Azithromycin Sumatrolide Solution dispersible tablets 500mg, No. 3

• Infectious and inflammatory diseases caused by microorganisms sensitive to azithromycin: infections of the upper respiratory tract and ENT organs (tonsillitis, sinusitis, tonsillitis, pharyngitis, otitis media);

• infections of the lower respiratory tract (acute bronchitis, exacerbation of chronic bronchitis, pneumonia, including those caused by atypical pathogens);

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

• uncomplicated urinary tract infections caused by Chlamydia trachomatis (urethritis and / or cervicitis);

• the initial stage of Lyme disease (borreliosis) is erythema migrans (erythema migrans).

For oral administration

The drug is taken orally 1 time / day 1 hour before or 2 hours after meals, without chewing.

Adults and children over 12 years old and weighing more than 45 kg

For infections of the upper and lower respiratory tract, ENT organs, for infections of the skin and soft tissues (except for chronic migratory erythema) - 500 mg / day for 1 dose for 3 days (course dose - 1.5 g).

For acne of average severity - 500 mg 1 time / day for 3 days, then 500 mg 1 time per week for 9 weeks; course dose - 6 g. The first weekly dose should be taken 7 days after taking the first daily dose (8th day from the start of treatment), the next 8 weekly doses - with an interval of 7 days.

In acute infections of the genitourinary organs (uncomplicated urethritis or cervicitis) - 1 g once.

In Lyme disease (borreliosis) for the treatment of stage I (erythema migrans) - 1 g on the 1st day and from the 2nd to the 5th day - 500 mg daily (course dose - 3 g).

For the treatment of elderly patients over 65 years of age, the same doses are used as for adults. Since this category of patients may have proarrhythmogenic factors, it is necessary to pay special attention to the possibility of developing arrhythmias and ventricular tachycardia of the 'pirouette' type in them.

In case of impaired renal function (CC more than 40 ml / min), dose adjustment is not required.

Dispersible tablets, white or white with a beige shade, with slight inclusions from beige to light brown, with a scored on one side and a characteristic odor.

1 tab. azithromycin dihydrate 530.6 mg,

? which corresponds to the content of azithromycin 500 mg

Excipients: microcrystalline cellulose - 451.8 mg, pregelatinized starch - 134 mg, crospovidone - 120.6 mg, colloidal silicon dioxide - 48 mg, sodium saccharinate - 30 mg, magnesium stearate - 12 mg, blackcurrant flavor - 10 mg, vanillin - 3 mg.

• Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides;

• hypersensitivity to excipients of the drug used;

• severe liver dysfunction;

• severe renal dysfunction (CC <40 ml / min);

• simultaneous use with ergotamine and dihydroergotamine;

  With care: myasthenia gravis; mild to moderate liver dysfunction; mild to moderate renal impairment (CC> 40 ml / min); patients with the presence of proarrhythmogenic factors (especially in old age) - with congenital or acquired prolongation of the QT interval, patients receiving therapy with antiarrhythmic drugs of classes IA (quinidine, procainamide) and III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs ( pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances in water and electrolyte balance, especially with hypokalemia or hypomagnesemia, with clinically significant bradycardia, arrhythmia, or with severe heart failure; simultaneous use of digoxin, warfarin, cyclosporin.

pharmachologic effect

An antibiotic of the macrolide group, is a representative of 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 ribosome subunit, it inhibits peptide translocase at the translation stage, inhibits protein synthesis, and slows down the growth and reproduction of bacteria. Acts bacteriostatically. In high concentrations, it has a bactericidal effect.

Has activity against a number of gram-positive, gram-negative, anaerobic, intracellular and other microorganisms.

Gram-positive cocci are sensitive to azithromycin: Streptococcus pneumoniae (penicillin-sensitive strains), Streptococcus pyogenes, Staphylococcus aureus (methicillin-sensitive strains); aerobic gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; some anaerobic microorganisms: Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyriomonas spp .; as well as Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

Microorganisms with acquired resistance to azithromycin: aerobic gram-positive microorganisms - Streptococcus pneumoniae (penicillin-resistant strains and strains with medium sensitivity to penicillin).

