Bi-sept-Farmak tablets 480 mg blister No. 20

Instructions for Bi-sept-Farmak tablets 480 mg blister No. 20

Composition

active ingredient: sulfamethoxazole, trimethoprim;

1 tablet contains sulfamethoxazole 400 mg, trimethoprim 80 mg;

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

Dosage form

Pills.

Main physicochemical properties: white or almost white tablets with a flat surface, a score and a bevel. It is allowed to write the inscription "Bs" on one side of the tablet.

Pharmacotherapeutic group

Antimicrobial agents for systemic use.

ATX code J01E E01.

Pharmacological properties

Pharmacodynamics

Bi-sepT–Farmak® is a combined antibacterial drug that contains sulfamethoxazole (a medium-acting sulfonamide) and trimethoprim. Both components of the drug act on the same chain of biochemical reactions (sulfamethoxazole inhibits the inclusion of para-aminobenzoic acid in the metabolic cycle of folic acid, and trimethoprim is an inhibitor of dihydrofolic acid reductase), which leads to enhanced antibacterial action and slower development of bacterial resistance.

Bi-sepT–Farmak® 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–Farmak® is also active against Toxoplasma gondii, Pneumocystis carinii. The drug does not act on viruses and pathogens of fungal diseases.

Pharmacokinetics

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

Indication

Treatment of infections caused by pathogenic microorganisms sensitive to the drug, in cases where the benefit of such treatment outweighs the possible risk; it is necessary to decide whether it is possible to use only one antibacterial agent.

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

Kidney and urinary tract infections: acute and chronic cystitis, pyelonephritis, urethritis, prostatitis, soft chancre.

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

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

Contraindication

Hypersensitivity to trimethoprim and sulfamethoxazole (including sulfonamide derivatives, sulfonylurea antidiabetic agents, and thiazide diuretics) and other components of the drug.

Acute hepatitis, liver dysfunction, severe hepatic failure, including diagnosed liver parenchymal damage, porphyria.

Blood diseases, hematopoiesis disorders, severe hematological disorders, megaloblastic anemia caused by folic acid deficiency, glucose-6-phosphate dehydrogenase deficiency (threat of hemolysis).

Severe renal failure, characterized by creatinine clearance less than 15 ml/min, if it is not possible to determine the concentration of the drug in the blood plasma (except in cases of hemodialysis).

The drug is contraindicated in patients undergoing chemotherapy.

The drug should not be prescribed in combination with dofetilide.

Interaction with other medicinal products and other types of interactions

Nonsteroidal anti-inflammatory drugs, antidiabetic sulfonylurea derivatives, diphenin, indirect anticoagulants, barbiturates increase the risk of side effects.

Ascorbic acid increases crystalluria.

Trimethoprim has a low affinity for human dehydrofolate reductase, but may increase the toxicity of methotrexate, especially in the presence of other risk factors: old age, hypoalbuminemia, impaired renal function, bone marrow suppression. This side effect of the drug may occur especially when methotrexate is used 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 described in patients using trimethoprim and methotrexate.

Co-trimoxazole increases the concentration of the free fraction of methotrexate in serum by displacing it from protein binding.

Bi-sepT-Farmak® may potentiate the effect of oral hypoglycemic agents, sulfonylurea derivatives, which increases the risk of hypoglycemia.

When used concomitantly with warfarin or other anticoagulants, Bi-sepT-Farmak® may increase prothrombin time, which requires a reduction in the dose of these drugs. In such cases, it is necessary to re-determine the blood clotting time.

In patients taking indomethacin, the concentration of sulfamethoxazole in the blood may increase. One case of toxic delirium has been described after simultaneous administration of Bi-sepT-Farmak® and amantadine.

Trimethoprim should not be used with dofetilide. Administration of trimethoprim 260 mg and sulfamethoxazole 800 mg twice daily in combination with dofetilide 500 mg twice daily for 4 days resulted in increased peak dofetilide concentrations, leading to serious ventricular arrhythmias.

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

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

When used simultaneously with tricyclic antidepressants, the activity of the latter decreases.

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

When co-administered with pyrimethamine, which is used for malaria prophylaxis at a dose above 25 mg/week, patients may develop megaloblastic anemia.

Application features

Precautions and special precautions for use.

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

Life-threatening skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with the use of sulfamethoxazole.

Patients should be informed about the subjective and objective symptoms of skin reactions and the need for close monitoring. The highest risk of serious skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis) is observed in the first weeks of treatment.

Treatment with Bi-sepT-Farmak® should be discontinued if subjective or objective symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis appear (such as sudden development of skin rashes, often with blisters, or lesions of the mucous membranes).

