Instructions Azitsin film-coated tablets 500 mg No. 3
Composition
active ingredient: azithromycin;
1 tablet contains azithromycin dihydrate equivalent to azithromycin 500 mg;
Excipients: lactose monohydrate, sodium lauryl sulfate, povidone, croscarmellose sodium, microcrystalline cellulose, magnesium stearate, talc, macrogol 4000, sepifilm 752 white.
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, white, oblong in shape, with a biconvex surface.
Pharmacotherapeutic group
Antibacterials for systemic use. Macrolides, lincosamides and streptogramins. ATX code J01F A10.
Pharmacological properties
Pharmacodynamics.
Azithromycin is a member of the macrolide group of antibiotics, the azalides, which have a broad spectrum of antimicrobial activity. The mechanism of action of azithromycin is to inhibit bacterial protein synthesis by binding to the 50S subunit of the ribosome and preventing peptide translocation without affecting polynucleotide synthesis. Resistance to azithromycin can be congenital or acquired. 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 spectrum of antimicrobial action of azithromycin:
| Sensitive species |
Aerobic Gram-positive bacteria Staphylococcus aureus (methicillin-sensitive) Streptococcus pneumoniae (penicillin-susceptible) Streptococcus pyogenes (group A) |
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 bacteria Chlamydia trachomatis Chlamydia pneumoniae Mycoplasma pneumoniae |
| Species that acquire resistance in isolated cases |
Aerobic Gram-positive bacteria Streptococcus pneumoniae (with intermediate susceptibility to penicillin, penicillin-resistant) |
| Inherently resistant species |
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 is listed here because of its rare susceptibility to azithromycin.
Pharmacokinetics.
The bioavailability of azithromycin 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. Pharmacokinetic studies have shown that the concentration of azithromycin in tissues is significantly higher (50 times) than in blood plasma, which indicates a strong binding of the drug to tissues.
Serum protein binding varies with plasma concentration 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, acne vulgaris (common acne) of moderate severity;
sexually transmitted infections: uncomplicated genital infections caused by Chlamydia trachomatis.
Contraindication
Hypersensitivity to azithromycin, as well as to other components of the drug or to any other antibiotic of the macrolide or ketolide group.
Severe liver and kidney dysfunction.
Should not be used concurrently with ergot derivatives due to the theoretical possibility of ergotism.
Interaction with other medicinal products and other types of interactions
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 and antacids should not be taken simultaneously.
Cetirizine: In healthy volunteers, coadministration of a five-day course of azithromycin with 20 mg of cetirizine at steady state did not result in a pharmacokinetic interaction or significant changes in the QT interval.
Didanosine: Coadministration of 1200 mg/day of azithromycin with 400 mg/day of didanosine in 6 HIV-positive patients had no effect on the steady-state pharmacokinetics of didanosine compared to placebo.
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 and colchicine concentrations should be considered when azithromycin is co-administered.
Zidovudine. Coadministration of azithromycin (single doses of 1000 mg and multiple doses of 1200 mg or 600 mg) 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 it may be of benefit to patients.
Azithromycin does not have a significant interaction with the hepatic cytochrome P450 system. It is believed that the drug has no pharmacokinetic interaction with erythromycin and other macrolides. Azithromycin does not induce or inactivate cytochrome P450 through the cytochrome-metabolite complex.
Ergot derivatives. Given the theoretical possibility of ergotism, azithromycin should not be used concomitantly with ergot derivatives.
Pharmacokinetic studies have been conducted on the simultaneous use of azithromycin and drugs metabolized by cytochrome P450.
Atorvastatin: Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on an HMG-CoA reductase inhibition assay). However, cases of rhabdomyolysis have been reported in post-marketing experience in patients receiving azithromycin with statins.
Carbamazepine: In pharmacokinetic studies in healthy volunteers, no significant effect on the plasma concentrations of carbamazepine and its active metabolite was observed in patients receiving concomitant azithromycin.
Cimetidine: In pharmacokinetic studies of the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin, no changes in the pharmacokinetics of azithromycin were found when cimetidine was administered 2 hours before azithromycin.
Oral Coumarin Anticoagulants. Azithromycin did not alter the anticoagulant effect of a single dose (15 mg) of warfarin in healthy volunteers. Potentiation of the anticoagulant effect has been reported after 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.
Cyclosporine: In a pharmacokinetic study in healthy volunteers who received 500 mg/day azithromycin orally for 3 days followed by a single dose of 10 mg/kg cyclosporine, there was a significant increase in Cmax and AUC0-5 of cyclosporine. Therefore, caution should be exercised when considering co-administration of these drugs. If such co-administration is necessary, cyclosporine levels should be monitored and the dose 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 interactions.
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 there was a decrease in Cmax of azithromycin (by 18%), which was not clinically significant.
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.
