Azitrox, 500 mg capsules, 3 pcs.

Composition

Active ingredient:

• azithromycin dihydrate (in terms of azithromycin) – 500 mg.

Auxiliary substances:

• mannitol( mannitol),

• corn starch,

• magnesium stearate,

• sodium lauryl sulfate.

Capsule composition: body and lid:

• titanium dioxide (E 171),
• quinoline yellow dye (E 104),
• sunset yellow dye (E 110),
• medical gelatin.

Pharmacological action

Pharmacotherapeutic group: antibiotic-azalide

ATX code: [J01FA10]

Pharmacological properties

Pharmacodynamics Broad-spectrum antibiotic. It is a representative of the subgroup of macrolide antibiotics-azalides. Binding to the 50S subunit of ribosomes, it inhibits peptidtranslase at the translation stage, suppresses protein synthesis, slows down the growth and reproduction of bacteria, acts bacteriostatically, and has a bactericidal effect in high concentrations. It acts on extracellular and intracellular pathogens.

Active against aerobic gram-positive microorganisms: Streptococcusspp. (groups A, B, C, G), Streptococcuspneumoniae (penicillinsusceptible), Streptococcuspyogenes, Staphylococcusaureus (methicillinsusceptible); aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxellacatarrhalis, Legionellapneumophila, Neisseriagonorrhoeae, Pasteurellamultocida; some anaerobic microorganisms: Prevotellaspp., Clostridiumperfringens, Fusobacteriumspp., Porphyriomonasspp. ; and Chlamydiatrachomatis, Chlamydiapneumoniae, Chlamydiapsittaci, Mycoplasmapneumoniae, Mycoplasmahominis, Borreliaburgdorferi.

Microorganisms capable of developing resistance to azithromycin: gram-positive aerobes (Streptococcus Pneumoniae (Penicillin-resistant)).

Initially resistant microorganisms: gram-positive aerobes (Enterococcus Faecalis, Staphylococcusspp. (methicillin-resistant staphylococci exhibit a very high degree of resistance to macrolides), gram-positive bacteria resistant to erythromycin); anaerobes (Bacteroidesfragilis).

Pharmacokinetics

Azithromycin is rapidly absorbed from the gastrointestinal tract, which is due to its stability in an acidic environment and lipophilicity. After oral administration of 500 mg, the maximum concentration of azithromycin in blood plasma is reached in 2.5-3.0 hours and is 0.4 mg/l. Bioavailability is 37%.

Azithromycin penetrates well into the respiratory tract, organs and tissues of the urogenital tract (in particular, the prostate gland), skin and soft tissues.

The high concentration in tissues (10-50 times higher than in blood plasma) and the long half-life are due to the low binding of azithromycin to plasma proteins, as well as its ability to penetrate eukaryotic cells and concentrate in a low pH environment surrounding lysosomes.

This, in turn, determines the large apparent volume of distribution (31.1 l / kg) and high plasma clearance. The ability of azithromycin to accumulate mainly in lysosomes is particularly important for the elimination of intracellular pathogens.

Phagocytes have been shown to deliver azithromycin to the sites of infection, where it is released during phagocytosis. The concentration of azithromycin in the foci of infection is significantly higher than in healthy tissues (on average by 24-34%) and correlates with the degree of inflammatory edema.

Despite the high concentration in phagocytes, azithromycin does not significantly affect their function. Azithromycin remains in bactericidal concentrations in the focus of inflammation for 5-7 days after the last dose, which made it possible to develop short (3-day and 5-day) treatment courses.

It is demethylated in the liver, and the resulting metabolites are not active.

The elimination of azithromycin from blood plasma takes place in 2 stages: the half-life is 14-20 hours in the range from 8 to 24 hours after taking the drug and 41 hours-in the range from 24 to 72 hours, which allows the drug to be used once a day.

Azithromycin is mainly excreted unchanged-50% by the intestines,12% by the kidneys.

