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Rovamycin - SUMMARY OF PRODUCT CHARACTERISTICS

1. TRADE NAME OF THE MEDICINAL PRODUCT ROVAMYCIN 1.5 M.I.U film-coated tablet 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active ingredient: each tablet contains 1.5 MIU spiramycin. Excipients: Magnesium stearate; Pregelatinized corn starch; Hydroxypropylcellulose; Croscarmellose sodium; Colloidal anhydrous silica; Microcrystalline cellulose; Methylhydroxypropylcellulose; Polyethylene glycol 6000; Titanium dioxide.

3.

PHARMACEUTICAL FORM Film-coated tablet

4.

CLINICAL PARTICULARS

Therapeutic indications Respiratory tract infections, infections caused by clamydia, cryptosporidiosis pregnancy toxoplasmosis. Posology and Method of Administration Posology In patients with normal renal function: Routine dose: Adults: 6 to 9 million IU/24 hours, i.e. 4 to 6 tablets per day in 2 to 3 intakes. Children: 1.5 to 3 million IU per 10 kg of body weight per day in 2 to 3 intakes. Sore throats should be treated for 10 days. Meningococcal meningitis prophylaxis Adults: 3 million IU/12 hours. Children: 75 000 IU/kg/12 hours. for 5 days. In patients with renal insufficiency: No dose adjustment is necessary.

Method of Administration
Tablets should be swallowed whole with a glass of water. Contraindications Hypersensitivity to spiramycin , other macrolids or any of the excipients It is not recommended for breast-feeding mothers (see 4.6 Pregnancy and Lactation).

Warnings and Precautions For Use If, at the start of treatment, patients experience generalized erythema and pustules, accompanied by fever, acute generalized exanthematous pustulosis should be suspected (see Section 4.8 Undesirable effects); if such a reaction occurs, treatment must be discontinued and any further administration of spiramycin alone or in combination is contraindicated.

Administration of tablets is contraindicated in children under 6 years of age because of the risk of choking.
Since the compound is not excreted via the kidney, there is no need to adjust dosage in patients with renal insufficiency. Very rare cases of hemolytic anemia have been reported in patients with glucose-6phosphate-dehydrogenase deficiency. Spriamycin is therefore not recommended for such patients. Interactions with other medicinal products and other forms of interaction

Interactions requiring precautions for use

+Levodopa (associated with carbidopa): inhibition of carbidopa absorption with decreased plasma concentrations of levodopa. Clinical monitoring and possible adjustment of levodopa dosage. Specific problems with INR imbalance Many cases of increased activity in oral anticoagulants have been reported for patients taking antibiotics. The marked infectious or inflammatory picture, age and general condition of the patient would appear to be risk factors. Under these circumstances, it is difficult to distinguish between the effect of the infection and its treatment in the onset of INR imbalance. However, certain classes of antibiotics are more involved; principally fluoroquinolones, macrolides, cyclines, cotrimoxazole and certain cephalosporins. Pregnancy and lactation

Pregnancy
Spiramycin can be used during pregnancy if necessary. Extensive use of spiramycin during pregnancy has shown no evidence of malformation or fetotoxicity to date.

Lactation
Spiramycin Is excreted into breast milk. Gastrointestinal disorders in neonates have been reported. Consequently, breast-feeding is not recommended to women taking spiramycin. Effects on ability to drive and use machines Not relevant. Undesirable effects

Gastrointestinal system: Skin and appendages:

. gastralgia, nausea, vomiting, diarrhea and, very rarely, pseudo-membranous colitis. - rash, urticaria, pruritis. - very rarely Quinckes edema, anaphylactic shock.
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- Very rarely, acute generalized exanthematous pustulosis (see Section 4.4 Special warnings and special precautions for use)

Central and peripheral nervous system:

. occasional and transient paresthesia.

Hepatic signs:

. very rare abnormal results to liver function tests.

