Azitrox, 250 mg capsules 6 pcs

Pharmacotherapeutic group: azalid antibiotic

ATX code: [J01FA10]

Pharmacological properties

Pharmacodynamics

A broad spectrum antibiotic. It is a representative of the subgroup of macrolide antibiotics – azalides. Binding to 50S subunit of ribosomes, it inhibits peptide translocation stage, inhibits protein synthesis, inhibits bacterial growth and reproduction, acts bacteriostatic, in high concentrations it has bactericidal effect. It acts on extra- and intracellular pathogens.

Active against Gram-positive aerobic microorganisms: Streptococcusspp. (groups A, B, C, G), Streptococcuspneumoniae (penicillin-sensitive), Streptococcuspyogenes, Staphylococcusaureus (methicillin-sensitive); Gram-negative aerobic 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 (Streptococcuspneumoniae (penicillin-resistant)).

Initially resistant microorganisms: Gram-positive aerobes (Enterococcusfaecalis, Staphylococcusspp. (methicillin-resistant Staphylococcus aureus shows a very high degree of resistance to macrolides), erythromycin-resistant gram-positive bacteria); anaerobes (Bacteroidesfragilis).

Pharmacokinetics

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

Asithromycin 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 long half-life are due to low binding of azithromycin to plasma proteins and also to its ability to penetrate into eukaryotic cells and to concentrate in low pH environment surrounding lysosomes.

This, in turn, determines a 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.

It is proved that phagocytes deliver azithromycin to sites of infection localization where it is released during phagocytosis. 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 high concentration in phagocytes, azithromycin has no significant effect on their function. Azithromycin remains in bactericidal concentrations in the focus of inflammation for 5-7 days after the last dose, that allowed to develop short (3-day and 5-day) courses of treatment.

It is demethylated in the liver; the resulting metabolites are inactive.

The excretion of azithromycin from blood plasma occurs in 2 stages: half-life is 14-20 hours within the period from 8 to 24 hours after taking the drug and 41 hours within the period from 24 to 72 hours, allowing to use the drug once a day.

Azithromycin is excreted mainly unchanged – 50% by the intestine, 12% by the kidneys.

Indications

Active ingredient

Composition

Active substance:

azithromycin dihydrate in terms of azithromycin – 250 mg.

Auxiliary substances:

Mannitol (mannitol) – 54.58 mg,

Corn starch – 13.10 mg,

Magnesium stearate – 2.0 mg,

sodium lauryl sulfate – 0.32 mg;

Solid gelatin capsules capsule composition: body and cap – titanium dioxide (E 171), gelatin (medical gelatin).

How to take, the dosage

Ingestion, once daily, at least 1 hour before or 2 hours after meals.

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

Infections of upper and lower respiratory tract, ENT organs, skin and soft tissue

500 mg (1 capsule) 1 time daily for 3 days (course dose 1.5 g).

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

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

In case of moderate acne on the 1st, 2nd and 3rd day of treatment 500 mg once a day, then a break on the 4th to 7th day, from the 8th day of treatment 500 mg once a week for 9 weeks (cumulative dose – 6 g).

Infections of the urogenital tract caused by Chlamydiatrachomatis (urethritis, cervicitis)

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

In patients with impaired renal function: in patients with a GFR of 10-80 ml/min, no dose adjustment is required.

In patients with hepatic impairment: No dose adjustment is required in patients with mild to moderate hepatic impairment.

Elderly patients: No dose adjustment is required. Since elderly people may already have current proarrhythmogenic conditions, caution should be exercised when using Azitrox® due to the high risk of cardiac arrhythmias, including “pirouette” arrhythmias.

Interaction

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

The concomitant use of ergotamine and dihydroergotamine derivatives may increase their toxic effects (vasospasm, dysesthesia).

When concomitant use with coumarin-type indirect anticoagulants (warfarin) and azithromycin (in usual doses), patients require close monitoring of prothrombin time.

Caution should be exercised when prescribing terfenadine and azithromycin concomitantly, because it has been found that concomitant administration of terfenadine and macrolides may cause arrhythmias and prolongation of the QT interval. Therefore, these complications cannot be excluded when terfenadine and azithromycin are taken together.

In concomitant use of azithromycin and cyclosporine, the dose of cyclosporine should be adjusted. When concomitant use of digoxin and azithromycin it is necessary to monitor the concentration of digoxin in blood, since many macrolides increase digoxin absorption in the intestine.

The concomitant use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times daily) causes increase of equilibrium plasma concentration of azithromycin, no clinically significant adverse effects were observed and no dose adjustment of azithromycin is required in concomitant use with nelfinavir.

When azithromycin and zidovudine are coadministered, azithromycin has little effect on the pharmacokinetics, including renal excretion, of zidovudine or its glucuronide metabolite; azithromycin interacts weakly with cytochrome P450 isoenzymes, azithromycin has not been found to be involved in pharmacological interactions similar to those with erythromycin and other macrolides, azithromycin is not an inducer or inhibitor of cytochrome P450 isoenzymes.

