Sumamed dispersible tablets 500 mg blister No. 3

Instructions Sumamed dispersible tablets 500 mg blister No. 3

Composition

active ingredient: azithromycin;

1 tablet contains 125 mg, 250 mg, 500 mg or 1000 mg of azithromycin in the form of azithromycin dihydrate;

excipients: saccharin sodium dihydrate, microcrystalline cellulose, crospovidone (type A), povidone, sodium lauryl sulfate, colloidal anhydrous silicon dioxide, magnesium stearate, aspartame (E 951), 125 mg tablets - banana flavor, 250 mg, 500 mg, 1000 mg tablets - orange flavor.

Dosage form

Dispersible tablets.

Main physicochemical properties:

125 mg tablets: round, flat, white or almost white tablets with a bevel and embossed "TEVA 125" on one side;

250 mg tablets: round, flat, white or almost white, beveled tablets, with a score on one side and embossed with “TEVA 250” on the other;

500 mg tablets: round, flat, white or almost white tablets with a bevel, with a score on one side and embossed “TEVA 500” on the other;

1000 mg tablets: round, flat, white or almost white, beveled tablets, with two perpendicular lines on one side and embossed with “TEVA 1000” on the other.

Pharmacotherapeutic group

Antibacterials for systemic use. Macrolides, lincosamides and streptogramins. Azithromycin. ATC 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 streptococci, 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, therefore local information on resistance is necessary, especially when treating 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 is 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 3 days. Particularly high concentrations of unchanged azithromycin have been found in human bile. Also found in bile are 10 metabolites 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 showed 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);

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

· sexually transmitted infections: uncomplicated genital infections caused by Chlamydia trachomatis.

Contraindication

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

Due to the theoretical possibility of ergotism, azithromycin should not be administered concomitantly with ergot derivatives.

Interaction with other medicinal products and other types of interactions

Azithromycin should be administered with caution to patients taking other drugs that may prolong the QT interval.

Antacids: When studying the effect of concomitant administration of antacids on the pharmacokinetics of azithromycin, there was generally no change in bioavailability, although peak plasma concentrations of azithromycin were reduced by approximately 25%. Azithromycin should be taken at least 1 hour before or 2 hours after taking an antacid.

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

Didanosine: Coadministration of 1200 mg daily doses of azithromycin with didanosine had no effect on the pharmacokinetics of didanosine compared to placebo.

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

Zidovudine. Single doses of 1000 mg and 1200 mg or multiple doses of 600 mg of azithromycin had no 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 unknown.

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

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 observed with erythromycin and other macrolides. Azithromycin does not induce or inactivate hepatic cytochrome P450 via the cytochrome-metabolite complex.

Pharmacokinetic studies have been conducted with azithromycin and the following drugs, the metabolism of which is largely mediated by cytochrome P450.

Atorvastatin: Concomitant administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter plasma concentrations of atorvastatin (based on an HMG CoA reductase inhibition assay).

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. There have been postmarketing reports of potentiation of the anticoagulant effect following concomitant administration of azithromycin and oral coumarin anticoagulants. Although a causal relationship has not been established, prothrombin time should be monitored when azithromycin is administered to patients receiving oral coumarin anticoagulants.

Cyclosporine. Some of the related macrolide antibiotics affect the metabolism of cyclosporine. Since pharmacokinetic and clinical studies of the possible interaction with the simultaneous use of azithromycin and cyclosporine have not been conducted, the therapeutic situation should be carefully considered before prescribing concomitant treatment with these drugs. If combination therapy is considered justified, cyclosporine levels should be carefully monitored and the dosage 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.

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

Midazolam: In healthy volunteers, concomitant administration of azithromycin 500 mg daily for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of midazolam.

Nelfinavir: Concomitant administration of azithromycin (1200 mg) and nelfinavir at steady-state concentrations (750 mg 3 times daily) resulted in increased azithromycin concentrations. No clinically significant adverse events were observed, therefore, 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: There was no evidence of an effect of azithromycin (500 mg daily for
3 days) on the AUC and Cmax of sildenafil or its main circulating metabolite in healthy male volunteers.

Terfenadine: No pharmacokinetic interaction has been reported between azithromycin and terfenadine. The possibility of such an interaction cannot be completely ruled out; however, there is no evidence of such an interaction.

Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction with the simultaneous use of azithromycin and theophylline.

Triazolam: Coadministration of azithromycin 500 mg on the first day and 250 mg on the second day with 0.125 mg of triazolam did not significantly affect 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 peak concentrations, total exposure, or urinary excretion of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were consistent with those observed in other studies.