The best results in treating Stevens-Johnson syndrome or toxic epidermal necrolysis are seen when early diagnosis is made and the drug that caused the reaction is promptly discontinued. Immediate discontinuation of the drug improves the prognosis.

If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis during treatment with Bi-sepT-Pharmak®, this drug should not be prescribed in the future.

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

Respiratory toxicity

Except in exceptional cases, Bi-sepT-Farmak® should not be administered to patients with serious persistent changes in the cellular composition of the blood. The drug has occasionally been used in patients receiving cytotoxic agents for the treatment of leukemia, with no signs of side effects on the bone marrow or peripheral blood.

Given the likelihood of hemolysis, Bi-sepT-Pharmak® should not be prescribed to patients with certain hemoglobinopathies (Hb-Zurich, Hb-Cologne), except in cases of urgent need and only in 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, high serum ferritin, cytopenias, and hemophagocytosis). Patients who develop early signs of pathological immune activation should be evaluated promptly. If hemophagocytic lymphohistiocytosis is diagnosed, treatment with sulfamethoxazole/trimethoprim should be discontinued.

Long-term treatment with the drug is not recommended. Treatment of elderly patients should not be prolonged. In elderly patients, when treated with Bi-sepT–Farmak®, the risk of kidney or liver damage, severe skin reactions, bone marrow suppression (including blood cell formation), as well as thrombocytopenia with or without purpura increases. Concomitant use of diuretics increases the risk of bleeding.

The use of co-trimoxazole for streptococcal pharyngitis is relatively often unsuccessful because it fails to eliminate the bacteria. Co-trimoxazole is not indicated for the treatment of pharyngitis and tonsillitis of streptococcal etiology.

Trimethoprim disrupts phenylalanine metabolism, but with an appropriate diet, it does not affect the condition of patients with phenylketonuria.

As with any sulfonamide, caution should be exercised in patients with porphyria and thyroid dysfunction. Patients with slow acetylation metabolism are more likely to develop idiosyncrasy to sulfonamides.

Bi-sepT-Farmak® should be used with caution in patients with impaired liver or kidney function, folic acid deficiency (e.g. elderly patients, alcohol-dependent patients, patients treated with anticonvulsants, patients with malabsorption syndrome or malnourished patients) and in cases of impaired hematopoiesis. Elderly patients, as well as patients with probable folic acid deficiency, should consider additional folic acid administration during treatment with the drug.

To prevent crystalluria and renal tubular obstruction, patients should consume sufficient fluids (at least 1.5 liters per day). The risk of crystalluria increases with malnutrition.

With longer treatment, it is necessary to carefully monitor the blood picture, liver and kidney function. To reduce hematological effects during treatment, folic acid (5–10 mg/day) can be added without the risk of any reduction in the antibacterial effects of the drug.

Caution should be exercised when prescribing Bi-sepT–Farmak® to patients with X-linked mental retardation, as folic acid deficiency may lead to exacerbation of psychomotor disorders associated with the disease.

In AIDS patients who use Bi-sepT–Farmak® in connection with pneumocystis infection, the following symptoms more often occur: rash, fever, leukopenia, increased aminotransferase levels, hyperkalemia, and hyponatremia.

During treatment, direct sunlight should be avoided or protective clothing and/or sunscreen should be used during treatment due to photosensitivity.

Pseudomembranous colitis may develop when taking co-trimoxazole (as well as when taking other antibacterial agents).

The nature of the disease can range from mild to life-threatening. Therefore, the correct diagnosis of this disease in patients who develop diarrhea while taking an antibacterial drug plays a major role. Treatment with antibacterial drugs affects the physiological flora of the colon and can cause an excessive increase in the number of anaerobic bacilli. Toxins produced by Clostridium difficile are one of the main causes of colitis.

In mild cases of pseudomembranous colitis, discontinuation of the drug is usually sufficient. In moderate to severe cases, patients should be given fluids, electrolytes, protein, and antibiotics active against Clostridium difficile (metronidazole or vancomycin). Drugs that inhibit peristalsis or other antidiarrheal drugs should not be given.

Effect on laboratory test results: Trimethoprim may interfere with the results of enzymatic assays of serum methotrexate concentrations, but does not affect them using radioimmunoassays.

Co-trimoxazole may increase the results of the Jaffe basic picrate test for creatinine by approximately 10%.

Since the excipients include lactose monohydrate, patients with rare galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

Use during pregnancy or breastfeeding

Bi-sepT–Farmak® should not be used during pregnancy and breastfeeding.

