Drug Info Services

1. Can pregnant women be given with meningococcal vaccine? Meningococcal Group C-CRM 197 conjugate vaccines can be given to pregnant woman because it falls under pregnancy category C (animals studies have not demonstrated risks to fetus). Reproductive studies in human however have not been connected. In a study, one birth defect was observed in an infant of a mother vaccinated at 33rd weeks of gestation. Reference 2. Can celecoxib be given to the nursing mothers? If cant what are the other options? Celecoxib cannot be given to the nursing mothers because the drug is excreted through milk. Fortunately, there are other options of drug that can be given to nursing mothers as shown in this following table: Drug Indication Dose Pregnancy Category Celecoxib Relieves signs and symptoms of osteoarthritis Rheumatoid arthritis Acute pain Adult: 300-400 mg 3-4 times daily (initial) Adult: C/D Excreted Adult: 500 mg t.d.s Category C Category D (In 3rd trimester or near delivery) Effect to Baby Teratogenic in animal studies Breast Feeding Excreted into breast milk

Ibuprofen

Pain and inflammation in rheumatic disease

Teratogenic in animal studies

Musculoskeletal disorder mild to moderate pain

Diclofenac

Relieve mild to moderate

pain

15 mg t.d.s

30 weeks gestation

into breast milk

Tramadol

Relief of moderate to severe pain

Initially given 25 mg/day

- Neonatal seizures - Fatal birth

It is important to noted that there are few pregnancy categories which are (taken from mims.com): Category A: Controlled studies in women fail to demonstrate a risk to the foetus in the 1st trimester (and there is no evidence of a risk in later trimesters), and the possibility of foetal harm remains remote. Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters). Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus. Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a lifethreatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Reference
Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information Handbook, 20th ed. Hudson, Ohio, Lexi-Comp, Inc.; 2011: 1028.

3. What are the safest antiepileptic drugs can be used during pregnancy? The safest antiepileptic drugs can be given to pregnant mothers are (i) Gabapentin, (ii) Lamotrigine as summarized in the following table. Drug Gabapentin Indication(s) Monotherapy and adjunctive treatment of focal seizures with or without secondary generalization. Pregnancy Category C - Studies in animals revealed adverse drug interactions on fetus, however there is no controlled studies in women. C Studies in animals revealed adverse drug interactions on fetus, but there are no controlled studies in human. Breastfeeding Gabapentin is excreted into breast milk but there is no data on it. Effects to Baby Gabapentin cross the placenta but did not have any adverse effect.

Lamotrigine

Monotherapy and adjunctive treatment of focal seizures and generalized seizures including tonic-clonic seizures associated with Lenox-Gastaut Syndrome, monotherapy of typical absence seizures in children, prevention of depressive episodes associated with bipolar disorders.

Lamotrigine is excreted through breast milk. Reports have been said that there is no adverse effect in nursing infant during breastfeeding or during weaning.

Infant should be carefully monitored for adverse effects although there are no adverse effects have been seen in nursing infant of mothers taking lamotrigine. Monitoring infant serum levels of lamotrigine should be considered.

Some anticonvulsants have produced adverse effects in nursing infants such as Phenobarbital and Primidone. However there are also a few anticonvulsants that have not produced adverse effects in nursing infants such as Carbamazepine, Phenytoid and Valproic Acid. 4. Age :59 years old Weight :60 kg Gender :Female Serum creatinine :280mmol/L Drugs recommended: Meropenem

Based on the information given, calculate the dose recommendation for this patient. ClCr = = = 140 - Age (years) x Weight (kg) x 1.04 / SrCr 140 59 x 60 x 1.04 / 280 18.05 ml/min

Recommended dose:- Adults: I.V.: 1.5-6 g/day divided every 8 hours. Administer one-half recommended dose based on indication every 12 hours. Reference

