Azithromycin Euro film-coated tablets 500 mg blister No. 3

Instructions for Azithromycin Euro film-coated tablets 500 mg blister No. 3

Composition

active ingredient: azithromycin;

1 tablet contains azithromycin dihydrate equivalent to azithromycin anhydrous – 125 mg or 250 mg, or 500 mg;

excipients: calcium hydrogen phosphate; lactose, monohydrate; pregelatinized starch; croscarmellose sodium; magnesium stearate; sodium lauryl sulfate; Opadry blue 03B50883: hypromellose, titanium dioxide (E 171), polyethylene glycol, indigo carmine (E 132).

Dosage form

Film-coated tablets.

Main physicochemical properties: 125 mg or 250 mg tablets are blue, round, biconvex, film-coated tablets; 500 mg tablets are blue, capsule-shaped, biconvex, film-coated tablets, with a score on one side.

Pharmacotherapeutic group

Antibacterials for systemic use. Macrolides, lincosamides and streptogramins. Azithromycin. ATC code J01F A10.

Pharmacological properties

Pharmacodynamics.

Azithromycin is a representative of a new subgroup of macrolide antibiotics - azalides. It binds to the 50S subunit of the 70S ribosome of sensitive microorganisms, inhibiting RNA-dependent protein synthesis, slowing down the growth and reproduction of bacteria, and at high concentrations, a bactericidal effect is possible.

Mechanism of resistance.

Complete cross-resistance exists among Streptococcus pneumoniae, group A beta-hemolytic streptococcus, Enterococcus faecalis, and Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA), to erythromycin, azithromycin, other macrolides, and lincosamides.

The prevalence of acquired resistance may vary with location and time for the species concerned, so local information on resistance is necessary, especially in the treatment of severe infections. Qualified advice may be sought if the local prevalence of resistance is such that the efficacy of the drug in the treatment of at least some types of infections is questionable.

Spectrum of antimicrobial activity of azithromycin

*Methicillin-resistant Staphylococcus aureus has a very high prevalence of acquired resistance to macrolides and has been listed here because of its rare susceptibility to azithromycin.

Pharmacokinetics.

Bioavailability after oral administration is approximately 37%. Maximum serum concentration is reached 2-3 hours after administration.

When taken orally, azithromycin is distributed throughout the body. Pharmacokinetic studies have shown that the concentration of azithromycin in tissues is significantly higher (50 times) than in blood plasma, which indicates strong binding of the drug to tissues.

Serum protein binding varies with plasma concentrations and ranges from 12% at 0.5 μg/mL to 52% at 0.05 μg/mL in serum. The apparent volume of distribution at steady state (VVss) was 31.1 L/kg.

The terminal plasma half-life fully reflects the tissue half-life of 2-4 days.

Approximately 12% of an intravenous dose of azithromycin is excreted unchanged in the urine over the next 3 days. Particularly high concentrations of unchanged azithromycin have been found in human bile. Also found in bile are 10 metabolites formed by N- and O-demethylation, hydroxylation of the desosamine and aglycone rings, and cleavage of the cladinose conjugate. Comparison of the results of liquid chromatography and microbiological analyses showed that the metabolites of azithromycin are not microbiologically active.

Indication

Infections caused by microorganisms sensitive to azithromycin:

ENT infections (bacterial pharyngitis/tonsillitis, sinusitis, otitis media);

respiratory tract infections (bacterial bronchitis, community-acquired pneumonia);

Skin and soft tissue infections: erythema migrans (initial stage of Lyme disease), erysipelas, impetigo, secondary pyodermatosis, acne vulgaris (common acne) of moderate severity;

sexually transmitted infections: uncomplicated genital infections caused by Chlamydia trachomatis.

Contraindication

Hypersensitivity to azithromycin, erythromycin or any other macrolide or ketolide antibiotics or to any other component of the drug.

Due to the theoretical possibility of ergotism, azithromycin should not be administered concomitantly with ergot derivatives.

Interaction with other medicinal products and other types of interactions

Azithromycin should be administered with caution with other drugs that may prolong the QT interval.

Antacids: Concomitant administration of antacids generally does not alter bioavailability, although peak plasma concentrations of azithromycin are reduced by approximately 25%. Azithromycin should be taken at least 1 hour before or 2 hours after taking antacids. Azithromycin and antacids should not be taken concurrently.

