Azimed powder for oral suspension 200 mg/5 ml bottle 30 ml

Instructions Azimed powder for oral suspension 200 mg/5 ml bottle 30 ml

Composition

active ingredient: azithromycin;

5 ml of suspension contains azithromycin dihydrate equivalent to azithromycin 200 mg;

excipients: sucrose, sodium phosphate, hydroxypropyl cellulose, xanthan gum, colloidal anhydrous silicon dioxide, cherry flavor, banana flavor, vanilla flavor.

Dosage form

Powder for oral suspension.

Main physicochemical properties: white to yellowish-white powder with a characteristic odor of banana, vanilla and cherry.

The reconstituted suspension is a homogeneous suspension from white to light yellow in color with a characteristic odor of banana, vanilla and cherry.

Pharmacotherapeutic group

Antimicrobials for systemic use. Antibacterial drugs for systemic use. Macrolides, lincosamides and streptogramins. Azithromycin.

ATX code J01F A10.

Pharmacological properties

Pharmacodynamics

Azithromycin is a macrolide antibiotic belonging to the azalide group. The molecule is formed by the introduction of a nitrogen atom into the lactone ring of erythromycin A. The mechanism of action of azithromycin is to inhibit bacterial protein synthesis by binding to the 50S subunit of ribosomes and inhibiting peptide translocation.

Mechanism of resistance.

Complete cross-resistance exists among Streptococcus pneumoniae, group A beta-hemolytic streptococcus, Enterococcus faecalis, and Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA), to erythromycin, azithromycin, other macrolides, and lincosamides.

The prevalence of acquired resistance may vary with location and time for the species concerned, so local information on resistance is necessary, especially in the treatment of severe infections. Qualified advice may be sought if the local prevalence of resistance is such that the efficacy of the drug in the treatment of at least some types of infections is questionable.

Spectrum of antimicrobial activity of azithromycin

*Methicillin-resistant Staphylococcus aureus has a very high prevalence of acquired resistance to macrolides and has been listed here because of its rare susceptibility to azithromycin.

Pharmacokinetics

Bioavailability after oral administration is approximately 37%. Maximum serum concentration is reached 2-3 hours after administration.

When taken orally, azithromycin is distributed throughout the body. Pharmacokinetic studies have shown that the concentration of azithromycin in tissues is significantly higher (50 times) than in blood plasma, which indicates strong binding of the drug to tissues.

Serum protein binding varies with plasma concentrations and ranges from 12% at 0.5 μg/mL to 52% at 0.05 μg/mL in serum. The apparent volume of distribution at steady state (VVss) was 31.1 L/kg.

The terminal plasma half-life fully reflects the tissue half-life of 2-4 days.

Approximately 12% of an intravenous dose of azithromycin is excreted unchanged in the urine over the next three days. Particularly high concentrations of unchanged azithromycin have been found in human bile. Ten metabolites have also been found in bile, which are formed by N- and O-demethylation, hydroxylation of the desosamine and aglycone rings, and cleavage of the cladinose conjugate. Comparison of the results of liquid chromatography and microbiological analyses has shown that the metabolites of azithromycin are not microbiologically active.

Indication

Infections caused by microorganisms sensitive to azithromycin:

ENT infections (bacterial pharyngitis/tonsillitis, sinusitis, otitis media);

respiratory tract infections (bacterial bronchitis, community-acquired pneumonia);

Skin and soft tissue infections: erythema migrans (initial stage of Lyme disease), erysipelas, impetigo, secondary pyodermatoses;

Contraindication

Hypersensitivity to azithromycin, erythromycin or any macrolide or ketolide antibiotic, or to any other component of the drug.

Interaction with other medicinal products and other types of interactions

Antacids: When studying the effect of concomitant administration of antacids on the pharmacokinetics of azithromycin, there was generally no change in bioavailability, although the peak plasma concentration of azithromycin was reduced by approximately 25%. Azithromycin and antacids should not be taken simultaneously.

Cetirizine: In healthy volunteers, coadministration of azithromycin for 5 days with cetirizine 20 mg at steady state did not result in any pharmacokinetic interaction or significant changes in the QT interval.

Didanosine: Coadministration of daily doses of 1200 mg azithromycin with 400 mg didanosine per day in six HIV-positive volunteers had no effect on the steady-state pharmacokinetics of didanosine compared to placebo.

Digoxin and Colchicine: Concomitant use of macrolide antibiotics, including azithromycin, and P-glycoprotein substrates such as digoxin and colchicine has been reported to increase serum levels of the P-glycoprotein substrate. Therefore, the possibility of increased serum substrate concentrations should be considered when azithromycin is coadministered with a P-glycoprotein substrate such as digoxin.

Zidovudine. Single doses of 1000 mg and multiple doses of 1200 mg or 600 mg of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolites. However, azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of these findings is unclear but may be useful for patients.

