Sumamed dispersible tablets 500 mg blister No. 6

Instructions Sumamed dispersible tablets 500 mg blister No. 6

Composition

active ingredient: azithromycin;

1 tablet contains 125 mg or 250 mg, or 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 tablets with a bevel, with a score on one side and embossed “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 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 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.

Based on the results of studies conducted in children, the use of azithromycin for the treatment of malaria is not recommended either as monotherapy or in combination with chloroquine- or artemisinin-based drugs, as superior efficacy compared to antimalarial drugs recommended for the treatment of uncomplicated malaria has not been established.

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.

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: In a study of 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 decreased 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. Clinical monitoring and, if possible, serum digoxin monitoring should be performed during and after azithromycin treatment.

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.

Ergotamine derivatives. Due to the theoretical possibility of ergotism, the simultaneous administration of azithromycin with ergotamine 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.

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 azithromycin 1200 mg did not alter the pharmacokinetics of a single dose of fluconazole 800 mg. 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.

Midazolam: In healthy volunteers, co-administration of azithromycin 500 mg daily for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of midazolam administered as a single 15 mg dose.

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 major 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 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 double-strength trimethoprim/sulfamethoxazole (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.

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

Hypersensitivity

As with erythromycin and other macrolide antibiotics, rare serious allergic reactions, including angioedema and anaphylaxis (in isolated cases fatal), dermatological reactions, including acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis (in isolated cases fatal), and drug reaction with eosinophilia and systemic symptoms, have been reported. Some of these reactions caused by azithromycin have resulted in recurrent symptoms.

If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that allergic symptoms may recur after discontinuation of symptomatic therapy.

Hepatotoxicity

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 dysfunction, 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. 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.

Superinfection

As with other antibiotics, observation for signs of superinfection due to non-susceptible organisms, including fungi, is recommended.

Clostridium difficile-associated diarrhea

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.

Kidney dysfunction

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

QT prolongation

Prolongation of cardiac repolarization and the QT interval, which increases the risk of cardiac arrhythmia and ventricular flutter/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 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 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 infection of the oropharynx; there are no data demonstrating the efficacy of azithromycin in the prevention of rheumatic fever.

Children

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.

Excipients

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

Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially ‘sodium-free’.

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® dispersible tablets are used once a day. 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 tablet should be dissolved in a sufficient amount of liquid, such as water, apple or orange juice (half a glass), stirring until a fine suspension is obtained. After the suspension has been drunk, any residue should also be stirred in a small amount of water and drunk. The prepared suspension can be taken regardless of food intake. The score on the tablet is not intended for dividing the tablet.

Adults, including elderly patients and children weighing >45 kg

For infections of the ENT organs, respiratory tract, skin and soft tissues (except erythema migrans), 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, followed by 500 mg once a day from the 2nd to the 5th day.

For uncomplicated sexually transmitted infections caused by Chlamydia trachomatis, the recommended dose of azithromycin is 1000 mg once.

Elderly patients

Elderly patients do not need to change the dosage.

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.

Patients with renal impairment

For patients with mild to moderate 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 hepatic impairment

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 in children weighing >45 kg, who can be given the adult dose.

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.

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 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 (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

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after a medicinal product has been authorised. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report all suspected adverse reactions through the national pharmacovigilance system.

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.

Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia.