Groseptol (Tablets) 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

Co-trimoxazole is a broad-spectrum synthetic antimicrobial agent. It acts bactericidally.Sulfamethoxazole has a bacteriostatic effect, which is associated with the inhibition of the utilization process of PABA and the disruption of dihydrofolic acid synthesis in bacterial cells. Trimethoprim inhibits the enzyme involved in the metabolism of folic acid, converting dihydrofolate to tetrahydrofolate. Thus, two successive stages in the biosynthesis of purines and, consequently, nucleic acids, which are necessary for the growth and reproduction of bacteria, are blocked. High concentrations are achieved in the tissues of the lungs, kidneys, prostate gland, in the cerebrospinal fluid, bile, and bones.

Co-trimoxazole is active against gram-positive bacteria: Staphylococcus spp. (including penicillinase-producing strains), Streptococcus spp. (including Streptococcus pneumoniae), Corynebacterium diphtheriae; gram-negative bacteria: Neisseria gonorrhoeae, Escherichia coli, Shigella spp., Salmonella spp., Proteus spp., Enterobacter spp., Klebsiella spp., Yersinia spp., Vibrio cholerae, Haemophilus influenzae; non-spore-forming anaerobic bacteria – Bacteroides spp.

Co-trimoxazole is also active against Chlamydia spp.

Pseudomonas aeruginosa, Treponema spp., Mycoplasma spp., Mycobacterium tuberculosis, as well as viruses and fungi are resistant to co-trimoxazole.

Pharmacokinetics

After oral administration, sulfamethoxazole and trimethoprim are rapidly absorbed from the gastrointestinal tract. Food intake slows down their absorption. They are widely distributed in body tissues and fluids. The plasma protein binding of trimethoprim is 50%, and that of sulfamethoxazole is 66%. The T_1/2 of trimethoprim is 8.6-17 hours, and that of sulfamethoxazole is 9-11 hours. Trimethoprim is excreted in the urine unchanged (about 50%) and as metabolites. Sulfamethoxazole is also excreted in the urine, predominantly unchanged.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to co-trimoxazole: respiratory tract infections (including acute and chronic bronchitis, pleural empyema, bronchiectasis, lung abscess, pneumonia, tonsillitis, pharyngitis); urinary tract infections (including gonococcal urethritis), cystitis, pyelonephritis, prostatitis; gastrointestinal tract infections (including enteritis, typhoid fever, paratyphoid fever, dysentery, cholecystitis, cholangitis); skin and soft tissue infections (including pyoderma, furunculosis, wound infection); septicemia, brucellosis.

ICD codes

Dosage Regimen

Tablets

The dose is set individually. Doses are given based on sulfamethoxazole. Orally for adults and children over 12 years old, the average dose is 0.4-2 g every 12 hours (2 times/day), the course of treatment is 5-14 days. Orally for children aged 2-5 months – 100 mg 2 times/day; from 6 months to 5 years – 200 mg 2 times/day; from 6 to 12 years – 400 mg 2 times/day.

If necessary, it is administered intravenously by drip at 0.8-1.6 g every 12 hours (2 times/day) for 5 days. For children aged from 6 weeks, the dose is set individually, depending on body weight and the clinical situation.

After parenteral therapy, if necessary, switch to oral administration.

The maximum daily dose for adults when taken orally is 3.6 g.

Adverse Reactions

From the digestive system: nausea, vomiting, diarrhea, glossitis, pseudomembranous colitis, cholestatic hepatitis.

Allergic reactions: skin rash, angioedema, Stevens-Johnson syndrome, Lyell’s syndrome.

From the hematopoietic system: leukopenia, neutropenia, thrombocytopenia, agranulocytosis, megaloblastic anemia.

From the urinary system: crystalluria, hematuria, interstitial nephritis.

Local reactions: phlebitis (with intravenous administration).

Other: purpura, thyroid dysfunction.

Contraindications

Parenchymal liver damage; severe renal impairment in the absence of the possibility to control the plasma concentration of sulfamethoxazole and trimethoprim; severe renal failure (CrCl<15 ml/min); severe blood diseases (aplastic anemia, B₁₂-deficiency anemia, agranulocytosis, leukopenia, megaloblastic anemia, anemia associated with folic acid deficiency); hyperbilirubinemia in children; glucose-6-phosphate dehydrogenase deficiency; pregnancy; lactation period (breastfeeding); children under 2 months of age or under 6 weeks (born to mothers with HIV infection) – for suspension and intravenous infusion; children under 2 years of age – for tablets; simultaneous use with dofetilide; hypersensitivity to sulfonamides and trimethoprim.

