Bi-septh-farmak®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BI-SEPT – FARMAK® (BI-SEPT – FARMAK)

Composition:

Active substances: sulfamethoxazole, trimethoprim;

One tablet contains sulfamethoxazole 400 mg, trimethoprim 80 mg;

Excipients: lactose monohydrate; sodium lauryl sulfate; povidone; colloidal silicon dioxide anhydrous; sodium croscarmellose; magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: white or almost white tablets with a flat surface, a score line and beveled edges. The inscription "Bs" may be printed on one side of the tablet.

Pharmacotherapeutic group.

Antibacterials for systemic use.

ATC code J01E E01.

Pharmacological Properties.

Pharmacodynamics.

Bi-sepT–Pharmak® is a combined antibacterial agent containing sulfamethoxazole (a sulfonamide with intermediate duration of action) and trimethoprim. Both components of the drug act on the same biochemical pathway (sulfamethoxazole inhibits the incorporation of para-aminobenzoic acid into the folic acid metabolic cycle, while trimethoprim is a dihydrofolate reductase inhibitor), resulting in enhanced antibacterial activity and slower development of bacterial resistance.

Bi-sepT–Pharmak® is active in vitro against Escherichia coli (including enteropathogenic strains), indole-positive strains of Proteus spp. (also against P. vulgaris), Morganella morganii, Moraxella catarrhalis, Klebsiella spp., Proteus mirabilis, Enterobacter spp., Haemophilus ducreyi, Haemophilus influenzae, Brucella spp., Shigella flexneri, Shigella sonnei; Streptococcus pneumoniae, Streptococcus spp., Staphylococcus spp., Listeria monocytogenes, Nocardia asteroides. Bi-sepT–Pharmak® is also active against Toxoplasma gondii and Pneumocystis carinii. The drug is not effective against viruses and fungal pathogens.

Pharmacokinetics.

Both components of the drug are rapidly absorbed from the gastrointestinal tract. Maximum plasma concentrations are reached within 2–4 hours after administration; therapeutic concentrations of the drug in plasma and tissues are maintained for 12 hours. Trimethoprim is 70% bound to plasma proteins, while sulfamethoxazole is 44–62% bound. High concentrations of trimethoprim are found in bronchial gland secretions, prostate gland, and bile. The concentration of sulfamethoxazole in body fluids is somewhat lower. Both compounds appear in high concentrations in sputum, vaginal secretions, and middle ear fluid. The volume of distribution is 0.36 L/kg for sulfamethoxazole and 2 L/kg for trimethoprim. The plasma half-life is approximately 10 hours for sulfamethoxazole and 8–10 hours for trimethoprim. Within 72 hours, 84.5% of the administered dose of sulfamethoxazole and 66.8% of trimethoprim are excreted in the urine.

Clinical characteristics.

Indications.

Treatment of infections caused by pathogenic microorganisms sensitive to the drug, when the benefit of such treatment outweighs the potential risk; it is necessary to determine whether monotherapy with a single antibacterial agent can be used.

Infections of the ear, nose, throat, and respiratory tract: sinusitis, otitis media, acute and chronic bronchitis, bronchiectasis, pneumonia (including that caused by Pneumocystis carinii), pharyngitis, tonsillitis (in infections caused by β-hemolytic streptococci group A, the eradication rate is not entirely sufficient).

Infections of the kidneys and urinary tract: acute and chronic cystitis, pyelonephritis, urethritis, prostatitis, chancroid.

Gastrointestinal tract infections: typhoid fever and paratyphoid, shigellosis (caused by sensitive strains of Shigella flexneri and Shigella sonnei, when antibacterial therapy is indicated), traveler's diarrhea caused by enterotoxigenic strains of Escherichia coli, cholera (in addition to rehydration and electrolyte replacement).

Other bacterial infections: acute and chronic osteomyelitis, brucellosis, nocardiosis, actinomycosis, toxoplasmosis, South American blastomycosis.

Contraindications.

