Azithromycin 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);

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

• Infections of the skin and soft tissues (acne vulgaris of moderate severity, erysipelas, impetigo, secondarily infected dermatoses);

• The initial stage of Lyme disease (borreliosis) is erythema migrans (erythema migrans);

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

Inside, without chewing, at least 1 hour before or 2 hours after meals, 1 time per day.

Adults and children over 12 years of age weighing more than 45 kg.

For infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: 500 mg (1 tablet 500 mg or 2 tablets 250 mg) 1 time per day for 3 days (course dose 1.5 g).

For moderate acne vulgaris: 500 mg (1 tablet 500 mg or 2 tablets 250 mg) once a day for 3 days, then 500 mg (1 tablet 500 mg or 2 tablets 250 mg) once a day week for 9 weeks (course dose 6.0 g). 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.

With Lyme disease (the initial stage of borreliosis) - erythema migrans (erythema migrans): once a day for 5 days: 1st day - 1.0 g (2 tablets of 500 mg or 4 tablets of 250 mg), then with 2nd to 5th day - 500 mg each (1 tablet 500 mg or 2 tablets 250 mg) (course dose 3.0 g).

Active ingredient: 125 mg / 250 mg / 500 mg (respectively for each dosage) azithromycin dihydrate - 131.0 mg / 262.0 mg / 524.0 mg (in terms of azithromycin) - 125.0 mg / 250.0 mg / 500.0 mg;

excipients of the tablet core: microcrystalline cellulose (type 101) - 30.5 mg / 61.0 mg / 122.0 mg, microcrystalline cellulose (type 12) - 29.0 mg / 58.0 mg / 116.0 mg, starch pregelatinized corn - 25.0 mg / 50.0 mg / 100.0 mg, croscarmellose sodium - 5.0 mg / 10.0 mg / 20.0 mg, magnesium stearate - 2.25 mg / 4.5 mg / 9 , 0 mg, talc - 2.25 mg / 4.5 mg / 9.0 mg, tablet core weight - 225 mg / 450 mg / 900.0 mg;

excipients of the film shell: hypromellose - 5.90 mg / 8.85 mg / 11.8 mg, macrogol (polyethylene glycol) 6000 - 2.30 mg / 3.45 mg / 4.6 mg, titanium dioxide - 0.93 mg / 1.40 mg / 1.86 mg, polysorbate 80 - 0.87 mg / 1.30 mg / 1.74 mg; weight of a film-coated tablet 235.0 mg / 465.0 mg / 920.0 mg

• Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the drug;

• severe liver dysfunction;

• children under 12 years of age with a body weight of less than 45 kg (for tablets of 500 mg and 250 mg);

• children under 3 years of age (for tablets 125 mg);

• simultaneous reception with ergotamine and dihydroergotamine.

  Carefully

• Myasthenia gravis; dysfunction of the liver of mild to moderate severity; end-stage renal failure with GFR (glomerular filtration rate) less than 10 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 antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine , antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with imbalance in water and electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, arrhythmia of the heart, or severe cardiac arrest; simultaneous use of digoxin, warfarin, cyclosporin.

Pharmacodynamics

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 ribosomes of bacterial cells, 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. Has activity against a number of gram-positive, gram-negative, anaerobic, intracellular and other microorganisms. Microorganisms may initially be resistant to antibiotic action or may acquire resistance to it. The scale of the sensitivity of microorganisms to azithromycin (Minimum inhibitory concentration (MIC),mg / l) In most cases, sensitive microorganisms:

1. Gram-positive aerobes Staphylococcus aureus (methicillin-sensitive strains) Streptococcus pneumoniae (penicillin-sensitive strains) Streptococcus pyogenes

2. Gram-negative aerobes Haemophilus influenzae Haemophilus parainfluenzae Legionella pneumophila Moraxella catarrhalis Pasteurella multocida Neisseria gonorrhoeae

3. Anaerobes Clostridium perfringens Fusobacterium spp. Prevotella spp. Porphyromonas spp.

4. Other microorganisms Chlamydia trachomatis Chlamydia pneumonia Chlamydia psittaci Mycoplasma pneumoniae Mycoplasma hominis Borrelia burgdorferi Microorganisms capable of developing resistance to azithromycin: Gram-positive aerobes Streptococcus pneumoniae (penicillin-resistant microorganism-resistant Entericillin-resistant microorganisms). (methicillin-resistant strains of staphylococcus with a very high frequency have acquired resistance to macrolides) Gram-positive bacteria resistant to erythromycin. Anaerobes Hacteroides fragilis.

Pharmacokinetics

Absorption: After oral administration, azithromycin is well absorbed and rapidly distributed in the body. After a single dose of 500 mg, bioavailability is 37% (due to the effect of the 'first pass' through the liver). The maximum concentration (0.4 mg / l) in the blood is created in 2-3 hours. Distribution: The apparent volume of distribution is 31.1 l / kg, protein binding is inversely proportional to the concentration in the blood and is 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 penetrates histohematogenous barriers and enters tissues. The concentration of azithromycin in tissues and cells is 10-50 times higher than in blood plasma, and in the focus of infection it is 24-34% higher than in healthy tissues.Metabolism: Azithromycin is demethylated in the liver, losing activity. Excretion: Azithromycin has a very long half-life - 35-50 hours. The half-life from tissues is much longer. The therapeutic concentration of azithromycin lasts up to 5-7 days after taking the last dose. Azithromycin is excreted mainly unchanged - 50% through the intestines, 6% by the kidneys

Application during pregnancy and during breastfeeding

During pregnancy and during breastfeeding, it is used only if the intended benefit to the mother outweighs the potential risk to the fetus and child. If it is necessary to use the drug during breastfeeding, it is recommended to suspend breastfeeding.