Indications

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

• infections of the upper respiratory tract and ENT organs (tonsillitis, sinusitis, tonsillitis, otitis media);
• scarlet fever;
• infections of the lower respiratory tract (bacterial and atypical pneumonia, bronchitis);
• infections of skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses);
• infection of the urogenital tract (uncomplicated urethritis and/or cervicitis);
• Lyme disease (borreliosis) in the initial stage (erythema migrans);
•   diseases of the stomach and duodenum associated with Helicobacter pylori.

Use during pregnancy and lactation

The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

Case reports and observational studies have shown that the use of azithromycin during pregnancy does not lead to an increase in the frequency of adverse pregnancy outcomes and is not associated with the occurrence of any specific malformations in the child.

WHO recommends azithromycin as the drug of choice for the treatment of chlamydia infection in pregnant women.

If it is necessary to prescribe the drug during lactation, stop breastfeeding.

Contraindications

• Hypersensitivity to azithromycin, erythromycin, other macrolides (including erythromycin, ketolides), components of the drug;
• severe liver failure: more than 9 points on a scale child-Pugh (no data on efficacy and safety);
• children under 12 years with body weight less than 45 kg (for this dosage form);
• simultaneous reception of ergotamine and dihydroergotamine.

With caution

In patients with mild to moderate hepatic impairment; in patients with end-stage renal failure with GFR (glomerular filtration rate) less than 10 ml / min; in patients with proarrhythmogenic factors (especially in elderly patients): 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 impaired water-electrolyte balance. especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, arrhythmia or severe heart failure; concomitant use of warfarin, digoxin, cyclosporine; with myasthenia gravis; during pregnancy.

Side effects

Most of the reported adverse reactions are reversible after the end of treatment or discontinuation of the drug.

WHO classification of frequency of side effects: very common (with a frequency of more than 1/10), common (with a frequency of at least 1/100, but less than 1/10), infrequent (with a frequency of at least 1/1000, but less than 1/100), rare (with a frequency of at least 1/10000, but less than 1/1000), very rare (with a frequency of less than 1/10000), including individual reports.

From the circulatory and lymphatic systems: often-lymphocytopenia, eosinophilia; infrequently-leukopenia, neutropenia; very rarely-thrombocytopenia, hemolytic anemia.

From the central nervous system: often – dizziness, headache, paresthesia, impaired perception of taste sensations, anorexia; infrequently-anxiety, nervousness, hyposthesia, insomnia, drowsiness; rarely-agitation, delirium, hallucinations; very rarely-fainting, convulsions, psychomotor hyperactivity, aggression, anosmia, loss of taste sensations, perversion of smell, exacerbation of myasthenia gravis.

Sensory disorders: infrequently – hearing disorder, vertigo, visual impairment; unknown frequency – hearing impairment, including deafness and / or tinnitus.

From the respiratory system and ENT organs: infrequently-shortness of breath, nosebleeds.

From the cardiovascular system: infrequently-palpitations, “flushes” of blood to the face; very rarely-decreased blood pressure, arrhythmia, ventricular tachycardia, increased QT interval, arrhythmia of the “pirouette” type.

Infectious diseases: infrequently-rhinitis, respiratory diseases, pharyngitis, pneumonia, candidiasis, including oral and genital mucosa, gastroenteritis.

From the digestive system: very often-nausea, diarrhea, abdominal pain, flatulence (bloating); often-vomiting; infrequently-dryness of the oral mucosa, ulcers of the oral mucosa, increased salivary gland secretion, belching, gastritis, dysphagia, constipation; very rarely – discoloration of the tongue, pseudomembranous colitis, pancreatitis.

From the liver and biliary tract: infrequently-hepatitis, hyperbilirubinemia, increased activity of “hepatic” transaminases; very rarely-cholestatic jaundice, liver failure (in rare cases with a fatal outcome, mainly against the background of impaired liver function), fulminant hepatitis, liver necrosis.