• Hypersensitivity to trimethoprim and sulfamethoxazole (including sulfonamide derivatives, sulfonylurea antidiabetic agents, as well as thiazide diuretics) and other components of the drug.
• Acute hepatitis, hepatic dysfunction, severe liver failure, including diagnosed parenchymal liver damage, porphyria.
• Blood disorders, hematopoietic disorders, severe hematological disorders, megaloblastic anemia caused by folic acid deficiency, glucose-6-phosphate dehydrogenase deficiency (risk of hemolysis).
• Severe renal failure characterized by creatinine clearance less than 15 ml/min, if plasma drug concentration monitoring is not feasible (except during hemodialysis).
• The drug is contraindicated in patients undergoing chemotherapy.
• The drug must not be administered in combination with dofetilide.

Interaction with other medicinal products and other types of interactions.

Nonsteroidal anti-inflammatory drugs, sulfonylurea antidiabetic agents, phenytoin, indirect anticoagulants, barbiturates increase the risk of adverse effects.

Ascorbic acid increases the risk of crystalluria.

In patients receiving Bi-sepT–Farmak® and cyclosporine after kidney transplantation, reversible deterioration of renal function may occur, manifested by increased creatinine levels and likely attributable to the action of trimethoprim.

Trimethoprim has low affinity for human dihydrofolate reductase but may enhance methotrexate toxicity, especially in the presence of other risk factors: advanced age, hypoalbuminemia, renal dysfunction, bone marrow suppression. This adverse effect may be particularly pronounced when methotrexate is administered in high doses. It is recommended to treat such patients with folic acid or calcium folinate to prevent effects on hematopoiesis.

Cases of pancytopenia have been reported in patients receiving trimethoprim and methotrexate.

Co-trimoxazole increases the concentration of free methotrexate fraction in serum due to displacement from protein binding.

Bi-sepT–Farmak® may potentiate the effect of oral hypoglycemic sulfonylurea derivatives, thereby increasing the risk of hypoglycemia.

When taken concomitantly with warfarin or other anticoagulants, Bi-sepT–Farmak® may prolong prothrombin time, necessitating dose reduction of these drugs. In such cases, blood clotting time should be reassessed.

In patients receiving indomethacin, the blood concentration of sulfamethoxazole may increase. One case of toxic delirium has been reported after concomitant administration of Bi-sepT–Farmak® and amantadine.

Trimethoprim must not be used in combination with dofetilide. Administration of trimethoprim 260 mg and sulfamethoxazole 800 mg twice daily in combination with dofetilide 500 mg twice daily for 4 days increases the maximum concentration of dofetilide, leading to severe ventricular arrhythmias.

In elderly patients, the combination of co-trimoxazole with certain diuretics, particularly thiazides, increases the risk of thrombocytopenia.

Co-trimoxazole may increase serum digoxin concentration, especially in elderly patients.

When administered concomitantly with tricyclic antidepressants, the activity of the latter is reduced.

The drug reduces the reliability of oral contraception; therefore, patients should be advised to use additional contraceptive measures during treatment with Bi-sepT–Farmak®.

The drug inhibits phenytoin metabolism: in individuals receiving both drugs, the half-life of phenytoin increases by approximately 39%, and phenytoin clearance decreases by approximately 27%.

When administered concomitantly with pyrimethamine, used for malaria prophylaxis at doses exceeding 25 mg/week, patients may develop megaloblastic anemia.

Special precautions for use.

Warnings and special precautions for use.

Rare cases of life-threatening complications associated with the use of sulfonamides have been described, including acute hepatic necrosis, aplastic anemia, agranulocytosis, other blood dyscrasias, and respiratory hypersensitivity reactions (lung infiltrates).

Life-threatening skin reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis, have been reported in association with sulfamethoxazole use.

Patients should be informed about subjective and objective symptoms of skin reactions and the need for careful monitoring. The highest risk of developing severe skin reactions (Stevens–Johnson syndrome and toxic epidermal necrolysis) occurs during the first weeks of treatment.

Treatment with Bisept-Farmak® should be discontinued immediately if subjective or objective symptoms of Stevens–Johnson syndrome or toxic epidermal necrolysis appear (such as sudden onset of skin rash, often with blisters, or mucosal lesions).

The best outcomes in treating Stevens–Johnson syndrome or toxic epidermal necrolysis are observed when early diagnosis is made and the causative drug is promptly discontinued. Immediate withdrawal of the drug improves the prognosis.

