Pharmacological properties of the drug Biseptol
A combined bactericidal drug containing sulfamethoxazole, a sulfonamide with an average duration of action, inhibiting the synthesis of folic acid by competitive antagonism with PABA, and trimethoprim, an inhibitor of bacterial dehydrofolic acid reductase, responsible for the synthesis of biologically active tetrahydrofolic acid. The combination of active components that influence one chain of biochemical transformations provides a synergistic antibacterial effect and contributes to a slower development of bacterial resistance to the drug. Biseptol is active in vitro against E. coli (including enteropathogenic strains), indole-positive strains of Proteus spp. (including P. vulgaris), Morganella morganii, Klebsiella spp., Proteus mirabilis, Enterobacter spp., Haemophilus influenzae, Str. pneumoniae, Shigella flexneri, Shigella sonnei. Both components of the drug are quickly absorbed into the blood in the digestive tract. The maximum concentration of both components in the blood serum is achieved 1–4 hours after oral administration. Trimethoprim is bound to plasma proteins by 70%, sulfamethoxazole by 44–62%. The distribution of both components is different: sulfamethoxazole is distributed exclusively in the extracellular environment, trimethoprim - in all body fluids. High concentrations of trimethoprim are determined in the secretions of the bronchial glands, prostate gland and bile. The concentration of sulfamethoxazole in body fluids is slightly lower. Both components are detected in high concentrations in sputum, vaginal secretions and middle ear fluid. The volume of distribution of sulfamethoxazole is 360 ml/kg body weight, trimethoprim - 2000 ml/kg. Both components are metabolized in the liver: sulfamethoxazole - by acetylation and binding to glucuronic acid, trimethoprim - by oxidation and hydroxylation. They are excreted mainly by the kidneys by filtration and active tubular secretion. The concentration of active compounds in urine is much higher than in blood. Over the course of 72 hours, 84.5% of the administered dose of sulfamethoxazole and 66.8% of trimethoprim are excreted in the urine. The half-life is 10 hours for sulfamethoxazole and 8–10 hours for trimethoprim. In renal failure, the half-life of both components is prolonged. Sulfamethoxazole and trimethoprim pass into breast milk and enter the fetal bloodstream.
Biseptol 480 mg No. 20 tablet.
Instructions for medical use of the drug BISEPTOL Trade name Biseptol International nonproprietary name No Dosage form Tablets 120 mg, 480 mg Composition One tablet contains active substances: trimethoprim 20 mg, 80 mg; sulfamethoxazole 100 mg, 400 mg, excipients: potato starch, talc, magnesium stearate, polyvinyl alcohol, methyl parahydroxybenzoate, propyl parahydroxybenzoate, propylene glycol. Description Tablets from white to white with a yellowish tint, round in shape, with a flat surface, chamfered, engraved “Bs” on one side, with a diameter of 7.8 to 8.3 mm (for a dosage of 120 mg). Tablets from white to white with a yellowish tint, round in shape, with a flat surface, with a bevel, a score and an engraving “Bs” above the score on one side, with a diameter of 12.80 to 13.40 mm (for a dosage of 480 mg). Pharmacotherapeutic group Antibacterial drugs for systemic use. Sulfonamides and trimethoprim. Sulfonamides in combination with trimethoprim and its derivatives. Co-trimoxazole. ATC code J01EE 01 Pharmacological properties Pharmacokinetics Both components of the drug are quickly absorbed from the digestive tract; the maximum concentration of both components in the blood serum is achieved 1-4 hours after oral administration. The volume of distribution of trimethoprim is about 130 l, sulfamethoxazole is about 20 l. 45% of trimethoprim and 66% of sulfamethoxazole are bound to plasma proteins. The distribution of both compounds differs; sulfonamide is distributed exclusively in the extracellular space, trimethoprim is distributed in all body fluids. High concentrations of trimethoprim are observed, among other things, in the secretions of the bronchial glands, prostate gland and bile. Concentrations of sulfamethoxazole in biological fluids are lower. Both compounds appear in effective concentrations in sputum, vaginal secretions, and middle ear fluid. The volume of distribution of sulfamethoxazole is 0.36 dm3kg, trimethoprim - 2.0 dm3kg. Both drugs are metabolized in the liver, sulfonamide by acetylation and binding to glucuronic acid, trimethoprim by oxidation and hydroxylation. Both drugs are eliminated from the body primarily through the kidneys, both by filtration and active tubular secretion. Concentrations of active compounds in urine are significantly higher than in blood. Within 72 hours, 84.5% of the administered dose of sulfonamide and 66.8% of trimethoprim are excreted in the urine. The serum half-life is 10 hours for sulfamethoxazole and 8-10 hours for trimethoprim. Both sulfamethoxazole and trimethoprim pass into human milk and the fetal circulatory system. Pharmacokinetics in special clinical cases Elderly and senile patients With normal renal function, the half-life of both components of the drug changes slightly. Patients with impaired renal function In patients with renal failure (creatinine clearance 15-30 ml/min), the half-lives of both components of the drug increase, which requires dose adjustment. Pharmacodynamics A combined bactericidal drug containing sulfamethoxazole, a sulfonamide with an average duration of action, inhibiting the synthesis of folinic acid by competitive antagonism with para-aminobenzoic acid, and trimethoprim, an inhibitor of bacterial dehydrofolinic acid reductase, responsible for the synthesis of biologically active tetrahydrofolinic acid. The combination of components acting on the same chain of biochemical transformations leads to a synergistic antibacterial effect; It is believed that due to the combination of two active substances, the development of bacterial resistance occurs more slowly than in the case of using a single active substance. Co-trimoxazole is a broad-spectrum bactericidal drug, active against almost all groups of microorganisms - gram-negative bacteria: Salmonella spp., Shigella spp., Neisseria spp., Proteus vulgaris, Vibrio cholerae, Yersinia spp., Escherichia coli, Corynebacterium spp.; gram-positive bacteria: Staphylococcus spp. and others. Chlamydia spp., Actinomyces spp., Klebsiella spp. are also sensitive to the drug. Indications for use Treatment of infectious and inflammatory diseases caused by microorganisms sensitive to the drug: - acute otitis media in children caused by strains of Str. that are sensitive to the drug. pneumoniae and H. influenzae - exacerbation of chronic bronchitis in adults caused by drug-sensitive strains of Streptococcus pneumoniae or H. influenzae, if, in the opinion of the