Active substance:

Azithromycin; 1 tablet contains azithromycin dehydrate equivalent to azithromycin 250 mg and 500 mg.

Additional ingredients:

MCC PH 102, Cross Carmellose Sodium, Colloidal Anhydrous Silicon, Sodium Lauryl Sulphate, Povidone K -90, IPA, Magnesium Stearate.

INDICATIONS:

Infections caused by microorganisms sensitive to azithromycin:

> Infections of ENT-organs (bacterial pharyngitis/tonsillitis, sinusitis, otitis media); > Infections of respiratory tract (bacterial bronchitis, out hospital pneumonia); > Infections of skin and soft tissues: erythema migrans (initial stage of Lyme disease), erysipelas, impetigo, secondary pyodermatosis.

Sexually transmitted infections:

Uncomplicated and complicated urethritis/cervicitis caused by Chlamydia trachomatis.

DOSAGE:

The preparation should be surely taken one hour before or two hours after meal, because synchronous use increases the absorption of azithromycin. The preparation is used 1 time per day.

Adults, including elderly patients, and children with body weight over 45 kg:

The preparation should be surely taken one hour before or two hours after meal, because synchronous use increases the absorption of azithromycin. The preparation is used 1 time per day. Tablets are swallowed without chewing.

Infections of ENT-organs, respiratory tract, skin and soft tissues (except of erythema migrans):

500 mg per day during 3 days.

Erythema migrans:

Adults – 1 time per day during 5 days, 1 g is in the first day following 500 mg in the 2d to 5th day.

Sexually transmitted infections:

Uncomplicated and complicated urethritis/cervicitis – 1 g of the preparation as a single use. Course dose – 1 g. In case of missed dose it should be taken as soon as possible and the following ones – at interval of 24 hours.

Renal insufficiency:

There is no need to change dosage to patients with minor renal dysfunction (creatinine clearance > 40 ml/min). There has not been any study in patients with creatinine clearance < 40 ml/min. Therefore, it is necessary to use azithromycin to those patients.

Liver impairment:

As azithromycin is metabolized in liver and excreted with bile, the preparation should not be used to patients with severe hepatic disease.

ADVERSE REACTIONS:

Rare – thrombocytopenia.

There were single reports about periods of transistor insignificant neutropenia. However, a causal relationship with azithromycin treatment has not been confirmed.

Psychics:

Rare – aggressiveness, anxiety, nervousness.

Central nervous system:

In single cases – dizziness/vertigo, somnolence, syncope, headache, convulsions (it was found that they are caused by other macrolide antibiotics), disturbance of taste and nose, rare – paresthesia, asthenia, insomnia.

Ear:

Rare – it was reported that macrolide antibiotics cause hearing impairment. It was reported about hearing disorders, appearance of deafness and tinnitus in some patients who took azithromycin. Most of these cases are related to experimental studies in which azithromycin was used in large doses for a long time. According to available reports about further medical observation most of these problems had a reversible nature.

Cardiovascular system:

Rare – palpitation sensation, arrhythmia with associated ventricular tachycardia (it was found that they are also caused by other macrolide antibiotics). There have been rare reports of QT lengthening and torsade de pointes ventricular, arterial hypotension.

Gastro-intestinal tract:

Often – nausea, vomiting, diarrhoea, sense of discomfort (pain/convulsions); infrequently – infrequent defecation, meteorism, indigestion, anorexia, dyspepsia, rare – constipation, tongue discoloration, pancreatitis. Pseudomembranous colitis has been reported.

Liver and gallbladder:

Rare – hepatitis and cholestatic jaundice, including abnormal liver function tests indices, in single cases – rare cases of necrotic hepatitis and liver dysfunction, which led to lethal outcome.

Skin:

Rare – allergic reactions, including itch and rash;

Rare – allergic reactions, including angioneurotic edema, urticaria and photosensitivity; severe skin reactions, namely polymorphic erythema, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Muscular-skeletal system:

Rare – arthralgia.

Urinary system:

Rare – interstitial nephritis and acute renal insufficiency.

Reproductive system:

Rare – vaginitis.

Systemic disturbance:

Rare – anaphylaxis, including edema (in rare cases it leads to death), candidiasis.

Drug interactions:

Azithromycin should be concurrently administered with other medicines, which can lengthen QT interval, to patients with caution.

Antacids:

During the study of the effect of synchronous use of antacids on pharmacokinetics of azithromycin the changes in bioavailability were not generally observed, although the peak plasma concentrations of azithromycin decreased by 30%. Azithromycin should be taken at least 1 hour before or 2 hours after antacid intake.

Carbamazepine:

In the study of pharmacokinetic interaction in healthy volunteers azithromycin did not show a significant effect on plasma levels of carbamazepine or its active metabolites.

Cyclosporine:

Some of affined macrolide antibiotics affect metabolism of cyclosporine. As there have been no pharmacokinetic and clinical studies of possible interactions while taking azithromycin and cyclosporine it should be carefully weighted a therapeutic situation before concurrent use of this preparation. If combination therapy is justified, it is necessary to monitor carefully cyclosporine levels and to adjust dosage correspondingly.

Cumarin anticoagulants:

It was reported about greater tendency to bleeding due to concurrent use of azithromycin and warfarin or coumarin-type oral anticoagulants. Attention should be given to a frequency of monitoring of prothrombin time.

Digoxin:

It was informed that in some patients certain macrolide antibiotics affect digoxin metabolism in intestine. Accordingly, in case of concurrent administration of azithromycin and digoxin it is necessary to remember about a possibility of digoxin concentrations increasing and monitor digoxin levels.