Ability to influence reaction speed when driving vehicles or other mechanisms

The drug does not cause a decrease in psychophysical activity and the ability to drive vehicles and operate machinery.

If side effects from the nervous system develop during treatment (dizziness, headache, seizures, nervousness, fatigue), which may lead to a decrease in the speed of psychomotor reactions, you should avoid driving and working with complex mechanisms.

Method of administration and doses

Adults and children over 12 years of age. The usual starting dose is 2 tablets 2 times a day (morning and evening). The tablets should be taken after meals with plenty of liquid. In severe infections, higher daily doses may be prescribed - up to 3 tablets 2 times a day. For maintenance therapy lasting more than 14 days, it is recommended to take 1 tablet 2 times a day.

Children 6–12 years of age: 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 doses.

The recommended daily dose for children aged 6 to 12 years is 1 tablet 2 times a day. Children under 6 years of age are recommended to be prescribed other dosage forms of the drug.

Duration of treatment: For acute infections, except gonorrhea, treatment should be continued for at least 5 days or for 2 days after symptoms have resolved. A 3-day course of treatment may be sufficient for women with uncomplicated acute cystitis. However, children with this condition are recommended to take the drug for 5–7 days.

In acute brucellosis, the duration of treatment should be at least 4 weeks, and in nocardiosis - even longer (6–8 tablets for 3 months).

For the prevention and treatment of toxoplasmosis: The dosage regimen for the treatment of pneumonia caused by Pneumocystis carinii can be used.

For uncomplicated gonorrhea, a one-day course of treatment is possible - 5 tablets 2 times a day (morning and evening) or a two-day course of treatment - 4 tablets 2 times a day.

For the treatment of pneumonia caused by Pneumocystis carinii, 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 doses, and the treatment should be continued for 14–21 days.

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

For prophylaxis in children, the usual therapeutic dose, calculated on the basis of the child's age and body weight, is administered once daily or 3 times a week for 3 consecutive days. This dose corresponds to approximately 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 can be selected according to the following scheme (adults and children over 12 years of age):

It is recommended to measure the plasma concentration of sulfamethoxazole after 2-3 days of treatment (12 hours after taking the drug). If the plasma concentration of sulfamethoxazole reaches 150 μg/ml, treatment should be suspended until the concentration of sulfamethoxazole decreases to 120 μg/ml.

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

Children. The drug is used to treat children aged 6 years and older. For children under 6 years of age, other dosage forms of the drug (suspension) are used if necessary.

Overdose

It is not known what dose of Bi-sepT-Farmak® can be life-threatening. In case of overdose of sulfonamides, there is a lack of appetite, colic-like pain, nausea, vomiting, diarrhea, dizziness, headache, drowsiness, loss of consciousness. Fever, hematuria and crystalluria may appear, in case of chronic overdose, bone marrow suppression and hepatitis may develop.

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

If symptoms of overdose appear, it is necessary to stop using the drug, induce vomiting, and drink plenty of fluids if diuresis is insufficient and kidney function is normal. Acidification of urine will accelerate the excretion of trimethoprim, but will increase the risk of sulfonamide crystallization in the kidneys. The patient's blood count, serum electrolytes, and other biochemical parameters should be monitored. If bone marrow damage or symptoms of hepatitis occur, typical treatment in such cases should be used. Hemodialysis is ineffective. Peritoneal dialysis is ineffective.

In chronic poisoning, spinal cord function is depressed, manifesting as thrombocytopenia, leukopenia, or megaloblastic anemia. In this case, leucovorin (5–15 mg/day) should be administered.

Side effects

The most common adverse reactions during treatment with Bi-sepT–Farmak® are from the digestive tract (nausea, vomiting, lack of appetite) and skin allergic reactions (rash, hives).

Life-threatening symptoms may rarely occur: Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), acute liver necrosis.

Fungal infections, such as candidiasis, may occur during treatment with the drug.

In addition, among the undesirable effects are the following:

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

On the part of the immune system: allergic myocarditis, chills, fever after use of the drug, photophobia, anaphylactic reactions (including severe, life-threatening), allergic vasculitis, angioedema, allergic skin reaction, Schönlein-Henoch disease, general skin reactions, exfoliative dermatitis, allergic rashes, serum sickness.

Rarely – periarteritis nodosa, lupus syndrome.

Symptoms of hypersensitivity from the respiratory system, hyperemia of the conjunctiva and sclera of the eye.