If a patient develops Stevens–Johnson syndrome or toxic epidermal necrolysis during treatment with Bisept-Farmak®, this medicinal product should not be prescribed again in the future.

The drug should be discontinued if skin rash or any other adverse reaction occurs (including sore throat, fever, joint pain, pallor, purpura, jaundice) that cannot be explained by other causes. Cough, dyspnea, and development of pulmonary infiltrates may also be signs of hypersensitivity reactions. Caution is required when prescribing the drug to patients with a history of severe allergic reactions or bronchial asthma.

Respiratory toxicity

Very rare, severe cases of respiratory toxicity have been reported during treatment with sulfamethoxazole/trimethoprim, sometimes progressing to acute respiratory distress syndrome (ARDS). The onset of pulmonary manifestations such as cough, fever, and dyspnea, in combination with radiological signs of pulmonary infiltrates and worsening lung function, may be early signs of ARDS. In such cases, sulfamethoxazole/trimethoprim should be discontinued and appropriate treatment initiated.

Except in exceptional cases, Bisept-Farmak® should not be prescribed to patients with serious, persistent blood dyscrasias. The drug has occasionally been used in patients receiving cytotoxic agents for leukemia treatment, without any observed adverse effects on bone marrow or peripheral blood.

Due to the potential for hemolysis, Bisept-Farmak® should not be administered to patients with certain hemoglobinopathies (Hb-Zurich, Hb-Cologne), except in cases of urgent need and only at minimal doses.

Hemophagocytic lymphohistiocytosis (HLH)

Very rare cases of hemophagocytic lymphohistiocytosis have been reported in patients receiving sulfamethoxazole/trimethoprim. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of pathological immune activation, characterized by clinical signs and symptoms of excessive systemic inflammation (such as fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, elevated serum ferritin levels, cytopenia, and hemophagocytosis). Patients developing early signs of pathological immune activation should be promptly evaluated. If the diagnosis of hemophagocytic lymphohistiocytosis is confirmed, treatment with sulfamethoxazole/trimethoprim should be discontinued.

Prolonged treatment is not recommended. Treatment in elderly patients should not be prolonged. In elderly patients, treatment with Bisept-Farmak® increases the risk of kidney or liver damage, severe skin reactions, bone marrow suppression (including blood cell formation), and thrombocytopenia with or without purpura. Concomitant use of diuretics increases the risk of bleeding.

Treatment of streptococcal pharyngitis with co-trimoxazole often results in unsatisfactory outcomes due to failure to eradicate the bacteria. Co-trimoxazole is not indicated for the treatment of streptococcal pharyngitis or tonsillitis.

Trimethoprim interferes with phenylalanine metabolism, but does not affect the condition of patients with phenylketonuria when an appropriate diet is followed.

As with any sulfonamide, caution is required in patients with porphyria or thyroid dysfunction. Patients who are slow acetylators are more susceptible to sulfonamide idiosyncrasy.

Bisept-Farmak® should be used cautiously in patients with impaired liver or kidney function, folate deficiency (e.g., elderly patients, patients with alcoholism, patients on anticonvulsant therapy, patients with malabsorption syndrome, or undernourished patients), and in those with hematopoietic disorders. Elderly patients and those with probable folate deficiency should be considered for additional folate supplementation during treatment.

To prevent crystalluria and tubular obstruction in the kidneys, patients should consume sufficient fluids (at least 1.5 L per day). The risk of crystalluria increases with poor nutrition.

During prolonged treatment, blood counts, liver, and kidney function should be closely monitored. Folic acid (5–10 mg/day) may be added during treatment to mitigate hematological effects without compromising the antibacterial efficacy of the drug.

Caution should be exercised when prescribing Bisept-Farmak® to patients with X-linked mental retardation, as folate deficiency may exacerbate psychomotor disorders associated with the condition.

In AIDS patients receiving Bisept-Farmak® for Pneumocystis infection, symptoms such as rash, fever, leukopenia, elevated aminotransferase levels, hyperkalemia, and hyponatremia occur more frequently.

During treatment, direct exposure to sunlight should be avoided, or protective clothing and/or photoprotective agents should be used due to photosensitivity.

