Zoksi tablets 500mg No. 3

Instructions for Zoksi tablets 500mg No. 3

Warehouse

active ingredient: azithromycin;

1 tablet contains azithromycin dihydrate equivalent to azithromycin 250 mg or 500 mg;

excipients: calcium hydrogen phosphate anhydrous, sodium lauryl sulfate, croscarmellose sodium, pregelatinized starch, magnesium stearate, Opadry White film coating (hypromellose, titanium dioxide (E 171)).

Dosage form

Film-coated tablets.

Main physicochemical properties:

film-coated tablets, 250 mg: film-coated tablets, white, oval-shaped, debossed with “2” on one side and “AZI” on the other side;

Film-coated tablets, 500 mg: white, oval-shaped, film-coated tablets debossed with “5” and a breakline on one side and “AZI” on the other side.

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 the ribosome and inhibiting the translocation of peptide chains from one ribosome subunit to another.

Mechanism of resistance

Resistance to azithromycin can be congenital or acquired. There are three main mechanisms of bacterial resistance: alteration of the target site, alteration of antibiotic transport, and modification of the antibiotic.

Azithromycin exhibits cross-resistance with erythromycin-resistant Gram-positive isolates. Decreased susceptibility to macrolides over time has been observed, in particular, in Streptococcus pneumoniae and Staphylococcus aureus. Similarly, decreased susceptibility of Streptococcus viridans and Streptococcus agalactiae (group B) to other macrolides and lincosamides has been observed.

Azithromycin susceptibility breakpoints for typical bacterial pathogens published by EUCAST

The prevalence of acquired resistance may vary geographically and over time for individual species, so it is advisable to have local information on resistance, particularly when treating severe infections. Expert advice should be sought if the local prevalence of resistance is such that the utility of the agent in 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.

Absorption.

Bioavailability after oral administration is approximately 37%. Maximum serum concentration is reached 2-3 hours after administration. Cmax after a single dose of 500 mg of the drug is 0.4 μg/ml.

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 (the apparent volume of distribution at steady state (VVss) was 31.1 l/kg). When taken in recommended doses, the drug does not accumulate in plasma/serum. According to research data, 3 days after a single dose of 500 mg of azithromycin, the following concentrations were found: in the lungs - 1.3-4.8 μg/g, in the prostate gland - 0.6-2.3 μg/g, in the tonsils - 2.0-2.8 μg/g, in blood plasma - 0-0.3 μg/ml. Concentrations observed in lung, prostate, and tonsil tissues exceed the MIC90 for the most common pathogens after a single dose of 500 mg azithromycin.

In vitro and in vivo experimental studies have shown accumulation of azithromycin in macrophages with subsequent release upon activation of phagocytosis. Animal experiments have also shown that this process contributes to the accumulation of azithromycin in organ tissues.

Serum protein binding varies with plasma concentrations and ranges from 18% at 0.5 μg/mL to 52% at 0.05 μg/mL in serum.

Biotransformation and excretion.

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 (mostly in the first 24 hours). Particularly high concentrations of unchanged azithromycin were found in human bile 2 days after a 5-day course of treatment (up to 237 μg/ml). Also in bile were found 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:

• infections of the upper respiratory tract, paranasal sinuses and middle ear (bacterial pharyngitis, tonsillitis, sinusitis, otitis media);
• lower respiratory tract infections (bacterial bronchitis, community-acquired pneumonia);
• skin and soft tissue infections (erythema migrans (stage I of Lyme disease), erysipelas, impetigo and secondary pyoderma);
• sexually transmitted infections (uncomplicated genital infections caused by Chlamydia trachomatis).

According to preclinical studies, azithromycin is effective against many sexually transmitted infections.

Contraindication

Hypersensitivity to azithromycin, erythromycin, macrolide/ketolide antibiotics or to any of the excipients 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.

In a pharmacokinetic study of the effect of concomitant administration of antacids with azithromycin, no effect on overall bioavailability was found, although peak serum concentrations were reduced by approximately 24%. Patients receiving azithromycin and antacids should not take these drugs concomitantly.

Cetirizine.

In healthy volunteers, co-administration 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. Azithromycin should be administered with caution to patients receiving other drugs that may prolong the QT interval.

Didanosine.