On the part of the digestive tract: diarrhea, abdominal pain, lack of appetite, nausea (with or without vomiting), vomiting, isolated cases of pseudomembranous enterocolitis, pseudodiphtheria inflammation of the intestines, glossitis, stomatitis, pancreatitis, increased bilirubin concentration, serum liver enzyme levels.

Hepatobiliary system: increased aminotransferase levels, hepatitis (sometimes with cholestatic jaundice), bile duct syndrome, liver necrosis, fulminant hepatitis.

On the part of the kidneys and urinary tract: increased diuresis, crystalluria, renal failure, interstitial nephritis, nephrotoxic syndrome with oliguria or anuria, increased non-protein nitrogen and creatinine in the blood serum.

Metabolic and nutritional disorders: hyperkalemia, hyponatremia, anorexia, hypoglycemia.

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

Nervous system: apathy, aseptic meningitis, ataxia, headache, convulsions, nervousness, tinnitus, peripheral neuritis, paresthesia, neuropathy, uveitis, dizziness.

On the part of the endocrine system: sulfonamides have a chemical affinity with some antithyroid drugs, diuretics (acetazolamide and thiazide), as well as with oral antidiabetic drugs, which may cause cross-allergy.

Skin and subcutaneous tissue disorders: rash, urticaria, pruritus, photosensitivity, erythema multiforme, desquamative dermatitis; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders: joint and muscle pain, isolated cases of rhabdomyolysis have been described.

On the part of the respiratory system, chest organs and mediastinum: shortness of breath, cough, infiltrates in the lungs.

General disorders: weakness, feeling of fatigue, insomnia.

HIV-infected patients with frequent comorbidities and their treatment usually receive long-term prophylaxis or treatment of pneumonia caused by Pneumocystis carinii (Pneumocystis jirovecii) with the use of high doses of the drug Bi-sepT-Farmak®. Apart from a small number of additional side effects, the profile of such effects in these patients is similar to the profile in the population of patients who are not HIV-infected. However, some side effects are observed more often (approximately 65% of patients) and are often more severe, which necessitates the interruption of treatment with Bi-sepT-Farmak® in 20-25% of patients. In particular, the following undesirable reactions were observed in addition or with a higher frequency.

From the blood and lymphatic system: mainly neutropenia, but also anemia, leukopenia, granulocytopenia and thrombocytopenia, agranulocytosis.

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

Metabolic and nutritional disorders: hyperkalemia - HIV-infected patients should be carefully monitored for serum potassium levels; hyponatremia, hypoglycemia.

Psychiatric disorders: acute psychosis.

Nervous system: neuropathy (including peripheral neuritis and paresthesia), hallucinations, uveitis. Aseptic meningitis or meningitis-like symptoms, ataxia, convulsions, Parkinson-like resting tremor, sometimes combined with apathy, leg cramps and shuffling gait, vertigo, tinnitus.

Respiratory: pneumonitis with eosinophilic infiltration.

On the part of the digestive tract: anorexia, nausea with or without vomiting, as well as diarrhea, stomatitis, glossitis, pancreatitis.

Hepatobiliary system: increased levels of liver enzymes/transaminases, cholestatic jaundice, severe hepatitis.

Skin and subcutaneous tissue disorders: maculopapular rashes, usually pruritic, which quickly disappear after discontinuation of the drug, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), Henoch-Schönlein purpura.

Musculoskeletal system: arthralgia, myalgia, rhabdomyolysis.

Renal and urinary disorders: renal dysfunction, azotemia, increased serum creatinine, crystalluria. Sulfonamides, including Bi-sepT-Farmak®, may increase diuresis, particularly in patients with edema due to cardiovascular disease.

Adverse reactions associated with Pneumocystis carinii (Pneumocystis jirovecii) infection, which causes pneumocystis pneumonia (PCP): severe hypersensitivity reactions, skin rashes, fever, neutropenia, thrombocytopenia, increased hepatic transaminases, rhabdomyolysis, hypocalcemia, hyponatremia.

Severe hypersensitivity reactions requiring discontinuation of the drug have been observed with high doses of PCP therapy. If signs of bone marrow suppression appear, the patient should be prescribed calcium folate correction (5–10 mg/day).

Severe hypersensitivity reactions have been observed in patients with PCP who were re-treated with trimethoprim and sulfamethoxazole after a break of several days.

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

Expiration date

3 years.

Do not use the drug after the expiration date indicated on the package.

Storage conditions

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

Keep out of reach of children.

Packaging

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

Vacation category

According to the recipe.

Producer

JSC "Farmak".

Location of the manufacturer and its business address.

Ukraine, 04080, Kyiv, Kyrylivska St., 74.