Azithromycin Ecomed tablets 500mg, No. 3

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

• infections of the upper respiratory tract and ENT organs: pharyngitis, tonsillitis, sinusitis, otitis media;

• infections of the lower respiratory tract: acute bronchitis, exacerbation of chronic bronchitis, pneumonia, incl. caused by atypical pathogens;

• infections of the skin and soft tissues: common acne of moderate severity, erysipelas, impetigo, secondarily infected dermatoses;

• the initial stage of Lyme disease (borreliosis) - erythema migrans (erythema migrans);

• urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis).

Azithromycin EcomedЃ is taken orally, without chewing, 1 time / day, regardless of the meal. The drug is taken at least 1 hour before or 2 hours after meals.

Adults (including the elderly) and children over 12 years of age weighing over 45 kg

For infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: 0.5 g / day for 3 days (course dose - 1.5 g).

For common acne of moderate severity: 0.5 g / day for 3 days, then 0.5 g 1 time per week for 9 weeks. The first weekly tablet should be taken 7 days after taking the first daily tablet (8th day from the start of treatment), the next 8 weekly tablets should be taken at intervals of 7 days. Heading dose 6.0 g.

With erythema migrans: 1 time / day for 5 days, 1st day 1.0 g, then from 2nd to 5th day for 0.5 g Heading dose 3.0 g.

For urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis): 1.0 g once.

When used in patients with mild renal impairment, dose adjustment is not required.

When used in patients with mild to moderate hepatic impairment, dose adjustment is not required in elderly patients.

Elderly patients: No dose adjustment required. Care should be taken in elderly patients with persistent proarrhythmogenic factors due to the high risk of developing arrhythmias, incl. arrhythmias of the 'pirouette' type

Film-coated tablets of yellow color, capsule-shaped, biconvex; the cross section shows two layers, the inner layer is white or almost white.

1 tab.

azithromycin (in the form of dihydrate) 500 mg

Excipients: lactulose - 600 mg, calcium phosphate dihydrate - 119.6 mg, corn starch - 48 mg, hypromellose - 10 mg, sodium lauryl sulfate - 2.4 mg, croscarmellose sodium - 40 mg, magnesium stearate - 12 mg, microcrystalline cellulose - up to 1400 mg ...

• Hypersensitivity to antibiotics of the macrolide group, hypersensitivity to other components of the drug;

• severe liver failure; severe renal failure (CC below 40 ml / min);

• children under 12 years of age with a body weight of less than 45 kg;

• breast-feeding; simultaneous reception with ergotamine and dihydroergotamine.

• With caution myasthenia gravis; dysfunction of the liver of mild to moderate severity; impaired renal function of mild and moderate severity (CC more than 40 ml / min); in patients with the presence of proarrhythmogenic factors (especially in elderly patients): with congenital or acquired prolongation of the QT interval, in patients receiving therapy with class IA antiarrhythmic drugs (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances in water and electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmias or severe heart failure; simultaneous use of terfenadine, warfarin, digoxin, cyclosporine.

pharmachologic effect

Azithromycin is a broad-spectrum bacteriostatic antibiotic from the group of macrolides-azalides. Possesses a wide spectrum of antimicrobial action. The mechanism of action of azithromycin is associated with the suppression of protein synthesis of the microbial cell. By binding to the 50S-subunit of the ribosome, it inhibits peptide translocase at the stage of translation and suppresses protein synthesis, slowing down the growth and reproduction of bacteria. In high concentrations, it has a bactericidal effect.

