International non-proprietary name: Azithromycin

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Composition

Active substance: 1 tablet contains azithromycin dihydrate equivalent to 500 mg of azithromycin

there is

Auxiliary substances: microcrystalline cellulose, sodium lauryl sulfate, gelatinized starch (starch 1500),

croscarmellose sodium, starch sodium glucolate (type A), microcrystalline cellulose

(PH 102), refined talc, magnesium stearate, white coloring SC-SP 3180,

purified water.

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Description

White or off-white, oblong, biconvex, coated tablets marked  on one side and smooth on the other.

 

Pharmacotherapeutic group

Antibacterial agent for systemic use. Macrolides.

ATC-code:J01FA10...

 

pharmacological properties

Pharmacodynamics

Azithromycin is a drug belonging to the azalide group of macrolide antibiotics with a wide spectrum of action. By combining with the 50S subunit of bacterial ribosomes, it prevents the translocation of peptides and inhibits the protein biosynthesis of sensitive microorganisms... It does not affect nucleic acid synthesis.

In in vitro studies, after 1-hour incubation of azithromycin in phagocytic cells and fibroblast cells, its intracellular concentration increased by 30 times (and more) compared to the cell environment.

Due to its high affinity for phagocytes, better transport of the drug to infected tissues is observed during in vivo administration.

Azithromycin is active against various gram-positive and gram-negative microorganisms, anaerobes, intracellular and clinical atypical pathogens. Sensitive microorganisms under in vitro conditions:

Aerobic gram-positive bacteria: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus spp. (belonging to group C, F and G), Streptococcus agalactiae, Streptococcus viridans, Staphylococcus aureus.

Aerobic gram-negative bacteria: Heamophilus ducreyi, Heamophilus influenzae, Moraxella catarrhalis, Bordetella pertussis, Bordetella parapertussis, Legionella pneumophila, Helicobacter pylori, Campylobacter jejuni, Neisseria gonorrhoeae, Gardnerella vaginalis, Pasteurella multocida.

Anaerobic bacteria: Bacteroides bivius, Clostridium perfringens, Peptostreptococcus spp.

Azithromycin is also active against Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Ureaplasma urealyticum, Treponema pallidum, Borrelia burgdorferi.

Pharmacokinetics

Being asked

Azithromycin is rapidly absorbed from the gastrointestinal tract after oral administration.

This is due to its resistance to acidic environment and lipophilicity. After a single dose of 500 mg, bioavailability is about 37% (34-52%; "first pass" effect from the liver).

Distribution

Its combination with plasma proteins is 7-50%.

Depending on the plasma concentration of azithromycin, the serum concentration varies from 12% at 0.5 μg azithromycin/ml to 52% at 0.05 μg azithromycin/ml. The volume of distribution (Vd) at equilibrium is 31.1 l/kg.

Penetration into tissue and fluids

After internal administration, it penetrates well into organs and tissues (widely distributed). Its concentration in tissues and cells is significantly higher than its level in plasma (10-50 times), which indicates that it is tightly bound to tissues. Azithromycin easily passes through histohematological barriers, penetrates well into the respiratory tract, urinary tract, genital organs and tissues (including the prostate gland), skin and soft tissues. It is delivered by phagocytes (polymorphonuclear leukocytes and macrophages) to the site of infection, where it is released in the presence of bacteria. Accumulation of high concentrations in cells (easily penetrates cell membranes) is critical for destruction and elimination of intracellular pathogens.

It has been proven that the concentration of azithromycin in the foci of infection is 24-34% higher than in healthy tissues and varies depending on the severity of the inflammatory process. Although azithromycin creates a high concentration in phagocytes, it does not significantly affect their function. The drug maintains the bactericidal concentration in the inflammatory site for 5-7 days after the last dose, which allows for a short treatment course of 3 and 5 days.

Metabolism

It is metabolized (demethylated) in the liver with the formation of inactive metabolites. CYP3A4, CYP3A5, CYP3A7 isoenzymes are involved in the metabolism of azithromycin. Plasma clearance - 630 ml/min: the half-life (t½) between 8 and 24 hours after administration is 14-20 hours, and between 24 and 72 hours is 41 hours, which makes it possible to take the drug once a day.

Exclusion

The half-life of azithromycin is 68-72 hours.

More than 50% of the received dose is excreted unchanged from the intestine, 6% with the kidneys. Food intake significantly changes the pharmacokinetics of azithromycin - Cmax increases by 31%, AUC does not change. In elderly men (65-85 years), pharmacokinetic indicators, and in women, Cmax increases by 30-50%.

 

Instructions for use

Azithromycin is indicated in the treatment of infectious-inflammatory diseases caused by microorganisms sensitive to:

• Upper respiratory tract infections (tonsillitis, pharyngitis, sinusitis).