doctor, the use of a combination drug is more effective than monotherapy - microbiologically confirmed pneumonia caused by Pneumocystis carinii, and prevention of infection with this microorganism in patients at high risk (for example, those infected with AIDS) - urinary tract infections in adults and children caused by strains of E. coli, Klebsiella sp., Enterobacter sp., Morganella morganii, Proteus mirabilis and Proteus vulgaris sensitive to the drug (with the exception of uncomplicated infections) - infections of the digestive tract in adults and children caused by Shigella flexneri and Shigella sonnei bacilli, if antibiotic therapy is indicated), travelers' diarrhea caused by enterotoxic strains of Escherichia coli, cholera (in addition to fluid and electrolyte replacement). Method of administration and dosage The drug is administered orally after meals with a sufficient amount of liquid. Children from 6 to 12 years: 240-480 mg 2 times a day every 12 hours. Adults and children over 12 years of age: 960 mg once, or 480 mg 2 times a day. The daily dose should not exceed 1920 mg (4 tablets of 480 mg). The course of treatment is from 7 to 10 days. For chronic infections, the course of treatment is longer and depends on the severity of the disease. For acute infectious diseases, the course of treatment is 5 days; if after 7 days there is no clinical improvement, it is necessary to consider correction of treatment due to possible resistance of the pathogen. Dosage in special cases: Pneumonia caused by Pneumocystis carinii in adults and children: The maximum daily dose for patients with diagnosed infection is 90-120 mg/kg body weight of Biseptol, divided into parts taken every 6 hours for 14 days. Prevention of Pneumocystis carinii infection and toxoplasmosis: Adults and children over 12 years of age: 960 mg of Biseptol (two 480 mg tablets) once a day. Children from 6 to 12 years old: 960 mg daily Biseptol, divided into two equal doses every 12 hours for three days. The daily dose should not exceed 1920 mg (4 tablets of 480 mg). For patients with a creatinine clearance of 15-30 cm3/min, the dose should be halved; for patients with a creatinine clearance of less than 15 cm3/min, the use of co-trimoxazole is not recommended. Elderly patients The drug should be used with caution in elderly patients due to the increased risk of side effects, especially in patients with renal/liver insufficiency or taking other medications concomitantly. In the absence of special instructions, standard doses of the drug should be taken. Side effects Often - nausea, vomiting - rash, itching Rarely - agranulocytosis, aplastic anemia, hemolytic anemia, megaloblastic anemia, eosinophilia, hypoprothrombinemia, leukopenia, methemoglobinemia, neutropenia, thrombocytopenia, autoimmune or aplastic pancytopenia, granulocytopenia - allergic myocarditis, oz nob, drug fever , liquefaction necrosis of the skin, photosensitivity, anaphylactic reactions, vasomotor edema, pruritus, allergic rash, Henoch-Schönlein disease, urticaria, erythema multiforme, generalized skin reactions, exfoliative dermatitis, serum sickness syndrome, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis, symptoms of respiratory hypersensitivity, periarteritis nodosa, lupus-like syndrome, hyperemia of the conjunctiva and sclera of the eye - diarrhea, abdominal pain, lack of appetite, nausea, pseudo-diphtheria inflammation of the intestines, vomiting, increased levels of transaminases and creatinine in the blood serum, inflammation of the oral cavity, inflammation tongue, pancreatitis, hepatitis, sometimes with cholestatic jaundice or liver necrosis - crystalluria, renal failure, interstitial nephritis, nephrotoxic syndrome with oliguria or anuria, increased non-protein nitrogen and serum creatinine, increased diuresis (in patients with edema of cardiac origin) - hypokalemia, hyponatremia , hyperglycemia - apathy, aseptic meningitis, motor coordination disorder, headache, depression, convulsions, hallucinations, nervousness, tinnitus, inflammation of peripheral nerves, dizziness, weakness, feeling tired, insomnia - joint pain, muscle pain, rhabdomyolysis - suffocation , cough, infiltrates in the lungs. Contraindications - hypersensitivity to the drug, its components, drugs from the co-trimoxazole group - severe damage to the liver parenchyma, hyperbilirubinemia (in children) - acute renal failure, in which it is impossible to determine the concentration of the drug in the blood plasma - blood diseases (aplastic anemia, B12 - deficiency anemia, agranulocytosis, leukopenia) - simultaneous use with dofetilide - lack of glucose-6-phosphate dehydrogenase (probability of hemolysis) - pregnancy and lactation. - children under 6 years of age Prescribe the drug with caution in cases of folic acid deficiency in the body, bronchial asthma, and thyroid diseases. Drug interactions Dofetilide may cause ventricular arrhythmias with QT prolongation, including torsades de pointes, which are directly related to dofelitide plasma concentrations. When taking certain diuretics (mainly thiazides) simultaneously, the risk of developing thrombocytopenia increases, especially in elderly and senile patients. Biseptol may enhance the effect of anticoagulants to a degree requiring dose modification. Biseptol inhibits the metabolism of phenytoin. In patients taking both drugs, the half-life of phenytoin is increased by approximately 39% and the clearance of phenytoin is decreased by approximately 27%. Biseptol increases the concentration of the free fraction of methotrexate in serum by displacing it from its bonds with proteins. Influence on laboratory test results. Trimethoprim may affect the results of determining the concentration of methotrexate in serum by the enzymatic method, but does not affect them if the determination is carried out by radioimmunological methods. Biseptol may overestimate the results of the Jaffe test with basic picrate for creatinine by approximately 10%. Biseptol may potentiate the effect of concomitantly taken hypoglycemic drugs, sulfonylurea derivatives, and thus increase the risk of hypoglycemia. Biseptol may increase plasma concentrations of digoxin in some elderly patients. Biseptol may reduce the effectiveness of tricyclic antidepressants. In patients after kidney transplantation treated with Biseptol and cyclosporine, transient dysfunction of the transplanted kidney is observed, manifested by an increase in serum creatinine levels, which is likely due to the effect of trimethoprim. Biseptol with pyrimethamine can cause megaloblastic anemia. Sulfonamides exhibit chemical similarities to some antithyroid drugs, diuretics (acetazolamide and thiazides), and oral antidiabetic drugs, which may cause cross-allergy. Special instructions Rare cases of life-threatening complications associated with the use of sulfonamides have been