Rovamycine^® (Tablets) Instructions for Use

Marketing Authorization Holder

Sanofi Winthrop Industrie (France)

Manufactured By

Sanofi, S.R.L. (Italy)

Contact Information

SANOFI

ATC Code

J01FA02 (Spiramycin)

Active Substance

Spiramycin (Rec.INN registered by WHO)

Dosage Forms

	Rovamycine®	Film-coated tablets, 1.5 million IU: 16 pcs.
		Film-coated tablets, 3 million IU: 10 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets from white to white with a creamy tint, round, biconvex, with an engraving “RPR 107” on one side.

Excipients: colloidal silicon dioxide – 1.2 mg, magnesium stearate – 4 mg, pregelatinized corn starch – 16 mg, hypromellose – 8 mg, croscarmellose sodium – 8 mg, microcrystalline cellulose (PH-101) – up to 400 mg.

Shell composition titanium dioxide (E171) – 1.694 mg, macrogol-6000 – 1.694 mg, hypromellose – 5.084 mg.

8 pcs. – blisters (2) – cardboard packs.

Film-coated tablets from white to white with a creamy tint, round, biconvex, with an engraving “ROVA 3” on one side.

Excipients: colloidal silicon dioxide – 2.4 mg, magnesium stearate – 8 mg, pregelatinized corn starch – 32 mg, hypromellose – 16 mg, croscarmellose sodium – 16 mg, microcrystalline cellulose (PH-101) – up to 800 mg.

Shell composition titanium dioxide (E171) – 2.96 mg, macrogol-6000 – 2.96 mg, hypromellose – 8.88 mg.

5 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the macrolide group

Pharmacotherapeutic Group

Systemic antibacterial agents; macrolides, lincosamides, and streptogramins; macrolides

Pharmacological Action

An antibiotic from the macrolide group. The mechanism of antibacterial action is due to inhibition of protein synthesis in the microbial cell by binding to the 50S ribosomal subunit.

Susceptible microorganisms (MIC<1 mg/L): Gram-positive aerobes – Bacillus cereus, Corynebacterium diphtheriae, Enterococcus spp., Rhodococcus equi, Staphylococcus spp. (methicillin-susceptible and methicillin-resistant strains), Streptococcus B, unclassified streptococcus, Streptococcus pneumoniae, Streptococcus pyogenes; Gram-negative aerobes – Bordetella pertussis, Branhamella catarrhalis, Campylobacter spp., Legionella spp., Moraxella spp.; anaerobes – Actinomyces spp., Bacteroides spp., Eubacterium spp., Mobiluncus spp., Peptostreptococcus spp., Porphyromonas spp., Prevotella spp., Propionibacterium acnes; miscellaneous – Borrelia burgdorferi, Chlamydia spp., Coxiella spp., Leptospira spp., Mycoplasma pneumoniae, Treponema pallidum, Toxoplasma gondii.

Moderately susceptible microorganisms (the antibiotic is moderately active in vitro at antibiotic concentrations at the site of inflammation ≥ 1 mg/L, but < 4 mg/L): Gram-negative aerobes – Neisseria gonorrhoeae; aerobes – Clostridium perfringens; miscellaneous – Ureaplasma urealyticum.

Resistant microorganisms (MIC>4 mg/L; at least 50% of strains are resistant): Gram-positive aerobes – Corynebacterium jekeium, Nocardia asteroides; Gram-negative aerobes – Acinetobacter spp., Enterobacter spp., Haemophilus spp., Pseudomonas spp.; anaerobes – Fusobacterium spp.; miscellaneous – Mycoplasma hominis.

Pharmacokinetics

Absorption

Spiramycin absorption is rapid but incomplete, with high variability (from 10% to 60%). After oral administration of Rovamycine^® at a dose of 6 million IU, the C_max of spiramycin in plasma is about 3.3 µg/mL. Food intake does not affect absorption.

Distribution

Binding to plasma proteins is low (approximately 10%). V_d is approximately 383 L. The drug penetrates well into saliva and tissues (concentration in the lungs is 20-60 µg/g, in tonsils 20-80 µg/g, in infected sinuses 75-110 µg/g, in bones 5-100 µg/g). Ten days after the end of treatment, the concentration of spiramycin in the spleen, liver, and kidneys is 5-7 µg/g.