When azithromycin was coadministered at a dose of 1200 mg/day with didanosine at a dose of 400 mg/day, no effect on the pharmacokinetics of didanosine was observed compared to placebo.

Digoxin and colchicine (P-glycoprotein substrates).

Concomitant use of macrolide antibiotics, including azithromycin, and P-glycoprotein substrates such as digoxin and colchicine has been shown to increase serum levels of the P-glycoprotein substrate. Therefore, the possibility of increased serum substrate concentrations should be considered when azithromycin is co-administered with a P-glycoprotein substrate such as digoxin. Clinical monitoring and possibly measurement of serum digoxin levels should be considered during and after treatment with azithromycin.

Zidovudine.

Single doses of 1000 mg and 1200 mg or multiple doses of 600 mg of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolites. However, azithromycin administration increased the concentration 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.

Derivatives of ergot.

It is not recommended to use azithromycin simultaneously with ergot derivatives, as ergotism may occur.

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.

Co-administration 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, post-marketing 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.

Coumarin-type oral 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. In the postmarketing period, there have been reports of potentiation of the anticoagulant effect after concomitant administration of azithromycin and oral coumarin anticoagulants. 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.

In a pharmacokinetic study in healthy volunteers given azithromycin 500 mg/day orally for 3 days followed by a single oral dose of 10 mg/kg cyclosporine, the Cmax and AUC0-5 of cyclosporine were significantly increased (by 24% and 21%, respectively), but no significant changes in AUC0-∞ were observed. Therefore, caution should be exercised when considering the concomitant use of these drugs. If concomitant use of such drugs is necessary, cyclosporine levels should be monitored and the dose adjusted accordingly.

Efavirenz.

Coadministration 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.

Co-administration 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 co-administration 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, which was taken at a dose of 800 mg 3 times a day 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, concomitant administration of azithromycin 500 mg/day 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 was observed in subjects receiving azithromycin and rifabutin concomitantly. Although neutropenia was associated with rifabutin, a causal relationship to concomitant azithromycin administration has not been established.

Sildenafil.

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

Terfenadine.

Pharmacokinetic studies have not reported any interaction 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 are no data on clinically significant pharmacokinetic interactions 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.

Coadministration of a double dose of trimethoprim/sulfamethoxazole (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 or chloroquine.

Observational data have shown that concomitant use of azithromycin with hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of cardiovascular events and cardiovascular mortality. The benefit-risk balance should be carefully considered before prescribing azithromycin to any patient taking hydroxychloroquine. The benefit-risk balance should also be carefully considered before prescribing azithromycin to any patient taking chloroquine because of the potential risk similar to chloroquine.

Other antibiotics.

The potential for cross-resistance between azithromycin and other macrolide antibiotics (e.g. erythromycin), as well as lincomycin and clindamycin, should be considered when co-administering azithromycin. The concomitant use of multiple drugs from this class is not recommended.

Application features

Allergic reactions.

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 (DRESS syndrome), have been reported. Some of these reactions caused by azithromycin have caused recurrent symptoms and required longer observation and treatment.

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

Liver dysfunction.

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, potentially leading to life-threatening hepatic 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 immediately 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 abnormalities are detected, azithromycin should be discontinued.

Derivatives of 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 and azithromycin. However, due to 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 non-susceptible organisms, including fungi, is recommended.

Cross-sensitivity.

Due to the existing cross-resistance of erythromycin-resistant Gram-positive strains and most strains of methicillin-resistant staphylococci, the use of azithromycin is not recommended.

Local epidemiology and susceptibility patterns should be taken into account.

Serious infection.

Azithromycin is not intended for the treatment of severe infections where rapid high concentrations of the antibiotic in the blood are required.

Clostridium difficile.

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.

1. 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 can occur within 2 months of antibiotic therapy. Consideration should be given to discontinuing azithromycin therapy and initiating specific therapy for C. difficile.

Kidney dysfunction.

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) can 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 myasthenia gravis symptoms and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

Long-term use.

There is no experience regarding the safety and efficacy of long-term use of azithromycin for the above indications. In rapidly recurring infections, treatment with other antibiotics should be considered.

Neurological and mental disorders.

Azithromycin should be used with caution in patients with neurological and psychiatric disorders.

Hearing damage.

