Zytrolide, 250 mg capsules 6 pcs

Azithromycin is a bacteriostatic broad-spectrum antibiotic of the macrolide-azalid group. It has a broad spectrum of antimicrobial action. Azithromycin mechanism of action is related to inhibition of microbial cell protein synthesis. Binding to 50S-subunit of ribosome, it inhibits peptide translocase at the translation stage and inhibits protein synthesis, slowing down bacterial growth and reproduction. In high concentrations it has bactericidal action.

It has activity against a number of Gram-positive, Gram-negative, anaerobic, intracellular and other microorganisms.
Microorganisms may be resistant to antibiotic action initially or may acquire resistance to it.

Absorption is high, acid-resistant, lipophilic. Bioavailability after a single use of 500 mg – 37% (effect of “first passage” through the liver), maximum concentration (Cmax) after an oral dose of 500 mg/L, time to reach maximum concentration (TCmax) – 2.5-2.9 hours; in tissues and cells concentration is 10-50 times higher than in blood serum, volume of distribution – 31.1 l/kg. Easily passes histohematic barriers. It penetrates well into respiratory tract, urogenital organs and tissues, prostate, skin and soft tissues; it accumulates in low pH environment, in lysosomes (which is especially important for eradication of intracellularly located pathogens). It is also transported by phagocytes, polymorphonuclear leukocytes and macrophages. It penetrates through cell membranes and generates high concentrations in cells.
Concentration in the foci of infection is significantly higher (24-34%) than in healthy tissues and correlates with the severity of inflammatory edema. It is maintained in effective concentrations in the focus of inflammation for 5-7 days after the last dose. Binding with plasma proteins is 7-50% (inversely proportional to the concentration in blood).

It is demethylated in liver, formed metabolites are not active. CYP3A4, CYP3A5, CYP3A7 isoenzymes are involved in metabolism of the drug. Plasma clearance is 630 ml/min: half-life (T1/2) between 8 and 24 hours after intake is 14-20 hours, T1/2 between 24 and 72 hours – 41 hours. 50% is excreted unchanged in bile, 6% – by kidneys.

Meal consumption significantly changes pharmacokinetics: Cmax decreases by 52%, area under pharmacokinetic curve “concentration-time” (AUC) – by 43%.
In elderly men (65-85 years old) pharmacokinetic parameters do not change, in women Cmax increases (by 30-50%), in children aged 1-5 years Cmax, T1/2, AUC decrease.

Indications

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

Active ingredient

Composition

1 capsule contains:

The active ingredients:

azithromycin 250 mg.

Associates:

Magnesium stearate,

Microcrystalline cellulose.

The composition of the capsule shell:

gelatin,

titanium dioxide,

Quinoline yellow,

azorubin,

Ponceau 4R.

There are 6 capsules in the blister.

There is 1 blister in the carton.

How to take, the dosage

In adults (including elderly people) and children over 12 years of age with body weight over 45 kg, once a day, at least 1 hour before or 2 hours after the meal.
Infections of upper and lower respiratory tract, ENT organs, skin and soft tissue.
500 mg (2 capsules) once a day for 3 days (course dose of 1.5 g).
In Lyme disease (initial stage of Borreliosis) – erythema migrans
Once a day for 5 days: 1 day – 1.0 g (4 capsules), then from day 2 to 5 days – 500 mg (2 capsules) (course dose – 3.0 g).
In case of urogenital tract infections caused by Chlamydia trachomatis (urethritis, cervicitis)
Uncomplicated urethritis/cervicitis – 1 g (4 capsules) once.
In patients with renal function disorders: In patients with a GFR of 10 – 80 ml/min the dose adjustment is not required.
In patients with liver dysfunction: In patients with liver dysfunction of mild to moderate degree the dose adjustment is not required.
Elderly patients: The dose adjustment is not required. Since elderly people may already have current proarrhythmogenic conditions, caution should be exercised when using azithromycin due to the high risk of cardiac arrhythmias, including pirouette-type arrhythmias.

Interaction

Antacids
Antacids do not affect the bioavailability of azithromycin, but decrease 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 meals.