• When allergic to penicillin, pharyngitis and tonsillitis caused by Streptococcus pyogenes.

• Lower respiratory tract infections (bronchitis, tracheitis, bacterial and atypical pneumonias)...

• Middle ear infections (acute otitis media).

• Skin and soft tissue infections (moderate acne (acne vulgaris), measles, abscess, impetigo, furuncle, "chronic migrating erythema" (erythema migrans, the initial stage of Lyme disease), secondary pyoderma).

• Sexually transmitted diseases caused by Chlamydia trachomatis (uncomplicated urethritis and cervicitis).

• Soft tissue ulcer caused by Haemophilus ducreyi.

• Sexually transmitted diseases caused by Neisseria gonorrhoeae (without other co-infections).

• Diseases of the stomach and duodenum associated with Helicobacter pylori.

 

Contraindications

Hypersensitivity to azithromycin or other antibacterial agents from the macrolide group (for example, erythromycin, clarithromycin), as well as any of the auxiliary substances (allergic reactions may cause skin rash and wheezing).

Severe liver failure.

Taking derivatives of ryegrass alkaloids such as ergotamine (used to treat migraines).

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Special instructions and precautions

The drug should be used with caution in the following cases:

• kidney diseases;

• heart diseases;

• epidemic infectious diseases;

• diagnosis or suspicion of infection of bacteria or bacterial toxins into the blood (septicemia);

• bed sickness;

• elderly and weak patients;

• other serious diseases (insufficiency of the immune system or congenital asplenia (absence of the spleen)/removal of the spleen through surgical intervention (asplenia), etc.);

• liver diseases;

• as with other antibacterial agents, the risk of secondary infection (caused by microorganisms insensitive to the drug, including fungi) in weakened patients;

• diarrhea.

If any of the above conditions occur, consult a doctor.

Precautions

Cardiac conduction disturbances: Macrolides can cause QT prolongation and ventricular arrhythmias (including torsade de pointes). It should be used with caution in patients with prolonged cardiac repolarization.

Allergic reactions: Macrolides can cause serious allergic reactions (rarely fatal) such as Quincke's edema (angioneurotic edema) or anaphylaxis.

Superinfection: As with other antibacterial agents, Clostridium difficile-associated diarrhea (CDAD) may occur during or after the use of azithromycin.

Hepatic impairment: As azithromycin is mainly eliminated via the liver, it should be used with extreme caution in patients with hepatic impairment.

Renal failure: The drug should be prescribed with caution in patients with severe renal impairment (glomerular filtration rate (GFR) <10 ml/min).

Streptococcal infections: Penicillin is the drug of first choice for the treatment of pharyngitis and tonsillitis, usually caused by Streptococcus pyogenes, as well as for the prevention of rheumatic fever. However, azithromycin is successfully used in the treatment of pharyngitis and tonsillitis.

Acute otitis media, sinusitis: Azithromycin is used successfully, although it is not the first choice drug for the treatment of acute otitis media and sinusitis.

 

Interaction with other drugs

Macrolides may increase plasma levels of drugs such as digoxin, theophylline, triazolam, phenytoin, carbamazepine, methylprednisolone, cyclosporine, and hexobarbital; it would be good to monitor when they are used together with azithromycin, although there is no information on the interaction of azithromycin with the above drugs.

Antacids: Aluminum and magnesium-containing antacids reduce the maximum plasma concentration of azithromycin, but the area under the "concentration-time" curve (AUC) does not change. Azithromycin should be taken at least 1 hour before or 2 hours after taking antacids.

Ergotamine or other rye alkaloids: When azithromycin is used in combination with ergotamine or non-hydrogenated rye alkaloids, serious toxic effects characterized by severe peripheral vasospasm (numbness or numbness in the upper and lower extremities, muscle spasms, headache, convulsions, chest pain or abdominal pain) should be consulted with a doctor before using at the same time.

Digoxin and colchicine (P-glycoprotein substrates): Macrolides, including azithromycin, may increase plasma levels of P-glycoprotein substrates such as digoxin and colchicine. During treatment with azithromycin and after discontinuation of treatment, clinical observation and monitoring of serum digoxin levels should be performed.

Drugs metabolized by the cytochrome P450 system: Azithromycin does not interact significantly with the cytochrome P450 system in the liver. Therefore, interactions known for erythromycin and other macrolides are not expected for azithromycin. Azithromycin does not induce or inactivate the cytochrome P450 system in the liver with the help of the cytochrome-metabolite complex. In clinical studies, no significant interactions between the following drugs metabolized by cytochrome P450 and azithromycin were found: atorvastatin, carbamazepine, efavirenz, fluconazole, indinavir, methylprednisolone, midazolam, sildenafil, triazolam, trimethoprim/sulfamethoxazole. However, caution should be exercised when using these drugs in combination with azithromycin.