Azithromycin does not have a significant interaction with the hepatic cytochrome P450 system. It is believed that the drug does not have the pharmacokinetic drug interactions characteristic of erythromycin and other macrolides. Azithromycin does not induce or inactivate hepatic cytochrome P450 through the cytochrome-metabolite complex.

Ergot: Due to the theoretical possibility of ergotism, the simultaneous administration of azithromycin with ergot derivatives is not recommended.

Pharmacokinetic studies have been conducted on the use of azithromycin and the following drugs, the metabolism of which occurs to a large extent with the participation of cytochrome P450.

Atorvastatin: Coadministration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter plasma concentrations of atorvastatin (based on HMG CoA reductase inhibition assay). However, postmarketing cases of rhabdomyolysis have been reported in patients receiving azithromycin with statins.

Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the plasma levels of carbamazepine or its active metabolites.

Cimetidine: In a pharmacokinetic study of the effect of a single dose of cimetidine taken 2 hours before azithromycin on the pharmacokinetics of azithromycin, no changes in the pharmacokinetics of azithromycin were observed.

Oral Coumarin Anticoagulants. In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. Postmarketing reports of potentiation of the anticoagulant effect following concomitant administration of azithromycin and oral coumarin anticoagulants have been received. Although a causal relationship has not been established, frequent monitoring of prothrombin time should be considered when prescribing azithromycin to patients receiving oral coumarin anticoagulants.

Cyclosporine: A pharmacokinetic study in healthy volunteers receiving oral azithromycin 500 mg/day for 3 days followed by a single oral dose of cyclosporine 10 mg/kg demonstrated a significant increase in Cmax and AUC0-5 of cyclosporine. Therefore, caution should be exercised when these drugs are used concomitantly. If concomitant use of these drugs is necessary, cyclosporine levels should be monitored and the dose adjusted accordingly.

Efavirenz: Co-administration of a single dose of azithromycin 600 mg and efavirenz 400 mg daily for 7 days did not result in any clinically significant pharmacokinetic interaction.

Fluconazole: Coadministration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. The total exposure and half-life of azithromycin were not altered by coadministration of fluconazole, but a clinically insignificant decrease in Cmax (18%) of azithromycin was observed.

Indinavir: Coadministration of a single dose of azithromycin 1200 mg did not have a statistically significant effect on the pharmacokinetics of indinavir administered at a dose of 800 mg 3 times daily for 5 days.

Methylprednisolone: In a pharmacokinetic interaction study in healthy volunteers, azithromycin did not significantly affect the pharmacokinetics of methylprednisolone.

Nelfinavir. Co-administration of azithromycin (1200 mg) and nelfinavir at steady-state concentrations (750 mg 3 times a day) resulted in increased azithromycin concentrations. No clinically significant adverse events were observed, and no dose adjustment is required.

Rifabutin. Concomitant administration of azithromycin and rifabutin did not affect the serum concentrations of these drugs. Neutropenia has been observed in subjects receiving azithromycin and rifabutin concomitantly. Although neutropenia has been associated with rifabutin, a causal relationship to concomitant azithromycin has not been established.

Sildenafil: In healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolite.

Terfenadine: No pharmacokinetic interaction has been reported between azithromycin and terfenadine. In some cases, the possibility of such an interaction cannot be completely excluded; however, there is no specific data on the existence of such an interaction.

Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are coadministered in healthy volunteers.

Triazolam: Coadministration of azithromycin 500 mg on the first day and 250 mg on the second day with 0.125 mg of triazolam in healthy volunteers had no significant effect on all pharmacokinetic parameters of triazolam compared to triazolam and placebo.

Trimethoprim/sulfamethoxazole: Coadministration of trimethoprim/sulfamethoxazole at a double strength (160 mg/800 mg) for 7 days with azithromycin 1200 mg on day 7 had no significant effect on the maximum concentrations, total exposure, or urinary excretion of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were consistent with those observed in other studies.

Hydroxychloroquine: Azithromycin should be used with caution in patients receiving drugs that prolong the QT interval and may cause cardiac arrhythmias, such as hydroxychloroquine.

Application features

Allergic reactions: As with erythromycin and other macrolide antibiotics, rare serious allergic reactions, including angioedema and anaphylaxis (in isolated cases fatal), and dermatological reactions, including acute generalized exanthematous pustulosis, have been reported. Some of these reactions caused by azithromycin have resulted in recurrent symptoms and have required longer observation and treatment.

Hepatic impairment. Since the liver is the primary route of elimination of azithromycin, caution should be exercised when prescribing azithromycin to patients with severe liver disease. Cases of fulminant hepatitis leading to life-threatening liver failure have been reported with azithromycin. Some patients may have a history of liver disease or may have been taking other hepatotoxic drugs.