described, including Stevens-Johnson syndrome, Lyell's syndrome, acute liver necrosis, aplastic anemia, other bone marrow damage and respiratory sensitization. If during treatment with Biseptol you experience symptoms indicating the possibility of complications, especially rash, sore throat, fever, joint pain, cough, shortness of breath or hepatitis, you should stop taking the drug and consult a doctor immediately. It is not recommended for use in cases of tonsillitis and pharyngitis caused by group A beta-hemolytic streptococcus due to widespread strain resistance. Use with caution is necessary when prescribing co-trimoxazole to patients with folic acid deficiency (elderly people, people suffering from alcohol dependence, malabsorption syndrome), porphyria, thyroid dysfunction, bronchial asthma and a history of allergic reactions. If a skin rash or diarrhea appears during treatment with Biseptol, its use should be stopped immediately. In patients with glucose-6-phosphate dehydrogenase deficiency, Biseptol can cause hemolysis. In elderly patients, the risk of severe side effects of Biseptol increases, including kidney or liver damage. The most commonly reported severe side effects of Biseptol in elderly patients are severe skin reactions, bone marrow depression, and thrombocytopenia with or without purpura. Taking Biseptol and diuretics together increases the risk of purpura. In AIDS patients taking Biseptol for diseases caused by Pneumocystis carinii, undesirable effects are more likely to occur, especially rash, fever, leukopenia, increased serum aminotransferase levels, hypokalemia and hyponatremia. When prescribing Biseptol to patients who are already receiving anticoagulants, one should be aware of the possible enhancement of the anticoagulant effect. In such cases, it is necessary to re-determine the blood clotting time. The drug should not be prescribed to patients with hereditary fructose intolerance. Caution must be exercised in patients with porphyria or thyroid dysfunction. In patients taking Biseptol in high doses, serum potassium levels should be regularly monitored. Large doses of Biseptol, such as those used in the treatment of Pneumocystis pneumonia, can lead to a progressive but reversible increase in serum potassium in a significant number of patients. Hyperkalemia can be caused even by taking recommended doses of the drug if it is prescribed against the background of potassium metabolism disorders, renal failure, or concomitant use of drugs that provoke hyperkalemia. When treating with large doses of Biseptol, the possibility of developing hypoglycemia should be taken into account, usually a few days after the start of treatment. The risk of hypoglycemia is higher in patients with impaired renal function, liver disease, and malnutrition. While taking Biseptol (as well as while taking other antibacterial drugs), pseudomembranous enterocolitis of varying severity from mild to life-threatening can develop, so timely diagnosis of this disease is important in patients who develop diarrhea while using an antibacterial drug. Treatment with antibacterial agents affects changes in 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 enterocolitis. In cases of mild pseudomembranous enterocolitis, drug withdrawal is usually sufficient; in more severe cases, correction of water and electrolyte balance, administration of proteins and antibacterial agents active against Clostridium difficile (metronidazole or vancomycin) are necessary. Drugs that inhibit peristalsis or other drugs that have an astringent effect should not be administered. The product contains parahydroxybenzoates, which can cause allergic reactions (rash, itching) as well as propylene glycol, which can cause symptoms similar to those after drinking alcohol. Excessive sun and UV exposure should be avoided. Features of the effect of the drug on the ability to drive a vehicle and potentially dangerous mechanisms. When using the drug, the following side effects may occur: headache, dizziness, convulsions, nervousness and fatigue, so you should be careful when driving a vehicle and potentially dangerous mechanisms. Overdose Symptoms: lack of appetite, colic-like pain, nausea, vomiting, dizziness, headache, drowsiness, loss of consciousness. Fever, hematuria, and crystalluria may occur. In a later period, bone marrow damage and hepatitis may develop. Long-term use of large doses of Biseptol for a long time can cause bone marrow suppression, manifested by thrombocytopenia, leukopenia or megaloblastic anemia. Treatment: gastric lavage (no later than 2 hours after taking the drug), drinking plenty of fluids, forced diuresis. Acidification of urine accelerates the elimination of trimethoprim, but may increase the risk of sulfonamide crystallization in the kidneys. It is necessary to monitor the blood picture, serum electrolytes and other biochemical indicators of the patient. Hemodialysis is moderately effective, peritoneal dialysis is ineffective. When symptoms of bone marrow damage occur, leakovorin should be used in a dose of 5-15 mg per day. The form of release and packaging of 20 tablets in the contour cell package from the polyvinyl chloride film and aluminum foil. 1 contour package, along with instructions for use in the state and Russian languages, are placed in a cardboard pack. Storage conditions Store at a temperature not exceeding 250C. Keep out of the reach of children! The shelf life of 5 years is not used after the expiration date. Conditions for the vacation from pharmacies according to the recipe manufacturer Pabyanitsky Pharmaceutical Plant Polf JSC st. march. Pilsudskoy 5, 95-200 Pabyanitsa, Poland owner of a registration certificate: Pabyanitsky Pharmaceutical Plant Polf Autonomous Okrug ul. march. Pilsudskoy 5, 95-200 Pabyanitsa, Poland address of the organization receiving in the Republic of Kazakhstan claims from consumers on the quality of products (goods) Representative Office of Pabyanitsky Pharmaceutical Plant Polf in the Republic of Kazakhstan 059000, Almaty, Abai Street, house 109V, business , floor 13, office 13-2. Tel/fax: +7 (727) 2776977. E-mail: [email Protected]
Indications for use of the drug Biseptol
Urinary tract infections caused by drug-sensitive strains of E. coli, Klebsiella spp., Enterobacter spp., Morganella morganii, Proteus mirabilis, Proteus vulgaris; acute otitis media caused by drug-sensitive N. influenzae, Str. pneumoniae; exacerbation of chronic bronchitis caused by drug-sensitive N. influenzae, Str. pneumoniae; bacteriologically confirmed pneumonia caused by Pneumocystis carinii and prevention of infection with this microorganism in patients at risk (for example, HIV-infected); infections of the digestive tract caused by susceptible Shigella flexneri, Shigella sonnei; travelers' diarrhea caused by enterotoxigenic strains of E. colli; toxoplasmosis; nocardiosis.