Allergic reactions: often-pruritus, rash; infrequently-Stevens-Johnson syndrome, photosensitization, urticaria; very rarely – anaphylactic reactions (including angioedema) in rare cases with fatal outcome, toxic epidermal necrolysis, erythema multiforme.

Skin and subcutaneous tissue disorders: dermatitis, dry skin, sweating.

From the musculoskeletal system: often-arthralgia; infrequently-osteoarthritis, myalgia, back pain, neck pain.

From the urinary system: infrequently-increased residual urea nitrogen and plasma creatinine concentration, dysuria, pain in the kidney area; very rarely-interstitial nephritis, acute renal failure.

From the genitals and breast: infrequently-metrorrhagia, testicular dysfunction.

Others: often-weakness; infrequently-chest pain, peripheral edema, asthenia (malaise, feeling tired), fever, facial edema.

Laboratory data: often-an increase in the number of basophils, monocytes, neutrophils, a decrease in the concentration of bicarbonates in blood plasma; infrequently-an increase in the activity of alkaline phosphatase, an increase in the content of chlorine, an increase in the concentration of glucose, an increase in the concentration of bicarbonates in blood plasma, an increase in the number of platelets, an increase in hematocrit, a change in the content of sodium and potassium in blood plasma.

Any side effect should be reported to the attending physician.

Interaction

Antacids (aluminum and magnesium-containing) They do not affect the bioavailability of azithromycin, but reduce its maximum concentration in the blood by 30%, so the interval between their intake should be at least 1 hour before or 2 hours after taking these drugs.

When taken simultaneously with derivatives of ergotamine and dihydroergotamine, their toxic effects may increase (vasospasm, dysesthesia).

When combined with coumarin-type indirect anticoagulants (warfarin) and azithromycin (in normal doses), patients should carefully monitor prothrombin time.

Caution should be exercised when co-prescribing terfenadine and azithromycin, as it has been found that concomitant administration of terfenadine and macrolides can cause arrhythmia and prolongation of the QT interval. Based on this, the above-mentioned complications cannot be excluded when taking terfenadine and azithromycin together.

When azithromycin and cyclosporine are co-administered, a dose adjustment of cyclosporine is necessary. When taking digoxin and azithromycin together, it is necessary to monitor the concentration of digoxin in the blood, since many macrolides increase the absorption of digoxin in the intestine.

Concomitant use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the steady-state concentration of azithromycin in blood plasma, no clinically significant side effects were observed, and dose adjustment of azithromycin with its simultaneous use with nelfinavir is not required.

During simultaneous administration of azithromycin and zidovudine, azithromycin had little effect on the pharmacokinetics, including the renal excretion of zidovudine or its glucuronide metabolite; azithromycin interacts weakly with the isoenzymes of cytochrome P-450, it is not revealed that azithromycin is involved in the pharmacological interactions, similar to erythromycin and other macrolides, azithromycin is not an inducer and inhibitor of the isozymes of cytochrome P-450.

With simultaneous administration of azithromycin and rifabutin, in rare cases, neutropenia may develop, the mechanism of development of which, as well as the presence of a causal relationship with taking the drug, have not been established.

Azithromycin does not affect the concentration of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim/sulfamethoxazole, cetirizine, sildenafil, atorvastatin, rifabutin and methylprednisolone in the blood when used simultaneously.

There have been isolated reports of rhabdomyolysis in patients taking azithromycin and statins at the same time.

How to take, course of administration and dosage

Inside, once a day, at least 1 hour before or 2 hours after a meal.

Adults (including the elderly) and children over 12 years of age with a body weight over 45 kg

For infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues

500 mg (1 capsule) 1 time a day for 3 days (a course dose of 1.5 g).

In the initial stage of Lyme disease (borreliosis – – erythema migrans (erythemamigrans)

1 time a day for 5 days: Day 1 – 1.0 g (2 capsules), then from day 2 to day 5-500 mg (1 capsule) (course dose-3.0 g).

