Biseptol^® 480 (Concentrate) Instructions for Use

ATC Code

J01EE01 (Sulfamethoxazole and trimethoprim)

Active Substance

Co-trimoxazole (BAN)

Clinical-Pharmacological Group

Antibacterial sulfonamide drug

Pharmacotherapeutic Group

Combined antimicrobial agent

Pharmacological Action

A combined antibacterial drug containing sulfamethoxazole, which has an average duration of action and inhibits the synthesis of folic acid through competitive antagonism with para-aminobenzoic acid, as well as trimethoprim, an inhibitor of bacterial dihydrofolic acid reductase.

The combination of both drugs produces a synergistic effect of antibacterial action, which is why bacterial resistance occurs less frequently compared to other drugs.

Biseptol has a broad spectrum of antibacterial action. It is active against : Streptococcus (Streptococcus pneumoniae), Neisseria meningitidis, Neisseria gonorrhoeae (including enterotoxigenic strains), Staphylococcus, Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis, Proteus spp., Haemophilus influenzae, Salmonella spp. (including Salmonella typhi and Salmonella paratyphi), Vibrio cholerae, Bacillus anthracis, Listeria spp., Nocardia asteroides, Bordetella pertussis, Enterococcus faecalis, Pasteurella spp., Brucella spp., Mycobacterium spp. (including Mycobacterium leprae), Citrobacter, Enterobacter spp., Legionella pneumonia, Providencia, some species of Pseudomonas (except P.aeruginosa), Serratia marcescens, Yersinia spp., Morganella spp., Chlamydia spp. (including Chlamydia trachomatis, Chlamydia psittaci), Shigella, Plasmodium spp., Toxoplasma gondii, Pneumocystis carini, Actinomyces israelii, Coccidioides immitis, Histoplasma capsulatum, Leishmania spp.

Resistant to the drug Corynebacterium spp., Pseudomonas aeruginosa, Mycobacterium tuberculosis, Troponema spp., Leptospira spp., viruses.

It suppresses the vital activity of Escherichia coli, leading to a decrease in the synthesis of thiamine, riboflavin, nicotinic acid and other B vitamins in the intestine. The duration of the therapeutic effect is 7 hours.

Pharmacokinetics

The drug quickly penetrates into tissues and biological fluids of the body.

It is well distributed. It penetrates the blood-brain barrier, the placental barrier and into breast milk. It creates concentrations in the lungs and urine that exceed the content in plasma. It accumulates to a lesser extent in bronchial secretions, vaginal discharge, secretions and tissues of the prostate gland, middle ear fluid, cerebrospinal fluid, bile, bones, saliva, aqueous humor of the eye, breast milk, and interstitial fluid.

The distribution of both drugs is different: sulfamethoxazole is distributed exclusively in the extracellular space, while trimethoprim is distributed both inside cells and in the extracellular space. Binding to plasma proteins is 66% for sulfamethoxazole and 45% for trimethoprim. Both drugs are metabolized in the liver.

Sulfamethoxazole is metabolized to a greater extent (with the formation of acetylated derivatives); metabolites do not have antimicrobial activity.

They are excreted by the kidneys, both by filtration and by active tubular secretion, in the form of metabolites (80% within 72 hours) and unchanged (20% of sulfamethoxazole, 50% of trimethoprim), the concentration of active substances in urine is significantly higher than in blood. An insignificant amount of the drug is excreted through the intestines. T_1/2 of sulfamethoxazole is 9-11 hours, of trimethoprim is 10-12 hours; in children it is significantly less and depends on age: up to one year – 7-8 hours, 1-10 years – 5-6 hours. In elderly patients and patients with impaired renal function, T_1/2 increases.