In concomitant use of azithromycin and rifabutin in rare cases development of neutropenia is possible; the mechanism of its development, as well as the presence of a causal relationship with taking the drug have not been determined.

Asithromycin does not affect blood concentrations of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim/sulfamethoxazole, cetirizine, sildenafil, atorvastatin, rifabutin and methylprednisolone when administered simultaneously.

Special Instructions

If one dose of the drug is missed, the missed dose should be taken as soon as possible, and subsequent doses should be taken 24 hours apart.

Azitrox® should be taken at least one hour before or two hours after taking antacids.

Azitrox® should be used with caution in patients with mild to moderate hepatic impairment because of the possibility of fulminant hepatitis and severe hepatic failure. In case of symptoms of liver dysfunction 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 kidney dysfunction: in patients with GFR 10-80 ml/min a dose adjustment is not required, treatment with Azitrox® should be performed with caution under renal function monitoring. As with other antibacterials, during therapy with Azitrox® patients should be regularly examined for the presence of non-susceptible microorganisms and signs of superinfections, including fungal.

Asitrox® should not be used for longer courses than directed, because the pharmacokinetic properties of azithromycin recommend a short and simple dosing regimen.

There are no data on possible interaction between azithromycin and ergotamine and dihydroergotamine derivatives, but because of the development of ergotism when using macrolides with ergotamine and dihydroergotamine derivatives simultaneously, this combination is not recommended.

Long-term use of Azitrox® may cause pseudomembranous colitis caused by Clostridium difficile, both as mild diarrhea and severe colitis. If antibiotic-associated diarrhea develops against the background of 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 peristalsis.

In treatment with macrolides, including azithromycin, prolongation of cardiac repolarization and QT interval have been observed, increasing the risk of cardiac arrhythmias, including pirouette arrhythmias.

Azitrox® should be used with caution 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, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disorders of fluid and electrolyte balance, especially in case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia or severe heart failure.

The use of Azitrox® may provoke myasthenic syndrome or worsen myasthenia gravis.

In case of adverse CNS reactions, patients are advised to refrain from driving and engaging in other potentially dangerous activities requiring increased concentration, rapid psychomotor and motor reactions.

Contraindications

With caution

Side effects

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

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

The blood and lymphatic system disorders: frequent – lymphocytopenia, eosinophilia; infrequent – leukopenia, neutropenia; very rare – thrombocytopenia, hemolytic anemia.

Central nervous system disorders: frequent – dizziness, headache, paresthesia, impaired taste perception, anorexia; infrequent – anxiety, nervousness, hyposthesia, insomnia, somnolence; rare – agitation, delirium, hallucinations; very rare – fainting, seizures, psychomotor hyperactivity, aggression, anosmia, loss of taste, perversion of sense of smell, aggravation of myasthenia gravis.

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

Respiratory and ENT system disorders: infrequent – shortness of breath, nasal bleeding.

The cardiovascular system: infrequent – feeling of palpitations, “rushes” of blood to the face; very rare – decreased blood pressure, arrhythmia, ventricular tachycardia, increased QT interval, arrhythmia type “pirouette”.

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

Digestive system disorders: very often – nausea, diarrhea, abdominal pain, flatulence (bloating); often – vomiting; infrequently – dry oral mucosa, oral mucosa ulcers, increased salivary gland secretion, belching, gastritis, dysphagia, constipation; very rarely – color change of tongue, pseudomembranous colitis, pancreatitis.

Hepatic and biliary tract disorders: infrequent – hepatitis, hyperbilirubinemia, increased “liver” transaminase activity; very rarely – cholestatic jaundice, liver failure (in rare cases with fatal outcome, mostly due to liver dysfunction), fulminant hepatitis, liver necrosis.

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

Skin and subcutaneous tissues: dermatitis, dry skin, sweating.

Musculoskeletal system: often – arthralgia; infrequently – osteoarthritis, myalgia, back pain, neck pain.

Urinary system disorders: infrequent – increase of residual urea nitrogen and creatinine concentration in blood plasma, dysuria, pain in the kidney; very rare – interstitial nephritis, acute renal failure.

Gender and mammary gland disorders: infrequent – metrorrhagia, impaired testicular function.

Others: common – weakness; infrequent – chest pain, peripheral edema, asthenia (malaise, feeling of fatigue), fever, facial edema.

Laboratory data: often – increased number of basophils, monocytes, neutrophils, decreased concentration of bicarbonates in plasma; infrequent – increased activity of alkaline phosphatase, increased chlorine, increased concentration of glucose, increased concentration of bicarbonates in plasma, increased number of platelets, increased hematocrit, changes of sodium and potassium in plasma.

Overdose

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

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

Pregnancy use

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

Descriptions of individual cases and observational studies have shown that azithromycin use during pregnancy does not increase the incidence of adverse pregnancy outcomes and is not associated with any specific malformations in the child.

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

Breastfeeding should be stopped if it is necessary to prescribe the drug during lactation.

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