Cisapride: Metabolized in the liver by the enzyme CYP3A4. Macrolides inactivate the CYP3A4 enzyme; simultaneous use of cisapride can cause prolongation of the QT interval, ventricular arrhythmia, as well as ventricular fibrillation. Azithromycin should not be used together with cisapride.

Atorvastatin or other statins: Azithromycin (500 mg/day) did not affect the plasma concentration of atorvastatin when administered concurrently with atorvastatin (10 mg/day). However, cases of rhabdomyolysis have been reported in patients taking azithromycin together with statins. 

Vitamin K antagonists (warfarin): Macrolides can increase the maximum concentration of vitamin K antagonists in blood serum and the anticoagulant effect. Even if a causal relationship has not been proven, prothrombin time monitoring should be considered. Caution should be exercised when taking azithromycin and warfarin together.

Tacrolimus: Macrolides may increase the maximum concentration of tacrolimus in blood serum.

Terfenadine: Azithromycin should be used with caution in combination with terfenadine.

Cyclosporine: In pharmacokinetic studies in healthy volunteers, Cmax and AUC of cyclosporine were significantly increased in patients receiving oral azithromycin 500 mg daily for 3 days, followed by cyclosporine 10 mg/kg intravenously as a single dose. Therefore, caution should be exercised during the joint use of these drugs. If it is necessary to use these drugs together, then it is necessary to monitor the level of ciclosporin and adjust the dose accordingly. 

Other antibiotics: The possibility of parallel resistance between azithromycin and macrolide antibiotics (eg, erythromycin), as well as lincomycin, clindamycin should be considered. Therefore, it is not recommended to use several drugs from this group together.

Drugs that prolong the QT interval: Azithromycin should not be used simultaneously with drugs that prolong the QT interval (for example, antiarrhythmic drugs of class IA and III, tricyclic antidepressants, fluoroquinolones, neuroleptics).

Zidovudine or nelfinavir: Azithromycin may increase the concentration of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. Co-administration of azithromycin with nelfinavir increases the risk of unwanted effects.

Rifabutin: When azithromycin and rifabutin were taken together, the plasma concentration of both drugs did not change, but neutropenia (a decrease in the number of blood cells) was observed in patients.

 

Use during pregnancy and lactation

Consult your doctor before taking any medication during pregnancy.

Pregnancy category: B.

There is insufficient data on the use of azithromycin in pregnant women. It should be used during pregnancy only if necessary.

If you become pregnant during treatment, inform your doctor.

Lactation period

Complete information on the excretion of azithromycin in breast milk is not available. If it is necessary to use the drug during lactation, breastfeeding should be temporarily stopped.

 

Effects on the ability to drive vehicles and other potentially dangerous mechanisms

It doesn't affect.

 

Method of use and dosage

Intended for internal admission only.

Tempazit coated tablets should be taken as a single dose 1 hour before or 2 hours after food.

Children and adolescents, adults and the elderly with a body weight of more than 45 kg

Upper and lower respiratory tract infections, skin and soft tissue infections (except erythema migrans)

The total dose of azithromycin is 1500 mg and 500 mg (1 tablet) is taken once a day for 3 days. Alternatively, the total dose can be divided into five days (500 mg on the first day of treatment, and 250 mg 1 time per day on days 2-5).

Moderate acne (acne vulgaris)

The total dose of azithromycin is 6 g, and the following treatment regimen is recommended: 500 mg once a day for 3 days, 500 mg once a week for the next 9 weeks. The second week's dose should be taken 7 days after the first tablet, and the next 8 doses should be taken at 7-day intervals.

Early stage of Lyme disease (erythema migrans - "chronic migrating rash")

The total dose of azithromycin is 3 g... 1000 mg on the first day of treatment (two 500 mg tablets as a single dose), 500 mg once a day on days 2-5.

In case of genital infections caused by Chlamydia trachomatis and sensitive Neisseria gonorrhoeae (uncomplicated urethritis and cervicitis), 1000 mg (two 500 mg tablets) is taken as a single dose.

Stomach and duodenal diseases associated with Helicobacter pylori: a single dose of 1000 mg (two 500 mg tablets) for 3 days is prescribed as part of combined treatment.

Soft tissue ulcer caused by Haemophilus ducreyi: 1000 mg (two 500 mg tablets) taken orally as a single dose.

During tonsillitis/pharyngitis caused by S. pyogenes, 500 mg on the first day, 250 mg on the following days (days 2-5) are prescribed for 5 days.