Use of the drug Biseptol
For inflammatory diseases of the urinary tract, infections of the digestive tract caused by Shigella , and exacerbation of chronic bronchitis in adults, the average dose is 960 mg (2 tablets of Biseptol 400/80 mg, 8 tablets of Biseptol 100/20 mg) orally 2 times a day. For inflammatory diseases of the urinary tract, the drug is taken for 10–14 days, for exacerbation of chronic bronchitis - 14 days, for infections of the digestive tract caused by Shigella - 5 days. In patients with a creatinine clearance of 15–30 ml/min, the dose should be reduced by half. If creatinine clearance is ≤15 ml/min, the drug is not used. For inflammatory diseases of the urinary tract, infections of the digestive tract caused by Shigella, and acute otitis media in children, a dose of 48 mg/kg (40/8 mg/kg) of body weight per day is prescribed in 2 doses with an interval of 12 hours. The dose for children is not should exceed the adult dose. For inflammation of the urinary tract and acute otitis, the drug is taken for 10 days, for infections of the digestive tract caused by Shigella - 5 days. For travelers' diarrhea, a dose of 960 mg is prescribed (2 tablets of Biseptol 400/80 mg, 8 tablets of Biseptol 100/20 mg) with an interval of 12 hours. For pneumonia caused by Pneumocystis carinii in adults and children, the recommended dose of the drug is 90–120 mg/day. kg (75/15 mg/kg - 100/20 mg/kg) body weight per day in divided doses taken every 6 hours for 14–21 days. To prevent pneumonia caused by Pneumocystis carinii, adults are prescribed 900/60 mg of the drug once a day. The daily dose should not exceed 1920 mg (16 tablets of 100/20 mg, 4 tablets of 400/80 mg).
Biseptol suspension (vial 240mg/5ml 80ml)
A country
Poland
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.
Active substance
Co-trimoxazole [Sulfamethoxazole + Trimethoprim]
Compound
Bottle 80 ml
Sulfamethoxazole 200 mg, trimethoprim 40 mg per 5 ml. Excipients: macrogol glyceryl hydroxystearate, magnesium aluminosilicate, carmellose sodium, citric acid monohydrate, methylhydroxybenzoate, propylhydroxybenzoate, sodium saccharinate, sodium hydrogen phosphate dodecahydrate, maltitol, strawberry flavoring, propylene glycol, purified water. Suspension for oral administration is white or light cream in color, with a strawberry odor.
pharmachologic effect
Co-trimoxazole is a combined antimicrobial drug consisting of sulfamethoxazole and trimethoprim in a ratio of 5:1. Sulfamethoxazole, similar in structure to para-aminobenzoic acid (PABA), disrupts the synthesis of dihydrofolic acid in bacterial cells, preventing the inclusion of PABA in its molecule. Trimethoprim enhances the effect of sulfamethoxazole by interfering with the reduction of dihydrofolic acid to tetrahydrofolic acid, the active form of folic acid responsible for protein metabolism and microbial cell division. Both components thus disrupt the formation of folic acid, which is necessary for the synthesis of purine compounds by microorganisms, and then nucleic acids (RNA and DNA). This disrupts the formation of proteins and leads to the death of bacteria. In vitro it is a broad-spectrum bactericidal agent, but sensitivity may vary by geographic location. Typically susceptible pathogens (minimum inhibitory concentration (MIC) less than 80 mg/l for sulfamethoxazole): Moraxella (Branhamella) catarrhalis, Haemophilus influenzae (beta-lactamase-forming and beta-lactamase-non-forming strains), Haemophilus parainfluenzae, Escherichia coli (including enterotoxogenic strains), Citrobacter spp. (including Citrobacter freundii), Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca), Enterobacter cloaceae, Enterobacter aerogenes, Hafnia alvei, Serratia spp. (including Serratia marcescens, Serratia liquefaciens), Proteus mirabilis, Proteus vulgaris, Morganella morganii. Shigella spp. (including Shigella flexneri. Shigella sonnet). Yersinia spp. (including Yersinia enterocolitica), Vibrio cholerae, Edwardsiella tarda, Alcaligenes faecalis, Burkholderia (Pseudomonas) cepacia, Burkholderia (Pseudomonas) pseudomallei. Also, Brucella spp.. Listeria monocytogenes, Nocardia asteroides, Pneumocystis carinii, Cyclospora cayetanensis may be sensitive. Partially sensitive pathogens (MIC 80-160 mg/l for sulfamethoxazole): coagulase-negative strains of Staphylococcus spp. (including methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus). Streptococcus pneumoniae (penicillin-sensitive and penicillin-resistant strains), Haemophilus ducreyi, Providencia spp. (including Providencia rettgeri), Salmonella typhi. Salmonella enteritidis, Slenotrdphomonas maltophilia (formerly called Xanthomonas maltophilia), Acinetobacter Iwoffii, Acinetobacter baumanii, Aeromonas hydrophila. Resistant pathogens (MIC more than 160 mg/l for sulfamethoxazole): Mycoplasma spp., Mycobacterium tuberculosis, Treponema pallidum, Pseudomonas aeruginosa. If the drug is prescribed empirically, it is necessary to take into account the local characteristics of drug resistance of possible pathogens of a particular infectious disease. For infections that may be caused by partially susceptible microorganisms, it is recommended to conduct a sensitivity test to exclude pathogen resistance.