Application features

Allergic reactions: As with erythromycin and other macrolide antibiotics, rare serious allergic reactions, including angioedema and anaphylaxis (in isolated cases fatal), have been reported. Some of these reactions caused by azithromycin have resulted in recurrent symptoms and have required prolonged 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, resulting in life-threatening liver failure, have been reported in patients receiving azithromycin. Some patients may have had a history of liver disease or were taking other hepatotoxic drugs.

Liver function tests should be performed if 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 an interaction between ergot 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 overproduce the 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. A careful history should be taken, as CDAD has been reported to occur within 2 months of antibiotic therapy.

Renal impairment: In patients with severe renal dysfunction (glomerular filtration rate <10 mL/min), a 33% increase in systemic exposure to azithromycin was observed.

with congenital or documented prolongation of the QT interval; who are currently being treated with other active substances that 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 disturbances, 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. 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. An antimicrobial agent with anaerobic activity should be given in combination with azithromycin if anaerobic organisms are suspected to be causing the infection.

Other.

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

The drug contains aspartame, a derivative of phenylalanine, which is dangerous for patients with phenylketonuria.

Use during pregnancy or breastfeeding

Pregnancy.

There are no adequate and well-controlled studies in pregnant women. Azithromycin should be used during pregnancy only if clearly needed.

breast-feeding.

Azithromycin has been reported to pass into human milk, but adequate and well-controlled clinical studies that would characterize the pharmacokinetics of azithromycin excretion into human breast milk have not been conducted. Azithromycin should be used during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the child.

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 dizziness, drowsiness, and visual disturbances should be taken into account.

Method of administration and doses

It is administered orally, 1 hour before or 2 hours after meals. 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.

The dispersible tablet is pre-dissolved in at least 50 ml of water. The resulting suspension should be thoroughly stirred before use.

Adults and children aged 12 years and over with a body weight ≥45 kg.

For infections of the ENT organs, respiratory tract, skin and soft tissues (except chronic migratory erythema), the total dose of azithromycin is 1500 mg (500 mg 1 time per day). The duration of treatment is 3 days.

For erythema migrans, the total dose of azithromycin is 3 g, which should be taken according to the following scheme: 1000 mg on the first day, then 500 mg once a day for
5 days.

For sexually transmitted infections, the recommended dose of azithromycin is 1000 mg once.

Children aged 3-12 years with a body weight < 45 kg.

For infections of the ENT organs, respiratory tract, skin and soft tissues (except chronic migratory erythema), azithromycin is used at the rate of 10 mg/kg of body weight once a day for 3 days (the total dose of azithromycin is 30 mg/kg).

Dose calculation for children weighing < 45 kg

Children under 3 years of age are recommended to use "Sumamed®", powder for oral suspension 100 mg/5 ml, or "Sumamed® forte", powder for oral suspension 200 mg/5 ml. For pharyngitis/tonsillitis caused by Streptococcus pyogenes, Sumamed® is used at a dose of 20 mg/kg/day for 3 days (course dose 60 mg/kg). The maximum daily dose is 500 mg/day.

For erythema migrans, azithromycin is used at a dose of 20 mg/kg once daily on the first day, followed by 10 mg/kg once daily from the 2nd to the 5th day.

For the convenience of using a course dose of 60 mg/kg, children are recommended to use "Sumamed" powder for oral suspension 100 mg/5 ml, or "Sumamed" forte, powder for oral suspension 200 mg/5 ml.

Elderly patients.

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

Since elderly patients may have impaired electrical conduction of the heart, caution is recommended when using azithromycin due to the risk of developing cardiac arrhythmias and torsade de pointes.

For patients with mild renal impairment (glomerular filtration rate 10-80 ml/min), the same doses can be used as for 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 use of azithromycin in such patients have not been conducted.

Children

Used for children aged 3 years and over.

Overdose

Clinical experience with azithromycin suggests that adverse reactions occurring at higher than recommended doses are similar to those seen at usual therapeutic doses. These 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.

Adverse reactions

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

Adverse reactions possibly related to azithromycin based on data obtained during clinical trials and during post-marketing surveillance

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

Expiration date

2 years.

Storage conditions

The medicine does not require any special storage conditions. Keep out of the reach of children.

Packaging

Tablets 125 mg, 250 mg: 6 tablets in a blister, 1 blister in a box.

500 mg tablets: 3 tablets in a blister, 1 or 2 blisters in a box.

1000 mg tablets: 1 tablet in a blister, 1 or 3 blisters in a box.

Vacation category

According to the recipe.

Producer

PLIVA Hrvatska d.o.o.

Location of the manufacturer and its business address

Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.