5. Give triple therapies for H. pylori infection Regimen PPIAC Agents/Dose/Frequency PPIa BID Clarithromycin 500 mg BID Amoxicillin 1,000 mg BID PPIa BID Clarithromycin 500mg BID Metronidazole 500 mg BID H2RAb Bismuth 2 tablets QID Tetracycline Metronidazole Ranitidine bismuth subcitratec Clarithromycin 500 mg BID Ranitidine 150 mg BID Duration (days) 7, 10, 14 Efficacy (%) 88-95

PPIMC

7,10,14

88-95

BMT-H2

14-28

75-85

RBC-C

14

75-80

Reference

6. How to administer the phenoxybenzamine hydrochloride capsule to pediatrics? The usual initial dose of phenoxybenzamine hydrochloride is 10 mg once or twice to be given orally, and increased increase every 4 days by 1 to 2 mg per kg body-weight daily in 2 divided doses, according to the patients response. It may be given intravenously for operative cover in patients with phaeochromocytoma in a daily dose of 1 mg per kg in 200 ml of sodium chloride 0.9% has been given in the management of severe shock. For urinary retention due to neurogenic bladder a dose of 10 mg twice daily by mouth has been given. Phenoxybenzamine which is also referring to Dibenzyline is an antihypertensive agent. It produces long-lasting non-competitive -adrenergic blockade of postganglionic synapses in exocrine glands and smooth muscles. It is prepared extemporaneously to be given for paediatrics. Extemporaneous Preparations A 2mg/ml oral liquid preparations made from capsules with 1.0% propylene glycol and with 0.15% citric acid in distilled water was stable for 7 days when stored in amber glass prescriptive bottles under refrigeration (4oC)

The vehicle is made by dissolving 150.0 mg of citric acid in a minimal amount of distilled water. 1.0 ml of propylene glycol is then added and the solution is mix well.

Q.s. ad with distilled water to 100.0 ml

Grind two 10.0 mg/ml capsules in motor into fine powders

Small amount of vehicle is added and mix well

Transfer to a graduated cylinder and q.s. ad with vehicle to 10.0 ml

Transfer to an amber glass prescription bottle with tight fitting cap

Label shake well and refrigerate

Reference
Carol K. Taketomo. Pediatric & Neonatal Dosage Handbook, 18th ed. Hudson, Ohio, LexiComp, Inc.; 2011.

7. How many moles of potassium in potassium chloride in 1g/15ml solution and Slow K tablet? Each gram of potassium chloride represents approximately 13.44 mmol of K+ Slow K 600 mg tablet is equilvalent to 8 mmol of K+. Reference 8. Is there any interaction between warfarin with ginkgo biloba, gingseng and tempeh. Ginkgo Biloba Ginkgo biloba is believed to be the oldest still living tree species (Abad, Bedoya, & Bermejo, 2010). Its survival without structural modifications for a long period of time are may be due to its exceptionally long-life span, resistance to bacteria, fungi and viruses, high level of adaptability to the environment, and the long time span between generations, which diminishes the probability of genetic mutations (Zhou & Zheng, 2003).The purported benefits of taking ginkgo includes the prevention of the onset of Alzheimers disease and dementia, increased mental concentration, prevention of vertigo, and improved blood flow through platelet

