilamino)nona6,8-dienoil][(2S)-2-aminobutanoil]-N-metilglicil-N-metil-L-leucil-L-valilN-methyl-L-leucina] inmunosupresor C63H111N11O12 515814-01-4

CH2 CH3 H3 C H3 C H3 C H3 C H O N H N O H3C N O CH3 O CH3 H H3C H H N O CH3 O O
voclosporine
voclosporina
OH H N H
CH3 H
CH3 N
O H3C H N CH3 O N
O CH3 H CH3
CH3 H N
H N
H3C O N H H3C CH3
H3C H
CH3 H H3 C
170
AMENDMENTS TO PREVIOUS LISTS MODIFICATIONS APPORTES AUX LISTES ANTRIEURES MODIFICACIONES A LAS LISTAS ANTERIORES
Proposed International Non Proprietary Names (Prop. INN): List 31 (WHO Chronicle, Vol. 28, No. 3, 1974) p. 22 dimemorfanum dimemorfan
replace graphic formula by the following

CH3
H H
H3C
Dnominations communes internationales proposes (DCI Prop.): Liste 31 (Chronique OMS, Vol. 28, No. 3, 1974) p. 22 dimemorfanum dimmorfane
remplacer la formule dveloppe par la suivante

CH3
H H
H3C
Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 31 (Crnica de la OMS, Vol. 28, No. 3, 1974) p. 23 dimemorfanum dimemorfano
sustityase la formla dsarollada por la siguiente

