Ziomycin film-coated tablets 500 mg No. 3

Instructions for Ziomycin film-coated tablets 500 mg No. 3

Composition

active ingredient: azithromycin;

1 tablet contains azithromycin dihydrate equivalent to azithromycin 250 mg or 500 mg;

excipients: microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, povidone K 90, talc, magnesium stearate, Opadry 04B52069 yellow coating: hypromellose, titanium dioxide (E 171), quinoline yellow (E 104), polyethylene glycols.

Dosage form

Film-coated tablets.

Main physicochemical properties:

250 mg tablets: capsule-shaped tablets, coated with a yellow shell, with the logo "A 250" on one side and smooth on the other;

500 mg tablets: yellow, capsule-shaped, film-coated tablets with the “A 500” logo on one side and smooth on the other.

Pharmacotherapeutic group

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

Pharmacological properties

Pharmacodynamics.

Azithromycin is a macrolide antibiotic belonging to the azalide group. The molecule is formed by the introduction of a nitrogen atom into the lactone ring of erythromycin A.

The mechanism of action of azithromycin is to inhibit bacterial protein synthesis by binding to the 50 S subunit of ribosomes and inhibiting peptide translocation.

Mechanism of resistance.

Complete cross-resistance exists among Streptococcus pyogenes, 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.

The spectrum of antimicrobial action 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%. The maximum concentration in the blood serum is reached 2–3 hours after taking the drug. When taken orally, azithromycin is distributed throughout the body. In pharmacokinetic studies, it was shown that the concentration of azithromycin in the tissues is significantly higher (50 times) than in the blood plasma, which indicates a strong binding of the drug to the 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 macrolide or ketolide antibiotic, or to any other component of the drug.

Interaction with other medicinal products and other types of interactions

Antacids: In a study of the effect of concomitant administration of antacids on the pharmacokinetics of azithromycin, there was generally no change in bioavailability, although peak plasma concentrations of azithromycin were decreased by approximately 25%. Azithromycin and antacids should not be taken concurrently.

Cetirizine: In healthy volunteers, coadministration of azithromycin with cetirizine 20 mg for 5 days at steady state did not result in any pharmacokinetic interaction or significant changes in the QT interval.

Didanosine: Coadministration of daily doses of 1200 mg azithromycin with 400 mg didanosine per day had no effect on the steady-state pharmacokinetics of didanosine compared to placebo.

Digoxin and Colchicine: Concomitant use of macrolide antibiotics, including azithromycin, and P-glycoprotein substrates such as digoxin and colchicine has been reported to increase serum levels of the P-glycoprotein substrate. Therefore, the possibility of increased serum digoxin concentrations should be considered when azithromycin is coadministered with P-glycoprotein substrates such as digoxin.

Zidovudine. Single doses of 1000 mg and multiple doses of 1200 mg or 600 mg of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolites. However, azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of these findings is unknown.

Azithromycin does not have a significant interaction with the hepatic cytochrome P450 system. It is believed that the drug does not have the pharmacokinetic drug interactions characteristic of erythromycin and other macrolides. Azithromycin does not induce or inactivate hepatic cytochrome P450 through the cytochrome-metabolite complex.

Ergot: Due to the theoretical possibility of ergotism, the simultaneous administration of azithromycin with ergot derivatives is not recommended.

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: Coadministration 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, postmarketing cases of rhabdomyolysis have been reported in patients receiving azithromycin with statins.

Carbamazepine: In a pharmacokinetic interaction study, azithromycin had no significant effect on the plasma levels of carbamazepine or its active metabolites in healthy volunteers.

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.

Oral 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. There is evidence of potentiation of the anticoagulant effect after concomitant administration of azithromycin and oral coumarin anticoagulants. Although a causal relationship has not been established, frequent determination of prothrombin time should be considered when prescribing azithromycin to patients receiving oral coumarin anticoagulants.

Cyclosporine: A pharmacokinetic study in healthy volunteers receiving oral azithromycin 500 mg/day for 3 days followed by a single oral dose of cyclosporine 10 mg/kg demonstrated a significant increase in Cmax and AUC0-5 of cyclosporine. Therefore, caution should be exercised when these drugs are used concomitantly. If concomitant use of these drugs is necessary, cyclosporine levels should be monitored and the dose adjusted accordingly.

