COMPOSITION:

Active substance:

Azithromycin;

1 tablet contains azithromycin dehydrate equivalent to azithromycin 250 mg and 500

mg.

Additional ingredients:

microcrystalline cellulose, sodium croscarmellose, sodium lauryl sulphate, povidon

K90, talk, magnesium stearate, Opadry 04B520691 Yellow coating:

polyethylene glycol, hypromellose, quinoline yellow (E 104), titanium dioxide (E

171).

INDICATIONS:



Infections caused by microorganisms sensitive to azithromycin:

– infections of ENT-organs (bacterial pharyngitis/tonsillitis, sinusitis, otitis media);

– infections of respiratory tract (bacterial bronchitis, outhospital 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:

Blood system:

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.

Pregnancy and lactation:



Due to insufficient number of clinical data it is not recommended to administer

the preparation to pregnant and nursing women (except cases when it is necessary

due to life-saving indication).



Children:



The preparation is not recommended to administer azithromycin drugs in the form

of tablet to children with body weight under 45 kg.

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.

Influence on velocity reactions while driving motor transport and operating

other mechanisms

Data concerning azithromycin effect on the ability to drive motor transport and

other mechanisms is absent. It is necessary to take into account a possibility of

adverse reactions (dizziness, confusion and disorientation) during such works.

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:

Film-coated, capsule-shaped, yellow tablets

with etching of “A 250” or “A 500” on one side and plain on the other one.

Shelf-life:

3 years.

Storage:

Store in a dry, protected from light place at a temperature not more than 25° C.

Keep it out of reach of children.

Package:



Tablets 250 mg:

6 or 21 tablets are in a blister; 1 blister is in a carton box No6

and No21.

Tablets 500 mg:

3 tablets are in a blister; 1 blister is in a carton box No3.

Conditions of supply:



By prescription.