CH3
H H
H3C
171
Proposed International Non Proprietary Names (Prop. INN): List 71 Dnominations communes internationales proposes (DCI Prop.): Liste 71 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 71 (WHO Drug Information, Vol. 8, No. 2, 1994) p. 26 suprimse afovirseno insrtese afovirsn
Proposed International Non Proprietary Names (Prop. INN): List 75 Dnominations communes internationales proposes (DCI Prop.): Liste 75 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 75 (WHO Drug Information, Vol. 10, No. 2, 1996) p. 100 suprimse fomivirseno insrtese fomivirsn
Proposed International Non Proprietary Names (Prop. INN): List 77 Dnominations communes internationales proposes (DCI Prop.): Liste 77 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 77 (WHO Drug Information, Vol. 11, No. 2, 1997) p. 102 suprimse trecovirseno insrtese trecovirsn
Proposed International Non Proprietary Names (Prop. INN): List 80 Dnominations communes internationales proposes (DCI Prop.): Liste 80 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 80 (WHO Drug Information, Vol. 12, No. 4, 1998) p. 276 solimastatum solimastat solimastat solimastat
insert the following CAS insrer le numro de CAS suivant insrtese el nombre del CAS siguiente 226072-63-5
Proposed International Non Proprietary Names (Prop. INN): List 81 Dnominations communes internationales proposes (DCI Prop.): Liste 81 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 81 (WHO Drug Information, Vol. 13, No. 2, 1999) p. 117 ganstigminum ganstigmine ganstigmine ganstigmina
172
Proposed International Non Proprietary Names (Prop. INN): List 82 Dnominations communes internationales proposes (DCI Prop.): Liste 82 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 82 (WHO Drug Information, Vol. 14, No. 4, 1999) p. 268 cangrelorum cangrelor cangrlor cangrelor
insert the following CAS number insrer le numro de CAS suivant insrtese el nombre del CAS siguiente 163706-06-7
p. 270
crobenetinum crobenetine crobntine crobenetina
p. 273
epitumomabum epitumomab pitumomab epitumomab
p. 277
figopitantum figopitant figopitant figopitant
p. 288
sulamserodum sulamserod sulamsrod sulamserod
Proposed International Non Proprietary Names (Prop. INN): List 85 Dnominations communes internationales proposes (DCI Prop.): Liste 85 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 85 (WHO Drug Information, Vol. 15, No. 2, 2001) p. 98 suprimse alicaforseno insrtese alicaforsn
173
p. 121
pralnacasanum pralnacasan pralnacasan pralnacasn
replace the action and use by the following remplacer les propriets et indications par les suivantes sustityase el accin y uso por los siguientes caspase inhibitor inhibiteur de la caspase inhibidor de la caspasa
Proposed International Non Proprietary Names (Prop. INN): List 86 Dnominations communes internationales proposes (DCI Prop.): Liste 86 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 86 (WHO Drug Information, Vol. 16, No. 1, 2002) p. 65 ozogamicinum ozogamicin ozogamicine ozogamicina
p. 70
zoticasonum zoticasone zoticasone zoticasona
Proposed International Non Proprietary Names (Prop. INN): List 87 Dnominations communes internationales proposes (DCI Prop.): Liste 87 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 87 (WHO Drug Information, Vol. 16, No. 2, 2002) p. 177 suprimse oblimerseno insrtese oblimersn
Proposed International Non Proprietary Names (Prop. INN): List 89 Dnominations communes internationales proposes (DCI Prop.): Liste 89 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 89 (WHO Drug Information, Vol. 17, No. 3, 2003) p. 186 suprimse aprinocarseno insrtese aprinocarsn
174
Proposed International Non Proprietary Names (Prop. INN): List 90 Dnominations communes internationales proposes (DCI Prop.): Liste 90 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 90 (WHO Drug Information, Vol. 18, No. 1, 2004) p. 49 certolizumabum pegolum certolizumab pegol certolizumab pgol certolizumab pegol
replace the description by the following remplacer la description par la suivante sustityase la descripcin por la siguiente immunoglobulin, anti-(human tumor necrosis factor ) Fab' fragment (human mouse monoclonal CDP870 heavy chain, disulfide bonded with human mouse monoclonal CDP870 light chain), pegylated at Cys-227 on the heavy chain immunoglobuline, anti-(facteur de ncrose tumorale humain) ; (disulfure entre le fragment Fab' de la chane lourde et la chane lgre de l'anticorps monoclonal de souris CDP870 humanis), pgyle Cyst-227 sur la chane lourde inmunoglobulina, anti-(factor de necrosis tumoral humano) fragmento Fab' (cadena pesada del anticuerpo monoclonal humanizado de ratn CDP870, disulfuro con la cadena ligera del anticuerpo monoclonal humanizado de ratn CDP870), pegilado Cis-227 de la cadena pesada
Proposed International Non Proprietary Names (Prop. INN): List 95 Dnominations communes internationales proposes (DCI Prop.): Liste 95 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 95 (WHO Drug Information, Vol. 20, No. 2, 2006) p. 117 aclidinii bromidum bromuro de aclidinio
sustityase el nombre qumico por el siguiente: bromuro de (3R)-1-(3-fenoxipropil)-3-[(hidroxibis(tiofen-2-il)acetiloxi)]-1-2-butil5 3-{4-[3-(dibutilamino)propil]benzoil}- 1 -azabiciclo[2.2.2]octan-1-ilio
p. 151
delete/supprimer/suprimse ticilimumabum ticilimumab ticilimumab ticilimumab
insert/insrer/insrtese tremelimumabum tremelimumab trmlimumab tremelimumab
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Proposed International Non Proprietary Names (Prop. INN): List 96 Dnominations communes internationales proposes (DCI Prop.): Liste 96 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 96 (WHO Drug Information, Vol. 20, No. 4, 2006) p. 290 managlinatum dialanetilum managlinat dialanetil replace graphic formula by the following: managlinat dialantil remplacer la formule dveloppe par la suivante: managlinat dialanetilo sustityase la formla dsarollada por la siguiente:
H2N S H 3C H3 C N O HN O O H CH3 O O CH3 CH3
P NH O H H3C
* Electronic structure available on Mednet: http://mednet.who.int/ * Structure lectronique disponible sur Mednet: http://mednet.who.int/ * Estructura electrnica disponible en Mednet: http://mednet.who.int/
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ANNEX 1
PROCEDURE FOR THE SELECTION OF RECOMMENDED INTERNATIONAL NONPROPRIETARY NAMES FOR PHARMACEUTICAL SUBSTANCES1
The following procedure shall be followed by the World Health Organization (hereinafter also referred to as WHO) in the selection of recommended international nonproprietary names for pharmaceutical substances, in accordance with resolution WHA3.11 of the World Health Assembly, and in the substitution of such names. Article 1 - Proposals for recommended international nonproprietary names and proposals for substitution of such names shall be submitted to WHO on the form provided therefore. The consideration of such proposals shall be subject to the payment of an administrative fee designed only to cover the corresponding costs of the Secretariat of WHO (the Secretariat). The amount of this fee shall be determined by the Secretariat and may, from time to time, be adjusted. Article 2 - Such proposals shall be submitted by the Secretariat to the members of the Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations designated for this purpose, such designated members hereinafter referred to as the INN Expert Group, for consideration in accordance with the General principles for guidance 2 in devising International Nonproprietary Names for Pharmaceutical Substances, annexed to this procedure . The name used by the person discovering or first developing and marketing a pharmaceutical substance shall be accepted, unless there are compelling reasons to the contrary. Article 3 - Subsequent to the examination provided for in article 2, the Secretariat shall give notice that a proposed international nonproprietary name is being considered. a) Such notice shall be given by publication in WHO Drug Information and by letter to Member States and to national and regional pharmacopoeia commissions or other bodies designated by Member States. i) Notice shall also be sent to the person who submitted the proposal (the original applicant) and other persons known to be concerned with a name under consideration. b) Such notice shall: i) set forth the name under consideration; ii) identify the person who submitted the proposal for naming the substance, if so requested by such person; iii) identify the substance for which a name is being considered; iv) set forth the time within which comments and objections will be received and the person and place to whom they should be directed; v) state the authority under which WHO is acting and refer to these rules of procedure. c) In forwarding the notice, the Secretariat shall request that Member States take such steps as are necessary to prevent the acquisition of proprietary rights in the proposed name during the period it is under consideration by WHO. Article 4 - Comments on the proposed name may be forwarded by any person to WHO within four months of the date of publication, under article 3, of the name in WHO Drug Information.
3
1 See Annex 1 in WHO Technical Report Series, No. 581, 1975; proposed amendments are shown in bold-face type. The original text was adopted by the Executive Board in resolution EB15.R7 and amended in resolution EB43.R9. 2 3
See Annex 2. Before 1987, lists of international nonproprietary names were published in the Chronicle of the World Health Organization.