Indications for use
Infectious and inflammatory diseases caused by microorganisms sensitive to the drug: - respiratory tract infections: chronic bronchitis (exacerbation), Pneumocystis pneumonia (treatment and prevention) in adults and children; — infections of the ENT organs: otitis media (in children); - infections of the genitourinary organs: urinary tract infections, chancroid; — gastrointestinal infections: typhoid fever, paratyphoid fever, shigellosis (caused by sensitive strains of Shigella flexneri and Shigella sonnei); - travelers' diarrhea caused by enterotoxic strains of Escherichia coli, cholera (in addition to fluid and electrolyte replacement); - other bacterial infections (possibly combined with antibiotics): nocardiosis, brucellosis (acute), actinomycosis, osteomyelitis (acute and chronic), South American blastomycosis, toxoplasmosis (as part of complex therapy).
Side effects
From the nervous system: headache, dizziness, aseptic meningitis, peripheral neuritis, convulsions, ataxia, tinnitus, depression, hallucinations, apathy, nervousness. From the respiratory system: pulmonary infiltrates: eosinophilic infiltrate, allergic alveolitis (cough, shortness of breath). From the digestive system: nausea, vomiting, loss of appetite, diarrhea, gastritis, abdominal pain, glossitis, stomatitis, cholestasis, increased activity of liver transaminases, hepatitis (including cholestatic), hepatonecrosis, “vanishing bile duct” syndrome ( ductopenia), hyperbilirubinemia, pseudomembranous colitis, acute pancreatitis. From the hematopoietic organs: leukopenia, neutropenia, thrombocytopenia, hypoprothrombinemia, agranulocytosis, anemia (megaloblastic, hemolytic/autoimmune or aplastic), methemoglobinemia, eosinophilia. From the urinary system: interstitial nephritis, impaired renal function, hematuria, increased blood urea, hypercreatininemia, toxic nephropathy with oliguria and anuria, crystalluria. From the musculoskeletal system: arthralgia, myalgia, rhabdomyolysis (mainly in patients with AIDS). Allergic reactions: fever, angioedema, itching, photosensitivity, skin rash, urticaria, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, allergic myocarditis, conjunctival hyperemia , sclera, anaphylactic/anaphylactoid reactions, serum sickness, hemorrhagic vasculitis (Henoch-Schönlein purpura), periarteritis nodosa, lupus-like syndrome. Other: hyperkalemia (mainly in AIDS patients during treatment of Pneumocystis pneumonia), hyponatremia, hypoglycemia, weakness, fatigue, insomnia, candidiasis.
Contraindications
- liver and/or renal failure (creatinine clearance less than 15 ml/min);
- aplastic anemia, B12-deficiency anemia, agranulocytosis, leukopenia; - deficiency of glucose-6-phosphate dehydrogenase; - simultaneous use with dofetilide; - lactation period; - children up to 2 months or up to 6 weeks at birth from a mother with HIV infection; - hypersensitivity to sulfonamides, trimethoprim and/or other components of the drug. With caution: dysfunction of the thyroid gland, history of severe allergic reactions, bronchial asthma, folic acid deficiency, porphyria, pregnancy. Use during pregnancy and lactation During pregnancy, the drug should be prescribed only if the expected benefit from its use outweighs the possible risk to the fetus, since both trimethoprim and sulfamethoxazole cross the placental barrier and, thus, can affect the metabolism of folic acid. acids. In late pregnancy, the use of the drug should be avoided due to the possible risk of developing kernicterus in newborns. Due to the fact that trimethoprim and sulfamethoxazole pass into breast milk, the use of co-trimaxazole during lactation is contraindicated. Pregnant women receiving the drug are recommended to take 5 mg of folic acid per day.
Use in children Contraindicated: - children under 2 months of age or up to 6 weeks at birth from a mother with HIV infection. Children: from 2 months (or 6 weeks at birth from mothers with HIV infection) to 5 months - 120 mg, from 6 months to 5 years - 240 mg, from 6 to 12 years - 480 mg every 12 hours, which approximately corresponds to a dose of 36 mg/kg per day.
Use in elderly patients The duration of treatment should be as short as possible, especially in elderly and senile patients.
Mode of application
Inside, after eating with a sufficient amount of liquid. Adults and children over 12 years of age: - 960 mg every 12 hours; - for severe infections - 1440 mg every 12 hours; - for urinary tract infection - 10-14 days, for exacerbation of chronic bronchitis - 14 days, for traveler's diarrhea and shigellosis - 5 days. The minimum dose and dose for long-term treatment (more than 14 days) is 480 mg every 12 hours. Children: from 2 months (or 6 weeks at birth from mothers with HIV infection) to 5 months - 120 mg, from 6 months to 5 years - 240 mg, from 6 to 12 years - 480 mg every 12 hours, which approximately corresponds to a dose of 36 mg/kg per day. The course of treatment for urinary tract infections and acute otitis media is 10 days, for shigellosis – 5 days. For severe infections, doses for children can be increased by 50%. For acute infections, the minimum duration of treatment is 5 days; after the symptoms disappear, therapy is continued for 2 days. If after 7 days of therapy there is no clinical improvement, the patient’s condition should be re-evaluated for possible treatment adjustment. Soft chancre - 960 mg every 12 hours; If after 7 days healing of the skin element does not occur, therapy can be extended for another 7 days. However, the lack of effect may indicate resistance of the pathogen. For women with acute uncomplicated urinary tract infections, a single dose of 1920-2880 mg is recommended, if possible in the evening after meals or before bed. For pneumonia caused by Pneumocystis carinii - 30 mg/kg 4 times a day with an interval of 6 hours for 14-21 days. For the prevention of pneumonia caused by Pneumocystis carinii, adults and children over 12 years of age - 960 mg/day. For children under 12 years of age - 450 mg/m2 every 12 hours, for 3 consecutive days every week. The total daily dose should not exceed 1920 mg. In this case, you can use the following instructions: for 0.26 m2 of body surface - 120 mg, respectively for 0.53 m2 - 240 mg, for 1.06 m2 - 480 mg. For other bacterial infections, the dose is selected individually depending on age, body weight, kidney function and severity of the disease, for example, for nocardiosis in adults - 2880-3840 mg/day for at least 3 months (sometimes up to 18 months). The course of treatment for acute brucellosis is 3-4 weeks, for typhoid fever and paratyphoid fever - 1-3 months.