inhibition (Stanger, Thompson, Young, & Lieberman, 2012).Ginkgo biloba is contains 33 known flavone glycosides. The main bioavailable component is reported to be terpenoides (gingkolides A, B, C and bilobalide). Terpene ginkgolide B is believed to be the active component in ginkgo responsible for its purported platelet-inhibiting qualities (Stanger et al., 2012). Ginkgo acts as anti-PAF agent. Several studies have noted that there are potential associations between ginkgo use and hemorrhage, including spontaneous intracerebral haemorrhage, when ginkgo is used in combination with warfarin (Meisel, Johne, & Roots).Research suggests a biologically plausible mechanism for an increased risk of bleeding with Ginkgo through interactions with PAF and collagen that lead to decreased platelet aggregation. Although a clear causality between Ginkgo intake and bleeding could not be established, these observations have generally been explained by the PAF antagonistic action of ginkgolides, which represent characteristic constituents of Ginkgo extract (Abad et al., 2010). Several controlled clinical studies and case reports were undertaken, to investigate whether these bleeding episodes have a pharmacodynamic, idiosyncratic or coincidental basis (Abad et al., 2010). There are a few case reports documented bleeding with Ginkgo biloba supplementation, at 120 mg, 80 mg, and 75 mg, respectively. It is reported that ingestion of 120 mg daily of standardized G. biloba extract for 3 months nonselectively inhibited cyclooxyengase1 (COX-1) mediated thromboxane A2 and COX-2 mediated prostaglandin-12 in patients with type 2 diabetes mellitus. Ginkgolide B, a constituent in G. biloba, has been shown to decrease platelet aggregation and ginkgolide B displaces platelet-activating factor (PAF) from its binding sites, thus potentially decreasing blood coagulation. In another study conducted on 12 healthy males showed no excessive bleeding when 125 mg extract of ginkgo was taken in combination with warfarin for 7 consecutive days (Bent, Goldberg, Padula, & Avins, 2005; Stanger et al., 2012). In a similar report with healthy male volunteers as the subjects tested, did not show any significant effect of ginkgo on platelet activating factor (at 1,2002,400 mg/day) (Koch, 2005; Stanger et al., 2012) or platelet function in vivo (at 120 mg/day) (Beckert, Concannon, Henry, Smith, & Puckett, 2007; Stanger et al., 2012). Therefore it can be concluded that the results from controlled studies consistently indicate that Ginkgo does not significantly impact haemostasis, nor adversely affect the safety of

coadministered warfarin or antiplatelet drugs such as aspirin ticlopidine, cilostazol or clopidogrel (Abad et al., 2010). However, the possibility of an idiosyncratic bleeding event due to Ginkgo use cannot be excluded on the basis of the available information, especially in elderly patients or patients reacted with drugs exerting relatively narrow therapeutic windows (Abad et al., 2010). Hence, patients on warfarin therapy should be advised to avoid concurrent use of G. biloba. Ginseng Ginseng (Panax ginseng) is a perennial herb found in Korea and China. It has been used in eastern Asian herbal remedies for thousands of years as a stimulant and aphrodisiac (Stanger et al., 2012). In vitro evidence suggests that ginsenosides, the bioactive components in ginseng, may inhibit platelet aggregation and the conversion of fibrinogen to fibrin (Chavez, Jordan, & Chavez, 2006; Yun et al., 2001). A study in 20 volunteers found that Asian ginseng 100 mg standardized to 4% ginsenosides twice daily for 14 days did not significantly change urinary 6--OH-cortisol/cortisol ratio, which suggests that Asian ginseng does not induce CYP3A4 (Anderson, Rosito, Mohustsy, & Elmer, 2003; Chavez et al., 2006). In a case report, a 47-year-old male with a mechanical heart valve experienced a decreased INR 2 weeks after a stabilized regimen of ginseng three times daily (no further information of product) was begun (Janetzky & Morreale, 1997). His drug regimen included diltiazem, nitroglycerin, and salsalate. The patient's INR of 34 had been stable for at least 9 months prior to the event on a dosing regimen of warfarin 5 mg daily (Chavez et al., 2006). However, when ginseng was used as supplement, his INR decreased to 1.5. Upon discontinuing ginseng, the INR of the patient returned to normal reading (Chavez et al., 2006). In a similar report of a possible interaction, a 58-year-old male with mechanical bileaflet aortic valve was admitted to the hospital with acute anterospectal myocardial infarction and diabetic ketoacidosis, when his INR became unsteady (Chavez et al., 2006; Rosado). He had been optimally maintained on warfarin until 3 months prior to admission. Echocardiography showed thrombosis on the valve of this patient. The author reported that the inability to maintain therapeutic INR levels was likely due to self-treatment with a commercial ginseng product (assumed to be Asian ginseng) for an unspecified time (Chavez et al., 2006; Rosado). These case reports suggest that concurrent use of Asian ginseng should be avoided in patients receiving warfarin because of the risk of thrombotic complications. However, a