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Article 5 - A formal objection to a proposed name may be filed by any interested person within four months of the date of publication, under article 3, of the name in WHO Drug Information. Such objection shall: i) identify the person objecting; ii) state his or her interest in the name; iii) set forth the reasons for his or her objection to the name proposed. Article 6 - Where there is a formal objection under article 5, WHO may either reconsider the proposed name or use its good offices to attempt to obtain withdrawal of the objection. Without prejudice to the consideration by WHO of a substitute name or names, a name shall not be selected by WHO as a recommended international nonproprietary name while there exists a formal objection thereto filed under article 5 which has not been withdrawn. Article 7 - Where no objection has been filed under article 5, or all objections previously filed have been withdrawn, the Secretariat shall give notice in accordance with subsection (a) of article 3 that the name has been selected by WHO as a recommended international nonproprietary name. Article 8 - In forwarding a recommended international nonproprietary name to Member States under article 7, the Secretariat shall: a) request that it be recognized as the nonproprietary name for the substance; and b) request that Member States take such steps as are necessary to prevent the acquisition of proprietary rights in the name and to prohibit registration of the name as a trademark or trade name. Article 9 a) In the extraordinary circumstance that a previously recommended international nonproprietary name gives rise to errors in medication, prescription or distribution, or a demonstrable risk thereof, because of similarity with another name in pharmaceutical and/or prescription practices, and it appears that such errors or potential errors cannot readily be resolved through other interventions than a possible substitution of a previously recommended international nonproprietary name, or in the event that a previously recommended international nonproprietary name differs substantially from the nonproprietary name approved in a significant number of Member States, or in other such extraordinary circumstances that justify a substitution of a recommended international nonproprietary name, proposals to that effect may be filed by any interested person. Such proposals shall be submitted on the form provided therefore and shall: i) identify the person making the proposal; ii) state his or her interest in the proposed substitution; and iii) set forth the reasons for the proposal; and iv) describe, and provide documentary evidence regarding the other interventions undertaken in an effort to resolve the situation, and the reasons why these other interventions were inadequate. Such proposals may include a proposal for a new substitute international nonproprietary name, devised in accordance with the General principles, which takes into account the pharmaceutical substance for which the new substitute international nonproprietary name is being proposed. The Secretariat shall forward a copy of the proposal, for consideration in accordance with the procedure described in subsection (b) below, to the INN Expert Group and the original applicant or its successor (if different from the person bringing the proposal for substitution and provided that the original applicant or its successor is known or can be found through diligent effort, including contacts with industry associations). In addition, the Secretariat shall request comments on the proposal from: i) Member States and national and regional pharmacopoeia commissions or other bodies designated by Member States (by including a notice to that effect in the letter referred to in article 3(a), and
178
ii) any other persons known to be concerned by the proposed substitution. The request for comments shall: i) state the recommended international nonproprietary name that is being proposed for substitution (and the proposed substitute name, if provided); ii) identify the person who submitted the proposal for substitution (if so requested by such person); iii) identify the substance to which the proposed substitution relates and reasons put forward for substitution; iv) set forth the time within which comments will be received and the person and place to whom they should be directed; and v) state the authority under which WHO is acting and refer to these rules of procedure. Comments on the proposed substitution may be forwarded by any person to WHO within four months of the date of the request for comments. b) After the time period for comments referred to above has elapsed, the Secretariat shall forward any comments received to the INN Expert Group, the original applicant or its successor and the person bringing the proposal for substitution. If, after consideration of the proposal for substitution and the comments received, the INN Expert Group, the person bringing the proposal for substitution and the original applicant or its successor all agree that there is a need to substitute the previously recommended international nonproprietary name, the Secretariat shall submit the proposal for substitution to the INN Expert Group for further processing. Notwithstanding the foregoing, the original applicant or its successor shall not be entitled to withhold agreement to a proposal for substitution in the event the original applicant or its successor has no demonstrable continuing interest in the recommended international nonproprietary name proposed for substitution. In the event that a proposal for substitution shall be submitted to the INN Expert Group for further processing, the INN Expert Group will select a new international nonproprietary name in accordance with the General principles referred to in article 2 and the procedure set forth in articles 3 to 8 inclusive. The notices to be given by the Secretariat under article 3 and article 7, respectively, including to the original applicant or its successor (if not the same as the person proposing the substitution, and provided that the original applicant or its successor is known or can be found through diligent effort, including contacts with industry associations), shall in such event indicate that the new name is a substitute for a previously recommended international nonproprietary name and that Member States may wish to make transitional arrangements in order to accommodate existing products that use the previously recommended international nonproprietary name on their label in accordance with national legislation. If, after consideration of the proposal for substitution and the comments received in accordance with the procedure described above, the INN Expert Group, the original applicant or its successor and the person bringing the proposal for substitution do not agree that there are compelling reasons for substitution of a previously recommended international nonproprietary name, this name shall be retained (provided always that the original applicant or its successor shall not be entitled to withhold agreement to a proposal for substitution in the event that the original applicant or its successor has no demonstrable continuing interest in the recommended international nonproprietary name proposed to be substituted). In such an event, the Secretariat shall advise the person having proposed the substitution, as well as the original applicant or its successor (if not the same as the person proposing the substitution, and provided that the original applicant or its successor is known or can be found through diligent effort, including contacts with industry associations), Member States, national and regional pharmacopoeia commissions, other bodies designated by Member States, and any other persons known to be concerned by the proposed substitution that, despite a proposal for substitution, it has been decided to retain the previously recommended international nonproprietary name (with a description of the reason(s) why the proposal for substitution was not considered sufficiently compelling). Article 10 - A working process, intended to serve as a guide for the INN Expert Group in the implementation of this procedure, is attached hereto as an appendix.
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ANNEX 2
GENERAL PRINCIPLES FOR GUIDANCE IN DEVISING INTERNATIONAL NONPROPRIETARY NAMES FOR PHARMACEUTICAL SUBSTANCES1
1. International Nonproprietary Names (INN) should be distinctive in sound and spelling. They should not be inconveniently long and should not be liable to confusion with names in common use. 2. The INN for a substance belonging to a group of pharmacologically related substances should, where appropriate, show this relationship. Names that are likely to convey to a patient an anatomical, physiological, pathological or therapeutic suggestion should be avoided. These primary principles are to be implemented by using the following secondary principles: 3. In devising the INN of the first substance in a new pharmacological group, consideration should be given to the possibility of devising suitable INN for related substances, belonging to the new group. 4. In devising INN for acids, one-word names are preferred; their salts should be named without modifying the acid name, e.g. oxacillin and oxacillin sodium, ibufenac and ibufenac sodium. 5. INN for substances which are used as salts should in general apply to the active base or the active acid. Names for different salts or esters of the same active substance should differ only in respect of the name of the inactive acid or the inactive base. For quaternary ammonium substances, the cation and anion should be named appropriately as separate components of a quaternary substance and not in the amine-salt style. 6. The use of an isolated letter or number should be avoided; hyphenated construction is also undesirable. 7. To facilitate the translation and pronunciation of INN, f should be used instead of ph, t instead of th, e instead of ae or oe, and i instead of y; the use of the letters h and k should be avoided. 8. Provided that the names suggested are in accordance with these principles, names proposed by the person discovering or first developing and marketing a pharmaceutical preparation, or names already officially in use in any country, should receive preferential consideration. 9. Group relationship in INN (see General principle 2) should if possible be shown by using a common stem. The following list contains examples of stems for groups of substances, particularly for new groups. There are many other stems in active 2 use. Where a stem is shown without any hyphens it may be used anywhere in the name. Latin -acum -adolum -adol-astum -astinum -azepamum bol -cain-cainum
1
English -ac -adol } -adol-} -ast -astine -azepam bol -cain-caine anti-inflammatory agents, ibufenac derivatives analgesics anti-asthmatic, anti-allergic substances not acting primarily as antihistaminics antihistaminics diazepam derivatives steroids, anabolic class I antiarrhythmics, procainamide and lidocaine derivatives local anaesthetics
