Aziwok (Capsules) Instructions for Use

Marketing Authorization Holder

Wockhardt Ltd. (India)

Manufactured By

Wockhardt Ltd. (India)

Packaged By

SCOPINSKIY PHARMACEUTICAL PLANT, CJSC (Russia)

ATC Code

J01FA10 (Azithromycin)

Active Substance

Azithromycin (Rec.INN registered by WHO)

Dosage Form

Aziwok

Capsules 250 mg: 6 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, yellowish-white in color with black imprint “AZIWOK” and “WOCKHARDT”; capsule contents – white or almost white powder; capsule size No.0.

Excipients: lactose, corn starch, magnesium stearate, sodium lauryl sulfate.
6 pcs. – blister packs (1) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the macrolide group – azalide

Pharmacotherapeutic Group

Antibiotic-azalide

Pharmacological Action

Broad-spectrum antibacterial agent, azalide, acts bacteriostatically. By binding to the 50S ribosomal subunit, it inhibits peptidyltransferase at the translation stage, suppresses protein synthesis, slows bacterial growth and reproduction, and in high concentrations has a bactericidal effect.

Pharmacodynamics

Azithromycin acts on extracellular and intracellular pathogens.

Sensitive: aerobic gram-positive microorganisms – Streptococcus pneumoniae (penicillin-susceptible), Streptococcus pyogenes, Staphylococcus aureus (methicillin-susceptible); aerobic gram-negative microorganisms – Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Haemophilus parainfluenzae, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic microorganisms – Prevotella spp., Clostridium perfringens, Fusobacterium spp., Porphyromonas spp.; others – Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

Moderately sensitive or insensitive: aerobic gram-positive microorganisms – Streptococcus pneumoniae (moderately sensitive or resistant to penicillin).

Resistant: aerobic gram-positive microorganisms – Enterococcus faecalis, Staphylococcus spp., (methicillin-resistant); anaerobes – Bacteroides fragilis group.

Streptococcus pneumoniae, beta-hemolytic Streptococcus spp. group A, Enterococcus faecalis and Staphylococcus aureus (including methicillin-resistant strains), resistant to erythromycin and other macrolides, lincosamides, are also resistant to azithromycin.

Pharmacokinetics

Absorption

Absorption is high, acid-stable, lipophilic. Bioavailability after a single 0.5 g dose is 37% (first-pass effect through the liver), C_max after oral administration of 0.5 g is 0.4 mg/l, time to reach C_max is 2.5-2.9 hours; concentration in tissues and cells is 10-50 times higher than in blood plasma, V_d is 31.1 l/kg.

Distribution

Easily passes through histohematic barriers. Penetrates well into the respiratory tract, genitourinary organs and tissues, including the prostate gland, into the skin and soft tissues.

Penetrates cell membranes and creates high concentrations within them, accumulates in lysosomes (which is especially important for eradicating intracellularly located pathogens). Also transported by phagocytes: polymorphonuclear leukocytes and macrophages.

The concentration at the site of infection is significantly higher (by 24-34%) than in healthy tissues and correlates with the severity of inflammatory edema. Remains at effective concentrations for 5-7 days after the last dose.

Plasma protein binding is 7-50% (inversely proportional to blood concentration).

Metabolism

Demethylated in the liver, forming inactive metabolites. Isoenzymes CYP3A4, CYP3A5, CYP3A7, which it inhibits, are involved in the drug’s metabolism.

Elimination

Plasma clearance is 630 ml/min. T_1/2 between 8 and 24 hours after administration is 14-20 hours, T_1/2 in the interval from 24 to 72 hours is 41 hours. 50% is excreted in bile unchanged, 6% – by the kidneys.

Pharmacokinetics in special clinical cases

Food intake significantly alters pharmacokinetics: C_max and AUC decrease by 52% and 43%, respectively.

In elderly men (65-85 years), pharmacokinetic parameters do not change; in women, C_max increases (by 30-50%).

Indications

Infectious and 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 (pneumonia (including that caused by atypical pathogens), bronchitis);
• Infections of the skin and soft tissues (acne vulgaris (moderate severity), erysipelas, impetigo, secondarily infected dermatoses);
• Infections of the urinary tract (urethritis, cervicitis (caused by Chlamydia trachomatis));
• Lyme disease (initial stage – erythema migrans).

ICD codes

Dosage Regimen

Adults and children over 12 years of age weighing more than 45 kg orally, 1 hour before or 2 hours after meals, once a day.

For infections of the upper and lower respiratory tracts, ENT organs, skin and soft tissues – 0.5 g/day in a single dose for 3 days (total course dose – 1.5 g).

For acne vulgaris – 0.5 g/day in a single dose for 3 days, then 0.5 g/day once a week for 9 weeks. The first weekly capsule should be taken 7 days after taking the first daily capsule (day 8 from the start of treatment), the subsequent 8 weekly capsules – at 7-day intervals.

For urinary tract infections (urethritis or cervicitis) – a single dose of 1 g.

For Lyme disease – for treatment of stage I (erythema migrans) – 1 g on the first day and 0.5 g daily from day 2 to day 5 (total course dose – 3 g).