Pharmacokinetics

After oral administration, azithromycin is well absorbed and rapidly distributed in the body. Bioavailability after a single dose of 500 mg is 37% ('first pass' effect), the maximum concentration (0.4 mg / l) in the blood is created after 2-3 hours, the apparent volume of distribution is 31.1 l / kg, binding to plasma proteins is inversely proportional to the concentration in the blood and leaves 7-50%. Penetrates through cell membranes (effective for infections caused by intracellular pathogens). It is transported by phagocytes to the site of infection, where it is released in the presence of bacteria. Easily passes histohematogenous barriers and enters the tissues. The concentration in tissues is 10-50 times higher than in plasma, and the focus of infection is 24-34% higher than in healthy tissues. Azithromycin has a very long T1 / 2 - 35-50 hours. T1 / 2 from tissues is much higher.The therapeutic concentration of azithromycin lasts up to 5-7 days after taking the last dose. Azithromycin is excreted mainly unchanged - 50% by the intestines, 6% by the kidneys. In the liver, it is demethylated, losing activity.

Side effect

Infectious diseases: infrequently - candidiasis, incl. oral mucosa and genitals, pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; unknown frequency - pseudomembranous colitis.

Blood and lymphatic system disorders: infrequently - leukopenia, neutropenia, eosinophilia; very rarely - thrombocytopenia, hemolytic anemia.

From the side of metabolism and nutrition: infrequently - anorexia.

Allergic reactions: infrequently - angioedema, hypersensitivity reaction; unknown frequency - anaphylactic reaction.

From the nervous system: often - headache; infrequently - dizziness, impaired taste, paresthesia, drowsiness, insomnia, nervousness; rarely - agitation; unknown frequency - hypesthesia, 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.

On the part of the organ of hearing and labyrinth disorders: infrequently - hearing disorder, vertigo; unknown frequency - hearing impairment, incl. deafness and / or tinnitus.

From the side of the cardiovascular system: infrequently - a feeling of palpitations, flushing of the face; unknown frequency - a decrease in blood pressure, an increase in the QT interval on the ECG, arrhythmia of the 'pirouette' type, ventricular tachycardia.

From the respiratory system: infrequently - shortness of breath, epistaxis.

From the gastrointestinal tract: very often - diarrhea; often - nausea, vomiting, abdominal pain; infrequently - flatulence, dyspepsia, constipation, gastritis, dysphagia, bloating, dryness of the oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands; very rarely - discoloration of the tongue, pancreatitis.

From the liver and biliary tract: infrequently - hepatitis; rarely - liver dysfunction, cholestatic jaundice; unknown frequency - liver failure (in rare cases with fatal outcome, mainly against the background of severe liver dysfunction); liver necrosis, fulminant hepatitis.

Skin and subcutaneous tissue disorders: infrequently - 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: infrequently - osteoarthritis, myalgia, back pain, neck pain; unknown frequency - arthralgia.

From the kidneys and urinary tract: infrequently - dysuria, pain in the kidney area; unknown frequency - interstitial nephritis, acute renal failure.

On the part of the genitals and mammary gland: infrequently - metrorrhagia, dysfunction of the testicles.

Other: infrequently - asthenia, malaise, fatigue, facial edema, 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 - an increase in the activity of AST, ALT, an increase in the concentration of bilirubin in the blood plasma, an increase in the concentration of urea in the blood plasma, an increase in the concentration of creatinine in the blood plasma, a change in the content of potassium in the blood plasma, an increase in the activity of alkaline phosphatase in the blood plasma, an increase in the content of chlorine in the blood plasma, an increase in the concentration of glucose in the blood, an increase in the number of platelets, an increase in hematocrit, an increase in the concentration of bicarbonates in the blood plasma, a change in the sodium content in the blood plasma.

Application during pregnancy and lactation

It is recommended to prescribe azithromycin during pregnancy only in cases where the expected benefit from taking it to the mother outweighs the potential risk to the fetus. During treatment with azithromycin, breastfeeding is suspended.

Application for violations of liver function

Contraindicated in severe hepatic impairment. The drug should be used with caution in patients with mild and moderate hepatic dysfunction due to the possibility of developing fulminant hepatitis and severe liver failure. In the presence of symptoms of liver dysfunction, such as rapidly increasing asthenia, jaundice, dark urine, a tendency to bleeding, hepatic encephalopathy, drug therapy should be discontinued and the functional state of the liver should be examined.