Spiramycin penetrates and accumulates in phagocytes (neutrophils, monocytes, and peritoneal and alveolar macrophages). In humans, the concentrations of the drug inside phagocytes are quite high. This explains the effectiveness of spiramycin against intracellular bacteria.

It crosses the placental barrier (concentration in fetal blood is about 50% of the concentration in maternal serum). Concentrations in placental tissue are 5 times higher than the corresponding concentrations in serum. It is excreted in breast milk.

Spiramycin does not penetrate into the cerebrospinal fluid.

Metabolism and Excretion

Spiramycin is metabolized in the liver to form active metabolites with an unestablished chemical structure.

T_1/2 from plasma is approximately 8 hours. It is excreted mainly with bile (concentration is 15-40 times higher than in serum). Renal excretion is about 10% of the administered dose. The amount of the drug excreted through the intestines (with feces) is very insignificant.

Indications

Infectious and inflammatory diseases caused by microorganisms susceptible to the drug

• Acute and chronic pharyngitis caused by beta-hemolytic streptococcus A (as an alternative to treatment with beta-lactam antibiotics, especially in case of contraindications to their use);
• Acute sinusitis (considering the susceptibility of the microorganisms most often causing this pathology, the use of Rovamycine^® is indicated in case of contraindications to the use of beta-lactam antibiotics);
• Acute and chronic tonsillitis caused by microorganisms susceptible to spiramycin;
• Acute bronchitis caused by a bacterial infection that developed after acute viral bronchitis;
• Exacerbation of chronic bronchitis;
• Community-acquired pneumonia in patients without risk factors for adverse outcome, severe clinical symptoms, and clinical signs of pneumococcal etiology of pneumonia;
• Pneumonia caused by atypical pathogens (such as Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp.) or suspected of it (regardless of severity and presence or absence of risk factors for adverse outcome);
• Infections of the skin and subcutaneous tissue, including impetigo, impetiginization, ecthyma, infectious dermohypodermatitis (especially erysipelas), secondary infected dermatoses, erythrasma;
• Oral infections (including stomatitis, glossitis);
• Non-gonococcal genital infections;
• Toxoplasmosis, including during pregnancy;
• Infections of the musculoskeletal system and connective tissue, including periodontitis.

Prevention of recurrence of rheumatism in patients allergic to beta-lactam antibiotics.

Eradication of Neisseria meningitidis from the nasopharynx (in case of contraindications to rifampicin) for the prevention (but not treatment) of meningococcal meningitis

• In patients after treatment and before discharge from quarantine;
• In patients who have been in contact within 10 days before hospitalization with persons shedding Neisseria meningitidis with saliva into the environment.

ICD codes

Dosage Regimen

The drug is taken orally.

Adults are prescribed 2-3 tablets of 3 million IU or 4-6 tablets of 1.5 million IU (i.e., 6-9 million IU) per day. The daily dose is divided into 2 or 3 doses. The maximum daily dose is 9 million IU.

In children and adolescents aged 6 to 18 years, only 1.5 million IU tablets should be used.

In children over 6 years of age, the daily dose is from 150-300 thousand IU per kg of body weight, which is divided into 2 or 3 doses up to 6-9 million IU. The maximum daily dose in children is 300 thousand IU per kg of body weight, but if the child’s body weight is more than 30 kg it should not exceed 9 million IU.

For prevention of meningococcal meningitis, adults are prescribed 3 million IU twice daily for 5 days, children – 75 thousand IU/kg body weight twice daily for 5 days.

For patients with impaired renal function, due to the insignificant renal excretion of spiramycin, dose adjustment is not required.

The tablets are taken orally with a sufficient amount of water.

Adverse Reactions

The following classification was used to indicate the frequency of adverse reactions: very common (≥10%), common (≥ 1%, <10); uncommon (≥ 0.1%, <1%); rare (≥0.01%, <0.1%), very rare, including isolated reports (<0.01%), frequency unknown (cannot be estimated from the available data).

From the digestive system nausea, vomiting, diarrhea; very rarely – pseudomembranous colitis (<0.01%); frequency unknown – ulcerative esophagitis, acute colitis, acute damage to the intestinal mucosa in AIDS patients using high doses of spiramycin for cryptosporidiosis (only 2 cases).