Indications

• Acute and chronic infections of the genitourinary organs: urethritis, pyelonephritis, cystitis, pyelitis, prostatitis, epididymitis, gonorrhea, chancroid, venereal lymphogranuloma, inguinal granuloma;
• Respiratory tract infections: bronchitis (acute and chronic), bronchiectasis, lobar pneumonia, bronchopneumonia, pneumocystis pneumonia, pleural empyema, lung abscess;
• ENT infections: otitis media, sinusitis, laryngitis, tonsillitis, scarlet fever;
• Gastrointestinal infections: typhoid fever, paratyphoid fever, salmonella carriage, cholera, dysentery, cholecystitis, cholangitis, gastroenteritis caused by enterotoxic strains of E.coli;
• Skin and soft tissue infections: acne, furunculosis, pyoderma, abscess and wound infections, infections after surgical interventions;
• Sepsis, acute brucellosis, toxoplasmosis, osteomyelitis, osteoarticular infections, South American blastomycosis, malaria (Plasmodium falciparum), whooping cough (as part of complex therapy).

ICD codes

Dosage Regimen

Concentrate

The drug should be administered intravenously by drip, after dilution (for example, with a 5% dextrose solution, 0.9% sodium chloride solution, Ringer’s solution or 0.45% sodium chloride solution with 2.5% dextrose solution). The solution for infusion must be prepared immediately before administration, with thorough mixing. After dilution, the resulting solution should be used within 6 hours.

The drug should not be used as a rapid intravenous injection.

Adults and children over 12 years of age are prescribed 960 mg (2 ampoules of 5 ml, diluted in 250 ml of solution) every 12 hours. In particularly severe cases, 1440 mg (3 ampoules) 2-3 times/day should be prescribed.

Children under 12 years of age are prescribed a daily dose based on 36 mg/kg of body weight in two equal doses.

Patients with renal failure (with creatinine clearance 15-30 ml/min) are prescribed 50% of the average therapeutic dose.

Adverse Reactions

Biseptol is usually well tolerated by patients. However, the following effects may be noted

From the gastrointestinal tract: anorexia, gastritis, abdominal pain, glossitis, stomatitis, cholestasis, increased activity of liver transaminases, hepatitis, pseudomembranous enterocolitis, nausea, vomiting, diarrhea, liver necrosis.

From the central nervous system headaches and dizziness. In some cases – aseptic meningitis, depression, apathy, tremor, peripheral neuritis.

From the respiratory system bronchospasm, pulmonary infiltrates.

From the hematopoietic organs rarely – neutropenia, agranulocytosis, megaloblastic anemia, leukopenia, thrombocytopenia, hypoprothrombinemia.

From the urinary system polyuria, interstitial nephritis, impaired renal function, crystalluria, hematuria, increased urea content, hypocreatininemia, toxic nephropathy with oliguria and anuria.

From the musculoskeletal system arthralgia, myalgia.

Allergic reactions skin rashes and itching, photosensitivity, rash, polymorphic erythema, exfoliative dermatitis, allergic myocarditis, increased body temperature, angioedema, redness of the sclera.

Local reactions thrombophlebitis (at the venipuncture site), pain at the injection site.

Other hypoglycemia

Contraindications

• Megaloblastic anemia due to folic acid deficiency, aplastic anemia, B₁₂-deficiency anemia, agranulocytosis, leukopenia;
• Glucose-6-phosphate dehydrogenase deficiency;
• Hyperbilirubinemia in children;
• Hepatic and/or renal failure (creatinine clearance less than 15 ml/min);
• Age under 6 years (only for intramuscular administration);
• Pregnancy;
• Lactation period;
• Increased individual sensitivity to sulfonamides or trimethoprim.

The drug should not be used in premature infants, newborns and infants under 2 months of age.

Use with caution in cases of folic acid deficiency, bronchial asthma, thyroid diseases, impaired liver and kidney function.

Use in Pregnancy and Lactation

The drug should not be prescribed during pregnancy and during breastfeeding.

Use in Hepatic Impairment

Contraindicated

• Hepatic insufficiency.

Use in Renal Impairment

Contraindicated

• Renal failure (creatinine clearance less than 15 ml/min).

Patients with renal failure (with creatinine clearance 15-30 ml/min) are prescribed 50% of the average therapeutic dose.

Pediatric Use

The drug should not be used in premature infants, newborns and infants under 2 months of age.

Children under 12 years of age are prescribed a daily dose based on 36 mg/kg of body weight in two equal doses.

Geriatric Use

Elderly patients are recommended to additionally prescribe 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 with suspected initial folate deficiency.