If indicated, acne vulgaris (acne) of moderate severity on the 1st,2nd and 3rd days of treatment, take 500 mg 1 time a day, then take a break from the fourth to the seventh day, from the eighth day of treatment, take 500 mg 1 time a week for 9 weeks (the course dose is 6 g).

For urinary tract infections caused by Chlamydiatrachomatis (urethritis, cervicitis)

Uncomplicated urethritis / cervicitis – 1 g (2 capsules) once.

With impaired renal function: No dose adjustment is required in patients with GFR of 10-80 ml / min.

Hepatic impairment: no dose adjustment is required for use in patients with mild to moderate hepatic impairment.

Elderly patients: no dose adjustment is required. Since older people may already have current proarrhythmogenic conditions, caution should be exercised when using Azitrox®, due to the high risk of developing cardiac arrhythmias, including pirouette-type arrhythmias.

Overdose

When taking high doses of the drug, there may be an increase in side effects: temporary hearing loss, severe nausea, vomiting, diarrhea.

In this case, gastric lavage, administration of activated charcoal, and symptomatic therapy are indicated.

Special instructions

If you miss taking one dose of the drug, the missed dose should be taken as early as possible, and the subsequent ones should be taken at intervals of 24 hours.

Azitrox should be taken at least one hour before or two hours after taking antacid medications.

Azitrox should be used with caution in patients with mild to moderate hepatic impairment due to the possibility of developing fulminant hepatitis and severe hepatic insufficiency. In the presence of symptoms of impaired liver function, such as rapidly increasing asthenia, jaundice, darkening of the urine, tendency to bleeding, hepatic encephalopathy, azithromycin therapy should be discontinued and a study of the functional state of the liver should be conducted.

With impaired renal function: In patients with GFR of 10-80 ml/min, no dose adjustment is required, and Azitrox therapy should be performed with caution under the control of renal function. As with other antibacterial agents, patients with Azitrox should be regularly evaluated for the presence of non-susceptible microorganisms and signs of superinfections, including fungal infections.

Azitrox® should not be used for longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin allow us to recommend a short and simple dosage regimen.

There are no data on possible interactions between azithromycin and ergotamine and dihydroergotamine derivatives, but due to the development of ergotism when macrolides are co-administered with ergotamine and dihydroergotamine derivatives, this combination is not recommended.

Psevodomembranous colitis caused by Clostridium difficile may develop with prolonged use of Azitrox®, both in the form of mild diarrhea and severe colitis. If antibiotic-associated diarrhea develops while taking the drug, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.

Do not use drugs that inhibit intestinal motility.

Macrolide treatment, including azithromycin, has been associated with prolonged cardiac repolarization and QT interval, which increases the risk of cardiac arrhythmias, including pirouette-type arrhythmias.

Caution should be exercised when using Azitrox in patients with proarrhythmogenic factors (especially in elderly patients). : 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 impaired water-electrolyte balance. especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia, or severe heart failure.

The use of Azitrox® may provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

Influence on the ability to drive vehicles and mechanisms

In case of adverse reactions from the central nervous system, patients are advised to refrain from driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention, speed of psychomotor and motor reactions.

Form of production

Capsules.

Storage conditions

Store in a dry place, protected from light, at a temperature of 15-25 °C

Shelf

life is 3 years.

Active ingredient

Azithromycin

Conditions of release from pharmacies

By prescription

Dosage form

of the capsule

Purpose

For adults as prescribed by a doctor, Children over 12 years of age, Pregnant women as prescribed by a doctor, Children as prescribed by a doctor

Indications

Respiratory Tract infections, Infectious diseases, Skin Infections, Pneumonia, Bronchitis, Pharyngitis, Sore Throat, Otitis media, Urethritis, Sinusitis, Tonsillitis

Weight

Weight: 10 g.