Instructions Azimed film-coated tablets 500 mg blister No. 3
Composition
active ingredient: azithromycin;
1 tablet contains azithromycin dihydrate, equivalent to azithromycin - 500 mg;
excipients: calcium hydrogen phosphate anhydrous; hypromellose (hydroxypropyl methylcellulose); corn starch; sodium starch glycolate (type A); microcrystalline cellulose; sodium lauryl sulfate; magnesium stearate; coating mixture "Opadry II BLUE" 33G30700 (polyethylene glycol (macrogol); lactose, monohydrate; titanium dioxide (E 171); hypromellose (hydroxypropyl methylcellulose); triacetin; indigo carmine (E 132)).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, light blue, oval in shape, with a biconvex surface, with a score on one side of the tablet. A white core is visible on the cross section.
Pharmacotherapeutic group
Antibacterials for systemic use. Macrolides, lincosamides and streptogramins. Azithromycin. ATX code J01F A10.
Pharmacological properties
Pharmacodynamics.
Azithromycin is a member of the macrolide group of antibiotics, the azalides. 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 to inhibit peptide translocation.
Mechanism of resistance.
Complete cross-resistance exists among Streptococcus pneumoniae, group A beta-hemolytic streptococci, 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 individual species, 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
Typically susceptible species:
- aerobic gram-positive bacteria: Staphylococcus aureus (methicillin-sensitive); Streptococcus pneumoniae (penicillin-sensitive); Streptococcus pyogenes;
- aerobic gram-negative bacteria: Haemophilus influenzae; Haemophilus parainfluenzae; Legionella pneumophila; Moraxella catarrhalis; Pasteurella multocida;
- anaerobic bacteria: Clostridium perfringens; Fusobacterium spp. (species); Prevotella spp.; Porphyromonas spp.;
- other microorganisms: Chlamydia trachomatis; Chlamydia pneumoniae; Mycoplasma pneumoniae.
Species for which acquired resistance may be problematic:
- aerobic gram-positive bacteria: Streptococcus pneumoniae (with intermediate sensitivity to penicillin and penicillin-resistant).
Inherently resistant organisms:
- aerobic gram-positive bacteria: Enterococcus faecalis; staphylococci MRSA, MRSE* (methicillin-resistant Staphylococcus aureus);
- anaerobic bacteria: Bacteroides fragilis group.
*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 administered, azithromycin is distributed throughout the body. Pharmacokinetic studies have shown that azithromycin concentrations in tissues are significantly higher (50 times) than in blood plasma, indicating strong tissue binding of the drug.
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 three days. Particularly high concentrations of unchanged azithromycin have been found in human bile. Ten metabolites have also been identified in bile, which are 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 has shown 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; treatment of mild forms of Acne vulgaris;
- sexually transmitted infections: uncomplicated and complicated urethritis/cervicitis caused by Chlamydia trachomatis.
Contraindication
- Hypersensitivity to azithromycin, erythromycin, to any macrolide or ketolide antibiotic, to any other component of the drug.
- Due to the theoretical possibility of ergotism, azithromycin should not be administered concurrently with ergot derivatives.
Interaction with other medicinal products and other types of interactions
Azithromycin should be administered with caution to patients taking other drugs that may prolong the QT interval.
Antacids: When studying 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 reduced by approximately 25%. Azithromycin should be taken at least 1 hour before or 2 hours after taking an antacid.
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: Co-administration of daily doses of 1200 mg of azithromycin with didanosine had no effect on the pharmacokinetics of didanosine.
Digoxin: Concomitant use of macrolide antibiotics, including azithromycin, and P-glycoprotein substrates such as digoxin 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 and digoxin are coadministered.
Zidovudine. Single doses of 1000 mg and 1200 mg or multiple doses of 600 mg of azithromycin did not affect 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 but may be useful for patients.
Ergot: Due to the theoretical possibility of ergotism, the simultaneous administration of azithromycin with ergot derivatives is not recommended.
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 observed with erythromycin and other macrolides. Azithromycin does not induce or inactivate hepatic cytochrome P450 via the cytochrome-metabolic complex.
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 an HMG CoA reductase inhibition assay).
Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the plasma levels of carbamazepine or its active metabolites.
Cimetidine: In a pharmacokinetic study of the effect of a single dose of cimetidine taken 2 hours before 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. Potentiation of the anticoagulant effect has been reported 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 azithromycin is administered to patients receiving oral coumarin anticoagulants.
Cyclosporine. Some of the related macrolide antibiotics affect the metabolism of cyclosporine. Since pharmacokinetic and clinical studies of the possible interaction with the simultaneous use of azithromycin and cyclosporine have not been conducted, the therapeutic situation should be carefully considered before prescribing concomitant treatment with these drugs. If combination therapy is considered justified, cyclosporine levels should be carefully monitored and the dosage adjusted accordingly.
Efavirenz: Coadministration 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 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 (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, azithromycin did not significantly affect the pharmacokinetics of methylprednisolone.
Midazolam: In healthy volunteers, concomitant administration of azithromycin 500 mg daily for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of midazolam.
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 coadministration with azithromycin 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. In some cases, the possibility of such an interaction cannot be completely excluded; however, there is no evidence of such an interaction.
Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction with the simultaneous use of azithromycin and theophylline.
Triazolam: Coadministration of azithromycin 500 mg on the first day and 250 mg on the second day with 0.125 mg of 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
Allergic reactions: As with erythromycin and other macrolide antibiotics, rare serious allergic reactions, including angioedema and anaphylaxis (in isolated cases fatal), have been reported. Some of these reactions, caused by azithromycin, resulted in recurrent symptoms and required longer observation and treatment.