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.

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

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

Methylprednisolone: In a pharmacokinetic interaction study in healthy volunteers, azithromycin did not significantly affect the pharmacokinetics of methylprednisolone.

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

Rifabutin. Concomitant administration of azithromycin and rifabutin did not affect the serum concentrations of these drugs. Neutropenia has been observed in subjects receiving azithromycin and rifabutin concomitantly. Although neutropenia has been associated with rifabutin use, a causal relationship to concomitant azithromycin use has not been established.

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

Terfenadine: No pharmacokinetic interaction has been reported between azithromycin and terfenadine. The possibility of such an interaction cannot be completely excluded; however, there is no specific evidence of such an interaction.

Theophylline: No clinically significant pharmacokinetic interaction was observed when azithromycin and theophylline were co-administered to healthy volunteers.

Triazolam: Coadministration of azithromycin 500 mg on the first day and 250 mg on the second day with 0.125 mg triazolam had no significant effect on all pharmacokinetic parameters of triazolam compared to triazolam and placebo.

Trimethoprim/sulfamethoxazole: Coadministration of double-strength trimethoprim/sulfamethoxazole (160 mg/800 mg) for 7 days with azithromycin 1200 mg 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.

Application features

Hypersensitivity

As with erythromycin and other macrolide antibiotics, serious allergic reactions, including angioedema and anaphylaxis (in isolated cases fatal), acute generalized exanthematous pustulosis, and drug-induced hypersensitivity with skin and systemic symptoms and eosinophilia (DRESS syndrome), have been reported. Some of these reactions caused by azithromycin have resulted in recurrent symptoms and have required longer observation and treatment.

Hepatotoxicity

Since the liver is the primary route of elimination of 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 should be investigated immediately if 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.

Horns.

In patients taking ergot derivatives, the simultaneous use of some macrolide antibiotics contributes to the rapid development of ergotism. There is no data on the possibility of interaction between ergot and azithromycin. However, due to the theoretical possibility of ergotism, azithromycin should not be prescribed simultaneously with ergot derivatives.

QT prolongation

Prolongation of cardiac repolarization and QT interval, which increased the risk of cardiac arrhythmia and ventricular fibrillation (torsade de pointes), has been observed with other macrolide antibiotics, including azithromycin. Since conditions associated with an increased risk of ventricular arrhythmias (including torsade de pointes) may lead to cardiac arrest, azithromycin should be administered with caution to patients with proarrhythmic conditions (especially women and the elderly), including patients with:

with congenital or registered prolongation of the QT interval;

who are currently being treated with other active substances that prolong the QT interval, such as: antiarrhythmics of classes 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.

Superinfections.

As with other antibiotics, observation for signs of superinfection due to non-susceptible organisms, including fungi, is recommended.

Clostridium difficile-associated diarrhea.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Toxin-hyperproducing strains of C. difficile cause 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. If CDAD occurs, azithromycin therapy should be discontinued and specific treatment for C. difficile should be initiated.

Streptococcal infections.

Azithromycin is generally effective in treating streptococcal infections of the oropharynx; however, there are no data demonstrating the efficacy of azithromycin in preventing rheumatic fever.

Kidney dysfunction.

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

Myasthenia gravis.

Exacerbation of symptoms of myasthenia gravis or new development of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

Other.

The safety and effectiveness of Musobacterium avium Sotrelex for the prevention or treatment of children have not been established.

Use during pregnancy or breastfeeding

Pregnancy

Animal reproduction studies have used doses that are moderately toxic to the mother. These studies have not shown evidence of fetal toxicity. However, there are no adequate and well-controlled studies in pregnant women. Since animal reproduction studies are not always representative of human effects, azithromycin should be used during pregnancy only if clearly needed.

Breastfeeding period

There are no studies on the excretion of azithromycin in human milk. Because many drugs are excreted in human milk, azithromycin should not be used during breastfeeding unless the physician considers the potential benefit justifies the potential risk to the infant.

Fertility.

Fertility studies have been conducted 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 dizziness, drowsiness, and visual disturbances should be taken into account.