special instructions
Co-trimoxazole should be prescribed only in cases where the advantage of such combination therapy over other antibacterial monotherapy drugs outweighs the possible risk. Because the sensitivity of bacteria to antibacterial drugs in vitro varies across different geographic areas and over time, local patterns of bacterial susceptibility should be taken into account when selecting a drug. With long courses of treatment, regular blood tests are necessary, since there is a possibility of hematological changes (most often asymptomatic). These changes can be reversible with the administration of folic acid (3-6 mg/day), which does not significantly impair the antimicrobial activity of the drug. Particular caution should be exercised when treating elderly patients or patients with suspected underlying folate deficiency. The administration of folic acid is also advisable for long-term treatment in high doses. If there is a significant decrease in the number of any blood cells, the drug should be discontinued. During treatment, it is also inadvisable to consume foods containing large quantities of PABA - green parts of plants (cauliflower, spinach, legumes), carrots, tomatoes. For long-term courses (especially in cases of renal failure), it is necessary to regularly conduct a general urine test and monitor kidney function. To prevent crystalluria, it is recommended to maintain a sufficient volume of urine excreted. The likelihood of toxic and allergic complications of sulfonamides increases significantly with a decrease in the filtration function of the kidneys. At the first appearance of skin rash or any other severe adverse reaction, the drug should be discontinued. If cough or shortness of breath suddenly appears or worsens, the patient should be re-examined and discontinuation of drug treatment should be considered. Excessive sunlight and ultraviolet radiation should be avoided. The risk of side effects is significantly higher in patients with AIDS. It is not recommended for use in diseases caused by group A beta-hemolytic streptococcus due to widespread strain resistance. Cases of pancytopenia have been described in patients taking co-trimoxazole. Trimethoprim has low affinity for human dehydrofolate reductase, but may increase the toxicity of methotrexate, especially in the presence of other risk factors such as old age, hypoalbuminemia, renal impairment, bone marrow suppression. Such adverse reactions are more likely if methotrexate is prescribed in large doses. To prevent myelosuppression, it is recommended to prescribe folic acid or calcium folinate to such patients. Trimethoprim disrupts phenylalanine metabolism, but this does not affect patients with phenylketonuria provided they follow an appropriate diet. Patients whose metabolism is characterized by “slow acetylation” are more likely. The duration of treatment should be as short as possible, especially in elderly and senile patients. Co-trimoxazole and, in particular, trimethoprim, which is part of it, can affect the results of determining the concentration of methotrexate in serum, carried out by the competitive protein binding method using bacterial dihydrofolate reductase as a ligand. However, when methotrexate is determined by the radioimmune method, interference does not occur. Trimethoprim and sulfamethoxazole can affect the results of the Jaffe test (determination of creatinine by reaction with picric acid in an alkaline medium), and in the normal range the results are overestimated by approximately 10%. Effect on the ability to drive vehicles and operate machinery. Considering the possibility of developing significant side effects, during the treatment period it is necessary to be careful when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Overdose
Symptoms: - nausea, vomiting, intestinal colic, dizziness, headache, drowsiness, depression, fainting, confusion, fever, hematuria, crystalluria; - with prolonged overdose - thrombocytopenia, leukopenia, megaloblastic anemia, jaundice. Treatment: gastric lavage, forced diuresis, acidification of urine increases the excretion of trimethoprim, IM - 5-15 mg/day of calcium folinate (eliminates the effect of trimethoprim on the bone marrow), if necessary - hemodialysis.
Interaction with other drugs
Increases the anticoagulant activity of indirect anticoagulants (anticoagulant dose adjustment), as well as the effect of hypoglycemic drugs and methotrexate (competes for protein binding and renal transport of methotrexate, increasing the concentration of free methotrexate). Reduces the intensity of hepatic metabolism of phenytoin (extends its T1/2 by 39%), increasing its effect and toxic effect. With simultaneous use of co-trimoxazole with pyrimethamine in doses exceeding 25 mg/week, the risk of developing megaloblastic anemia increases. Diuretics (usually thiazides and in elderly patients) increase the risk of thrombocytopenia. May increase serum digoxin concentrations, especially in elderly patients; monitoring of serum digoxin concentrations is necessary. The effectiveness of tricyclic antidepressants when taken in combination with co-trimoxazole may be reduced. Patients receiving co-trimoxazole and cyclosporine after kidney transplantation may experience a reversible deterioration in renal function, manifested by an increase in creatinine levels. Medicines that inhibit bone marrow hematopoiesis increase the risk of myelosuppression. When co-trimoxazole is used together with indomethacin, the concentration of sulfamethoxazole in the blood may increase. One case of toxic delirium has been described after simultaneous administration of co-trimoxazole and amantadine. When used simultaneously with ACE inhibitors, especially in elderly patients, hyperkalemia may develop. Trimethoprim, by inhibiting the renal transport system, increases the AUC of dofetilide by 103% and the Cmax of dofetilide by 93%. With increasing concentrations, dofetilide may cause ventricular arrhythmias with prolongation of the QT interval, including tachycardia. The simultaneous administration of dofetilide and trimethoprim is contraindicated.