Special Precautions

In AIDS patients treated with co-trimoxazole for Pneumocystis carinii infection, adverse effects are more common: skin rashes, increased body temperature, leukopenia.

It is advisable to determine the concentration of sulfamethoxazole in plasma every 2-3 days immediately before the next infusion. If the concentration of sulfamethoxazole exceeds 150 µg/ml, treatment should be interrupted until it drops below 120 µg/ml.

During long-term treatment, peripheral blood tests, liver and kidney function should be systematically performed.

Elderly patients are recommended to additionally prescribe 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 with suspected initial folate deficiency.

To prevent crystalluria, it is recommended to maintain a sufficient volume of urine output.

The likelihood of toxic and allergic complications from sulfonamides increases significantly when the filtration function of the kidneys is impaired.

It is also inappropriate to consume food products containing large amounts of PABA during treatment – green parts of plants (cauliflower, spinach, legumes), carrots, tomatoes.

Excessive sun and ultraviolet exposure should be avoided.

It is not recommended for use in tonsillitis and pharyngitis caused by group A beta-hemolytic streptococcus due to the widespread resistance of strains.

Effect on the ability to drive vehicles and mechanisms

The drug does not affect the ability to drive vehicles and operate moving machinery.

Overdose

Symptoms: nausea, vomiting, intestinal colic, dizziness, headache, drowsiness, depression, fainting, confusion, blurred vision, fever, hematuria, crystalluria; with prolonged overdose – thrombocytopenia, leukopenia, megaloblastic anemia, jaundice.

Treatment: gastric lavage, acidification of urine increases the excretion of trimethoprim, oral fluid intake, intramuscularly – 5-15 mg/day, calcium folinate (eliminates the effect of trimethoprim on the bone marrow), in case of inhibition of bone marrow hematopoietic functions caused by trimethoprim, folic acid preparations are used intramuscularly to stimulate erythropoiesis (3-6 mg/day. The course of treatment is 5-7 days), if necessary – hemodialysis.

Drug Interactions

Biseptol enhances the effect of phenytoin, oral hypoglycemic agents, warfarin derivatives (prolongation of prothrombin time, bleeding).

In elderly patients, in combination with diuretics (in particular, thiazide diuretics), the risk of thrombocytopenia increases.

Simultaneous use with cyclosporine reduces its concentration in the blood.

The drug should not be administered intravenously in combination with drugs and solutions containing bicarbonates.

Biseptol is pharmaceutically compatible with the following drugs: dextrose for intravenous infusion 5%, sodium chloride for intravenous infusion 0.9%, a mixture of 0.18% sodium chloride and 4% dextrose for intravenous infusion, 6% dextran 70 for intravenous infusion in 5% dextrose or in saline, 10% dextran 40 for intravenous infusion in 5% dextrose or saline, Ringer’s solution for injection.

It increases the anticoagulant activity of indirect coagulants, enhances the effect of hypoglycemic agents and methotrexate.

It reduces the intensity of hepatic metabolism of phenytoin (prolongs its T1/2 by 39%) and warfarin, enhancing their effect.

Rifampicin reduces the T_1/2 of trimethoprim.

Pyrimethamine in doses exceeding 25 mg/week increases the risk of megaloblastic anemia.

Diuretics (more often thiazides) increase the risk of thrombocytopenia.

Benzocaine, procaine, procainamide and other drugs, as a result of the hydrolysis of which PABA is formed, reduce the effect.

Between diuretics (thiazides, furosemide, etc.) and oral hypoglycemic drugs (sulfonylurea derivatives) on the one hand and antimicrobial sulfonamides on the other, a cross-allergic reaction may develop.

Phenytoin, barbiturates, and PAS (para-aminosalicylic acid) enhance the manifestations of folic acid deficiency.

Salicylic acid derivatives enhance the action.

Ascorbic acid, hexamethylenetetramine, and other medicines that acidify urine increase the risk of crystalluria.

Cholestyramine reduces absorption; therefore, it should be taken 1 hour after or 4-6 hours before taking Co-trimoxazole.

It reduces the reliability of oral contraception (inhibits intestinal microflora and reduces the enterohepatic circulation of hormonal compounds).

Storage Conditions

List B. In a place protected from light, at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 5 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.