Cetirizine
Simultaneous use for 5 days in healthy volunteers of azithromycin with cetirizine (20 mg) did not result in pharmacokinetic interaction or significant change in QT interval.
Didanosine (didezoxynosine)
Simultaneous use of azithromycin (1200 mg/day) and didanosine (400 mg/day) in 6 HIV-infected patients showed no change in the pharmacokinetic indication of didanosine compared with the placebo group.

Digoxin (P-glycoprotein substrates)
Concomitant use of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin results in higher serum P-glycoprotein substrate concentrations. Thus, when concomitant use of azithromycin and digoxin is necessary to consider the possibility of increasing the concentration of digoxin in the blood serum.

Zidovudine
Concomitant use of azithromycin (single administration of 1000 mg and multiple administration of 1200 mg or 600 mg) has little effect on pharmacokinetics, including renal excretion of zidovudine or its glucuronide metabolite. However, azithromycin administration caused an increase in the concentration of phosphorylated zidovudine, the clinically active metabolite in peripheral blood mononuclear cells. The clinical significance of this fact is unclear.
Azithromycin interacts weakly with cytochrome P450 isoenzymes. Azithromycin has not been found to be involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor and inducer of cytochrome P450 isoenzymes.

Given the theoretical possibility of ergotism, concomitant use of azithromycin with derivatives of ergot alkaloids is not recommended.
Pharmacokinetic studies have been performed on concomitant use of azithromycin and drugs whose metabolism involves cytochrome P450 isoenzymes.

Atorvastatin
Concomitant administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in plasma concentrations of atorvastatin (based on HMK-CoA reductase inhibition assay). However, in the post-registration period there were isolated reports of cases of rhabdomyolysis in patients receiving azithromycin and statins simultaneously.

Carbamazepine
Pharmacokinetic studies with healthy volunteers showed no significant effect on plasma concentrations of carbamazepine and its active metabolite in patients receiving azithromycin concomitantly.

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 found, provided that cimetidine was used 2 hours before azithromycin.

Special Instructions

In case of missing one dose of azithromycin – the missed dose should be taken as soon as possible, and the subsequent ones should be taken 24 hours apart.
Azithromycin should be taken at least one hour before or two hours after taking antacids.
Azithromycin should be used with caution in patients with liver function abnormalities of mild to moderate severity because of possible development of fulminant hepatitis and severe hepatic insufficiency.

In the presence of symptoms of hepatic impairment such as rapidly increasing asthenia, jaundice, darkened urine, bleeding tendency, hepatic encephalopathy, treatment with azithromycin should be stopped and liver function tests should be performed.
In patients with renal dysfunction: in patients with GFR 10 – 80 ml/min the dose adjustment is not required, therapy with azithromycin should be performed with caution under monitoring of renal function.
As with other antibacterial agents during azithromycin therapy patients should be regularly tested for susceptible microorganisms and signs of superinfections, including fungal.

Azithromycin should not be used for longer courses than indicated, since the pharmacokinetic properties of azithromycin allow recommending a short and simple dosing regimen.
There is no evidence of a possible interaction between azithromycin and ergotamine and dihydroergotamine derivatives, but because of the development of ergotism when macrolides are used simultaneously with ergotamine and dihydroergotamine derivatives, this combination is not recommended.
Long-term use of azithromycin may result in pseudomembranous colitis caused by Clostridium difficile, both as mild diarrhea and severe colitis. If antibiotic-associated diarrhea develops during azithromycin therapy, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Do not use drugs that inhibit intestinal peristalsis.

During treatment with macrolides, including azithromycin, prolongation of cardiac repolarization and QT interval were observed, increasing the risk of cardiac arrhythmias, including “pirouette” type arrhythmias.
Caution should be exercised when using azithromycin 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 electrolyte balance disorders, especially in case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia, or severe heart failure.
Administration of azithromycin may provoke myasthenic syndrome or aggravation of myasthenia gravis.

Synopsis

Contraindications

– Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides or other components of the drug;
– severe hepatic insufficiency (class C on the Child-Pugh scale);
– children under 12 years of age with body weight less than 45 kg;
– simultaneous use with ergotamine and dihydroergotamine.

Side effects

Overdose

Symptoms:

Serious nausea, temporary hearing loss, vomiting, diarrhea.

Treatment:

Cancellation of the drug, symptomatic therapy.

Pregnancy use

Similarities