Dispensing conditions in pharmacies
On prescription
Side effects of the drug Biseptol
The most common side effects observed during treatment with Biseptol are from the digestive tract (nausea, vomiting, anorexia) and allergic skin reactions (rash, urticaria). Rarely, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), acute liver necrosis, and aplastic anemia may occur. In addition, hemolytic, megaloblastic anemia, eosinophilia, methemoglobinemia, hypoprothrombinemia may develop; allergic myocarditis; chills, fever, photophobia, anaphylactic reactions, vascular edema, skin itching, Henoch-Schönlein disease, urticaria, erythema multiforme, allergic rashes, desquamation dermatitis, serum sickness, and rarely, periarteritis nodosa, lupus syndrome may occur. From the digestive tract - diarrhea, abdominal pain, anorexia, nausea, pseudomembranous colitis, vomiting, increased activity of liver enzymes and serum creatinine levels, stomatitis, glossitis, pancreatitis, hepatitis (sometimes with cholestatic jaundice). From the genitourinary system : renal failure, interstitial nephritis, nephrotoxic syndrome, anuria, increased levels of non-protein nitrogen and creatinine in the blood serum. Possible metabolic disorders - hyperkalemia, hyponatremia. From the nervous system : apathy, meningitis, ataxia, headache, depression, convulsions, hallucinations, increased excitability, tinnitus, peripheral neuritis. Sulfonamides are close in chemical structure to some antithyroid drugs, diuretics (acetazolamide and thiazides), as well as oral antidiabetic drugs, which may cause the development of cross-allergy. Hypoglycemia and increased diuresis are rarely noted. From the musculoskeletal system : arthralgia, myalgia. From the respiratory system : shortness of breath, cough, formation of infiltrates in the lungs. Possible weakness, feeling tired, insomnia.
BISEPTOL
Directions for use and doses
The drug is taken orally after a meal with a sufficient amount of liquid.
The dose is prescribed individually.
Children from 3 to 5 years: 2 tablets (120 mg) 2 times a day.
Children from 6 to 12 years old: 4 tablets (120 mg) or 1 tablet (480 mg) 2 times a day.
For pneumonia - 100 mg/kg/day (based on sulfamethoxazole), interval between doses - 6 hours, course of treatment - 14 days.
For gonorrhea - 2 g of sulfamethoxazole 2 times a day with an interval of 12 hours.
Adults and children over 12 years of age: 960 mg 2 times a day, with long-term therapy 480 mg 2 times a day. The drug is usually well tolerated.
From the nervous system: headache, dizziness; in some cases - aseptic meningitis, depression, apathy, tremor, peripheral neuritis.
From the respiratory system: bronchospasm, suffocation, cough, pulmonary infiltrates.
From the digestive system: nausea, vomiting, loss of appetite, diarrhea, gastritis, abdominal pain, glossitis, stomatitis, cholestasis, increased activity of liver transaminases, hepatitis, sometimes with cholestatic jaundice, hepatonecrosis, pseudomembranous enterocolitis, pancreatitis.
From the hematopoietic organs: leukopenia, neutropenia, thrombocytopenia,
agranulocytosis, megaloblastic anemia, aplastic and hemolytic anemia, eosinophilia, hypoprothrombinemia, methemoglobinemia.
From the urinary system: polyuria, interstitial nephritis, impaired renal function, crystalluria, hematuria, increased urea concentration, hypercreatininemia, toxic nephropathy with oliguria and anuria.
From the musculoskeletal system: arthralgia, myalgia.
Allergic reactions: itching, photosensitivity, urticaria, drug fever, rash, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrosis (Lyell's syndrome), exfoliative dermatitis, allergic myocarditis, fever, angioedema, scleral hyperemia.
Other: hypoglycemia, hyperkalemia, hyponatremia.
The duration of treatment is from 5 to 14 days. In case of severe and/or chronic form of infectious diseases, it is permissible to increase the single dose by 30-50%.
If the course of treatment is extended for more than 5 days and/or the dose is increased, hematological monitoring is necessary; in case of changes in the blood picture, it is necessary to prescribe folic acid 5-10 mg per day.
Dosage in patients with renal failure: in patients with creatinine clearance 15-30 ml/min. half the standard dose should be used; if creatinine clearance is less than 15 ml/min. The use of co-trimoxazole is not recommended.
Special instructions for the use of the drug Biseptol
Biseptol should be used with caution in patients with liver or kidney failure, folic acid deficiency (for example, in the elderly, alcoholics, patients receiving anticonvulsants, in people with malabsorption syndrome or nutritional deficiency), with severe allergic diseases, asthma and hematopoietic disorders. Patients should consume sufficient fluids to prevent crystalluria and renal tubular blockage. With prolonged treatment, it is necessary to regularly monitor the blood count, liver and kidney function. In elderly patients, when treated with Biseptol, the risk of kidney or liver damage, the development of severe skin reactions, and inhibition of erythropoiesis increases. AIDS patients who use Biseptol in connection with Pneumocystis infection more often develop symptoms such as rash, fever, leukopenia, increased aminotransferase activity, hyperkalemia and hyponatremia. During treatment, direct sunlight exposure should be avoided (due to the risk of photosensitivity). The drug should not be used for tonsillitis caused by β-hemolytic streptococci. Trimethoprim can affect the results of determining the concentration of methotrexate in blood serum using the enzymatic method, but does not affect the results when using the radioimmunological method. Biseptol can increase the results of the Jaffe test for creatinine using basic picrate by approximately 10%.
Biseptol® 480 (Biseptol® 480)
Hypersensitivity and allergic reactions:
At the first appearance of skin rash or any other severe adverse reaction, the drug should be discontinued. Patients with a tendency to allergic reactions and bronchial asthma should be prescribed co-trimoxazole with caution.
Infiltrates in the lungs (like eosinophilic and allergic alveolitis) can manifest themselves with symptoms such as cough or shortness of breath. If these symptoms appear or suddenly increase, it is necessary to re-examine the patient and consider stopping treatment with co-trimoxazole.
Kidney disorders:
Sulfonamides, including co-trimoxazole, may increase diuresis, especially in patients with edema caused by heart failure. Careful monitoring of renal function and serum potassium concentrations is necessary in patients receiving high doses of co-trimoxazole (including in the treatment of pneumonia caused by P. jirovecii), as well as in the following groups of patients: patients with a history of impaired potassium metabolism receiving standard doses drug; patients with renal failure; patients receiving drugs that contribute to the development of hyperkalemia.
Serious adverse reactions:
Fatalities, although rare, have been reported due to adverse reactions such as blood abnormalities, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), drug reaction with eosinophilia and systemic manifestations (DRESS syndrome) and fulminant liver necrosis.