Liver function tests should be performed if signs and symptoms of liver dysfunction develop, such as rapidly progressive asthenia accompanied by jaundice, dark urine, bleeding tendency, or hepatic encephalopathy.

If liver function impairment is detected, azithromycin should be discontinued.

Ergot. In patients taking ergot derivatives, the simultaneous use of some macrolide antibiotics contributes to the rapid development of ergotism. There is no data on the possibility of interaction between ergot derivatives and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin should not be prescribed simultaneously with ergot derivatives.

Superinfections: As with other antibiotics, observation for signs of superinfection due to nonsusceptible organisms, including fungi, is recommended.

Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including azithromycin, and has ranged in severity from mild diarrhea to fatal colitis. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. C. difficile strains that hyperproduce toxins are associated with increased morbidity and mortality, as these infections may be resistant to antimicrobial therapy and require colectomy. The possibility of CDAD should be considered in all patients with antibiotic-associated diarrhea. Careful medical history is required, as CDAD has been reported to occur within two months of antibiotic administration.

Prolongation of cardiac repolarization and QT interval, which increased the risk of cardiac arrhythmia and ventricular fibrillation (torsade de pointes), has been observed with other macrolide antibiotics, including azithromycin. Since conditions associated with an increased risk of ventricular arrhythmias (including torsade de pointes) may lead to cardiac arrest, azithromycin should be administered with caution to patients with pre-existing proarrhythmic conditions (especially women and the elderly), including patients with:

with congenital or registered prolongation of the QT interval;

who are currently being treated with other active substances known to prolong the QT interval, such as antiarrhythmics of classes IA (quinidine and procainamide) and III (dofetilide, amiodarone and sotalol), cisapride and terfenadine, neuroleptics such as pimozide; antidepressants such as citalopram, and fluoroquinolones such as moxifloxacin and levofloxacin;

with electrolyte imbalance, especially in the case of hypokalemia and hypomagnesemia;

with clinically relevant bradycardia, cardiac arrhythmia or severe heart failure.

Myasthenia gravis: Exacerbation of symptoms of myasthenia gravis or new development of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

Streptococcal infections. Penicillin is usually the drug of choice for the treatment of pharyngitis/tonsillitis caused by Streptococcus pyogenes, and is also used for prophylaxis in acute rheumatic fever. Azithromycin is generally effective in the treatment of streptococcal infections of the oropharynx; there are no data demonstrating the efficacy of azithromycin in the prevention of rheumatic fever.

Other.

The safety and effectiveness of intravenous azithromycin for the treatment of infections in children have not been established.

Safety and effectiveness for the prevention or treatment of Mycobacterium Avium Complex in children have not been established.

Azithromycin powder for oral suspension contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

The drug contains sodium phosphate (24.25 mg in 1 ml of suspension). This should be taken into account when prescribing the drug to patients on a controlled sodium diet.

Use during pregnancy or breastfeeding

Pregnancy

There are no adequate data on the use of azithromycin in pregnant women. In animal reproductive toxicity studies, no teratogenic harmful effects of azithromycin on the fetus were noted, however, the drug penetrated the placenta. The safety of azithromycin during pregnancy has not been confirmed. Therefore, azithromycin is prescribed during pregnancy only when the benefit outweighs the risk.

Breastfeeding period

Azithromycin has been reported to pass into human breast milk, but adequate and well-controlled clinical studies to characterize the pharmacokinetics of azithromycin excretion into human breast milk have not been conducted.

Fertility.

Fertility studies have been performed in rats; pregnancy rates were reduced following administration of azithromycin. The relevance of these findings to humans is unknown.

Ability to influence reaction speed when driving vehicles or other mechanisms

There is no evidence that azithromycin can impair the ability to drive or operate other mechanisms, but the possibility of developing adverse reactions such as delirium, hallucinations, dizziness, drowsiness, fainting, and seizures, which may affect the ability to drive or operate other mechanisms, should be taken into account.

Method of administration and doses

Azimed® powder for oral suspension should be taken once a day, at least 1 hour before or 2 hours after a meal.

If you miss a dose of the drug, take the missed dose as soon as possible, and the following doses should be taken at 24-hour intervals.

The package contains a dosing syringe and a spoon. Your doctor will advise you to use a spoon or a syringe. The spoon is marked with 2.5 ml and 5 ml. The syringe has a minimum unit of 0.1 ml.

Children

For infections of the ENT organs and respiratory tract, skin and soft tissues (except chronic migratory erythema), the daily dose of azithromycin is 10 mg/kg body weight, which corresponds to 0.25 ml/kg body weight of the prepared suspension. The duration of treatment is 3 days.

Depending on the child's body weight, the following dosage regimen for Azimed® suspension is recommended:

Preparation and use of suspension

Distilled or boiled and cooled water must be added to the bottle containing the powder.

