Azithromycin Ecomed 500 mg 3 tablets, film-coated

Infectious-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, including that caused by atypical pathogens;

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

• early stage of Lyme disease (borreliosis) - migrating erythema (erythema migrans);

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

Method of Use and Dosage

Ekomed® is taken orally, without chewing, once a day, regardless of food intake.

For adults (including the elderly) and children over 12 years old with a body weight over 45 kg.

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

For moderate acne: 0.5 g per day for 3 days, then 0.5 g once a 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), and the subsequent 8 weekly tablets should be taken at 7-day intervals. Total course dose 6.0 g.

For migrating erythema: once a day for 5 days, 1st day 1.0 g, then from the 2nd to the 5th day 0.5 g. Total course dose 3.0 g.

For urogenital infections caused by Chlamydia trachomatis (urethritis, cervicitis): 1.0 g as a single dose.

Prescription for patients with impaired kidney function.

For patients with moderate kidney function impairment (creatinine clearance > 40 ml/min), dose adjustment is not required.

Section: Composition

One tablet contains:
active ingredient: azithromycin dihydrate calculated as azithromycin 500 mg;
excipients: lactulose 600 mg, calcium phosphate dihydrate 119.6 mg, corn starch 48.0 mg, hypromellose 10.0 mg, sodium lauryl sulfate 2.4 mg, sodium croscarmellose 40.0 mg, magnesium stearate 12.0 mg, microcrystalline cellulose to obtain a tablet without a coating weighing 1400 mg; excipients of the coating: hypromellose 18.98 mg, titanium dioxide 10.4 mg, macrogol-4000 8.32 mg, talc 2.24 mg, dye tropaeolin - 0.06 mg, to obtain a coated tablet weighing 1440 mg.

Description of the dosage form

Tablets coated with a yellow film, capsule-shaped, biconvex. Two layers are visible in a cross-section. The inner layer is white or almost white.

• hypersensitivity to macrolide antibiotics;

• severe liver and/or kidney failure;

• children under 12 years of age with a body weight of less than 45 kg (for this dosage form);

• breastfeeding;

• simultaneous use with ergotamine and dihydroergotamine.
With caution:

• moderate liver and kidney function impairment;

• in cases of arrhythmias or predisposition to arrhythmias and prolonged QT interval;

• when used together with terfenadine, warfarin, digoxin.
Pregnancy and lactation:
Azithromycin during pregnancy is recommended to be prescribed only in cases where the expected benefit to the mother outweighs the potential risk to the fetus.
During treatment with azithromycin, breastfeeding is suspended.

Section: Special Instructions

In case of a missed dose of the antibiotic, the missed dose should be taken as soon as possible, and subsequent doses should be taken at 24-hour intervals.
After discontinuation of azithromycin therapy, hypersensitivity reactions in some patients may persist for an extended period and may require specific therapy under medical supervision.
Effect on the ability to drive vehicles and operate machinery:
Given the likelihood of side effects from the central nervous system, caution should be exercised when driving vehicles and operating machinery.

Section: Side Effects

From the digestive system: nausea, vomiting, diarrhea, abdominal pain, loose stools, flatulence, digestive disorders, anorexia, constipation, change in tongue color, pseudomembranous colitis, cholestatic jaundice, hepatitis, changes in laboratory indicators of liver function, liver failure, liver necrosis (possibly with fatal outcome).
Allergic reactions: itching, skin rashes, angioedema, urticaria, photosensitization, anaphylactic reaction (rarely with fatal outcome), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
From the cardiovascular system: feeling of palpitations, arrhythmia, ventricular tachycardia, prolonged QT interval, bidirectional ventricular tachycardia.
From the central nervous system: dizziness/vertigo, headache, seizures, drowsiness, paresthesia, asthenia, insomnia, hyperactivity, aggressiveness, anxiety, nervousness.
From the sensory organs: tinnitus, reversible hearing impairment up to deafness (with high doses taken for a long time), disturbance of taste and smell perception.
From the blood and lymphatic systems: thrombocytopenia, neutropenia, eosinophilia.
From the musculoskeletal system: arthralgia.
From the urogenital system: interstitial nephritis, acute renal failure.
Others: vaginitis, candidiasis.