Application for impaired renal function

Contraindicated in severe renal failure. In case of impaired renal function of mild and moderate severity (CC more than 40 ml / min), azithromycin therapy should be carried out with caution under the control of the state of renal function.

Application in children

Contraindicated in children under 12 years of age with a body weight of less than 45 kg.

Use in elderly patients

No dose adjustment is required. Care should be taken in elderly patients with persistent proarrhythmogenic factors due to the high risk of developing arrhythmias, incl. arrhythmias of the 'pirouette' type.

special instructions

If one dose is missed, the missed dose should be taken as early as possible, and the subsequent ones should be taken at intervals of 24 hours. The drug should be taken at least 1 hour before or 2 hours after taking antacids. The drug should be used with caution in patients with mild to moderate liver dysfunction due to the possibility of developing fulminant hepatitis and severe liver failure. In the presence of symptoms of liver dysfunction, such as rapidly increasing asthenia, jaundice, dark urine, a tendency to bleeding, hepatic encephalopathy, drug therapy should be discontinued and a study of the functional state of the liver should be carried out.In case of impaired renal function of mild and moderate severity (CC more than 40 ml / min), azithromycin therapy should be carried out with caution under the control of the state of renal function. As with the use of other antibacterial drugs, during therapy with azithromycin, patients should be regularly examined for the presence of refractory microorganisms and signs of the development of superinfections, incl. the number of fungal. The drug should not be used for longer courses than indicated in the instructions, because the pharmacokinetic properties of azithromycin make it possible to recommend a short and simple dosing regimen. There is no data on the possible interaction between azithromycin and derivatives of ergotamine and dihydroergotamine, but due to the development of ergotism with the simultaneous use of macrolides with derivatives of ergotamine and dihydroergotamine, this combination is not recommended.With prolonged use of azithromycin, it is possible to develop pseudomembranous colitis caused by Clostridium difficile, both in the form of mild diarrhea and severe colitis. With the development of antibiotic-associated diarrhea while taking the drug, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. When treating with macrolides, incl. azithromycin, lengthening of cardiac repolarization and QT interval was observed, increasing the risk of developing cardiac arrhythmias, incl. arrhythmias of the 'pirouette' type. Caution should be exercised when using the drug in patients with the presence of proarrhythmogenic factors (especially in elderly patients): with congenital or acquired prolongation of the QT interval, in patients taking class IA antiarrhythmic drugs (quinidine, procainamide), III (dofetilide, amiodarone and sotalol),cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances in water and electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, with clinically significant heart failure or arrhythmia. The use of azithromycin can provoke the development of myasthenic syndrome or exacerbate myasthenia gravis.The use of azithromycin can provoke the development of myasthenic syndrome or exacerbate myasthenia gravis.The use of azithromycin can provoke the development of myasthenic syndrome or exacerbate myasthenia gravis.

Influence on the ability to drive vehicles and use mechanisms

With the development of undesirable effects on the part of the nervous system and organs of vision, care should be taken when performing actions that require an increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms: temporary hearing loss, nausea, vomiting, diarrhea. Treatment is symptomatic.

Drug interactions

Antacids

Antacids do not affect the bioavailability of azithromycin, but reduce the maximum concentration in the blood by 30%, so the drug should be taken at least 1 hour before or 2 hours after taking these drugs and food.

Cetirizin

Simultaneous use for 5 days in healthy volunteers of azithromycin with cetirizine (20 mg) did not lead to pharmacokinetic interaction and 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 with the placebo group.