Cimetidine: In a pharmacokinetic study of the effect of a single dose of cimetidine taken 2 hours before azithromycin on the pharmacokinetics of azithromycin, no changes in the pharmacokinetics of azithromycin were observed.

Carbamazepine: The pharmacokinetic interaction of azithromycin does not show a significant effect on the plasma levels of carbamazepine or its active metabolites.

Cyclosporine: A pharmacokinetic study in healthy volunteers receiving oral doses of azithromycin 500 mg/day for 3 days followed by a single oral dose of ciclosporin 10 mg/kg demonstrated a significant increase in Cmax and AUC0-5 of ciclosporin. Therefore, caution should be exercised when these drugs are administered concomitantly. Some of the related macrolide antibiotics affect the metabolism of ciclosporin. Since pharmacokinetic and clinical studies of the possible interaction of azithromycin and ciclosporin have not been conducted, the therapeutic situation should be carefully considered before prescribing these drugs together. If combination therapy is considered warranted, ciclosporin levels should be closely monitored and the dosage adjusted accordingly.

Coumarin anticoagulants: In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. Postmarketing reports of potentiation of the anticoagulant effect have been received following concomitant administration of azithromycin and oral coumarin anticoagulants. Although a causal relationship has not been established, frequent monitoring of prothrombin time should be considered when prescribing azithromycin to patients receiving oral coumarin anticoagulants.

Digoxin and colchicine: Concomitant use of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin and colchicine results in increased serum levels of the P-glycoprotein substrate. Therefore, the possibility of increased serum digoxin concentrations should be considered when azithromycin and digoxin are co-administered.

Methylprednisolone: Azithromycin does not have a significant effect on the pharmacokinetics of methylprednisolone.

Terfenadine: No interaction has been reported between azithromycin and terfenadine. As with other macrolide antibiotics, azithromycin should be administered with caution in combination with terfenadine.

Theophylline: There are no data on a clinically significant pharmacokinetic interaction with the simultaneous use of azithromycin and theophylline in healthy volunteers.

Zidovudine: Coadministration of azithromycin (single 1000 mg and multiple 1200 mg or 600 mg doses) had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, azithromycin administration increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unknown but may be useful for patients.

Didanosine: Coadministration of 1200 mg daily doses of azithromycin with 400 mg daily of didanosine in six HIV-positive volunteers had no effect on the pharmacokinetics of didanosine compared to placebo.

Efavirenz: Co-administration of a single dose of azithromycin 600 mg and efavirenz 400 mg daily for 7 days did not result in any clinically significant pharmacokinetic interaction.

Rifabutin: Concomitant use of azithromycin and rifabutin does not affect the plasma concentrations of these drugs. Neutropenia has been observed in subjects receiving azithromycin and rifabutin concomitantly. Although neutropenia has been associated with the use of

rifabutin, a causal relationship with concomitant administration with azithromycin has not been established.

Cetirizine: simultaneous use of a five-day course of azithromycin with 20 mg of cetirizine at steady state does not lead to pharmacokinetic interaction and significant changes in the QT interval.

Ergot: Due to the theoretical possibility of ergotism, azithromycin should not be used concomitantly with ergot derivatives.

Pharmacokinetic studies have been conducted on the use of azithromycin and the following drugs, the metabolism of which occurs to a large extent with the participation of cytochrome P450.

Atorvastatin: Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter plasma concentrations of atorvastatin (based on HMG-CoA reductase inhibition assay). However, post-marketing cases of rhabdomyolysis have been reported in patients receiving azithromycin with statins.

Cimetidine: no changes in the pharmacokinetics of azithromycin are detected when cimetidine is administered 2 hours before azithromycin.

Fluconazole: Coadministration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. The total exposure and half-life of azithromycin were not altered by coadministration of fluconazole, but a clinically insignificant decrease in Cmax of azithromycin (by 18%) was observed.

Indinavir: Coadministration of a single dose of azithromycin 1200 mg had no statistically significant effect on the pharmacokinetics of indinavir administered at 800 mg 3 times daily for 5 days.

Midazolam: Co-administration of 500 mg azithromycin daily for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single dose of 15 mg midazolam.

Triazolam: Coadministration of azithromycin 500 mg on the first day and 250 mg on the second day with 0.125 mg of triazolam did not significantly affect all pharmacokinetic parameters of triazolam compared to triazolam and placebo.

Nelfinavir: Co-administration of azithromycin (1200 mg) and nelfinavir at steady-state concentrations (750 mg 3 times daily) resulted in increased azithromycin concentrations. No clinically significant adverse events were observed, and no dose adjustment is required.