In its Twentieth report (WHO Technical Report Series, No. 581, 1975), the WHO Expert committee on Nonpropriety Names for Pharmaceutical Substances reviewed the general principles for devising, and the procedures for selecting, INN in the light of developments in pharmaceutical compounds in recent years. The most significant change has been the extension to the naming of synthetic chemical substances of the practice previously used for substances originating in or derived from natural products. This practice involves the use of a characteristic stem indicative of a common property of the members of a group. The reason for, and the implications of, the change are fully discussed. The guiding principles were updated during the 13th consultation on nonproprietary names for pharmaceutical substances (Geneva, 27-29 April 1983) (PHARM S/NOM 928 13 May 1983, revised 18 August 1983).
2
A more extensive listing of stems is contained in the working document WHO/PSM/QSM/2006.3 which is regularly updated and can be requested from the INN Programme, WHO, Geneva.
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cef-cillinum -conazolum cort -coxibum -entanum gab gado-gatranum gest gli io-metacinum -mycinum -nidazolum -ololum -oxacinum -platinum -poetinum -pril(at)um -profenum prost -relinum -sartanum -vaptanum vin-vin-
cef-cillin -conazole cort -coxib -entan gab gado-gatran gest gli io-metacin -mycin -nidazole -olol -oxacin -platin -poetin -pril(at) -profen prost -relin -sartan -vaptan vin- } -vin-}
antibiotics, cefalosporanic acid derivatives antibiotics, 6-aminopenicillanic acid derivatives systemic antifungal agents, miconazole derivatives corticosteroids, except prednisolone derivatives selective cyclo-oxygenase inhibitors endothelin receptor antagonists gabamimetic agents diagnostic agents, gadolinium derivatives thrombin inhibitors, antithrombotic agents steroids, progestogens antihyperglycaemics iodine-containing contrast media anti-inflammatory, indometacin derivatives antibiotics, produced by Streptomyces strains antiprotozoal substances, metronidazole derivatives -adrenoreceptor antagonists antibacterial agents, nalidixic acid derivatives antineoplastic agents, platinum derivatives erythropoietin type blood factors angiotensin-converting enzyme inhibitors anti-inflammatory substances, ibuprofen derivatives prostaglandins pituitary hormone release-stimulating peptides angiotensin II receptor antagonists, antihypertensive (non-peptidic) vasopressin receptor antagonists vinca-type alkaloids
ANNEXE 1
PROCEDURE A SUIVRE EN VUE DU CHOIX DE DENOMINATIONS COMMUNES INTERNATIONALES RECOMMANDEES POUR LES SUBSTANCES PHARMACEUTIQUES1
LOrganisation mondiale de la Sant (galement dsigne ci-aprs sous lappellation OMS ) observe la procdure expose ci-dessous pour lattribution de dnominations communes internationales recommandes pour les substances pharmaceutiques, conformment la rsolution WHA3.11 de lAssemble mondiale de la Sant, et pour le remplacement de telles dnominations. Article 1 - Les propositions de dnominations communes internationales recommandes et les propositions de remplacement de telles dnominations sont soumises lOMS sur la formule prvue cet effet. Lexamen de telles propositions est soumis au paiement dune taxe administrative destine uniquement couvrir les cots correspondants assums par le Secrtariat de lOMS ( le Secrtariat ). Le montant de cette taxe est dtermin par le Secrtariat et peut tre modifi de temps autre. Article 2 - Ces propositions sont soumises par le Secrtariat aux experts dsigns cette fin parmi les personnalits inscrites au Tableau dexperts de la Pharmacope internationale et des Prparations pharmaceutiques, ci-aprs dsigns sous lappellation le Groupe dexperts des DCI ; elles sont examines par les experts conformment aux Directives gnrales pour la formation de dnominations communes internationales pour les substances pharmaceutiques 2 reproduites ci-aprs . La dnomination accepte est la dnomination employe par la personne qui dcouvre ou qui, la premire, fabrique et lance sur le march une substance pharmaceutique, moins que des raisons majeures nobligent scarter de cette rgle.
Voir annexe 1 dans OMS, Srie de Rapports techniques, N 581, 1975 ; les amendements proposs sont indiqus en caractres gras. Le texte original a t adopt par le Conseil excutif dans sa rsolution EB15.R7 et amend dans sa rsolution EB43.R9.
2 1
Voir annexe 2.
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Article 3 - Aprs lexamen prvu larticle 2, le Secrtariat notifie quun projet de dnomination commune internationale est ltude. a) Cette notification est faite par une insertion dans WHO Drug Information et par lenvoi dune lettre aux Etats Membres et aux commissions nationales et rgionales de pharmacope ou autres organismes dsigns par les Etats Membres. i) Notification est galement faite la personne qui a soumis la proposition ( le demandeur initial ) et dautres personnes portant la dnomination mise ltude un intrt notoire. b) Cette notification contient les indications suivantes : i) dnomination mise ltude; ii) nom de lauteur de la proposition tendant attribuer une dnomination la substance, si cette personne le demande ; iii) dfinition de la substance dont la dnomination est mise ltude ; iv) dlai pendant lequel seront reues les observations et les objections lgard de cette dnomination ; nom et adresse de la personne habilite recevoir ces observations et objections ; v) mention des pouvoirs en vertu desquels agit lOMS et rfrence au prsent rglement. c) En envoyant cette notification, le Secrtariat demande aux Etats Membres de prendre les mesures ncessaires pour prvenir lacquisition de droits de proprit sur la dnomination propose pendant la priode au cours de laquelle cette dnomination est mise ltude par lOMS. Article 4 - Des observations sur la dnomination propose peuvent tre adresses lOMS par toute personne, dans les quatre mois qui suivent la date de publication de la dnomination dans WHO Drug Information (voir larticle 3). Article 5 - Toute personne intresse peut formuler une objection formelle contre la dnomination propose dans les quatre mois qui suivent la date de publication de la dnomination dans WHO Drug Information (voir larticle 3). Cette objection doit saccompagner des indications suivantes : i) nom de lauteur de lobjection ; ii) intrt quil ou elle porte la dnomination en cause ; iii) raisons motivant lobjection contre la dnomination propose. Article 6 - Lorsquune objection formelle est formule en vertu de larticle 5, lOMS peut soit soumettre la dnomination propose un nouvel examen, soit intervenir pour tenter dobtenir le retrait de lobjection. Sans prjudice de lexamen par lOMS dune ou de plusieurs appellations de remplacement, lOMS nadopte pas dappellation comme dnomination commune internationale recommande tant quune objection formelle prsente conformment larticle 5 nest pas leve. Article 7 - Lorsquil nest formul aucune objection en vertu de larticle 5, ou que toutes les objections prsentes ont t leves, le Secrtariat fait une notification conformment aux dispositions du paragraphe a) de larticle 3, en indiquant que la dnomination a t choisie par lOMS en tant que dnomination commune internationale recommande. Article 8 - En communiquant aux Etats Membres, conformment larticle 7, une dnomination commune internationale recommande, le Secrtariat : a) demande que cette dnomination soit reconnue comme dnomination commune de la substance considre ; et b) demande aux Etats Membres de prendre les mesures ncessaires pour prvenir lacquisition de droits de proprit sur cette dnomination et interdire le dpt de cette dnomination comme marque ou appellation commerciale.
1
Avant 1987, les listes de dnominations communes internationales taient publies dans la Chronique de lOrganisation mondiale de la Sant.
182
Article 9 a) Dans le cas exceptionnel o une dnomination commune internationale dj recommande donne lieu des erreurs de mdication, de prescription ou de distribution ou en comporte un risque dmontrable, en raison dune similitude avec une autre appellation dans la pratique pharmaceutique et/ou de prescription, et o il apparat que ces erreurs ou ces risques derreur ne peuvent tre facilement vits par dautres interventions que le remplacement ventuel dune dnomination commune internationale dj recommande, ou dans le cas o une dnomination commune internationale dj recommande diffre sensiblement de la dnomination commune approuve dans un nombre important dEtats Membres, ou dans dautres circonstances exceptionnelles qui justifient le remplacement dune dnomination commune internationale recommande, toute personne intresse peut formuler une proposition dans ce sens. Cette proposition est prsente sur la formule prvue cet effet et doit saccompagner des indications suivantes : i) nom de lauteur de la proposition ; ii) intrt quil ou elle porte au remplacement propos ; iii) raisons motivant la proposition ; et iv) description, faits lappui, des autres interventions entreprises pour tenter de rgler le problme et expos des raisons pour lesquelles ces interventions ont chou. Les propositions peuvent comprendre une proposition de nouvelle dnomination commune internationale de remplacement, tablie conformment aux Directives gnrales, compte tenu de la substance pharmaceutique pour laquelle la nouvelle dnomination commune internationale de remplacement est propose. Le Secrtariat transmet une copie de la proposition pour examen, conformment la procdure expose plus loin au paragraphe b), au Groupe dexperts des DCI et au demandeur initial ou son successeur (sil sagit dune personne diffrente de celle qui a formul la proposition de remplacement et pour autant que le demandeur initial ou son successeur soit connu ou puisse tre retrouv moyennant des efforts diligents, notamment des contacts avec les associations industrielles). De plus, le Secrtariat demande aux entits et personnes ci-aprs de formuler des observations sur la proposition : i) les Etats Membres et les commissions nationales et rgionales de pharmacope ou dautres organismes dsigns par les Etats Membres (en insrant une note cet effet dans la lettre mentionne larticle 3.a), et ii) toutes autres personnes portant au remplacement propos un intrt notoire. La demande dobservations contient les indications suivantes : i) dnomination commune internationale recommande pour laquelle un remplacement est propos (et la dnomination de remplacement propose, si elle est fournie) ; ii) nom de lauteur de la proposition de remplacement (si cette personne le demande) ; iii) dfinition de la substance faisant lobjet du remplacement propos et raisons avances pour le remplacement ; iv) dlai pendant lequel seront reus les commentaires et nom et adresse de la personne habilite recevoir ces commentaires ; et v) mention des pouvoirs en vertu desquels agit lOMS et rfrence au prsent rglement. Des observations sur la proposition de remplacement peuvent tre communiques par toute personne lOMS dans les quatre mois qui suivent la date de la demande dobservations. b) Une fois chu le dlai prvu ci-dessus pour la communication dobservations, le Secrtariat transmet les observations reues au Groupe dexperts des DCI, au demandeur initial ou son successeur et lauteur de la proposition de remplacement. Si, aprs avoir examin la proposition de remplacement et les observations reues, le Groupe dexperts des DCI, lauteur de la proposition de remplacement et le demandeur initial ou son successeur reconnaissent tous quil est ncessaire de remplacer la dnomination commune internationale dj recommande, le Secrtariat soumet la proposition de remplacement au Groupe dexperts des DCI pour quil y donne suite. Nonobstant ce qui prcde, le demandeur initial ou son successeur nest pas habilit refuser son accord une 183