Methylprednisolone:

During the study of pharmacokinetic interactionin in healthy volunteers azithromycin did not show a significant effect on pharmacokinetics of methylprednisolone

Terfenadine:

In pharmacokinetic studies it was not reported about interaction between azithromycin and terfenadine. As well as with other macrolide antibiotics, azithromycin should be carefully administered in combination with terfenadine.

Theophylline:

Azithromycin did not affect pharmacokinetics of theophylline while concurrent use of azithromycin and theophylline in healthy volunteers. Combined use of theophylline and other macrolide antibiotics sometimes caused increased levels of theophylline in serum.

Zidovudine:

1000 mg single doses and 1200 mg or 600 mg multiple-doses of azithromycin had no effect on plasma pharmacokinetics and urinary excretion of zidovudine or glucuronid metabolites. However, azithromycin use increased concentrations of phosphorylated zidovudine, a clinically active metabolite in mononuclear cells in peripheral circulation. Clinical significance of this data is unclear, but may be useful for patients.

Didanosine:

In concurrent use of daily doses of 1200 mg of azithromycin with didanosine there was six subjects had no effect on didanosine pharmacokinetics compared with placebo.

Rifabutin:

Simultaneous use of azithromycin and rifabutin did not affect plasma concentrations of these drugs. Neutropenia was observed in subjects who received both azithromycin and rifabutin.

Although neutropenia was associated with rifabutin use, a causal relationship with simultaneous azithromycin use has not been determined.

Allergic reactions:

In rare cases it was reported that azithromycin had severe allergic (sometimes fatal) reactions, such as angioedema and anaphylaxis. Some of these reactions caused the development of recurrent symptoms and required a longer observation and treatment.

Lenghthened cardiac repolarization and QT interval, which increased the risk of cardiac arrhythmia and torsade de pointes ventricular, were observed during the treatment by other macrolide antibiotics. Such an effect of azithromycin can not be completely excluded in patients with an increased risk of lengthened cardiac repolarization.

Streptococcic infection:

Penicillin is the drug of first choice in the treatment of pharyngitis/tonsillitis caused by Streptococcus pyogenes, as well as in the prevention of acute rheumatic polyarthritis. In general, azithromycin is effective in the treatment of streptococcus in oropharynx, but there is no data which demonstrates the efficacy of azithromycin in the prevention of acute rheumatic polyarthritis.

Superinfection:

As in case of other antibacterial drugs, there is a possibility of superinfection (eg., mycosis).

Overdose:

Symptoms: reversible hearing disorder, expressed nausea, vomiting, diarrhea.

Treatment: In case of overdose it is necessary to take activated carbon and carry out a symptomatic therapy aimed at maintaining of vital body functions.

CONTRAINDICATIONS:

Hypersensitivity to active substance or other component of the preparation or other macrolide antibiotics. Azithromycin should not be concurrently used with ergot derivatives due to theoretical possibility of ergotism.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics:

Azithromycin is a representative of group of macrolide antibiotics, named azalides. It gets bound to 50S subunits of 70S ribosome of sensitive microorganisms, inhibiting RNA-dependent protein synthesis and retards the growth and reproduction of bacteria; bactericidal effect is possible at high concentrations.

It has a wide spectrum of antimicrobial action.

The following microorganisms are sensitive to the preparation:

Gram-positive cocci – Streptococcus pneumoniae, S. pyogenes, S. agalacticae, streptococcus of C, F and G groups, S. viridans; Staphylococcus aureus; Gram-negative bacteria – Haemophilus influenzae, Н. parainfluenzae, Moraxella catarrhalis, Bordetella pertussis, B. parapertussis, Legionella pneumophila, H. ducrei, Campylobacter jejuni, Neisseria gonorrhoeae, Gardnerella vaginalis; some of anaerobic microorganisms – Bacteroides fragilis, Clostridium perfringens, Peptostreptococcus species, а также Chlamydia trachomatis, Mycoplasma pneumoniae, Ureaplasma urealyticum, Treponema pallidum, Borrelia burgdoferi. It does not affect Gram-positive microorganisms resistant to erythromycin.

Pharmacokinetics:

The bioavailability of azithromycin after oral administration is approximately 37%. Its maximal concentration in plasma is reached in 2–3 hours after the preparation use.

In per oral use azithromycin is widely distributed throughout the body.

In pharmacokinetic studies it was shown that azithromycin concentration in tissues is much higher (50 times) than in plasma, indicating a strong preparation binding to tissues.

Serum protein binding varies depending on plasma concentrations and it is from 12% at 0.5 mg/ml and to 52% at 0.05 mg/ml in serum. Imaginary volume of distribution at equilibrium state (VVSS) was 31.1 l/kg. The final period of plasma half life fully displays tissue half life for a period of 2–4 days. Approximately 12% of intravenous dose of azithromycin are excreted with urine as unchanged ones within the next three days. Very high concentrations of unchanged azithromycin were found in human bile. There were also found was found 10 metabolites which were formed by N-and O-demethylation, hydroxylation of desosamine and aglycone rings and splitting of cladinose conjugate in bile. Comparison of the results of liquid chromatography and microbiological analysis showed that the metabolites of azithromycin are not microbiologically active.

PHARMACEUTICAL CHARACTERISTICS:

General physic-chemical properties: Yellow, capsule shaped, film coated tablet with A250 engraved on one side & other side plain.

Shelf-life:

3 years

Storage:

Store in a dry, protected from light place at a temperature not more than 30oC. Keep it out of reach of children.

Package:

Tablets 250 mg: 6 tablets are in a blister; 1 blister is in a carton box

Tablets 500 mg: 3 tablets are in a blister; 1 blister is in a carton box

Conditions of supply:

By prescription.