Macrolide antibiotics have been described to cause hearing loss. Hearing impairment, deafness, and tinnitus have been reported in some patients receiving azithromycin. Many of these cases were from experimental studies in which azithromycin was used at high doses for long periods of time. However, most of these problems were reversible according to available follow-up reports.

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; there are no data demonstrating the efficacy of azithromycin for the prevention of rheumatic fever.

Hydroxychloroquine or chloroquine

Before prescribing azithromycin to any patient taking hydroxychloroquine or chloroquine, the benefit-risk balance should be carefully considered due to the potential increased risk of cardiovascular events and mortality from cardiovascular disease (see section 4.4).

An antimicrobial with anaerobic activity should be taken in combination with azithromycin if anaerobic microorganisms are suspected to be causing the infection.

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

This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.

Use during pregnancy or breastfeeding

Pregnancy.

There are no adequate and well-controlled studies of azithromycin in pregnant women. Animal reproduction studies have been performed at doses that are moderately toxic to the mother. These studies have not produced any evidence of fetal toxicity. Since animal reproduction studies are not always predictive of human effects, azithromycin should be used during pregnancy only if clearly needed.

Breastfeeding period.

Azithromycin has been reported to be excreted in human milk, but adequate and well-controlled clinical studies to characterize the pharmacokinetics of azithromycin excretion in human milk have not been conducted. Since it is unknown whether azithromycin can have a harmful effect on the infant during lactation, breastfeeding should be discontinued during treatment with azithromycin. Possible complications in the infant include diarrhea, fungal infections of the mucous membrane, and hypersensitivity due to azithromycin in breast milk. It is recommended to discontinue breastfeeding during use of the drug and for 2 days after discontinuation of its use. Breastfeeding can be resumed thereafter.

Fertility.

Fertility studies have been performed in animals; 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, however, the possibility of developing adverse reactions such as delirium, hallucinations, dizziness, drowsiness, visual disturbances, and seizures should be taken into account.

Method of administration and doses

ZOXI should be taken in the prescribed dose once a day, regardless of food intake. The tablets should be swallowed without chewing, with half a glass of water. If you miss a dose of the drug, the missed dose should be taken as soon as possible, and the following doses should be taken at intervals of 24 hours.

Adults and children weighing ≥45 kg.

The course dose is usually 1500 mg and is prescribed to be taken at 500 mg/day for 3 days. An alternative regimen may be to prescribe a course dose for 5 days: 500 mg on the 1st day and 250 mg from the 2nd to the 5th day of treatment.

In the case of treatment of uncomplicated urethritis or cervicitis caused by Chlamydia trachomatis, the drug should be taken once at a dose of 1000 mg.

In the treatment of gonorrhea, the recommended course dose is 1000 mg or 2000 mg in combination with the administration of 250 mg or 500 mg of ceftriaxone in accordance with current clinical guidelines.

Patients with allergies to cephalosporins or penicillins should be given an alternative treatment regimen.

Elderly patients.

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

Patients with renal impairment.

For patients with mild renal impairment (glomerular filtration rate 10-80 mL/min), the same dosage 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). In patients with severe renal dysfunction (glomerular filtration rate <10 mL/min), a 33% increase in systemic exposure to azithromycin was observed.

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.

The drug should not be used in children weighing less than 45 kg.

Overdose

Clinical experience with azithromycin suggests that adverse reactions that occur with higher than recommended doses of the drug are similar to those seen with normal therapeutic doses, and may include diarrhea, nausea, vomiting, and reversible hearing loss. In case of overdose, activated charcoal and general symptomatic and supportive treatment are recommended if necessary.

Adverse reactions

The following adverse reactions have been identified from clinical trials and post-marketing surveillance with all dosage forms of azithromycin by system organ class and frequency. The frequency groups are defined using the following scale: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000); not known (cannot be estimated from the available data). Within each frequency group, undesirable effects are presented in order of decreasing seriousness.

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

Infections and infestations: uncommon – candidiasis, oral candidiasis, vaginal infections, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory dysfunction, rhinitis, oral candidiasis; frequency unknown – pseudomembranous colitis.

From the blood and lymphatic system: infrequently - leukopenia, neutropenia, eosinophilia; frequency unknown - thrombocytopenia, hemolytic anemia.