proposition de remplacement au cas o il ne peut tre dmontr quil porte un intrt durable la dnomination commune internationale recommande quil est propos de remplacer. Dans le cas o une proposition de remplacement est soumise au Groupe dexperts des DCI pour quil y donne suite, le Groupe choisit une nouvelle dnomination commune internationale conformment aux Directives gnrales mentionnes larticle 2 et selon la procdure dcrite dans les articles 3 8 inclus. La notification faite par le Secrtariat en vertu de larticle 3 et de larticle 7, respectivement, y compris au demandeur initial ou son successeur (si ce nest pas la mme personne que celle qui a propos le remplacement et pour autant que le demandeur initial ou son successeur soit connu ou puisse tre retrouv moyennant des efforts diligents, notamment des contacts avec les associations industrielles), doit dans un tel cas indiquer que la nouvelle dnomination remplace une dnomination commune internationale dj recommande et que les Etats Membres peuvent souhaiter prendre des mesures transitoires pour les produits existants qui utilisent la dnomination commune internationale dj recommande sur leur tiquette conformment la lgislation nationale. Si, aprs examen de la proposition de remplacement et des observations communiques conformment la procdure expose plus haut, le Groupe dexperts des DCI, le demandeur initial ou son successeur et lauteur de la proposition de remplacement ne saccordent pas sur le fait quil y a des raisons impratives de remplacer une dnomination commune internationale dj recommande, cette dernire est conserve (tant entendu toujours que le demandeur initial ou son successeur nest pas habilit refuser son accord une proposition de remplacement au cas o il ne peut tre dmontr quil porte un intrt durable la dnomination commune internationale recommande quil est propos de remplacer). Dans un tel cas, le Secrtariat informe lauteur de la proposition de remplacement, ainsi que le demandeur initial ou son successeur (sil sagit dune personne diffrente de celle qui a formul la proposition de remplacement et pour autant que le demandeur initial ou son successeur soit connu ou puisse tre retrouv moyennant des efforts diligents, notamment des contacts avec les associations industrielles), les Etats Membres, les commissions nationales et rgionales de pharmacope, les autres organismes dsigns par les Etats Membres et toutes autres personnes portant un intrt notoire au remplacement propos que, malgr une proposition de remplacement, il a t dcid de conserver la dnomination commune internationale dj recommande (avec une brve description de la ou des raisons pour lesquelles la proposition de remplacement na pas t juge suffisamment imprative). Article 10 - Une mthode de travail, destine servir de guide pour le Groupe dexperts des DCI en vue de la mise en uvre de cette procdure, est jointe en appendice au prsent texte.
ANNEXE 2
DIRECTIVES GENERALES POUR LA FORMATION DE DENOMINATIONS COMMUNES INTERNATIONALES APPLICABLES AUX SUBSTANCES PHARMACEUTIQUES1
1. Les dnominations communes internationales (DCI) devront se distinguer les unes des autres par leur consonance et leur orthographe. Elles ne devront pas tre dune longueur excessive, ni prter confusion avec des appellations dj couramment employes. 2. La DCI de chaque substance devra, si possible, indiquer sa parent pharmacologique. Les dnominations susceptibles dvoquer pour les malades des considrations anatomiques, physiologiques, pathologiques ou thrapeutiques devront tre vites dans la mesure du possible. Outre ces deux principes fondamentaux, on respectera les principes secondaires suivants : 3. Lorsquon formera la DCI de la premire substance dun nouveau groupe pharmacologique, on tiendra compte de la possibilit de former ultrieurement dautres DCI appropries pour les substances apparentes du mme groupe.
1
Dans son vingtime rapport (OMS, Srie de Rapports techniques, N 581, 1975), le Comit OMS dexperts des Dnominations communes pour les Substances pharmaceutiques a examin les directives gnrales pour la formation des dnominations communes internationales et la procdure suivre en vue de leur choix, compte tenu de lvolution du secteur pharmaceutique au cours des dernires annes. La modification la plus importante a t lextension aux substances de synthse de la pratique normalement suivie pour dsigner les substances tires ou drives de produits naturels. Cette pratique consiste employer des syllabes communes ou groupes de syllabes communes (segments-cls) qui sont caractristiques et indiquent une proprit commune aux membres du groupe des substances pour lequel ces segments-cls ont t retenus. Les raisons et les consquences de cette modification ont fait lobjet de discussions approfondies. Les directives ont t mises jour lors de la treizime consultation sur les dnominations communes pour les substances pharmaceutiques (Genve, 27-29 avril 1983) (PHARM S/NOM 928, 13 mai 1983, rvision en date du 18 aot 1983).
184
4. Pour former des DCI des acides, on utilisera de prfrence un seul mot. Leurs sels devront tre dsigns par un terme qui ne modifie pas le nom de lacide dorigine : par exemple oxacilline et oxacilline sodique, ibufnac et ibufnac sodique. 5. Les DCI pour les substances utilises sous forme de sels devront en gnral sappliquer la base active (ou lacide actif). Les dnominations pour diffrents sels ou esters dune mme substance active ne diffreront que par le nom de lacide inactif (ou de la base inactive). En ce qui concerne les substances base dammonium quaternaire, la dnomination sappliquera de faon approprie au cation et lanion en tant qulments distincts dune substance quaternaire. On vitera de choisir une dsignation voquant un sel amin. 6. On vitera dajouter une lettre ou un chiffre isol ; en outre, on renoncera de prfrence au trait dunion. 7. Pour simplifier la traduction et la prononciation des DCI, la lettre f sera utilise la place de ph , t la place de th , e la place de ae ou oe , et i la place de y ; lusage des lettres h et k sera aussi vit. 8. On retiendra de prfrence, pour autant quelles respectent les principes noncs ici, les dnominations proposes par les personnes qui ont dcouvert ou qui, les premires, ont fabriqu et lanc sur le march les prparations pharmaceutiques considres, ou les dnominations dj officiellement adoptes par un pays. 9. La parent entre substances dun mme groupe (voir Directive gnrale 2) sera si possible indique dans les DCI par lemploi de segments-cls communs. La liste ci-aprs contient des exemples de segments-cls pour des groupes de 1 substances, surtout pour des groupes rcents. Il y a beaucoup dautres segments-cls en utilisation active. Les segmentscls indiqus sans trait dunion pourront tre insrs nimporte o dans une dnomination. Latin -acum -adolum -adol-astum -astinum -azepamum bol -cain-cainum cef-cillinum -conazolum cort -coxibum -entanum gab gado-gatranum gest gli io-metacinum -mycinum -nidazolum -ololum -oxacinum -platinum -poetinum -pril(at)um -profenum prost
1
Franais -ac -adol -adol-ast } } substances anti-inflammatoires du groupe de libufnac analgsiques antiasthmatiques, antiallergiques nagissant pas principalement en tant quantihistaminiques antihistaminiques substances du groupe du diazpam strodes anabolisants antiarythmiques de classe I, drivs du procanamide et de la lidocane anesthsiques locaux antibiotiques, drivs de lacide cphalosporanique antibiotiques, drivs de lacide 6-aminopnicillanique agents antifongiques systmiques du groupe du miconazole corticostrodes, autres que les drivs de la prednisolone inhibiteurs slectifs de la cyclo-oxygnase antagonistes du rcepteur de lendothline gabamimtiques agents diagnostiques, drivs du gadolinium antithrombines, antithrombotiques strodes progestognes antihyperglycmiants produits de contraste iods substances anti-inflammatoires du groupe de lindomtacine antibiotiques produits par des souches de Streptomyces substances antiprotozoaires du groupe du mtronidazole antagonistes des rcepteurs -adrnergiques substances antibactriennes du groupe de lacide nalidixique antinoplasiques, drivs du platine facteurs sanguins de type rythropotine inhibiteurs de lenzyme de conversion de langiotensine substances anti-inflammatoires du groupe de libuprofne prostaglandines
-astine -azpam bol -can-cane cf-cilline -conazole cort -coxib -entan gab gado-gatran gest gli io-mtacine -mycine -nidazole -olol -oxacine -platine -potine -pril(ate) -profne prost
Une liste plus complte de segments-cls est contenue dans le document de travail WHO/PSM/QSM/2006.3 qui est rgulirement mis jour et qui peut tre demand auprs du programme des DCI, OMS, Genve.
185
-relinum -sartanum -vaptanum vin-vin-
-rline -sartan -vaptan vin-vin} }
peptides stimulant la libration dhormones hypophysaires antagonistes dun rcepteur de langiotensine II, antihypertenseurs (non peptidiques) antagonistes du rcepteur de la vasopressine alcalodes du type vinca
ANEXO 1
PROCEDIMIENTO DE SELECCIN DE DENOMINACIONES COMUNES INTERNACIONALES RECOMENDADAS PARA SUSTANCIAS FARMACUTICAS1