Adverse Reactions

From the blood system thrombocytopenia, neutropenia.

From the nervous system dizziness/vertigo, headache, convulsions, drowsiness, paresthesia, asthenia, insomnia, hyperactivity, aggressiveness, anxiety, nervousness.

From the sensory organs tinnitus, reversible hearing impairment up to deafness (when taking high doses for a long time), impaired perception of taste and smell.

From the cardiovascular system palpitations, arrhythmia, ventricular tachycardia, QT interval prolongation, bidirectional ventricular tachycardia.

From the digestive system nausea, vomiting, diarrhea, abdominal pain/cramps, flatulence, dyspepsia, anorexia, constipation, discoloration of the tongue, pseudomembranous colitis, cholestatic jaundice, hepatitis, changes in liver function laboratory parameters, liver failure, liver necrosis (possibly fatal).

Allergic reactions itching, skin rash, angioedema, urticaria, eosinophilia, anaphylactic reaction, including angioedema (in rare cases fatal), erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome.

From the musculoskeletal system: arthralgia.

From the genitourinary system interstitial nephritis, acute renal failure.

Others vaginitis, candidiasis, photosensitivity.

Contraindications

• Severe hepatic and/or renal impairment;
• Concomitant use of ergotamine and dihydroergotamine;
• Lactation period;
• Childhood (under 12 years of age weighing less than 45 kg, for this dosage form);
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption (because the drug contains lactose);
• Hypersensitivity (including to other macrolides).

With caution: moderate impairment of liver and kidney function; arrhythmias (including predisposition to arrhythmias and QT interval prolongation); concomitant use with terfenadine, warfarin, digoxin.

Use in Pregnancy and Lactation

During pregnancy, the drug should be used only if the expected benefit to the mother outweighs the potential risk to the fetus.

During lactation, breastfeeding should be discontinued during treatment.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment.

With caution: moderate hepatic impairment.

Use in Renal Impairment

Contraindicated in severe renal impairment.

With caution: moderate renal impairment.

Pediatric Use

Contraindicated in children (under 12 years of age weighing less than 45 kg, for this dosage form).

Special Precautions

If a dose is missed, the missed dose should be taken as soon as possible, and subsequent doses should be taken at 24-hour intervals.

As with any antibiotic therapy, superinfection (including fungal) may occur during treatment with azithromycin.

The drug should be taken at least 1 hour before or 2 hours after taking antacids.

After discontinuation of treatment, hypersensitivity reactions may persist in some patients, requiring specific therapy under medical supervision.

Effect on ability to drive vehicles and operate machinery

Given the drug’s side effects on the CNS, caution should be exercised when driving vehicles and operating machinery requiring concentration.

Overdose

Symptoms severe nausea, temporary hearing loss, vomiting, diarrhea.

Treatment gastric lavage, symptomatic therapy, hemodialysis is not effective.

Drug Interactions

Antacids do not affect the bioavailability of azithromycin but reduce C_max in blood by 30%, so the drug should be taken 1 hour before or 2 hours after taking these drugs and food.

Azithromycin does not affect the blood concentration of carbamazepine, didanosine, rifabutin, and methylprednisolone when used concomitantly.

When administered parenterally, Azithromycin does not affect the blood concentration of cimetidine, efavirenz, fluconazole, indinavir, midazolam, triazolam, co-trimoxazole when used concomitantly; however, the possibility of such interactions when prescribing oral azithromycin cannot be excluded.

Azithromycin does not affect the pharmacokinetics of theophylline; however, when taken concomitantly with other macrolides, the plasma concentration of theophylline may increase.

If concomitant use with cyclosporine is necessary, it is recommended to monitor cyclosporine blood levels. Although there are no data on the effect of azithromycin on changes in cyclosporine blood concentration, other representatives of the macrolide class can change its plasma concentration.

When digoxin and azithromycin are taken concomitantly, digoxin blood concentration should be monitored, as many macrolides increase the absorption of digoxin in the intestine, thereby increasing its plasma concentration.

If concomitant use with warfarin is necessary, careful monitoring of prothrombin time is recommended.

Concomitant use of terfenadine and macrolide antibiotics has been found to cause arrhythmia and QT interval prolongation. Based on this, the above complications cannot be excluded with the concomitant use of terfenadine and azithromycin.

Since there is a possibility of inhibition of the CYP3A4 isoenzyme by azithromycin in parenteral form when used concomitantly with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole and other drugs whose metabolism involves this enzyme, the possibility of such interaction should be considered when prescribing oral azithromycin.

When azithromycin and zidovudine are taken concomitantly, Azithromycin does not affect the pharmacokinetic parameters of zidovudine in plasma or its renal excretion and that of its glucuronated metabolite. However, the concentration of the active metabolite – phosphorylated zidovudine – increases in peripheral blood mononuclear cells. The clinical significance of this fact is unclear.

Concomitant use of macrolides with ergotamine and dihydroergotamine may lead to manifestation of their toxic effects.

Storage Conditions

The drug should be stored in a light-protected place at a temperature not exceeding 30°C (86°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.