randomized, open-label, three-way crossover study of co-administration of ginseng and warfarin in 12 healthy volunteer did not affect INR, platelet aggregation or pharmacokinetics of S- and Rwarfarin (Jiang et al., 2004). There is another distinct species of ginseng related to Asian ginseng namely American ginseng. American ginseng is native to North America has some differences in chemical

constituents from Asian ginseng (Chavez et al., 2006). A randomized, placebo-controlled study in 20 healthy young volunteers showed American ginseng antagonized the efficacy of warfarin. Subjects received warfarin 5 mg daily for 3 days during weeks 1 and 4, and American ginseng 1 g twice daily or placebo for 2 weeks (Yuan et al., 2004). This article reported that American ginseng produced a modest reduction in INR, peak warfarin levels, and warfarin area under the curve (Stanger et al., 2012). Therefore, patients receiving warfarin should also avoid taking American ginseng any type of ginsengs at all.

Tempeh Tempeh is a soy product which contains high content of Vitamin K. While Warfarin (Coumadin) is used to slow blood clotting, Soy has been reported to decrease the effectiveness of warfarin (Coumadin). Decreasing the effectiveness of warfarin (Coumadin) might increase the risk of clotting. It is unclear why this interaction might occur. Blood need to be checked regularly and the dose of warfarin (Coumadin) might need to be changed. Vitamin K deficiency can lead to excessive bleeding (hemorrhage), which may begin as oozing from the gums or nose. Because of the potential for side effects and interactions with medications, dietary supplements shall be taken only under the supervision of a knowledgeable health care provider as at recommended doses, vitamin K has few side effects. Therefore it is important to know the daily requirement for dietary vitamin K (according to the U.S. RDA) as shown below: Paediatrics Infants birth 6 months: 2 mcg Infants 7 12 months: 2.5 mcg Children 1 3 years: 30 mcg Adults Males 19 years and older: 120 mcg Females 19 years and older: 90 mcg Pregnant and breastfeeding females 14 18 years: 75 mcg

Children 4 8 years: 55 mcg Children 9 13 years: 60 mcg Adolescents 14 18 years: 75 mcg

Pregnant and breastfeeding females 19 years and older: 90 mcg

There are no reported cases that can be found regarding the interaction between tempeh and warfarin. Fortunately there was a case on interaction between soy product with warfarin had been reported. A 70-year-old male with a history of coronary artery bypass and coronary artery disease taking warfarin 3 mg daily for 7 months in addition to digoxin 0.125 mg daily, atenolol 25 mg daily, lansoprazole 30 mg daily, and lorazepam 0.5 mg twice daily as needed began drinking 480 mL of soy milk daily (Cambria-Kiely, 2002). Four weeks after consuming soy milk, the patient's INR decreased from 2.3 to 1.6, and returned to normal upon discontinuation of soy milk consumption (Cambria-Kiely, 2002; Chavez et al., 2006). Probe extracts administered to 20 volunteers who received a soy extract containing 50 mg isoflavones twice daily found no significantly altered urinary 6--OH-cortisol/cortisol ratio suggesting soy extract does not induce CYP3A4 (Anderson et al., 2003). Unhydrolyzed soy extract had little effect on CYP1A2, CYP2A6, and CP2D6 but hydrolyzed soy extract inhibited CPY2C9 and CYP3A4. Patients undergoing anticoagulation therapy should be cautioned against use of large amounts of soy products or should be closely monitored for changes in anticoagulation (Chavez et al., 2006).