La Organizacin Mundial de la Salud (OMS) seguir el procedimiento que se expone a continuacin tanto para seleccionar denominaciones comunes internacionales recomendadas para las sustancias farmacuticas, de conformidad con lo dispuesto en la resolucin WHA3.11, como para sustituir esas denominaciones. Artculo 1 - Las propuestas de denominaciones comunes internacionales recomendadas y las propuestas de sustitucin de esas denominaciones se presentarn a la OMS en los formularios que se proporcionen a estos efectos. El estudio de estas propuestas estar sujeto al pago de una tasa destinada a sufragar los costos de administracin que ello suponga para la Secretara de la OMS (la Secretara). La Secretara establecer la cuanta de esa tasa y podr ajustarla peridicamente. Artculo 2 - Estas propuestas sern sometidas por la Secretara a los miembros del Cuadro de Expertos en Farmacopea Internacional y Preparaciones Farmacuticas encargados de su estudio, en adelante designados como el Grupo de Expertos en DCI, para que las examinen de conformidad con los Principios generales de orientacin para formar 2 denominaciones comunes internacionales para sustancias farmacuticas, anexos a este procedimiento. A menos que haya poderosas razones en contra, la denominacin aceptada ser la empleada por la persona que haya descubierto o fabricado y comercializado por primera vez esa sustancia farmacutica. Artculo 3 - Tras el examen al que se refiere el artculo 2, la Secretara notificar que est en estudio un proyecto de denominacin internacional. a) Esa notificacin se har mediante una publicacin en Informacin Farmacutica OMS y el envo de una carta a los Estados Miembros y a las comisiones nacionales y regionales de las farmacopeas u otros organismos designados por los Estados Miembros. i) La notificacin ser enviada tambin a la persona que haya presentado la propuesta (el solicitante inicial) y a otras personas que tengan un inters especial en una denominacin objeto de estudio. b) En esa notificacin se incluirn los siguientes datos: i) la denominacin sometida a estudio; ii) la identidad de la persona que ha presentado la propuesta de denominacin de la sustancia, si lo pide esa persona; iii) la identidad de la sustancia cuya denominacin est en estudio; iv) el plazo fijado para recibir observaciones y objeciones, as como el nombre y la direccin de la persona a quien deban dirigirse; y v) los poderes conferidos para el caso a la OMS y una referencia al presente procedimiento.
1
Vase el anexo 1 en OMS, Serie de Informes Tcnicos, N 581, 1975; las modificaciones propuestas se indican en negrita. El texto vigente fue adoptado por el Consejo Ejecutivo en su resolucin EB15.R7 y modificado en la resolucin EB43.R9.
2 3
Vase el anexo 2. Hasta 1987 las listas de DCI se publicaban en la Crnica de la Organizacin Mundial de la Salud.
186
c) Al enviar esa notificacin, la Secretara solicitar de los Estados Miembros la adopcin de todas las medidas necesarias para impedir la adquisicin de derechos de patente sobre la denominacin propuesta, durante el periodo en que la OMS la tenga en estudio. Artculo 4 - Toda persona puede formular a la OMS observaciones sobre la denominacin propuesta dentro de los cuatro meses siguientes a su publicacin en Informacin Farmacutica OMS, conforme a lo dispuesto en el artculo 3. Artculo 5 - Toda persona interesada puede presentar una objecin formal a una denominacin propuesta dentro de los cuatro meses siguientes a su publicacin en Informacin Farmacutica OMS, conforme a lo dispuesto en el artculo 3. Esa objecin deber acompaarse de los siguientes datos: i) la identidad de la persona que formula la objecin; ii) las causas que motivan su inters por la denominacin; y iii) las causas que motivan su objecin a la denominacin propuesta. Artculo 6 - Cuando se haya presentado una objecin formal en la forma prevista en el artculo 5, la OMS podr reconsiderar el nombre propuesto o utilizar sus buenos oficios para intentar lograr que se retire la objecin. La OMS no seleccionar como denominacin comn internacional una denominacin a la que se haya hecho una objecin formal, presentada segn lo previsto en el artculo 5, que no haya sido retirada, todo ello sin perjuicio de que la Organizacin examine otra denominacin o denominaciones sustitutivas. Artculo 7 - Cuando no se haya formulado ninguna objecin en la forma prevista en el artculo 5, o cuando todas las objeciones presentadas hayan sido retiradas, la Secretara notificar, conforme a lo dispuesto en el prrafo a) del artculo 3, que la denominacin ha sido seleccionada por la OMS como denominacin comn internacional recomendada. Artculo 8 - Al comunicar a los Estados Miembros una denominacin comn internacional, conforme a lo previsto en el artculo 7, la Secretara: a) solicitar que esta denominacin sea reconocida como denominacin comn para la sustancia de que se trate; y b) solicitar a los Estados Miembros que adopten todas las medidas necesarias para impedir la adquisicin de derechos de patente sobre la denominacin, y prohban que sea registrada como marca de fbrica o como nombre comercial. Artculo 9 a) En el caso excepcional de que, debido a su semejanza con otra denominacin utilizada en las prcticas farmacuticas y/o de prescripcin, una denominacin comn internacional recomendada anteriormente ocasione errores de medicacin, prescripcin o distribucin, o suponga un riesgo manifiesto de que esto ocurra, y parezca que tales errores o potenciales errores no sean fcilmente subsanables con otras medidas que no sean la posible sustitucin de esa denominacin comn internacional recomendada anteriormente; en el caso de que una denominacin comn internacional recomendada anteriormente difiera considerablemente de la denominacin comn aprobada en un nmero importante de Estados Miembros, o en otras circunstancias excepcionales que justifiquen el cambio de una denominacin comn internacional recomendada, cualquier persona interesada puede presentar propuestas en este sentido. Esas propuestas se presentarn en los formularios que se proporcionen a estos efectos e incluirn los siguientes datos: i) la identidad de la persona que presenta la propuesta; ii) las causas que motivan su inters en la sustitucin propuesta; iii) las causas que motivan la propuesta; y iv) una descripcin, acompaada de pruebas documentales, de las otras medidas que se hayan adoptado con el fin de resolver la situacin y de los motivos por los cuales dichas medidas no han sido suficientes. Entre esas propuestas podr figurar una relativa a una nueva denominacin comn internacional sustitutiva, formulada con arreglo a los Principios generales y que tenga en cuenta la sustancia farmacutica para la que se proponga la nueva denominacin comn internacional sustitutiva. La Secretara enviar al Grupo de Expertos en DCI y al solicitante inicial o a su sucesor (en el caso de que sea una persona diferente de la que ha presentado la propuesta de sustitucin y siempre que el solicitante inicial o su sucesor sean conocidos o puedan ser encontrados mediante esfuerzos diligentes, como el contacto con las asociaciones 187
industriales) una copia de la propuesta, para que sea examinada de conformidad con el procedimiento descrito en el prrafo b) infra. Adems, la Secretara solicitar observaciones sobre la propuesta: i) a los Estados Miembros y a las comisiones nacionales y regionales de las farmacopeas u otros organismos designados por los Estados Miembros (ello se har incluyendo una notificacin a tal efecto en la carta a la que se refiere el prrafo a) del artculo 3), y ii) a cualquier persona que tenga un inters especial en la sustitucin propuesta. Al solicitar que se formulen estas observaciones se facilitarn los siguientes datos: i) la denominacin comn internacional recomendada que se propone sustituir (y la denominacin sustitutiva propuesta, si se ha facilitado); ii) la identidad de la persona que ha presentado la propuesta de sustitucin (si lo pide esa persona); iii) la identidad de la sustancia a la que se refiere la sustitucin propuesta y las razones para presentar la propuesta de sustitucin; iv) el plazo fijado para recibir observaciones, as como el nombre y la direccin de la persona a quien deban dirigirse; y v) los poderes conferidos para el caso a la OMS y una referencia al presente procedimiento. Toda persona puede formular a la OMS observaciones sobre la sustitucin propuesta dentro de los cuatro meses siguientes a la fecha en que se realiz la solicitud de observaciones. b) Una vez agotado el mencionado plazo para la formulacin de observaciones, la Secretara enviar todos los comentarios recibidos al Grupo de Expertos en DCI, al solicitante inicial o a su sucesor, y a la persona que haya presentado la propuesta de sustitucin. Si despus de examinar la propuesta de sustitucin y las observaciones recibidas, el Grupo de Expertos en DCI, la persona que haya presentado la propuesta de sustitucin y el solicitante inicial, o su sucesor, estn de acuerdo en la necesidad de sustituir la denominacin comn internacional recomendada anteriormente, la Secretara remitir la propuesta