Digoxin (P-glycoprotein substrates)

The simultaneous use of macrolide antibiotics, incl. azithromycin, with P-glycoprotein substrates such as digoxin, leads to an increase in the serum P-glycoprotein substrate concentration. 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 (a single dose of 1000 mg and a multiple dose of 1200 or 600 mg) has an insignificant effect on pharmacokinetics, incl. excretion by the kidneys 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 finding is unclear. Azithromycin weakly interacts with isoenzymes of the cytochrome P450 system. It was not revealed that azithromycin is involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor and inducer of cytochrome P450 isoenzymes.

Ergot alkaloids

Given the theoretical possibility of ergotism, the simultaneous use of azithromycin with derivatives of ergot alkaloids is not recommended. Pharmacokinetic studies were carried out for the simultaneous use of azithromycin and drugs, the metabolism of which occurs with the participation of isoenzymes of the cytochrome P450 system.

Atorvastatin

The simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in plasma concentrations of atorvastatin (based on the analysis of inhibition of HMG-CoA reductase). However, in the post-registration period, there were isolated reports of cases of rhabdomyolysis in patients receiving both azithromycin and statins.

Carbamazepia

Pharmacokinetic studies involving healthy volunteers did not reveal a significant effect on the concentration of carbamazepine and its active metabolite in the blood plasma in patients who received azithromycin at the same time.

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 detected, 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 taken by healthy volunteers. It was reported about the potentiation of the anticoagulant effect after the simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives). Although a causal relationship has not been established, consideration should be given to the need for frequent PT monitoring 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) and then cyclosporine (10 mg / kg / day once) orally for 3 days, a significant increase in Cmax in blood plasma and AUC0-5 of cyclosporine was found ... Caution should be exercised with the simultaneous use of these drugs. If it is necessary to use these drugs simultaneously, it is necessary to monitor the concentration of cyclosporine in the blood plasma and adjust the dose accordingly.

Efavirenz

The simultaneous 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

The simultaneous 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 the simultaneous use of fluconazole, however, a decrease in the Cmax of azithromycin (by 18%) was observed, which had no clinical significance.

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 / day for 5 days).

Methylprednisolone

Azithromycin does not significantly affect the pharmacokinetics of methylprednisolone.

Nelfinavir

ќдновременное применение азитромицина (1200 мг) и нелфинавира (по 750 мг 3 раза/сут) вызывает повышение Css азитромицина в сыворотке крови.  линически значимые побочные эффекты не наблюдались, и коррекци¤ дозы азитромицина при его одновременном применении с нелфинавиром не требуетс¤.

–ифабутин

ќдновременное применение азитромицина и рифабутина не вли¤ет на концентрацию каждого из препаратов в сыворотке крови. ѕри одновременном применении азитромицина и рифабутина иногда наблюдалась нейтропени¤. Ќесмотр¤ на то, что нейтропени¤ ассоциировалась с применением рифабутина, причинно-следственна¤ св¤зь между применением комбинации азитромицина и рифабутина и нейтропенией не установлена.

—илденафил

ѕри применении у здоровых добровольцев не получены доказательства вли¤ни¤ азитромицина (500 мг/сут ежедневно в течение 3 дней) на AUC и Cmax силденафила или его основного циркулирующего метаболита.

“ерфенадин

¬ фармакокинетических исследовани¤х не были получены доказательства взаимодействи¤ между азитромицином и терфенадином. —ообщалось о единичных случа¤х, когда возможность такого взаимодействи¤ нельз¤ было исключить полностью, однако не было ни одного конкретного доказательства, что такое взаимодействие имело место. Ѕыло установлено, что одновременное применение терфенадина и макролидов может вызвать аритмию и удлинение интервала QT.

“еофиллин

Ќе вы¤влено взаимодействие между азитромицином и теофиллином.

“рuазолам/мuдазолам

Significant changes in pharmacokinetic parameters with the simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses have not been identified.

Trimethoprim / Sulfamethoxazole

The simultaneous use of trimethoprim / sulfamethoxazole with azithromycin did not reveal a significant effect on Cmax, total exposure or renal excretion of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were consistent with those found in other studies.