References Abad, M. J., Bedoya, L. M., & Bermejo, P. (2010). An update on drug interactions with the herbal medicine Ginkgo biloba. Current Drug Metabolism, 11(2), 171-181. Anderson, G. D., Rosito, G., Mohustsy, M. A., & Elmer, G. W. (2003). Drug interaction potential of soy extract and Panax ginseng. [Clinical Trial Research Support, Non-U S Gov't Research Support, U S Gov't, P H S]. J Clin Pharmacol, 43(6), 643-648. Beckert, B. W., Concannon, M. J., Henry, S. L., Smith, D. S., & Puckett, C. L. (2007). The effect of herbal medicines on platelet function: an in vivo experiment and review of the literature. [Clinical Trial Comparative Study Review]. Plast Reconstr Surg, 120(7), 2044-2050.

Bent, S., Goldberg, H., Padula, A., & Avins, A. L. (2005). Spontaneous Bleeding Associated with Ginkgo biloba. Journal of General Internal Medicine, 20(7), 657-661. doi: 10.1111/j.15251497.2005.0121.x Cambria-Kiely, J. A. (2002). Effect of soy milk on warfarin efficacy. [Case Reports]. Ann Pharmacother, 36(12), 1893-1896. Chavez, M. L., Jordan, M. A., & Chavez, P. I. (2006). Evidence-based drugherbal interactions. Life Sciences, 78(18), 2146-2157. doi: 10.1016/j.lfs.2005.12.009 Janetzky, K., & Morreale, A. P. (1997). Probable interaction between warfarin and ginseng. [Case Reports]. Am J Health Syst Pharm, 54(6), 692-693. Jiang, X., Williams, K. M., Liauw, W. S., Ammit, A. J., Roufogalis, B. D., Duke, C. C., . . . McLachlan, A. J. (2004). Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. [Clinical Trial Randomized Controlled Trial Research Support, Non-U S Gov't]. Br J Clin Pharmacol, 57(5), 592-599. Koch, E. (2005). Inhibition of platelet activating factor (PAF)-induced aggregation of human thrombocytes by ginkgolides: considerations on possible bleeding complications after oral intake of Ginkgo biloba extracts. Phytomedicine, 12(1-2), 10-16. Meisel, C., Johne, A., & Roots, I. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen: Atherosclerosis. 2003 Apr;167(2):367. Rosado, M. F. Thrombosis of a prosthetic aortic valve disclosing a hazardous interaction between warfarin and a commercial ginseng product: Cardiology. 2003;99(2):111. Stanger, M. J., Thompson, L. A., Young, A. J., & Lieberman, H. R. (2012). Anticoagulant activity of select dietary supplements. Nutrition Reviews, 70(2), 107-117. doi: 10.1111/j.1753-4887.2011.00444.x Yuan, C. S., Wei, G., Dey, L., Karrison, T., Nahlik, L., Maleckar, S., . . . Moss, J. (2004). Brief communication: American ginseng reduces warfarin's effect in healthy patients: a randomized, controlled Trial. [Clinical Trial Randomized Controlled Trial Research Support, Non-U S Gov't Research Support, U S Gov't, P H S]. Ann Intern Med, 141(1), 23-27. Yun, Y.-P., Do, J.-H., Ko, S.-R., Ryu, S.-Y., Kim, J.-H., Song, H.-C., . . . Kim, S.-H. (2001). Effects of Korean red ginseng and its mixed prescription on the high molecular weight dextran-induced blood stasis in rats and human platelet aggregation. Journal of Ethnopharmacology, 77(23), 259-264. doi: 10.1016/s0378-8741(01)00303-8 Zhou, Z., & Zheng, S. (2003). Palaeobiology: The missing link in Ginkgo evolution. [10.1038/423821a]. Nature, 423(6942), 821-822. doi: http://www.nature.com/nature/journal/v423/n6942/suppinfo/423821a_S1.html