de sustitucin al Grupo de Expertos en DCI para que la tramite. No obstante lo anterior, el solicitante inicial o su sucesor no tendrn derecho a impedir el acuerdo sobre una propuesta de sustitucin en el caso de que hayan dejado de tener un inters demostrable en la denominacin comn internacional cuya sustitucin se propone. En caso de que la propuesta de sustitucin sea presentada al Grupo de Expertos en DCI para que la tramite, este grupo seleccionar una nueva denominacin comn internacional de conformidad con los Principios generales a los que se refiere el artculo 2 y al procedimiento establecido en los artculos 3 a 8 inclusive. En ese caso, en las notificaciones que la Secretara ha de enviar con arreglo a los artculos 3 y 7, respectivamente, incluida la notificacin al solicitante inicial o a su sucesor (en el caso de que no sea la misma persona que propuso la sustitucin y siempre que el solicitante inicial o su sucesor sean conocidos o puedan ser encontrados mediante esfuerzos diligentes, como el contacto con las asociaciones industriales), se indicar que la nueva denominacin sustituye a una denominacin comn internacional recomendada anteriormente y que los Estados Miembros podrn, si lo estiman oportuno, adoptar disposiciones transitorias aplicables a los productos existentes en cuya etiqueta se utilice, con arreglo a la legislacin nacional, la denominacin comn internacional recomendada anteriormente que se haya sustituido. En caso de que, despus de haber estudiado la propuesta de sustitucin y los comentarios recibidos de conformidad con el procedimiento descrito anteriormente, el Grupo de Expertos en DCI, el solicitante inicial o su sucesor y la persona que haya presentado la propuesta de sustitucin no lleguen a un acuerdo sobre la existencia de razones poderosas para sustituir una denominacin comn internacional recomendada anteriormente, esta denominacin se mantendr (siempre en el entendimiento de que el solicitante inicial o su sucesor no tendrn derecho a impedir el acuerdo sobre una propuesta de sustitucin en el caso de que hayan dejado de tener un inters demostrable en la denominacin comn internacional cuya sustitucin se propone). En ese caso, la Secretara comunicar a la persona que haya propuesto la sustitucin, as como al solicitante inicial o a su sucesor (en el caso de que no sea la misma persona que propuso la sustitucin y siempre que el solicitante inicial o su sucesor sean conocidos o puedan ser encontrados mediante esfuerzos diligentes, como el contacto con las asociaciones industriales), a los Estados Miembros, a las comisiones nacionales y regionales de las farmacopeas o 188
a otros organismos designados por los Estados Miembros y a cualquier otra persona que tenga inters en la sustitucin propuesta, que, pese a la presentacin de una propuesta de sustitucin, se ha decidido mantener la denominacin comn internacional recomendada anteriormente (con una descripcin de la o las razones por las que se ha considerado que la propuesta de sustitucin no estaba respaldada por razones suficientemente poderosas). Artculo 10 - A fin de proporcionar orientacin al Grupo de Expertos en DCI para la aplicacin del presente procedimiento, se incluye como apndice un texto relativo al mtodo de trabajo.
ANEXO 2
PRINCIPIOS GENERALES DE ORIENTACIN PARA FORMAR DENOMINACIONES COMUNES INTERNACIONALES PARA SUSTANCIAS FARMACUTICAS1
1. Las denominaciones comunes internacionales (DCI) debern diferenciarse tanto fontica como ortogrficamente. No debern ser incmodamente largas, ni dar lugar a confusin con denominaciones de uso comn. 2. La DCI de una sustancia que pertenezca a un grupo de sustancias farmacolgicamente emparentadas deber mostrar apropiadamente este parentesco. Debern evitarse las denominaciones que puedan tener connotaciones anatmicas, fisiolgicas, patolgicas o teraputicas para el paciente. Estos principios primarios se pondrn en prctica utilizando los siguientes principios secundarios: 3. Al idear la DCI de la primera sustancia de un nuevo grupo farmacolgico, deber tenerse en cuenta la posibilidad de poder formar DCI convenientes para las sustancias emparentadas que se agreguen al nuevo grupo. 4. Al idear DCI para cidos, se preferirn las de una sola palabra; sus sales debern denominarse sin modificar el nombre del cido: p. ej. oxacilina y oxacilina sdica, ibufenaco y ibufenaco sdico. 5. Las DCI para las sustancias que se usan en forma de sal debern en general aplicarse a la base activa o al cido activo. Las denominaciones para diferentes sales o esteres de la misma sustancia activa solamente debern diferir en el nombre del cido o de la base inactivos. En los compuestos de amonio cuaternario, el catin y el anin debern denominarse adecuadamente por separado, como componentes independientes de una sustancia cuaternaria y no como sales de una amina. 6. Deber evitarse el empleo de letras o nmeros aislados; tambin es indeseable el empleo de guiones. 7. Para facilitar la traduccin y la pronunciacin, se emplearn de preferencia las letras f en lugar de ph, t en lugar de th, e en lugar de ae u oe, e i en lugar de y; se deber evitar el empleo de las letras h y k. 8. Siempre que las denominaciones propuestas estn de acuerdo con estos principios, recibirn una consideracin preferente las denominaciones propuestas por la persona que haya descubierto las sustancias, o que fabrique y comercialice por primera vez una sustancia farmacutica, as como las denominaciones ya adoptadas oficialmente en cualquier pas. 9. El parentesco entre sustancias del mismo grupo se pondr de manifiesto en las DCI (vase el Principio 2) utilizando una partcula comn. En la lista que figura a continuacin se indican ejemplos de partculas para grupos de sustancias, en 2 particular para grupos nuevos. Existen muchas otras partculas que se usan habitualmente. Cuando una partcula aparece sin guin alguno, puede utilizarse en cualquier lugar de la palabra.
1
En su 20 informe (OMS, Serie de Informes Tcnicos, N 581, 1975), el Comit de Expertos de la OMS en Denominaciones Comunes para las Sustancias Farmacuticas revis los Principios generales para formar denominaciones comunes internacionales (DCI), y su procedimiento de seleccin, a la luz de las novedades registradas en los ltimos aos en materia de compuestos farmacuticos. El cambio ms importante haba consistido en hacer extensivo a la denominacin de sustancias qumicas sintticas el mtodo utilizado hasta entonces para las sustancias originadas en productos naturales o derivadas de stos. Dicho mtodo conlleva la utilizacin de una partcula caracterstica que indica una propiedad comn a los miembros de un grupo. En el citado informe se examinan en detalle las razones y consecuencias de este cambio. Los Principios generales de orientacin se actualizaron durante la 13 consulta sobre denominaciones comunes para sustancias farmacuticas (Ginebra, 27 a 29 de abril de 1983) (PHARM S/NOM 928, 13 de mayo de 1983, revisado el 18 de agosto de 1983). En el documento de trabajo WHO/PSM/QSM/2006.3, que se actualiza peridicamente y puede solicitarse al Programa sobre Denominaciones Comunes Internacionales, OMS, Ginebra, figura una lista ms amplia de partculas.
189
Latin -acum -adolum -adol-astum -astinum -azepamum bol -cain-cainum cef-cillinum -conazolum cort -coxibum -entanum gab gado-gartranum gest gli io-metacinum -mycinum -nidazolum -ololum -oxacinum -platinum -poetinum -pril(at)um -profenum prost -relinum -sartanum -vaptanum vin-vin-
Espaol -aco -adol ) -adol- ) -ast -astina -azepam bol -cana-canacef- cilina -conazol cort -coxib -entn gab gado-gatrn gest gli io-metacina -micina -nidazol -olol -oxacino -platino -poetina -pril(at) -profeno prost -relina -sartn -vaptn vin) -vin) antiinflamatorios derivados del ibufenaco analgsicos antiasmticos, sustancias antialrgicas cuya accin principal no es la antihistamnica antihistamnicos derivados del diazepam esteroides anabolizantes antiarrtmicos de clase I, derivados de procainamida y lidocana anestsicos locales antibiticos, derivados del cido cefalospornico antibiticos derivados del cido 6-aminopenicilnico antifngicos sistmicos derivados del miconazol corticosteroides, excepto derivados de prednisolona inhibidores selectivos de ciclooxigenasa antagonistas del receptor de endotelina gabamimticos agentes para diagnstico derivados de gadolinio inhibidores de la trombina antitrombticos esteroides progestgenos hipoglucemiantes, antihiperglucmicos medios de contraste iodados antiinflamatorios derivados de indometacina antibiticos producidos por cepas de Streptomyces antiprotozoarios derivados de metronidazol antagonistas de receptores -adrenrgicos antibacterianos derivados del cido nalidxico antineoplsicos derivados del platino factores sanguneos similares a la eritropoyetina inhibidores de la enzima conversora de la angiotensina antiinflamatorios derivados del ibuprofeno prostaglandinas pptidos estimulantes de la liberacin de hormonas hipofisarias antihipertensivos (no peptdicos) antagonistas del receptorde angiotensina II antagonistas del receptor de vasopresina alcaloides de la vinca
190