Microorganisms with natural resistance: aerobic gram-positive microorganisms - Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis (methicillin-resistant strains), anaerobic microorganisms - Bacteroides fragilis.

Cases of cross-resistance have been reported between Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococcus), Enterococcus faecalis and Staphylococcus aureus (methicillin-resistant strains) to erythromycin, azithromycin, other macrolamides and other macrolamides.

Azithromycin has not been used to treat infectious diseases caused by Salmonella typhi (MIC <16 mg / L) and Shigella spp.

Pharmacokinetics

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 'first pass' effect through the liver. Cmax in blood plasma is reached after 2-3 hours and is 0.4 mg / l.

Protein binding is inversely proportional to plasma concentration and is 7-50%. The apparent Vd is 31.1 l / kg. 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. Concentration in tissues and cells is 10-50 times higher than in plasma, and in the focus of infection - 24-34% higher than in healthy tissues.

The drug is metabolized in the liver. Metabolites have no antimicrobial activity.

T1 / 2 is very long - 35-50 hours. T1 / 2 of tissues is much larger. 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.

Side effect

Infectious diseases: infrequently - candidiasis (including the mucous membrane of the oral cavity 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: 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 up to deafness and / or tinnitus.

From the side of the cardiovascular system: infrequently - a feeling of palpitations, flushing of the face; unknown frequency - decrease in blood pressure, 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 digestive system: 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 a 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.

Local reactions: often - pain and inflammation at the injection site.

Others: 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

Azithromycin crosses the placental barrier. Use during pregnancy is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

If it is necessary to use azithromycin during lactation, the question of stopping breastfeeding should be resolved.

Application for violations of liver function

Not recommended for use in patients with impaired liver function.

Application for impaired renal function

Use with caution in case of impaired renal function.

Application in children

Application is possible according to the dosage regimen.

special instructions

It should be used with caution in patients with mild to moderate impaired liver function due to the possibility of developing fulminant hepatitis and severe hepatic failure. In the presence of symptoms of liver dysfunction, 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 mild to moderate renal impairment (CC> 40 ml / min), azithromycin therapy should be carried out with caution under the control of the state of renal function.

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 against the background of the use of azithromycin, as well as 2 months after the end of therapy, pseudomembranous colitis caused by Clostridium difficile 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.

Use in pediatrics

The efficacy and safety of using azithromycin for intravenous infusion in children and adolescents under the age of 18 has not been established.

When using azithromycin for oral administration in children, the compliance of the dosage form of the drug with the patient's age should be strictly observed.

Influence on the ability to drive vehicles and mechanisms

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

Drug interactions

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. With the simultaneous use of digoxin or digitoxin with azithromycin, a significant increase in the concentration of cardiac glycosides in the blood plasma and the risk of developing glycosidic intoxication are possible.

The simultaneous use of azithromycin (a single dose of 1000 mg and repeated administration of 1200 mg or 600 mg has a slight 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 mononuclear cells The clinical significance of this is unclear.

With the simultaneous use of azithromycin with warfarin, cases of increased effects of the latter are described.

Azithromycin weakly interacts with isoenzymes of the cytochrome P450 system.

Given the theoretical possibility of ergotism, the simultaneous use of azithromycin with derivatives of ergot alkaloids is not recommended.

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 post-registration period, there were isolated reports of cases of rhabdomyolysis in patients receiving both azithromycin and statins.

It was found that the simultaneous use of terfenadine and macrolides can cause arrhythmias and prolongation of the QT interval.

With simultaneous use with disopyramide, a case of ventricular fibrillation has been described.

With simultaneous use with lovastatin, cases of the development of rhabdomyolysis are described.

With simultaneous use with rifabutin, the risk of developing neutropenia and leukopenia increases.

With simultaneous use, the metabolism of cyclosporine is disrupted, which increases the risk of developing side and toxic reactions caused by cyclosporine.