Pseudomembranous colitis may develop during treatment with co-trimoxazole, as with other antibacterial agents.

The disease may range from mild to life-threatening. Therefore, correct diagnosis is crucial in patients who develop diarrhea during antibacterial therapy. Antibacterial treatment alters the normal flora of the colon and may lead to overgrowth of anaerobic bacilli. Toxins produced by Clostridium difficile are a major cause of colitis.

In mild cases of pseudomembranous colitis, discontinuation of the drug is usually sufficient. In moderate to severe cases, patients require fluid, electrolyte, protein replacement, and antibacterial agents active against Clostridium difficile (metronidazole or vancomycin). Antiperistaltic agents or other antidiarrheal drugs should not be used.

Prolonged treatment may lead to overgrowth of resistant microorganisms and fungi. In case of superinfection, appropriate treatment should be initiated immediately.

Effect on laboratory test results. Trimethoprim may interfere with enzymatic assay methods for serum methotrexate concentration determination, but does not affect radioimmunoassay methods.

Co-trimoxazole may increase creatinine values by approximately 10% in the Jaffe test using alkaline picrate.

Since the formulation contains lactose monohydrate, this product should not be taken by patients with rare hereditary problems of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding.

Bisept-Farmak® must not be used during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

The drug does not impair psychomotor performance or the ability to drive vehicles or operate machinery.

If adverse effects on the nervous system occur during treatment (dizziness, headache, convulsions, nervousness, fatigue), which may impair psychomotor reaction speed, driving and operating complex machinery should be avoided.

Dosage and Administration

Adults and children aged 12 years and older. The usual initial dose is 2 tablets twice daily (in the morning and evening). The tablets should be taken after meals with plenty of fluid. In severe infections, higher daily doses may be prescribed—up to 3 tablets twice daily. For maintenance therapy lasting more than 14 days, a dose of 1 tablet twice daily is recommended.

Children aged 6–12 years. The recommended daily dose for children is 6 mg of trimethoprim and 30 mg of sulfamethoxazole per kg of body weight. This dose should be divided into two administrations.

The recommended daily dose for children aged 6 to 12 years is 1 tablet twice daily. For children under 6 years of age, other dosage forms of the drug are recommended.

Duration of treatment: In acute infections, except gonorrhea, treatment should last at least 5 days or at least 2 days after symptoms have disappeared. A 3-day course may be sufficient for women with uncomplicated acute cystitis. However, in children with this condition, the drug is recommended for 5–7 days.

In acute brucellosis, treatment should last at least 4 weeks; in nocardiosis, even longer (6–8 tablets daily for 3 months).

For prophylaxis and treatment of toxoplasmosis (Toxoplasmosis): The dosing regimen used for the treatment of Pneumocystis carinii pneumonia may be applied.

In uncomplicated gonorrhea, a single-day treatment course is possible—5 tablets twice daily (morning and evening), or a two-day course—4 tablets twice daily.

For the treatment of Pneumocystis carinii pneumonia, the recommended daily dose is 20 mg of trimethoprim and 100 mg of sulfamethoxazole per kg of body weight (15–16 tablets). This dose should be divided into 2 or more administrations, and treatment should continue for 14–21 days.

For the prophylaxis of Pneumocystis carinii pneumonia, the recommended dose for adults is 2 tablets once daily, or 2 tablets every other day, or 2 tablets twice daily during periods of increased infection risk.

For prophylaxis in children, the usual therapeutic dose calculated based on the child’s age and body weight should be administered once daily or 3 times weekly for 3 consecutive days. This dose corresponds approximately to 150 mg/m² of trimethoprim and 750 mg/m² of sulfamethoxazole. The maximum daily doses of trimethoprim and sulfamethoxazole are 320 mg and 1600 mg, respectively.

Special patient groups

For patients with impaired renal function, the dose may be adjusted according to the following scheme (adults and children aged 12 years and older):

Plasma concentration measurement of sulfamethoxazole is recommended on the 2nd–3rd day of treatment (12 hours after drug administration). If the plasma concentration of sulfamethoxazole reaches 150 mcg/mL, treatment should be suspended until the sulfamethoxazole concentration decreases to 120 mcg/mL.