Side effect

Infectious diseases: infrequently - candidiasis, including oral mucosa, vaginal infection, pneumonia, fungal infection, bacterial infection, 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, including deafness and / or tinnitus. From the side of the cardiovascular system: infrequently - a feeling of palpitations, 'hot flushes' of blood to the face; unknown frequency - a decrease in blood pressure, an increase in the QT interval on the electrocardiogram, 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 - fatal, 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, drug rash with eosinophilia and systemic manifestations (DRESS syndrome). From the side of 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. Others: infrequently - edema, 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 aspartate aminotransferase, alanine aminotransferase, 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 concentration of chlorides in the blood plasma, an increase in the concentration of glucose in the blood, an increase in the number of platelets, a decrease in hematocrit, an increase concentration of bicarbonates in blood plasma, changes in sodium content in blood plasma.

Overdose

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

Interaction with other medicinal products

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.

Cetirizine

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 changes in the pharmacokinetic indications of didanosine compared with the placebo group.

Digoxin (P-glycoprotein substrates)

The simultaneous use of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates, such as digoxin, leads to an increase in the concentration of P-glycoprotein substrate in the blood serum. Thus, with the simultaneous use of digoxin and azithromycin, 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 repeated administration of 1200 mg or 600 mg) has little effect on pharmacokinetics, including the excretion of zidovudine or its glucuronide metabolite by the kidneys. 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 contraindicated. Pharmacokinetic studies of the simultaneous use of azithromycin and drugs, the metabolism of which occurs with the participation of zoenzymes of the cytochrome P450 system, were carried out.

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 MMC-CoA reductase). However, in the acute registration period, there were separate reports of cases of rhabdomyolysis in patients receiving both azithromycin and statins.

Carbamazepine

In pharmacokinetic studies with the participation of healthy volunteers, there was no significant effect on the concentration of carbamazepine and its active metabolite in the blood plasma in patients receiving simultaneously 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 detected, provided that cimetidine was used 2 hours before azithromycin.

Indirect anticoagulants (coumarin derivatives)

In pharmacokinetic studies, azithromycin did not affect the anti-coagulant 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). Despite the fact that a causal relationship has not been established, one should take into account the need for frequent monitoring of prothrombin time when using azithromycin in patients who receive 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) for 3 days, a significant increase in the maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-5) of cyclosporin. Caution should be exercised with the simultaneous use of these drugs. If the 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

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 half-life of azithromycin did not change with the simultaneous use of fluconazole, however, a decrease in Cmax of azithromycin (by 18%) was noted, which had no clinical significance.

Indinavir

The simultaneous use of azithromycin (1200 mg once) did not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg three times a day for 5 days).

Methylprednisolone

Azithromycin has no 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 equilibrium concentration of azithromycin in the blood serum. No clinically significant side effects were observed and dose adjustment of azithromycin is not required when used simultaneously with nelfinavir.

Rifabutin

The simultaneous use of azithromycin and rifabutin does not affect the concentration of each drug in the blood serum. With the simultaneous use of azithromycin and rifabutin, neutropenia was sometimes observed. Despite the fact that neutropenia was associated with the use of rifabutin, a causal relationship between the use of a 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 and its main circulating metabolite.

Terfenadine

In pharmacokinetic studies, there was no evidence of an interaction between azithromycin and terfenadine. Isolated cases were reported where the possibility of such an interaction could not be completely ruled out, but there was no concrete evidence that such an interaction took place. It was found that the simultaneous use of terfenadine and antibiotics of the macrolide class can cause arrhythmias and prolongation of the QT interval.

Theophylline

There was no interaction between azithromycin and theophylline.

Triazolam / Midazolam

There were no significant changes in pharmacokinetic parameters with the simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses.

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. Special instructions In case of missing one dose of the drug Azithromycin - the missed dose should be taken as early as possible, and the next - at intervals of 24 hours. Azithromycin should be taken at least 1 hour before or 2 hours after taking antacids. The drug Azithromycin 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 case of impaired liver function: in the presence of symptoms of impaired liver function, such as: rapidly increasing asthenia, jaundice, dark urine, a tendency to bleeding, hepatic encephalopathy, therapy with Azithromycin should be discontinued and a study of the functional state of the liver should be carried out.

In case of impaired renal function: in patients with a GFR of 10-80 ml / min, dose adjustment is not required. 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, including fungal infections. The drug Azithromycin should not be used for longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin make it possible to recommend a short and simple dosing regimen. There is no data on a possible interaction between azithromycin and ergotamine and dihydroergotamine derivatives, but due to the development of ergotism with the simultaneous use of macrolides with ergotamine and dihydroergotamine derivatives, this combination is contraindicated.With prolonged use of the drug 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 azithromycin, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.

Drugs that inhibit intestinal motility are contraindicated. When treated with macrolides, including azithromycin, lengthening of cardiac repolarization and QT interval was observed, increasing the risk of developing cardiac arrhythmias, including arrhythmias of the 'pirouette' type. Caution should be exercised when using azithromycin in patients with the presence of proarrhythmogenic factors (especially in elderly patients), including those with congenital or acquired prolongation of the QT interval; in patients taking class IA antiarrhythmics (quinidine, procainamide), III (dofetilide, amiodarone, and sotalol), cisapride, terfenadine, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), in patients with water disorders - electrolyte balance, especially in the case of hypokalemia or hypomagnesemia,clinically significant bradycardia, cardiac arrhythmias, or severe heart failure. The use of azithromycin can provoke the development of myasthenic syndrome or exacerbate myasthenia gravis.

Influence on the ability to drive vehicles, mechanisms

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