Sildenafil: In men, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax of sildenafil or its main circulating metabolite.

Trimethoprim/sulfamethoxazole: Coadministration of double-strength trimethoprim/sulfamethoxazole (160 mg/800 mg) for 7 days with 1200 mg azithromycin on day 7 had no significant effect on the peak concentrations, total exposure, or urinary excretion of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were consistent with those observed in other studies.

Doxorubicin: No clinical drug interaction studies have been conducted with azithromycin and doxorubicin. The clinical significance of these nonclinical studies is unknown.

Application features

Allergic reactions: Azithromycin has been rarely reported to cause serious allergic (rarely fatal) reactions, such as angioedema and anaphylaxis, and dermatological reactions, including acute generalized exanthematous pustulosis. Some of these reactions have resulted in recurrent symptoms and have required longer-term observation and treatment.

Prolonged cardiac repolarization and QT interval.

Prolongation of cardiac repolarization and QT interval, associated with the risk of cardiac arrhythmia and ventricular fibrillation (torsade de pointes), has been observed with other macrolide antibiotics. A similar effect of azithromycin cannot be completely excluded in patients at increased risk of prolonged cardiac repolarization, therefore, caution should be exercised when prescribing treatment to patients:

with congenital or registered prolongation of the QT interval;

who are currently being treated with other active substances known to prolong the QT interval, such as antiarrhythmics of class IA (quinidine and procainamide) and III (dofetilide, amiodarone and sotalol), cisapride and terfenadine, neuroleptics such as pimozide; antidepressants such as citalopram, and fluoroquinolones such as moxifloxacin and levofloxacin;

with electrolyte imbalance, especially in the case of hypokalemia and hypomagnesemia;

with clinically relevant bradycardia, cardiac arrhythmia or severe heart failure.

Myasthenia gravis: Cases of myasthenic syndrome and exacerbation of myasthenia gravis symptoms have been reported in patients receiving azithromycin.

Streptococcal infections. Penicillin is usually the drug of choice for the treatment of pharyngitis/tonsillitis caused by Streptococcus pyogenes, and is also used for prophylaxis in acute rheumatic fever. Azithromycin is generally effective in the treatment of streptococcal oropharyngeal infections; however, there are no data demonstrating the efficacy of azithromycin in the prevention of rheumatic fever.

The safety and effectiveness of intravenous azithromycin for the treatment of infections in children have not been established.

Safety and effectiveness for the prevention or treatment of Mycobacterium Avium Complex in children have not been established.

Superinfections. As with other antibacterial drugs, there is a possibility of superinfection (e.g. mycosis).

C. difficile strains produce toxins A and B, which contribute to the development of CDAD. C. difficile strains that overproduce the toxins are associated with increased morbidity and mortality, as these infections may be resistant to antimicrobial therapy and require colectomy. The possibility of CDAD should be considered in all patients with antibiotic-associated diarrhea. Careful medical history is required, as CDAD has been reported to occur within 2 months of antibiotic therapy.

Renal impairment: In patients with severe renal dysfunction (glomerular filtration rate <10 mL/min), a 33% increase in systemic exposure to azithromycin was observed.

Hepatic impairment. Since the liver is the primary route of elimination for azithromycin, caution should be exercised when prescribing azithromycin to patients with severe liver disease. Cases of fulminant hepatitis, resulting in life-threatening liver failure, have been reported with azithromycin. Some patients may have a history of liver disease or may be taking other hepatotoxic drugs.

Liver function tests should be performed if signs and symptoms of liver dysfunction develop, such as rapidly progressive asthenia accompanied by jaundice, dark urine, bleeding tendency, or hepatic encephalopathy.

If liver function impairment is detected, azithromycin should be discontinued.

Ergot: Ergotism has occasionally been reported in patients taking ergot derivatives when given concomitantly with certain macrolide antibiotics. There is no evidence of a drug interaction between ergot and azithromycin, but because of the theoretical possibility of ergotism, azithromycin should not be administered concomitantly with ergot derivatives.

Other.

Safety and effectiveness for the prevention or treatment of Mycobacterium Avium Complex in children have not been established.

Use during pregnancy or breastfeeding

Pregnancy.

There are no adequate data on the use of azithromycin in pregnant women. In animal reproductive toxicity studies, azithromycin did not show teratogenic effects on the fetus, but the drug crossed the placenta. The safety of azithromycin during pregnancy has not been established. Therefore, azithromycin should be used during pregnancy only if the benefit outweighs the risk.