Blood cell line:

. very rare cases of hemolytic anemia have been reported (see 4.4. Warnings and special precautions for use). 4.9 Overdose There is no known toxic dose for spiramycin. Expected signs of overdose are gastrointestinal: nausea, vomiting, diarrhea. Lengthening of the QT interval, resolving on discontinuation of treatment, has been observed in neonates treated with high doses of spiramycin, and also after IV administration to people at risk of QT lengthening. In the event of overdose, the QT interval should be determined, especially where other risk factors are present (hypokalemia, congenital lengthening of QT interval, other medicinal products lengthening QT interval and/or inducing torsades de pointes). There is no specific antidote. Symptomatic treatment is recommended. 5. PHARMACOLOGICAL PROPERTIES Pharmacodynamic properties Pharmacotherapeutic class: SYSTEMIC ANTIBACTERIAL AGENT ATC code: J01FA02 Antibacterial antibiotic belonging to the macrolides family. ANTIBACTERIAL ACTIVITY SPECTRUM Critical concentrations differentiate sensitive from moderate strains, and both from resistant ones: S < 1 mg/l and R > 4 mg/l For certain species, the prevalence of acquired resistance may vary according to place and time. It is useful, therefore, to have information on the prevalence of local resistance, particularly when treating severe infections. These data can only provide an indication of the sensitivity of a bacterial strain to this antibiotic. When the variability in the prevalence of resistance for a given species of bacteria is known in France, it is shown in the table below:

Categories SENSITIVE SPECIES

Frequency of acquired resistance in France (> 10%) (extreme values)

Bacillus cereus Corynebacterium diphtheriae

Enterococci

Gram positive aerobic organisms 50% 70% 70 80% 30 40% 35 70% 16-31%

Rhodococcus equi Methicillin-sensitive staphylococcus Methicillin-resistant staphylococcus* Streptococcus B Streptococcus (not classifiable) Streptococcus pneumoniae Streptococcus pyogenes Bordetella pertussis Branhamella catarrhalis Campylobacter Legionella Moraxella
Gram negative aerobic organisms

Anaerobic organisms

Actinomyces Bacteroides Eubacterium Mobilincus Peptostreptococcus Porphyromonas Prevotella Propionibacterium acnes

30 60% 30 40%

Categories

Others Borrelia burgdorferi Chlamydia Coxiella

Leptospires

Frequency of acquired resistance in France (> 10%) (extreme values)

Mycoplasma pneumoniae Treponema pallidum

MODERATELY SENSITIVE SPECIES (of intermediary sensitivity in vitro)

Neisseria gonorrhoeae

Gram negative aerobic organisms

Anaerobic organisms

Clostridium perfringens
Others

Ureaplasma urealyticum
RESISTANT SPECIES Gram positive aerobic organisms

Corynebacterium jeikeium Nocardia asteroides Acinetobacter

Gram negative aerobic organisms

Haemophilus Pseudomonas

Enterobacteria

Anaerobic organisms

Fusobacterium
Others

Mycoplasma hominis
Spiramycin is active against Toxoplasma gondii in vitro and in vivo. * The frequency of acquired resistance to methicillin is between about 30 50 % for all staphylococci and is usually found in the hospital environment. Pharmacokinetic properties

Absorption

Spiramycin is rapidly but incompletely absorbed and is not modified by food intake.

Distribution

After oral administration of 6 million IU of spiramycin, the peak serum concentration is 3.3 g/ml. Plasma half-life is about 8 hours. Spiramycin does not enter the CSF and is excreted into breast milk. Plasma protein binding is low (10%).

Tissue and saliva diffusion is excellent (lungs: 20-60 g/g, tonsils: 20-80 g/g, infected sinuses: 75-110 g/g, bones: 5-100 g/g). Ten days after the end of treatment, there is 5 to 7 g/g of active substance in the spleen, liver and kidneys. Macrolides penetrate and accumulate in phagocytes (polynuclear neutrophils, monocytes, peritoneal and alveolar macrophages). Intra-phagocyte concentrations are high in man. These properties explain macrolides activity against intra-cellular bacteria.

Metabolism

Spiramycin is metabolised in the liver with the formation of chemically unknown but active metabolites.

Excretion
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Preclinical safety data

urine: 10% of the administered dose. extensive biliary excretion: concentrations 15 to 40 times higher than serum concentrations. small amounts of spiramycin are present in feces.

Not relevant. MANUFACTURER Famar Lyon, France for Aventis, France Marketing Authorization Holder sanofi-aventis Israel ltd P.O.box 8090 Netanya 42504 Registration number: 465923868