1. Press the bottle cap down and turn it counterclockwise.

Vial with powder for preparation of 15 ml of oral suspension 200 mg/5 ml: add 8.3 ml of water to the contents of the vial. Shake the contents of the vial thoroughly until a homogeneous suspension is obtained. The volume of the resulting suspension is approximately 20 ml*.

Vial with powder for preparation of 30 ml of oral suspension 200 mg/5 ml: add 14.5 ml of water to the contents of the vial. Shake the contents of the vial thoroughly until a homogeneous suspension is obtained. The volume of the resulting suspension is approximately 35 ml*.

* After dissolving the powder, the vial will contain an additional 5 ml of suspension (to compensate for possible losses of suspension during use).

**Information regarding the volume of the bottle is located on the box and bottle label.

3. Dip the syringe into the suspension and, pulling the piston upwards, measure the required amount of suspension.

4. If there are air bubbles in the syringe, return the drug to the vial and repeat procedure 3.

5. Position the baby as for feeding.

6. Place the tip of the syringe in the child's mouth and slowly expel the contents.

7. Give the child the opportunity to gradually swallow the entire amount.

8. After taking the drug, let the child drink some tea or juice to wash away and swallow any remaining suspension in the oral cavity.

9. Disassemble the used syringe, rinse with running water, dry and store in a dry and clean place together with the drug.

10. After the child has taken the last dose of the drug, the syringe and bottle should be disposed of.

In case of erythema migrans, the duration of treatment is 5 days. On the 1st day, you should take

20 mg/kg body weight of azithromycin, corresponding to 0.5 ml/kg of the prepared suspension. From the 2nd to the 5th day, take 10 mg/kg body weight, corresponding to 0.25 ml/kg of the prepared suspension.

The total course dose is 60 mg/kg.

Azithromycin has been shown to be effective in the treatment of streptococcal pharyngitis in children at a single dose of 10 mg/kg or 20 mg/kg for 3 days. When these two doses were compared in clinical trials, similar clinical efficacy was found, although bacterial eradication was greater with the daily dose of 20 mg/kg. However, penicillin is usually the drug of choice for the prevention of pharyngitis caused by Streptococcus pyogenes and secondary rheumatoid arthritis.

Adults

For infections of the ENT organs and respiratory tract, skin and soft tissues (except chronic migratory erythema), the total dose of azithromycin is 1500 mg: 500 mg once a day. The duration of treatment is 3 days.

For erythema migrans, the total dose of azithromycin is 3 g: 1 g should be taken on day 1, then 500 mg once a day from day 2 to day 5. The duration of treatment is 5 days.

Elderly patients.

There is no need to change the dosage for elderly people.

Since elderly patients may be at risk for cardiac conduction disorders, caution is recommended when using azithromycin due to the risk of developing cardiac arrhythmias and torsade de pointes.

Patients with renal impairment.

In patients with mild renal impairment (glomerular filtration rate 10-80 ml/min), the same dosage can be used as in patients with normal renal function. Azithromycin should be administered with caution to patients with severe renal impairment (glomerular filtration rate < 10 ml/min).

Patients with impaired liver function.

Since azithromycin is metabolized in the liver and excreted in the bile, the drug should not be used in patients with severe hepatic impairment. Studies related to the treatment of such patients with azithromycin have not been conducted.

Children

Use in children weighing more than 15 kg. Children weighing less than 15 kg are recommended to be prescribed Azimed®, 100 mg/5 ml.

Overdose

Clinical experience with azithromycin suggests that adverse reactions occurring at higher than recommended doses are similar to those seen at normal therapeutic doses and may include diarrhoea, nausea, vomiting, and reversible hearing loss. In the event of overdose, administration of activated charcoal and general symptomatic and supportive measures are recommended.

Side effects

The following table lists adverse reactions identified in clinical trials and during post-marketing surveillance with all formulations of azithromycin, by system organ class and frequency. Adverse reactions reported during post-marketing surveillance are in italics. The frequency groups are defined using the following convention: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Information on adverse reactions possibly associated with the prevention and treatment of Mycobacterium Avium Complex is based on data from clinical trials and post-marketing surveillance. These adverse reactions differ in type or frequency from those reported with the immediate-release and long-release formulations.

Adverse reactions possibly associated with the prevention and treatment of Mycobacterium Avium Complex

Expiration date

2 years.

The shelf life of the suspension is 10 days.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Store the prepared suspension in its original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

600 mg of azithromycin in a vial for the preparation of 15 ml of oral suspension or 1200 mg of azithromycin in a vial for the preparation of 30 ml of oral suspension. 1 vial together with a calibrated syringe and a measuring spoon in a pack.

Vacation category

According to the recipe.

Producer

PJSC "Kyivmedpreparat".

Address

Ukraine, 01032, Kyiv, Saksaganskoho St., 139.