Compound:
One tablet contains:
active substance
: azithromycin dihydrate in terms of azithromycin 250 mg/500 mg;
Excipients
: lactitol 300.0 mg / 600.0 mg, calcium phosphate dihydrate 59.8 mg / 119.6 mg, corn starch 24.0 mg / 48.0 mg, croscarmellose sodium 20.0 mg / 40.0 mg, magnesium stearate 6.0 mg / 12.0 mg, hypromellose 5.0 mg / 10.0 mg, sodium lauryl sulfate 1.2 mg / 2.4 mg, microcrystalline cellulose to obtain an uncoated tablet weighing 700 mg / 1400 mg;
Excipients of the shell:
hypromellose 9.49 mg/
18.98 mg, titanium dioxide 5.2 mg/10.4 mg, macrogol-4000 3.744 mg/7.488 mg, talc 1.12 mg/2.24 mg, povidone-K17 0.416 mg/0.832 mg, dye tropeolin O 0.030 mg / 0.060 mg to obtain a coated tablet weighing 720 mg / 1440 mg
Side effect
The frequency of side effects is classified in accordance with WHO recommendations: very often - at least 10%; often - at least 1%, but less than 10%; infrequently - not less than 0.1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%; unknown frequency—cannot be estimated from available data.
Infectious diseases:
uncommon - candidiasis, incl. mucous membrane of the oral cavity and genitals, pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; unknown frequency - pseudomembranous colitis.
From the blood and lymphatic system:
uncommon - leukopenia, neutropenia, eosinophilia; very rarely - thrombocytopenia, hemolytic anemia.
Metabolism and nutrition:
infrequently - anorexia.
Allergic reactions:
uncommon - angioedema, hypersensitivity reaction; unknown frequency - anaphylactic reaction.
From the nervous system:
often - headache; infrequently - dizziness, disturbance of taste, paresthesia, drowsiness, insomnia, nervousness; rarely - agitation; unknown frequency - hypoesthesia, anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell, perversion of smell, loss of taste, myasthenia gravis, delirium, hallucinations.
From the side of the organ of vision:
infrequently - visual impairment.
Hearing and labyrinth disorders:
uncommon - hearing loss, vertigo; unknown frequency - hearing loss, incl. deafness and/or tinnitus.
From the cardiovascular system:
infrequently - palpitations, flushing of the face; unknown frequency - decreased blood pressure, increased QT interval on ECG, ari, ventricular tachycardia.
From the respiratory system:
infrequently - shortness of breath, nosebleeds.
From the gastrointestinal tract:
very often - diarrhea; often - nausea, vomiting, abdominal pain; uncommon - flatulence, dyspepsia, constipation, gastritis, dysphagia, bloating, dry oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands; very rarely - change in tongue color, pancreatitis.
From the liver and biliary tract:
uncommon - hepatitis; rarely - impaired liver function, cholestatic jaundice; unknown frequency - liver failure (in rare cases with death, mainly due to severe liver dysfunction); liver necrosis, fulminant hepatitis.
For the skin and subcutaneous tissues:
uncommon - skin rash, itching, urticaria, dermatitis, dry skin, sweating; rarely - photosensitivity reaction; unknown frequency - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
From the musculoskeletal system:
uncommon - osteoarthritis, myalgia, back pain, neck pain; unknown frequency - arthralgia.
From the kidneys and urinary tract:
uncommon - dysuria, pain in the kidney area; unknown frequency - interstitial nephritis, acute renal failure.
From the genital organs and breast:
infrequently - metrorrhagia, testicular dysfunction.
Other:
uncommon - asthenia, malaise, feeling of fatigue, facial swelling, chest pain, fever, peripheral edema.
Laboratory data:
often - a decrease in the number of lymphocytes, an increase in the number of eosinophils, an increase in the number of basophils, an increase in the number of monocytes, an increase in the number of neutrophils, a decrease in the concentration of bicarbonates in the blood plasma; infrequently - increased activity of AST, ALT, increased concentration of bilirubin in the blood plasma, increased concentration of urea in the blood plasma, increased concentration of creatinine in the blood plasma, change in the potassium content in the blood plasma, increased activity of alkaline phosphatase in the blood plasma, increased chlorine content in the blood plasma, increased blood glucose concentration, increased platelet count, increased hematocrit, increased plasma bicarbonate concentration, change in plasma sodium content.
Interaction with other drugs.
Antacids
Antacids do not affect the bioavailability of azithromycin, but reduce the maximum blood concentration by 30%, so the drug should be taken at least one hour before or two hours after taking these drugs and eating.
Cetirizine
Concomitant use of azithromycin with cetirizine (20 mg) for 5 days in healthy volunteers did not lead to pharmacokinetic interaction or a significant change in the QT interval.