Section: Overdose

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

Interaction

Antacids do not affect the bioavailability of azithromycin but reduce the maximum concentration in the blood by 30%. Therefore, the drug should be taken at least one hour before or two hours after taking these medications and food.
When administered parenterally, azithromycin does not affect the concentration of cimetidine, efavirenz, fluconazole, indinavir, midazolam, triazolam, or co-trimoxazole in plasma when used together; however, the possibility of such interactions should not be excluded when prescribing azithromycin for oral use.
If co-administration with cyclosporine is necessary, it is recommended to monitor the level of cyclosporine in the blood.
When digoxin and azithromycin are taken together, it is necessary to monitor the concentration of digoxin in the blood, as many macrolides increase the absorption of digoxin in the intestine, thereby increasing its concentration in the plasma. If co-administration with warfarin is necessary, careful monitoring of prothrombin time is recommended.
Simultaneous use of terfenadine and macrolide antibiotics can cause arrhythmia and prolong the QT interval. Therefore, the aforementioned complications cannot be excluded when terfenadine and azithromycin are taken together. Since there is a possibility of CYP3A4 isoenzyme inhibition by azithromycin in parenteral form when used together with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole, and other drugs whose metabolism involves this isoenzyme, the possibility of such interaction should be considered when prescribing azithromycin for oral use.
When azithromycin and zidovudine are taken together, azithromycin does not affect the pharmacokinetic parameters of zidovudine in plasma or its renal excretion and that of its glucuronidated metabolite. However, the concentration of the active metabolite - phosphorylated zidovudine in mononuclear cells of peripheral vessels increases. The clinical significance of this fact is unclear.
When macrolides are taken simultaneously with ergotamine and dihydroergotamine, their toxic effects may manifest.

Pharmacodynamics

Antibacterial drug with a broad spectrum of action from the macrolide-azalide group, exhibits a bacteriostatic effect. By binding to the 50S ribosomal subunit, it inhibits peptidyl transferase during translation, suppresses protein synthesis, slows down the growth and reproduction of bacteria, and at high concentrations exerts a bactericidal effect. It acts on both extracellular and intracellular pathogens. Microorganisms may be initially resistant to the action of the antibiotic or may acquire resistance to it.
Sensitive:
aerobic gram-positive microorganisms: Staphylococcus aureus (methicillin-sensitive), Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes;
aerobic gram-negative microorganisms:
Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae;
anaerobic microorganisms:
Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyromonas spp.;
others: Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.
Moderately sensitive or resistant: aerobic gram-positive microorganisms:
Streptococcus pneumoniae (moderately sensitive or resistant to penicillin).
Resistant:
aerobic gram-positive microorganisms: Enterococcus faecalis,
Staphylococci spp. (methicillin-resistant).
Anaerobes:
Bacteroides fragilis group.
Streptococcus pneumoniae, beta-hemolytic Streptococcus spp. group A, Enterococcus faecalis, and Staphylococcus aureus (including methicillin-sensitive strains), resistant to erythromycin and other macrolides, lincosamides, are also resistant to azithromycin.

Pharmacokinetics

After oral administration, azithromycin is well absorbed and rapidly distributed in the body. The bioavailability after a single dose of 0.5 g is 37% (the "first-pass" effect through the liver), the maximum concentration (Cmax) after oral administration of 0.5 g is 0.4 mg/L, and the time to reach maximum concentration (Tmax) is 2-3 hours. The concentration in tissues and cells is 10-50 times higher than in blood serum. The volume of distribution is 31.1 L/kg, and the binding to plasma proteins is inversely proportional to the concentration in the blood, ranging from 7-50%. Azithromycin is acid-stable and lipophilic. It easily passes through histohematological barriers and penetrates well into the respiratory tract, urogenital organs, and tissues, including the prostate gland, skin, and soft tissues. It is also transported to the site of infection by phagocytes, polymorphonuclear leukocytes, and macrophages, where it is released in the presence of bacteria. It penetrates cell membranes and creates high concentrations within them, which is particularly important for eradicating intracellular pathogens. In infection foci, the concentration is 24-34% higher than in healthy tissues and correlates with the severity of the inflammatory process. Effective concentrations are maintained for 5-7 days after the last dose. In the liver, it is demethylated, and the resulting metabolites are inactive. The metabolism of the drug involves the isoenzymes CYP3A4, CYP3A5, and CYP3A7, of which it is an inhibitor. The plasma clearance is 630 mL/min: the half-life after administration is between 8 and 24 hours, averaging 14-20 hours, and the half-life in the interval from 24 to 72 hours is 41 hours. More than 50% of the drug is excreted unchanged by the intestines, and 6% by the kidneys. Food intake significantly alters pharmacokinetics: Cmax increases (by 31%), while the area under the concentration-time curve (AUC) remains unchanged. In elderly men (65-85 years), pharmacokinetic parameters do not change, while in women, Cmax increases (by 30-50%).