Sumamed capsules 250 mg No. 6

Instructions for Sumamed capsules 250 mg No. 6

Composition

active ingredient: azithromycin;

1 capsule contains 250 mg of azithromycin in the form of dihydrate;

excipients: microcrystalline cellulose, sodium lauryl sulfate, magnesium stearate, gelatin, titanium dioxide (E 171), indigo carmine (E 132), sulfur dioxide (E 220).

Dosage form

Capsules.

Main physicochemical properties: hard gelatin capsules No. 1 with an opaque blue body and an opaque blue cap; capsule contents: white to yellowish crystalline powder or a lump of white to yellowish crystalline powder.

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 streptococcus, Enterococcus faecalis, and Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA), to erythromycin, azithromycin, other macrolides, and lincosamides.

The prevalence of acquired resistance for selected species may vary with location and time, therefore local information on resistance is required, particularly when treating severe infections. Qualified advice may be sought if the local prevalence of resistance is such that the efficacy of the drug in treating 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 concentrations are 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);

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

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.

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 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 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 unknown 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 had no 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. Concomitant 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

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 required longer observation and treatment.

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 with azithromycin. Some patients may have had a history of liver disease or were 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. Azithromycin should be discontinued if liver function abnormalities are detected.

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 and azithromycin. However, due to the theoretical possibility of ergotism, azithromycin should not be prescribed simultaneously with ergot derivatives.

As with other antibiotics, observation for signs of superinfection due to non-susceptible 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. Careful medical history is required, as CDAD has been reported to occur within 2 months of antibiotic therapy.

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 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.

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 oropharyngeal infections; however, there are no data demonstrating the efficacy of azithromycin in the prevention of rheumatic fever.

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.

Use during pregnancy or breastfeeding

Pregnancy.

There are no adequate data on the use of azithromycin in pregnant women. In animal reproductive toxicity studies, azithromycin did not show teratogenic effects on the fetus, but the drug crossed the placenta. The safety of azithromycin during pregnancy has not been established. Therefore, azithromycin should be used during pregnancy only if the benefit outweighs the risk.

Breast-feeding.

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

Sumamed® should be taken 1 hour before or 2 hours after meals, as simultaneous administration disrupts the absorption of azithromycin. The capsules should be swallowed whole. The drug should be taken once a day.

Adults and children weighing ≥45 kg.

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: on the 1st day, 1 g (4 capsules at a time) should be taken, then 500 mg (2 capsules at a time) from the 2nd to the 5th day. The duration of treatment is 5 days.

For sexually transmitted infections: the total dose of azithromycin is 1 g (4 capsules at a time).

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.

Elderly patients.

There is no need to change the dosage in elderly patients.

Since elderly patients may be at risk for cardiac conduction abnormalities, caution is recommended when using azithromycin due to the risk of cardiac arrhythmia 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 using azithromycin have not been conducted.

Children.

Sumamed® capsules should be used in children weighing ≥45 kg.

Overdose

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

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 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 (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Adverse reactions possibly or probably 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 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

The drug contains sulfur dioxide (E 220), so it may rarely cause hypersensitivity reactions and bronchospasm.

Expiration date

3 years.

Storage conditions

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Packaging

6 capsules in a blister, 1 blister in a cardboard box.

Vacation category

According to the recipe.

Producer

PLIVA Hrvatska d.o.o.

Address

Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.