Methylprednisolone: Azithromycin does not significantly affect the pharmacokinetics of methylprednisolone.
Midazolam: Coadministration of 500 mg of azithromycin daily for 3 days did not produce clinically significant changes in the pharmacokinetics and pharmacodynamics of a single dose of 15 mg of midazolam.
Rifabutin. Concomitant use of azithromycin and rifabutin does not affect the serum concentrations of these drugs. Neutropenia has been reported with concomitant use of azithromycin and rifabutin. Although neutropenia has been associated with rifabutin, a causal relationship with the combination 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 main circulating metabolite.
Terfenadine: No evidence of an interaction between azithromycin and terfenadine has been reported in pharmacokinetic studies. Isolated cases have been reported where the possibility of such an interaction could not be completely ruled out; however, there was no specific evidence that such an interaction occurred.
Theophylline: There was no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline were co-administered in healthy volunteers.
Triazolam: Coadministration of azithromycin 500 mg on day 1 and 250 mg on day 2 with triazolam 0.125 mg on day 2 had no significant effect on the pharmacokinetics of triazolam compared to triazolam and placebo.
Trimethoprim/sulfamethoxazole: Coadministration of 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 similar to 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 reported to cause serious allergic reactions, such as angioedema and anaphylaxis (in isolated cases, fatal), and dermatological reactions, including acute generalized exanthematous pustulosis. Some of these reactions have resulted in recurrent symptoms and have required longer observation and treatment.
Hepatic impairment: Since the liver is the primary route of metabolism of azithromycin, azithromycin should be used with extreme caution in patients with hepatic impairment.
Liver function should be monitored in case of symptoms of liver dysfunction, such as rapidly developing asthenia accompanied by jaundice, dark urine, bleeding tendency and hepatic encephalopathy.
If liver function impairment is detected, azithromycin should be discontinued.
Renal impairment: In patients with severe renal dysfunction (glomerular filtration rate < 10 mL/min), a 33% increase in systemic exposure to azithromycin was observed.
Cardiac arrhythmias. Prolongation of cardiac repolarization and QT interval, which increases the risk of cardiac arrhythmias and ventricular fibrillation, 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 pre-existing 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 known to prolong the QT interval, such as class IA and III antiarrhythmics, cisapride and terfenadine;
with electrolyte disturbances, especially in the case of hypokalemia and hypomagnesemia;
with clinically relevant bradycardia, 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 oropharyngeal inflammatory diseases caused by streptococci, but there are no data demonstrating the efficacy of azithromycin in the prevention of acute rheumatic polyarthritis.
Superinfections. As with other antibacterial drugs, there is a possibility of superinfection (mycoses).
Cases of C. difficile-associated diarrhea have been reported with nearly all antibacterial agents, including azithromycin. Antibacterial therapy alters the normal flora of the large intestine, leading to overgrowth of C. difficile.
You should not drink alcoholic beverages while using the medicine.
AZITROMYCIN-DARNYTSYA contains lactose, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use the drug.
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.
breast-feeding.
Azithromycin has been reported to pass into human milk, but adequate and well-controlled clinical studies that would characterize the pharmacokinetics of azithromycin excretion into human breast 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 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
Given the possibility of developing such adverse reactions as dizziness, drowsiness, and visual impairment, it is not recommended to use the drug when driving or working with other mechanisms.
Method of administration and doses
AZITHROMYCIN-DARNYTSYA should be used in adults and children weighing more than 45 kg.
Azithromycin should be taken orally once a day, at least 1 hour before or 2 hours after meals.
For infections of the ENT organs, respiratory tract, skin and soft tissues (except chronic migratory erythema): 500 mg (1 tablet) once a 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 seven days after the first tablet, and the next 8 doses should be taken at 7-day intervals.
For erythema migrans: on the 1st day – 1 g per day (2 tablets at a time), from the 2nd to the 5th day – 500 mg (1 tablet) per day.
For sexually transmitted infections: 1 g (2 tablets) once. Course dose – 1 g.
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.
In renal failure with minor renal dysfunction (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).
In hepatic insufficiency, the drug should not be used in patients with severe liver disease, since azithromycin is metabolized in the liver and excreted in the bile. Studies related to the treatment of such patients with azithromycin have not been conducted.
Elderly patients do not require dose adjustment.
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.
Children.
AZITHROMYCIN-DARNYTSYA in this dosage form should be used in children weighing more than 45 kg.
Children and those weighing less than 45 kg are recommended to use azithromycin in a different dosage form.
Overdose
Symptoms: possible symptoms of general intoxication, hearing disorders, abdominal pain, severe nausea, vomiting, diarrhea.
Treatment: gastric lavage, administration of activated charcoal, symptomatic therapy aimed at maintaining vital functions of the body. There is no specific antidote.