From the liver and biliary tract: very rarely (<0.01%) – deviation of liver function tests from normal values; cholestatic or mixed hepatitis.

From the nervous system very rarely (isolated cases) – transient paresthesia.

From the hematopoietic system very rarely (<0.01%) – acute hemolysis.

From the cardiovascular system very rarely – QT interval prolongation on ECG.

From the immune system skin rash, urticaria, skin itching; very rarely (<0.01%) – angioedema, anaphylactic shock; in isolated cases – vasculitis, including Henoch-Schönlein purpura.

From the skin and subcutaneous tissues very rarely – acute generalized exanthematous pustulosis.

Contraindications

• Lactation period;
• Glucose-6-phosphate dehydrogenase deficiency (risk of acute hemolysis);
• Childhood (for 1.5 million IU tablets – up to 6 years, for 3 million IU tablets – up to 18 years);
• Hypersensitivity to the components of the drug.

Rovamycine^® should be prescribed with caution in case of biliary tract obstruction, in case of hepatic insufficiency.

Use in Pregnancy and Lactation

Rovamycine^® can be prescribed during pregnancy if indicated.

There is extensive experience with the use of Rovamycine^® during pregnancy. A reduction in the risk of transmission of toxoplasmosis to the fetus during pregnancy is noted from 25% to 8% when using the drug in the first trimester, from 54% to 19% in the second trimester, and from 65% to 44% in the third trimester. No teratogenic or fetotoxic effects were observed.

When prescribing Rovamycine^® during lactation, breastfeeding should be discontinued, as spiramycin may pass into breast milk.

Use in Hepatic Impairment

Rovamycine^® should be prescribed with caution in case of biliary tract obstruction or hepatic insufficiency.

Use in Renal Impairment

For patients with impaired renal function, due to the low renal excretion of spiramycin, no dose change is required.

Pediatric Use

Contraindication: childhood (for 1.5 million IU tablets – up to 6 years, for 3 million IU tablets – up to 18 years).

Special Precautions

During treatment with the drug, patients with liver diseases should periodically monitor its function.

If generalized erythema and pustules accompanied by high body temperature occur at the beginning of treatment, acute generalized exanthematous pustulosis should be suspected; if such a reaction occurs, treatment should be discontinued, and further use of spiramycin, both as monotherapy and in combination, is contraindicated.

Use in pediatrics

3 million IU tablets are not used in children due to difficulties in swallowing them because of the large tablet diameter and the risk of airway obstruction.

Effect on ability to drive vehicles and machinery

There is no information on the negative effect of the drug on the ability to drive a car and engage in other potentially hazardous activities. However, the severity of the patient’s condition, which may affect attention and the speed of psychomotor reactions, should be taken into account. Therefore, the decision on the possibility of driving a car or engaging in other potentially hazardous activities for a particular patient should be made by the attending physician.

Overdose

No cases of spiramycin overdose are known.

Symptoms: possible – nausea, vomiting, diarrhea. Cases of QT interval prolongation, which resolved upon drug discontinuation, were observed in newborns receiving high doses of spiramycin or after intravenous administration of spiramycin in patients predisposed to QT interval prolongation.

Treatment: In case of spiramycin overdose, ECG monitoring with determination of the QT interval duration is recommended, especially in the presence of risk factors (hypokalemia, congenital long QT syndrome, concurrent use of drugs that prolong the QT interval and cause the development of torsades de pointes ventricular tachycardia). There is no specific antidote. In case of suspected spiramycin overdose, symptomatic therapy is recommended.

Drug Interactions

Inhibition of carbidopa absorption by spiramycin with a decrease in plasma concentration of levodopa. When spiramycin is co-administered, clinical monitoring and dose adjustment of levodopa are necessary.

Numerous cases of increased activity of indirect anticoagulants have been reported in patients taking antibiotics. The type of infection or severity of the inflammatory reaction, age, and general condition of the patient are predisposing risk factors. Under such circumstances, it is difficult to determine to what extent the infection itself or its treatment plays a role in the change in INR. However, this effect is observed more frequently with the use of certain groups of antibiotics, in particular with the use of fluoroquinolones, macrolides, cyclines, the sulfamethoxazole+trimethoprim combination, and some cephalosporins.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life for 1.5 million IU tablets is 3 years, for 3 million IU tablets – 4 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.