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INTERNATIONAL NONPROPRIETARY NAMES FOR P H A R M A C E U T I C A L SUBSTANCES

WHO Drug Information Vol 21, No. 2, 2007

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Proposed International Nonproprietary Names: List 97

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WHO Drug Information Vol 21, No. 2, 2007

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nitrous oxide oxygen

1.2 Local anaesthetics

Injection: 0.25%; 0.5% (hydrochloride) in via.

2.2 Opioid analgesics

lidocaine + epinephrine (adrenaline)

Dental cartridge: 2% (hydrochloride) + epinephrine 1:80 000

Injection: 1%; 2% (hydrochloride) + epinephrine 1:200 000 in vial

2.3 Medicines used to treat gout

1.3 Preoperative medication and sedation for short-term procedures

2.4 Disease modifying agents used in rheumatoid disorders (DMARDs)

Injection: 1 mg (sulfate) in 1-ml ampoule Injection: 5 mg/ml in 2-ml ampoule Tablet: 5 mg

azathioprine methotrexate penicillamine sulfasalazine

Injection: 10 mg (sulfate or hydrochloride) in 1-ml ampoule Oral liquid: 5 mg (hydrochloride)/5 ml

WHO Drug Information Vol 21, No. 2, 2007

15th Model List of Essential Medicines

3. Antiallergics and medicines used in anaphylaxis

sodium nitrite sodium thiosulfate

Injection: 30 mg/ml in 10-ml ampoule Injection: 250 mg/ml in 50-ml ampoule

Injection: 10 mg (hydrogen maleate) in 1-ml ampoule Tablet: 4 mg (hydrogen maleate)

4. Antidotes and other substancess used in poisonings

Oral liquid: 15 mg/5 ml (phenobarbital) or 5 ml (phenobarbital sodium) Tablet: 15-100 mg (phenobarbital)

Capsule: 25 mg; 50 mg;

potassium ferric hexacyanoferrate(II) -2H20 (Prussian blue) sodium calcium edetate