Patients undergoing regular hemodialysis should receive 50% of the usual dose of the drug before hemodialysis and 50% of the dose after completion of the procedure. Hemodialysis lasts 4 hours, during which 44% of trimethoprim and 57% of sulfamethoxazole are removed from the body. The drug is not recommended to be used on days when hemodialysis is not performed.

Bisept-Farmak® should be used with particular caution in elderly patients, as adverse reactions occur more frequently in this patient group, especially in individuals with renal or hepatic impairment or when other medicinal products are used concomitantly.

Children. The drug is indicated for treatment of children aged 6 years and older. For children under 6 years of age, other dosage forms of the drug (e.g., suspension) should be used as needed.

Overdose.

The potentially life-threatening dose of Bisept-Farmak® is unknown. In case of sulfonamide overdose, symptoms may include loss of appetite, colicky abdominal pain, nausea, vomiting, diarrhea, dizziness, headache, drowsiness, and loss of consciousness. Fever, hematuria, and crystalluria may occur. With chronic overdose, bone marrow suppression and hepatitis may develop.

Acute trimethoprim overdose may cause nausea, vomiting, dizziness, headache, mental depression, confusion, and bone marrow suppression.

In case of overdose symptoms, the drug should be discontinued immediately. Induce vomiting and administer large amounts of fluid, provided diuresis is insufficient and renal function is normal. Acidification of urine accelerates the elimination of trimethoprim but increases the risk of sulfonamide crystallization in the kidneys. Blood count, serum electrolytes, and other biochemical parameters should be monitored. In case of bone marrow damage or symptoms of hepatitis, standard treatment for such conditions should be administered. Hemodialysis is poorly effective. Peritoneal dialysis is ineffective.

Chronic poisoning is characterized by bone marrow suppression, manifesting as thrombocytopenia, leukopenia, or megaloblastic anemia. In such cases, leucovorin (5–15 mg daily) should be administered.

Adverse reactions.

The most common adverse reactions during treatment with Bi-sepT–Farmak® are gastrointestinal (nausea, vomiting, anorexia) and skin allergic reactions (rash, urticaria).

Rarely, life-threatening symptoms may occur: Stevens–Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), acute liver necrosis.

Fungal infections such as candidiasis may develop during treatment.

Other adverse effects include:

Blood and lymphatic system disorders: hemolytic or aplastic anemia, megaloblastic anemia, eosinophilia, methemoglobinemia, hypoprothrombinemia, leukopenia, neutropenia and thrombocytopenia, agranulocytosis, pancytopenia or purpura, hemolysis.

Immune system disorders: allergic myocarditis, chills, fever following administration of the drug, photophobia, anaphylactic reactions (including severe, life-threatening reactions), allergic vasculitis, angioneurotic edema, allergic skin reactions, Schönlein–Henoch disease, generalized skin reactions, skin inflammation with desquamation, allergic rashes, serum sickness.

Rarely – polyarteritis nodosa, lupus syndrome.

Symptoms of hypersensitivity affecting the respiratory system, conjunctival and scleral hyperemia.

Gastrointestinal disorders: diarrhea, abdominal pain, anorexia, nausea (with or without vomiting), vomiting, isolated cases of pseudomembranous enterocolitis, pseudodiphtheritic intestinal inflammation, glossitis, stomatitis, pancreatitis, increased bilirubin concentration, elevated liver enzyme levels in serum.

Hepatobiliary disorders: elevated aminotransferase levels, hepatitis (sometimes with cholestatic jaundice), vanishing bile duct syndrome, liver necrosis, fulminant hepatitis.

Renal and urinary disorders: increased diuresis, crystalluria, renal failure, interstitial nephritis, nephrotoxic syndrome with oliguria or anuria, increased serum non-protein nitrogen and creatinine levels.

Metabolism and nutrition disorders: hyperkalemia, hyponatremia, anorexia, hypoglycemia.

Psychiatric disorders: depression, hallucinations, acute psychosis, delirium and psychosis in elderly patients.

Nervous system disorders: apathy, aseptic meningitis, ataxia, headache, convulsions, restlessness, tinnitus, peripheral nerve inflammation, paresthesia, neuropathy, uveitis, dizziness.