On the part of the immune system: infrequently - angioedema, hypersensitivity reactions; very rarely - anaphylactic shock.

Metabolic: often - anorexia (lack of appetite).

On the part of the psyche: infrequently - nervousness, insomnia; rarely - agitation; very rarely - aggressiveness, restlessness, delirium, hallucinations.

Nervous system: often - headache; infrequently - dizziness, drowsiness, paresthesia, dysgeusia; frequency unknown - fainting, convulsions, psychomotor hyperactivity, anosmia, parosmia, ageusia, myasthenia gravis, hypoesthesia.

On the part of the organs of vision: often - visual disturbances.

On the part of the auditory system: infrequently - hearing impairment, vertigo; very rarely - hearing impairment, including deafness and/or tinnitus.

Cardiac disorders: infrequently - palpitations; very rarely - ventricular fibrillation (torsade de pointes), arrhythmia, including ventricular tachycardia, prolongation of the QT interval on the ECG.

Vascular disorders: infrequently - hot flashes; very rarely - arterial hypotension.

From the respiratory system: infrequently - dyspnea, epistaxis.

On the part of the digestive tract: very often - diarrhea, colic, flatulence, nausea; often - vomiting, dyspepsia; infrequently - gastritis, constipation, dysphagia, bloating, dry mouth, belching, mouth ulcers, hypersecretion of saliva; very rarely - pancreatitis, tongue discoloration.

Skin and subcutaneous tissue disorders: uncommon: rash, pruritus, urticaria, dermatitis, dry skin, hyperhidrosis; rare: photosensitivity, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)*; not known: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

Musculoskeletal system: infrequently - osteoarthritis, myalgia, back pain, neck pain; unknown - arthralgia.

From the urinary system: infrequently - dysuria, kidney pain; unknown - acute renal failure, interstitial nephritis.

Reproductive system and breast disorders: uncommon – uterine bleeding, testicular disorders.

General disorders and local reactions: infrequently - fatigue; chest pain, edema, malaise, asthenia, facial edema, hyperthermia, pain, peripheral edema.

Changes in laboratory parameters: often - decreased leukocyte count, increased eosinophil count, decreased blood bicarbonate level, increased basophils, monocytes, neutrophils; infrequently - increased levels of AST, ALT, alkaline phosphatase, bilirubin, urea, creatinine in the blood, changes in blood electrolytes, increased glucose level, increased platelet level, decreased hematocrit level, increased bicarbonate level, deviation from the norm of sodium level.

Injury and poisoning: uncommon: post-procedural complications.

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 extended-release formulations:

Metabolism and nutritional disorders: common: anorexia.

Nervous system disorders: common: dizziness, headache, paresthesia, dysgeusia; rare: hypoesthesia.

On the part of the organs of vision: often: visual impairment.

From the side of the organs of hearing and labyrinth: often: deafness; rarely: hearing impairment, tinnitus.

From the side of the cardiovascular system: rarely: palpitations.

On the part of the digestive tract: very often: diarrhea, abdominal pain, nausea, flatulence, gastrointestinal discomfort, frequent loose stools.

Hepatobiliary system: rarely: hepatitis.

Skin and subcutaneous tissue disorders: common: rash, itching; rare: Stevens-Johnson syndrome, photosensitivity.

Musculoskeletal and connective tissue disorders: common: arthralgia.

General disorders and administration site conditions: common: fatigue; rare: asthenia, malaise.

Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the link: https://aisf.dec.gov.ua.

Expiration date

Dosage 250 mg - 3 years; dosage 500 mg - 3.5 years.

Storage conditions

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

Keep out of reach of children.

Packaging

3 tablets in a blister, 1 blister in a cardboard pack.

3 tablets in a blister, 2 blisters in a cardboard pack.

Vacation category

According to the recipe.

Producer

Evertogen Life Sciences Limited.

Location of the manufacturer and address of its place of business.

Plot No.: S-8, S-9, S-13/P and S-14/P T E C I A C, S I Z Pharma, Green Industrial Park, Polepally (V), Yedcherla (M), Mahabubnagar, Telangana, IH-509 301, India/

Plot No: S-8, S-9, S-13/P & S-14/P TSIIC, Pharma SEZ, Green Industrial Park, Polepally (V), Jadcherla (M), Mahabubnagar, Telangana, IN-509 301, India.