Method of administration and doses

The drug should be used as a single daily dose, regardless of meals. Swallow the tablets without chewing. If you miss a dose, take the missed dose as soon as possible, and the next dose should be taken at intervals of 24 hours.

Adults and children weighing > 45 kg.

* Administer the 2nd week dose 7 days after the first day of dosing. Administer the 3rd through 10th week doses at 7-day intervals.

Elderly patients.

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

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

Patients with renal impairment.

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

The drug should be used in children weighing more than 45 kg. Children weighing less than 45 kg are recommended to use azithromycin preparations in the appropriate dosage.

Overdose

Symptoms: side effects that develop when taking higher than recommended doses of the drug are similar to those observed when using normal therapeutic doses, namely: they may include diarrhea, nausea, vomiting, reversible hearing loss.

Treatment: if necessary, administration of activated charcoal and general symptomatic and supportive treatment measures are recommended.

Side effects

Infections and infestations: candidiasis, oral candidiasis, vaginal infections, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, rhinitis, pseudomembranous colitis.

From the blood and lymphatic system: leukopenia, neutropenia, eosinophilia, thrombocytopenia, hemolytic anemia.

3 Immune system disorders: hypersensitivity reactions, including anaphylactic reactions and angioedema.

3 metabolic side effects: anorexia, asthenia.

3 aspects of the psyche: aggressiveness, nervousness, anxiety, insomnia, agitation, aggressiveness, restlessness, delirium, hallucinations.

3 nervous system: headache, dizziness, drowsiness, insomnia, paresthesia, dysgeusia, fainting, syncope, convulsions, psychomotor hyperactivity, anosmia, parosmia, ageusia, myasthenia gravis, hypoesthesia.

3 aspects of the organs of vision: visual disturbances, visual impairment.

On the part of the organ of hearing: hearing impairment, hearing impairment, including deafness and/or tinnitus, vertigo.

Cardiac: palpitations, palpitations, ventricular flutter-fibrillation (torsde de pointes), arrhythmia, including ventricular tachycardia, prolongation of the QT interval on the ECG.

3 vascular side: hot flashes, arterial hypotension.

From the respiratory system: dyspnea, respiratory dysfunction, epistaxis.

Gastrointestinal: gastrointestinal discomfort, diarrhea, frequent loose stools, vomiting, abdominal pain, nausea, gastritis, constipation, flatulence, dyspepsia, dysphagia, dry mouth, belching, mouth ulcers, salivary hypersecretion, pancreatitis, tongue discoloration, anorexia, gastrointestinal discomfort.

Hepatobiliary disorders: hepatic dysfunction, cholestatic jaundice, hepatic failure (which has rarely resulted in death), hepatitis (including fulminant hepatitis and necrotizing hepatitis).

Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, dermatitis, dry skin, hyperhidrosis, photosensitivity reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, acute generalized exanthematous pustulosis, DRESS syndrome.

3 musculoskeletal system: osteoarthritis, myalgia, back pain, neck pain, arthralgia.

From the urinary system: dysuria, kidney pain, acute renal failure, interstitial nephritis.

3 Reproductive system and breast disorders: vaginitis, uterine bleeding, testicular disorders.

General disorders and local reactions: chest pain, malaise, asthenia, fatigue, hyperthermia, pain, edema, including facial edema and peripheral edema.

Laboratory indicators: decreased white blood cell count, increased eosinophil count, decreased blood bicarbonate level, increased basophil level, increased monocyte level, increased neutrophil level, increased aspartate aminotransferase level, increased alanine aminotransferase level, increased bilirubin level in the blood, increased urea level in the blood, increased creatinine level in the blood, changes in blood potassium levels, increased alkaline phosphatase level, increased chloride level, increased glucose level, increased platelet level, decreased hematocrit level, increased bicarbonate level, abnormal sodium level.

Injury and poisoning: complications after the procedure.

Expiration date

3 years.

Storage conditions

Store at a temperature not exceeding 25 ºС.

Keep out of reach of children.

Packaging

250 mg tablets: 6 or 21 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

"KUSUM FARM" LLC.

Address

40020, Ukraine, Sumy region, Sumy city, Skryabina st., 54.