Didanosine (dideoxyinosine)
The simultaneous use of azithromycin (1200 mg/day) and didanosine (400 mg/day) in 6 HIV-infected patients did not reveal any changes in the pharmacokinetic indications of didanosine compared to the placebo group.
Digoxin (P-glycoprotein substrates)
Simultaneous use of macrolide antibiotics, incl. azithromycin, with P-glycoprotein substrates such as digoxin, leads to increased concentrations of P-glycoprotein substrate in the blood serum. Thus, with the simultaneous use of azithromycin and digoxin, it is necessary to take into account the possibility of increasing the concentration of digoxin in the blood serum.
Zidovudine
The simultaneous use of azithromycin (single dose of 1000 mg and multiple doses of 1200 or 600 mg) has a minor effect on pharmacokinetics, incl. renal excretion of zidovudine or its glucuronide metabolite. However, the use of azithromycin caused an increase in the concentration of phosphorylated zidovudine, a clinically active metabolite in peripheral blood mononuclear cells. The clinical significance of this fact is unclear.
Azithromycin interacts weakly with isoenzymes of the cytochrome P450 system. Azithromycin has not been shown to participate in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor or inducer of cytochrome P450 isoenzymes.
Ergot alkaloids
Given the theoretical possibility of ergotism, the simultaneous use of azithromycin with ergot alkaloid derivatives is not recommended.
Pharmacokinetic studies were conducted on the simultaneous use of azithromycin and drugs whose metabolism occurs with the participation of isoenzymes of the cytochrome P450 system.
Atorvastatin
Concomitant use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in atorvastatin plasma concentrations (based on HMG-CoA reductase inhibition assay). However, in the post-marketing period, isolated case reports of rhabdomyolysis have been received in patients receiving concomitant azithromycin and statins.
Carbamazepine
Pharmacokinetic studies involving healthy volunteers did not reveal a significant effect on the plasma concentrations of carbamazepine and its active metabolite in patients receiving concomitant azithromycin.
Cimetidine
Pharmacokinetic studies of the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin did not reveal changes in the pharmacokinetics of azithromycin, provided that cimetidine was used 2 hours before azithromycin.
Indirect anticoagulants (coumarin derivatives)
In pharmacokinetic studies, azithromycin did not affect the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. Potentiation of the anticoagulant effect has been reported after simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives). Although a causal relationship has not been established, the need for frequent monitoring of PT should be considered when using azithromycin in patients receiving indirect oral anticoagulants (coumarin derivatives).
Cyclosporine
In a pharmacokinetic study involving healthy volunteers who took azithromycin (500 mg/day once) orally for 3 days, followed by cyclosporine (10 mg/kg/day once), a significant increase in plasma Cmax and AUC0-5 of cyclosporine was detected. . Caution is advised when using these drugs together. If simultaneous use of these drugs is necessary, it is necessary to monitor the concentration of cyclosporine in the blood plasma and adjust the dose accordingly.
Efavirenz
Concomitant use of azithromycin (600 mg/day once) and efavirenz (400 mg/day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction.
Fluconazole
Concomitant use of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and T1/2 of azithromycin did not change with simultaneous use of fluconazole, however, a decrease in Cmax of azithromycin was observed (by 18%), which was not clinically significant.
Indinavir
The simultaneous use of azithromycin (1200 mg once) did not have a statistically significant effect on the pharmacokinetics of indinavir (800 mg 3 times a day for 5 days).
Methylprednisolone
Azithromycin does not have a significant effect on the pharmacokinetics of methylprednisolone.
Nelfinavir
The simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the Css of azithromycin in the blood serum. No clinically significant side effects were observed, and no dose adjustment of azithromycin is required when used concomitantly with nelfinavir.
Rifabutin
The simultaneous use of azithromycin and rifabutin does not affect the concentration of each drug in the blood serum. Neutropenia has sometimes been observed with simultaneous use of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship between the use of the combination of azithromycin and rifabutin and neutropenia has not been established.
Sildenafil
When used in healthy volunteers, there was no evidence of the effect of azithromycin (500 mg/day daily for 3 days) on the AUC and Cmax of sildenafil or its main circulating metabolite.
Terfenadine
Pharmacokinetic studies have not provided evidence of an interaction between azithromycin and terfenadine. There have been isolated cases reported where the possibility of such an interaction could not be completely excluded, but there was no concrete evidence that such an interaction occurred. It has been found that the simultaneous use of terfenadine and macrolides can cause arrhythmia and prolongation of the QT interval.
Theophylline
No interaction has been detected between azithromycin and theophylline.
Triazolam/midazolam
Significant changes in pharmacokinetic parameters with simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses were not detected.
Trimethoprim/sulfamethoxazole
Concomitant use of trimethoprim/sulfamethoxazole with azithromycin did not show a significant effect on Cmax, total exposure or renal excretion of trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were consistent with those found in other studies.