Special patient groups:
in elderly and senile patients, as well as in patients with concomitant diseases, for example, impaired renal and/or liver function, or while taking other drugs, there is an increased risk of severe adverse reactions; in these cases, the risk is related to the dose and duration of therapy. Patients should be informed of the signs and symptoms of these serious side effects and closely monitored for skin reactions.
The risk of severe skin reactions is greatest in the first few weeks of treatment. If signs or symptoms of severe skin reactions occur (eg, progressive rash, often with blisters or associated mucosal lesions), cotrimoxazole therapy should be discontinued. The course of these reactions is largely determined by early diagnosis and immediate cessation of all suspected medications, which improves the prognosis. Following the occurrence of severe skin reactions associated with the use of co-trimoxazole, the patient should never re-use co-trimoxazole.
The duration of treatment with co-trimoxazole should be as short as possible, especially in elderly and senile patients.
If renal function is impaired, the dose should be adjusted. Patients with severe renal impairment (creatinine clearance 15-30 ml/min) receiving co-trimoxazole should be carefully monitored for the development of symptoms of toxicity (nausea, vomiting, hyperkalemia).
In elderly and senile patients, as well as in patients with pre-existing folic acid deficiency or renal failure, hematological changes characteristic of folic acid deficiency may occur. They disappear after administration of folic acid.
Due to the possibility of hemolysis, co-trimoxazole should not be prescribed to patients with glucose-6-phosphate dehydrogenase deficiency.
As with any sulfonamides, caution must be exercised in patients with thyroid dysfunction.
Patients whose metabolism is characterized by “slow acetylation” are more likely to develop idiosyncrasy to sulfonamides.
Long-term therapy:
with long-term administration of co-trimoxazole, it is necessary to regularly determine the number of blood cells.
If there is a significant decrease in the number of any blood cells, co-trimoxazole should be discontinued.
Patients receiving long-term treatment with co-trimoxazole (especially with renal failure) should regularly undergo a general urine test and monitor kidney function. During treatment, it is necessary to ensure sufficient fluid intake and adequate diuresis to prevent crystalluria.
Pseudomembranous colitis caused by Clostridium difficile
, may appear both during long-term use and 2-3 weeks after stopping treatment; manifested by diarrhea, leukocytosis, fever, abdominal pain (sometimes accompanied by the release of blood and mucus in the stool). If these phenomena occur, in mild cases, it is sufficient to discontinue treatment and use ion exchange resins (colestyramine, colestipol); in severe cases, replacement of the loss of fluid, electrolytes and protein, and the appointment of oral vancomycin or metronidazole are indicated. Do not use medications that inhibit intestinal motility.
The drug Biseptol 480 should not be used in the treatment of pharyngitis caused by beta-hemolytic streptococci from group A. The eradication of these bacteria in the nasopharynx with this drug is less effective than with the use of penicillin.
The administration of co-trimoxazole should be avoided in patients with established porphyria or in patients at risk of developing porphyria. Both trimethoprim and sulfonamides (although not specific to sulfamethoxazole) are associated with clinical exacerbations of porphyria.
Due to the propylene glycol content (2000 mg/5 ml), the drug may cause symptoms similar to those that occur after drinking alcohol.
One ampoule of the drug contains 12.4% vol. ethanol (alcohol), i.e. up to 500 mg/5 ml, which is equivalent to 11.88 ml beer or 4.95 ml wine. It is harmful for patients with alcohol disease. The alcohol content should be taken into account when using the drug in pregnant or breastfeeding women, children and patients at high risk, such as those with liver disease or epilepsy.
Biseptol 480 contains sodium disulfite (5 mg/5 ml), which in rare cases can cause severe hypersensitivity reactions and bronchospasm.
The drug Biseptol 480 contains sodium (39 mg/5 ml). This should be taken into account in patients on a controlled sodium diet.
Biseptol 480 contains two antibacterial components. The drug Biseptol 480 should be used only in cases where, in the opinion of the doctor, the expected benefit from its use exceeds any possible risk; the possibility of using single-component effective antibacterial drugs should be considered.
Interactions of the drug Biseptol
NSAIDs, antidiabetic drugs of the sulfonylurea group, diphenin, indirect anticoagulants, barbiturates increase the risk of side effects. Ascorbic acid increases the risk of developing crystalluria. In elderly patients, the combined use of Biseptol with certain diuretics, especially thiazides, increases the risk of developing thrombocytopenia. Biseptol may increase serum digoxin concentrations, especially in elderly patients. When the drug is used simultaneously with tricyclic antidepressants, the effectiveness of the latter is reduced. The drug reduces the reliability of oral contraception. Biseptol may enhance the effect of anticoagulants, which requires a reduction in the dose of these drugs. Biseptol inhibits the metabolism of phenytoin: in individuals taking both drugs simultaneously, the half-life of phenytoin increases by approximately 39%, and its clearance decreases by approximately 27%. Biseptol increases the concentration of the free fraction of methotrexate in the blood serum due to its displacement from protein bonds. With simultaneous use of the drug by patients who take pyrimitamine at a dose higher than 25 mg/week for the prevention of malaria, megaloblastic anemia may develop.
Overdose of the drug Biseptol
The dose of Biseptol that poses a threat to life is unknown. In case of an overdose of sulfonamides, anorexia, colic-like pain, nausea, vomiting, dizziness, headache, drowsiness, and loss of consciousness are observed. Fever, hematuria, crystalluria, bone marrow suppression, and hepatitis are possible. Acute overdose of trimethoprim may cause nausea, vomiting, dizziness, headache, depression, confusion, and bone marrow depression. If symptoms of overdose appear, it is necessary to stop using the drug, induce vomiting, and prescribe a large amount of fluid in case of insufficient diuresis and normal renal function. Acidification of urine accelerates the elimination of trimethoprim, but may increase the risk of sulfonamide crystallization in the kidneys. The blood picture, the level of electrolytes in the blood serum and other biochemical parameters should be monitored. If symptoms of bone marrow suppression or hepatitis occur, appropriate therapy is prescribed. Hemodialysis is ineffective. With chronic intoxication, thrombocytopenia, leukopenia or megaloblastic anemia develops. In this case, calcium folinate should be prescribed at a dose of 5–15 mg/day.