Endocrine system disorders: sulfonamides have chemical similarities to certain antithyroid drugs, diuretics (acetazolamide and thiazides), and oral antidiabetic agents, which may lead to cross-allergy.

Skin and subcutaneous tissue disorders: rash, urticaria, pruritus, photosensitization, polymorphic erythema, desquamative dermatitis; very rarely – Stevens–Johnson syndrome, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders: joint pain, muscle pain, isolated cases of rhabdomyolysis reported.

Respiratory, thoracic and mediastinal disorders: dyspnea, cough, lung infiltrates.

General disorders: weakness, fatigue, insomnia.

Adverse reactions in AIDS patients: the incidence of adverse reactions, particularly rash, fever, leukopenia, and elevated serum aminotransferase activity, is significantly higher in AIDS patients than in other patients.

HIV-infected patients with frequent comorbidities and their treatments usually receive long-term prophylaxis or treatment for Pneumocystis carinii (Pneumocystis jirovecii) pneumonia using high doses of Bi-sepT–Farmak®. Apart from a small number of additional adverse effects, the adverse effect profile in these patients is similar to that in non-HIV-infected patient populations. However, some adverse effects occur more frequently (in approximately 65% of patients) and are often more severe, necessitating discontinuation of Bi-sepT–Farmak® treatment in 20–25% of patients. Specifically, the following adverse reactions have been observed additionally or with higher frequency:

Blood and lymphatic system disorders: predominantly neutropenia, but also anemia, leukopenia, granulocytopenia and thrombocytopenia, agranulocytosis.

Immune system disorders: fever, usually associated with skin rashes, allergic reactions such as angioneurotic edema, anaphylactoid reactions and serum sickness, hypersensitivity reactions.

Metabolism and nutrition disorders: hyperkalemia – HIV-infected patients require careful monitoring of serum potassium levels; hyponatremia, hypoglycemia.

Psychiatric disorders: acute psychosis.

Nervous system disorders: neuropathy (including peripheral neuritis and paresthesia), hallucinations, uveitis. Aseptic meningitis or meningitis-like symptoms, ataxia, convulsions, resting tremor resembling Parkinson’s disease, sometimes combined with apathy, foot spasms and ataxic gait, vertigo, tinnitus.

Respiratory disorders: pneumonitis with eosinophilic infiltration.

Gastrointestinal disorders: anorexia, nausea with or without vomiting, as well as diarrhea, stomatitis, glossitis, pancreatitis.

Hepatobiliary disorders: elevated liver enzymes/aminotransferases, cholestatic jaundice, severe hepatitis.

Skin and subcutaneous tissue disorders: maculopapular rashes, usually itchy, which rapidly resolve after discontinuation of the drug, photosensitivity, multiform erythema, Stevens–Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), Schönlein–Henoch purpura.

Musculoskeletal disorders: arthralgia, myalgia, rhabdomyolysis.

Renal and urinary disorders: impaired renal function, azotemia, elevated serum creatinine levels, crystalluria. Sulfonamides, including Bi-sepT–Farmak®, may enhance diuresis, particularly in patients with edema due to cardiovascular disorders.

Adverse reactions associated with Pneumocystis carinii (Pneumocystis jirovecii) infection causing Pneumocystis pneumonia (PCP): severe hypersensitivity reactions, skin rashes, fever, neutropenia, thrombocytopenia, elevated liver transaminase levels, rhabdomyolysis, hypocalcemia, hyponatremia.

Severe hypersensitivity reactions have been observed when high doses are used in PCP therapy, requiring discontinuation of the drug. If signs of bone marrow suppression occur, folate deficiency should be corrected with calcium folinate (5–10 mg/day).

Severe hypersensitivity reactions have occurred in PCP patients who were re-administered trimethoprim and sulfamethoxazole after a several-day interruption.

Rhabdomyolysis has been observed in HIV-positive patients taking co-trimoxazole for prophylaxis or treatment of PCP.

Shelf life.

3 years.

Do not use the medication after the expiry date stated on the packaging.

Storage conditions.

Store in a light-protected place at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 20 tablets in a blister. 1 blister per pack.

Prescription category. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.

74 Kyrylivska Street, Kyiv, 04080, Ukraine.