9. What are the options of drugs available and how it is administered for patients having scabies?

The drug available in Hospital Putrajaya for patient having scabies is Benzene hexachloride. Benzene hexachloride is also known as Lindane. Lindane is directly absorbed by parasites and ova through the exoskeleton, stimulates the nervous system resulting in seizures and death of parasitic arthropods. It is normally use for topical application on the skin. A thin layer of lotion shall be apply and massage it on skin from neck to toes. After 8-12 hours, bathe and remove the drug. Skin should be clean and free of any other lotions, oils or creams prior to lindane application. Reference
Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information Handbook, 20th ed. Hudson, Ohio, Lexi-Comp, Inc.; 2011: 1028.

10. Describe how we shall taper down the dose of Dexamethasone 8 mg t.d.s before discontinuation.

Dexamethasone (corticosteroid) Indications Dose : : Anti-inflammatory and Immunosuppressant Agent Oral 1 mg at 2300, draw blood at 0800 on the following day (Indication for immunosuppression test) MOA : Dexamethasone decreases inflammation by suppression of neutrophil migration, thereby decreasing the production of inflammatory mediatiors hence suppresses normal immune response.

Dexamethasone has long duration of action and acts to supress corticotropin secretion. Their suppressive action on hypothalamic pituitary adrenal is greatest and most prolong when given at night. A single dose of 1 mg of dexamethasone at night is sufficient to inhibit corticotropin secretion for 24 hours. Dexamethasone is categorized under pregnancy group C where adverse events have been observed in animal. It falls under risk factor D when is used in first trimester of pregnancy.

In breast-feeding mothers, there has been no case reported on the usage dexamethasone during lactation been located, therefore dexamethasone can be used during lactation period. Reference

11. Describe SBE prophylaxis for patient undergoing thyroidectomy. Antibiotic regimens for endocarditis prophylaxis for patient undergoing thyroidectomy are directed toward S viridans, and the recommended standard prophylactic regimen is a single dose of oral amoxicillin. Amoxicillin, ampicillin, and penicillin V are equally effective in vitro against alpha-hemolytic streptococci; however, amoxicillin is preferred because of superior gastrointestinal absorption that provides higher and more sustained serum levels. All doses shown below are administered once as a single dose 30-60 min before the procedure. Antibiotic Regimens for Endocarditis Prophylaxis to be Given 30-60 Minutes Before Procedure Situation Standard general prophylaxis Unable to take oral medication Allergic to penicillin Cephalexin or other first- or secondgeneration oral cephalosporin in equivalent dose (do not use cephalosporins in patients with a history of immediate-type Allergic to penicillin hypersensitivity penicillin allergy, such as urticaria, angioedema, anaphylaxis) Azithromycin or clarithromycin
500 mg PO

Agent Amoxicillin
Ampicillin

Adult Regimen 2 g PO

Children 50 mg/kg PO 50 mg/kg IV/IM; not to exceed 2 g/dose 20 mg/kg PO; not to exceed 600 mg/dose

2 g IV/IM

Clindamycin 600 mg PO

2 g PO

50 mg/kg PO; not to exceed 2 g/dose

15 mg/kg PO; not to exceed 500 mg/dose 20 mg/kg IV; not to exceed 600 mg/dose 50 mg/kg IV/IM; not to exceed 1 g/dose

Clindamycin
600 mg IV

Allergic to penicillin and unable to take oral medication

Cefazolin or ceftriaxone (do not use cephalosporins in patients with a history of immediate-type

1 g IV/IM

hypersensitivity penicillin allergy, such as urticaria, angioedema, anaphylaxis)

References Wilson, W., Taubert, K. A., Gewitz, M., Lockhart, P. B., Baddour, L. M., Levison, M., . . . Durack, D. T. (2007). Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. [Practice Guideline]. Circulation, 116(15), 1736-1754.