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 abnormalities are detected, azithromycin should be discontinued.
The drug contains lactose, which should be taken into account in patients with lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome.
Ergot. 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 an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin should not be prescribed simultaneously with ergot derivatives.
Superinfections: As with other antibiotics, observation for signs of superinfection due to nonsusceptible organisms, including fungi, is recommended.
Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including azithromycin, and has ranged in severity from mild diarrhea to fatal colitis. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C. difficile.
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 administration.
Renal impairment: In patients with severe renal dysfunction (glomerular filtration rate < 10 mL/min), a 33% increase in systemic exposure to azithromycin was observed.
Prolongation of cardiac repolarization and QT interval, which increased the risk of cardiac arrhythmia and ventricular fibrillation (torsade de pointes), was observed during treatment with other macrolide antibiotics. A similar effect of azithromycin cannot be completely excluded in patients with an increased risk of prolonged cardiac repolarization, therefore, caution should be exercised when prescribing the drug to patients:
- with congenital or registered prolongation of the QT interval;
- with electrolyte imbalance, especially in the case of hypokalemia and hypomagnesemia;
- with clinically relevant bradycardia, cardiac arrhythmia or severe heart failure.
Myasthenia gravis: Exacerbation of symptoms of myasthenia gravis or new development of myasthenic syndrome have been reported in patients receiving azithromycin therapy.
Streptococcal infections. Azithromycin is generally effective in the treatment of streptococcal infections of the oropharynx; there are no data demonstrating the efficacy of azithromycin in the prevention of rheumatic fever. An antimicrobial agent with anaerobic activity should be given in combination with azithromycin if anaerobic organisms are suspected to be causing the infection.
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. Animal reproduction studies have been performed at doses that are moderately toxic to the mother. These studies have not produced any 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. Azithromycin has been reported to pass into breast milk, but adequate and well-controlled clinical studies to characterize the pharmacokinetics of azithromycin excretion in human milk have not been conducted. Azithromycin should be used during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the child.
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
Azimed® tablets 500 mg should be used as a single 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 24-hour intervals.
Adults and children weighing ≥ 45 kg
For infections of the ENT organs, respiratory tract, skin and soft tissues (except chronic migratory erythema): the total dose of azithromycin is 1500 mg (500 mg 1 time per day). The duration of treatment is 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 course 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, then 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).
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 hepatic impairment
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 up to 45 kg are recommended to be prescribed azithromycin in other dosage forms.
Overdose
. Experience with clinical use of azithromycin suggests that adverse reactions that develop when taking higher than recommended doses of the drug are similar to those observed with the use of usual therapeutic doses, namely: they may include diarrhea, nausea, vomiting, reversible hearing loss. In case of overdose, if necessary, it is recommended to take activated charcoal and carry out general symptomatic and supportive treatment.
Adverse reactions
Infections and infestations: candidiasis, oral candidiasis, vaginal infections, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory dysfunction, rhinitis, pseudomembranous colitis.
3. Blood and lymphatic system disorders: leukopenia, neutropenia, eosinophilia, thrombocytopenia, hemolytic anemia.
3 Immune system disorders: angioedema, hypersensitivity reactions, anaphylactic reaction.
3 metabolic side effects: anorexia.
3 aspects of the psyche: nervousness, insomnia, agitation, aggressiveness, restlessness, delirium, hallucinations.
3 nervous system: headache, dizziness, drowsiness, paresthesia, dysgeusia, fainting, convulsions, psychomotor hyperactivity, anosmia, parosmia, ageusia, myasthenia gravis, hypoesthesia.
3 aspects of the organs of vision: visual disorders.
3. Hearing: hearing impairment, vertigo, hearing impairment, including deafness and/or tinnitus.
3 sides of the heart: palpitations, ventricular flutter-fibrillation (torsade de pointes), arrhythmia, including ventricular tachycardia, prolongation of the QT interval on the ECG.
3 vascular side: hot flashes, arterial hypotension.
3 respiratory system: dyspnea, epistaxis.
3 Gastrointestinal tract: diarrhea, vomiting, abdominal pain, nausea, gastritis, constipation, flatulence, dyspepsia, dysphagia, dry mouth, belching, mouth ulcers, hypersecretion of saliva, pancreatitis, tongue discoloration, frequent loose stools.
3 Hepatobiliary system: liver dysfunction, cholestatic jaundice, hepatic failure (which rarely resulted in death), hepatitis, fulminant hepatitis, necrotizing hepatitis.
Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, dermatitis, dry skin, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
3 musculoskeletal system: osteoarthritis, myalgia, back pain, neck pain, arthralgia.
3 urinary system side effects: dysuria, kidney pain, acute renal failure, interstitial nephritis.
3 Reproductive system and breast disorders: uterine bleeding, testicular disorders.
General disorders and local reactions: chest pain, edema, malaise, asthenia, fatigue, facial edema, hyperthermia, pain, peripheral edema.
Laboratory indicators: 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 potassium levels in the blood, 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
In the original packaging at a temperature not exceeding 25 0 C. Keep out of the reach of children.
Packaging
Film-coated tablets, 500 mg, 3 or 10 tablets in a blister, 1 blister in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyivmedpreparat".
Location of the manufacturer and its business address
Ukraine, 01032, Kyiv, Saksaganskoho St., 139.