Use in different age groups

Pediatric patients

For children with a body weight of more than 45 kg, the dose used in adults is prescribed.

With the exception of tonsillitis/pharyngitis, the maximum recommended total dose for the treatment of other diseases is 1500 mg. In the treatment of tonsillitis/pharyngitis, 500 mg is prescribed on the first day, 250 mg on the following days (days 2-5).

Children weighing less than 45 kg should be prescribed the suspension form of azithromycin.

Elderly patients

Elderly patients are prescribed in the dose intended for adults.

As there are risk factors for the occurrence of arrhythmias in the elderly, caution should be exercised regarding the risk of cardiac rhythm disturbances and the development of ventricular tachycardia of the "pirouette" type.

Patients with kidney failure

No dose adjustment is needed in patients with mild to moderate renal impairment (creatinine clearance >40 ml/min). Azithromycin should be prescribed with caution in patients with severe renal insufficiency (creatinine clearance <40 ml/min).

Patients with liver failure

Dosing in patients with mild to moderate hepatic impairment is the same as in patients with normal liver function. The drug should not be used in case of severe liver failure.

If you forget to take the drug

If you forget to take the drug, you should not worry, you can take the dose as early as possible and then continue taking the drug as usual.

A double dose should not be taken instead of the forgotten dose.

 

Side effects

As with all medicines, there may be unwanted side effects in people who are sensitive to any of the ingredients in the preparation.

Azithromycin is usually well tolerated by the body. Side effects are usually mild and transient. Serious adverse reactions are very rare. Observed additional reactions are classified according to organ systems and frequency of occurrence as follows: very often (≥1/10); often (≥1/100 to <1/10); sometimes (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10000); with an unknown frequency (the available data are insufficient to determine the frequency of occurrence).

Blood and lymphatic system

Rare: thrombocytopenia (a decrease in the number of platelets in the peripheral blood), eosinophilia, mild transient neutropenia (but the causal relationship with azithromycin intake has not been confirmed).

To the immune system

Uncommon: angioneurotic edema.

Not known frequency: severe (sometimes fatal) anaphylactic reaction, such as anaphylactic shock.

Mental disorders

Rare: aggressiveness, anxiety, agitation, irritability.

To the nervous system

Sometimes: dizziness (vertigo), drowsiness, headache, convulsions, dysgeusia.

Rare: paresthesia, asthenia, insomnia, hyperactivity.

To the organ of hearing and the labyrinth system

Rare: hearing impairment or loss, tinnitus.

To the cardiovascular system

Rare: tachycardia, arrhythmia associated with ventricular tachycardia.

To the digestive system

Often: nausea, vomiting, diarrhea, abdominal pain, cramps.

Sometimes: flatulence, dyspepsia, anorexia.

Rare: constipation, tongue discoloration, pseudomembranous colitis.

To the liver and bile ducts

Rare: hepatitis, cholestatic jaundice, liver dysfunction.

Not known frequency: liver failure, rarely fatal liver necrosis.

To the skin and subcutaneous adipose tissue

Sometimes: rash, itching.

Rare: angioneurotic edema, urticaria, photosensitivity reactions.

With unknown frequency: Stevens-Johnson syndrome, toxic epidermal necrolysis, multiform exudative erythema.

To the musculoskeletal system, connective tissue

Sometimes: arthralgia.

To the kidney and urinary tract

Rare: interstitial nephritis, acute renal failure.

To the genitals and mammary glands

Sometimes: vaginitis.

General disorders and local reactions

Sometimes: reactions at the injection site (pain, redness).

Consult your doctor if unwanted effects occur.

If you experience any side effects not listed in this leaflet, tell your doctor...

 

Overdose

Symptoms

Typical symptoms of macrolide antibiotic overdose include reversible hearing loss, severe nausea, vomiting, and diarrhea (diarrhea).

Treatment

General symptomatic and supportive therapy should be carried out.

 

Release form

Coated tablets, 500 mg.

3 tablets, in a blister. 1 blister is packed in a cardboard box with an insert.

 

Storage conditions 

It should be stored at a temperature not higher than 25°C, protected from light and out of the reach of children.

 

Expiry date

3 years.

Do not use after expiration date.

 

Condition of release from pharmacy

It is released on the basis of a prescription.

 

Producer

Opes Healthcare Pvt. Ltd., India...

G-203, Shri kabir Enclave, OPP. Homeopathic college, Bopal Ghuma Road, Ghuam, Ahmedabad-380058, Gujarat...

 

Holder of registration card

TEMPUS LLC

Javadkhan str. 5 micro district, home 11, flat 60, Nasimi dist., AZ 1102 - Baku city, Azerbaijan