Breast-feeding.

Azithromycin has been reported to pass into human milk, but adequate and well-controlled clinical studies to characterize the pharmacokinetics of azithromycin excretion into human milk have not been conducted. Fertility.

Fertility studies have been performed in rats; pregnancy rates were reduced following administration of azithromycin. The relevance of these findings to humans is unknown.

Ability to influence reaction speed when driving vehicles or other mechanisms

There is no evidence that azithromycin can impair the ability to drive or operate other mechanisms, but the possibility of developing adverse reactions such as delirium, hallucinations, dizziness, drowsiness, fainting, and seizures, which may affect the ability to drive or operate other mechanisms, should be taken into account.

Method of administration and doses

Azithromycin Euro tablets should be taken as a single daily dose, regardless of meals. Swallow the tablets without chewing. If you miss a dose,
1 dose of the drug, the missed dose should be taken as soon as possible, and subsequent doses should be taken at intervals of 24 hours.

Adults and children weighing more than 45 kg.

For infections of the ENT organs and respiratory tract, skin and soft tissues (except chronic migratory erythema): the total dose of azithromycin is 1500 mg, 500 mg per day for 3 days.

For acne vulgaris, the recommended total dose of azithromycin is 6 g, which should be taken as follows: 1 500 mg tablet once daily for 3 days, followed by 1 500 mg tablet once weekly for 9 weeks. The second week's dose should be taken 7 days after the first tablet, and the next 8 doses should be taken at 7-day intervals.

For erythema migrans: the total dose of azithromycin is 3 g, which should be taken according to the following scheme: 1 g (2 tablets of 500 mg once) on the first day, followed by 500 mg once a day from the 2nd to the 5th day.

For sexually transmitted infections: the recommended dose of azithromycin is 1000 mg (2 tablets of 500 mg taken once).

If you miss a dose of the drug, take the missed dose as soon as possible, and the following doses should be taken at 24-hour intervals.

Elderly patients.

There is no need to change the dosage for elderly people.

Since elderly patients may be at risk for cardiac conduction abnormalities, caution is recommended when using azithromycin due to the risk of cardiac arrhythmia and torsade de pointes.

For patients with mild renal impairment (glomerular filtration rate 10-80 ml/min), the same dosage can be used as for patients with normal renal function. Azithromycin should be administered with caution to patients with severe renal impairment (glomerular filtration rate <10 ml/min).

Patients with impaired liver function.

Since azithromycin is metabolized in the liver and excreted in the bile, the drug should not be used in patients with severe hepatic impairment. Studies related to the treatment of such patients with azithromycin have not been conducted.

Children

Azithromycin Euro tablets are recommended for use in children weighing more than 45 kg.

Overdose

Experience with the clinical use of azithromycin indicates that the side effects that develop when taking higher than recommended doses of the drug are similar to those observed when using normal therapeutic doses.

These may include diarrhea, nausea, vomiting, reversible hearing loss. In case of overdose, activated charcoal and general symptomatic and supportive treatment are recommended if necessary.

Adverse reactions

The following table lists adverse reactions identified from clinical trials and post-marketing surveillance with all formulations of azithromycin. Adverse reactions are listed by system organ class and frequency. Adverse reactions reported during post-marketing surveillance are in italics. The frequency is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (frequency cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Adverse reactions possibly related to azithromycin based on data obtained during clinical trials and during post-marketing surveillance

Information on adverse reactions possibly associated with the prevention and treatment of Mycobacterium Avium Complex is based on clinical trial data and post-marketing surveillance. These adverse reactions differ in type or frequency from those reported with the immediate-release and long-release formulations.

Adverse reactions possibly associated with the prevention and treatment of Mycobacterium Avium Complex

Expiration date

3 years.

Storage conditions

Store at a temperature not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Packaging

Tablets of 125 mg or 250 mg - 6 tablets in a blister; 1 blister in a cardboard box.

500 mg tablets – 3 tablets in a blister; 1 blister in a cardboard box.

Vacation category

According to the recipe.

Producer

Unique Pharmaceutical Laboratories (a division of J.B. Chemicals and Pharmaceuticals Ltd.).

Location of the manufacturer and address of its place of business.

Plot No. 215-219, G. I. D. C. Industrial Area, Panoli - 394 116, Bharuch District, India.