Side effects
The following table lists adverse reactions identified from clinical trials and post-marketing experience with all formulations of azithromycin by system organ class and frequency. Adverse reactions reported during post-marketing experience are in italics. The frequency categories are defined using the following convention: 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 (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions possibly or probably related to azithromycin based on data obtained during clinical trials and during post-marketing surveillance
| System organ class | Adverse reaction | Frequency |
| Candidiasis, oral candidiasis, vaginal infections, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory dysfunction, rhinitis | Infrequently |
| Pseudomembranous colitis | Unknown |
| Blood and lymphatic system disorders | Leukopenia, neutropenia, eosinophilia | Infrequently |
| Thrombocytopenia, hemolytic anemia | Unknown |
| On the part of the immune system | Angioedema, hypersensitivity reactions | Infrequently |
| Anaphylactic reaction | Unknown |
| Metabolic | Anorexia | Often |
| From the psyche | Nervousness, insomnia | Infrequently |
| Agitation | Rarely |
| Aggression, restlessness, delirium, hallucinations | Unknown |
| From the nervous system | Headache | Often |
| Dizziness, drowsiness, dysgeusia, paraesthesia | Infrequently |
| Syncope, convulsions, hypoesthesia, psychomotor hyperactivity, anosmia, ageusia, parosmia, myasthenia gravis | Unknown |
| From the organs of vision | Visual disorders | Infrequently |
| From the hearing organs | Hearing impairment, vertigo | Infrequently |
| Hearing loss, including deafness and/or tinnitus | Unknown |
| From the heart | Palpitation | Infrequently |
| Torsade de pointes, arrhythmia including ventricular tachycardia, prolonged QT interval on ECG | Unknown |
| From the vascular side | Tides | Infrequently |
| Arterial hypotension | Unknown |
| From the respiratory system | Dyspnea, epistaxis | Infrequently |
| From the digestive tract | Diarrhea | Very often |
| Vomiting, abdominal pain, nausea | Often |
| Constipation, flatulence, dyspepsia, gastritis, dysphagia, dry mouth, eructation, mouth ulcers, salivary hypersecretion | Infrequently |
| Pancreatitis, tongue discoloration | Unknown |
| Hepatobiliary system | Liver dysfunction, cholestatic jaundice | Rarely |
| Hepatic failure (rarely fatal), fulminant hepatitis, necrotizing hepatitis | Unknown |
| Skin and subcutaneous tissue disorders | Rash, pruritus, urticaria, dermatitis, dry skin, hyperhidrosis | Infrequently |
| Photosensitivity, acute generalized exanthematous pustulosis | Rarely |
| Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms | Unknown |
| Musculoskeletal system | Osteoarthritis, myalgia, back pain, neck pain | Infrequently |
| Arthralgia | Unknown |
| From the urinary system | Dysuria, kidney pain | Infrequently |
| Acute renal failure, interstitial nephritis | Unknown |
| Reproductive system and breast disorders | Uterine bleeding, testicular disorders | Infrequently |
| General disorders and local reactions | Oedema, asthenia, malaise, fatigue, facial oedema, chest pain, hyperthermia, pain, peripheral oedema | Infrequently |
| Laboratory indicators | Decreased lymphocyte count, increased eosinophil count, decreased blood bicarbonate, increased basophil count, increased monocyte count, increased neutrophil count | Often |
| Aspartate aminotransferase increased, alanine aminotransferase increased, blood bilirubin increased, blood urea increased, blood creatinine increased, blood potassium changes, alkaline phosphatase increased, chloride increased, glucose increased, platelets increased, haematocrit decreased, bicarbonate increased, sodium abnormal | Infrequently |
| Injury and poisoning | Complications after the procedure | Infrequently |
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:
| System organ class | Adverse reaction | Frequency |
| Metabolic | Anorexia | Often |
| From the psyche | Dizziness, headache, paresthesia, dysgeusia | Often |
| Hypoesthesia | Infrequently |
| From the organs of vision | Vision impairment | Often |
| From the hearing organs | Deafness | Often |
| Hearing loss, ringing in the ears | Infrequently |
| From the heart | Palpitation | Infrequently |
| From the digestive tract | Very often |
| Hepatobiliary system | Hepatitis | Infrequently |
| Skin and subcutaneous tissue disorders | Rash, itching | Often |
| Stevens-Johnson syndrome, photosensitivity | Infrequently |
| Musculoskeletal system | Arthralgia | Often |
| General disorders and local reactions | Increased fatigue | Often |
| Asthenia, malaise | Infrequently |
Expiration date
3 years.
Storage conditions
Store out of the reach of children in the original packaging at a temperature not exceeding 25 °C.
Packaging
3 tablets in a contour blister pack; 1 contour blister pack in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and address of its place of business.
Ukraine, 02093, Kyiv, Boryspilska St., 13.