Use in Pregnancy and Lactation

Sulfonamides and trimethoprim cross the placental barrier and are excreted in breast milk. They can cause the development of kernicterus and hemolytic anemia in the fetus and newborn infants. In addition, the risk of developing fatty liver infiltration in pregnant women increases. Therefore, the use of co-trimoxazole during pregnancy is contraindicated. If it is necessary to prescribe co-trimoxazole during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction. Use with caution in cases of impaired liver function.

Use in Renal Impairment

Contraindicated in severe renal impairment.

In cases of renal impairment, the dose should be reduced and the intervals between doses should be increased.

With parenteral use in patients with renal failure, the plasma concentration of sulfamethoxazole should be determined every 2-3 days before the next intramuscular injection. If the concentration exceeds 150 mcg/ml, treatment should be interrupted until the concentration decreases to 120 mcg/ml.

Geriatric Use

Elderly patients are recommended to be additionally prescribed folic acid.

The risk of adverse reactions increases in elderly patients.

Special Precautions

Co-trimoxazole should be used with caution in patients with possible folic acid deficiency, with a history of allergic reactions, bronchial asthma, impaired liver, kidney, and thyroid function.

With long-term treatment, systematic studies of peripheral blood, liver and kidney functional status should be conducted.

Elderly patients are recommended to be additionally prescribed folic acid.

During treatment with co-trimoxazole, adequate hydration should be ensured (to avoid the development of crystalluria).

In cases of renal impairment, the dose should be reduced and the intervals between doses should be increased.

The risk of developing adverse reactions increases in elderly patients and patients with AIDS.

With parenteral use in patients with renal failure, the plasma concentration of sulfamethoxazole should be determined every 2-3 days before the next intramuscular injection. If the concentration exceeds 150 mcg/ml, treatment should be interrupted until the concentration decreases to 120 mcg/ml.

Children should only be prescribed those co-trimoxazole preparations that are intended for use in pediatrics.

Drug Interactions

With simultaneous use of co-trimoxazole, the effect of indirect anticoagulants is significantly enhanced due to the slowing of their inactivation and their release from plasma protein binding.

With simultaneous use with some sulfonylurea derivatives, an enhancement of the hypoglycemic effect is possible, which is associated with an increase in the concentration of the free fraction of co-trimoxazole.

Simultaneous use of co-trimoxazole and methotrexate may lead to increased toxicity of the latter (in particular, the occurrence of pancytopenia) due to its release from plasma protein binding.

Under the influence of butadione, indomethacin, naproxen, salicylates and some other NSAIDs, an enhancement of the effect of co-trimoxazole with the development of undesirable effects is possible, since active substances are released from blood protein binding and their concentration increases.

Simultaneous intake of diuretics and co-trimoxazole increases the likelihood of thrombocytopenia caused by the latter, especially in elderly patients.

With simultaneous use with sulfamethoxazole, the risk of QT interval prolongation on the ECG increases, so simultaneous use of indapamide with co-trimoxazole should be avoided.

In case of simultaneous prescription of pyrimethamine with co-trimoxazole, the antimicrobial effect is enhanced, since pyrimethamine inhibits the formation of tetrahydrofolic acid, necessary for the synthesis of nucleic acids and proteins. In turn, sulfonamides inhibit the formation of dihydrofolic acid, which is a precursor of tetrahydrofolic acid. This combination is widely used in the treatment of toxoplasmosis.

The absorption of sulfamethoxazole and trimethoprim when taken together with cholestyramine decreases as a result of the formation of insoluble complexes, which leads to a decrease in their concentration in the blood.

It reduces the intensity of hepatic metabolism of phenytoin (prolongs its T_1/2 by 39%), enhancing its effect and toxic action.

With simultaneous use of co-trimoxazole with pyrimethamine in doses exceeding 25 mg/week, the risk of developing megaloblastic anemia increases.

May increase serum concentrations of digoxin, 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.

In patients receiving Co-trimoxazole and cyclosporine after kidney transplantation, reversible deterioration of renal function, manifested by an increase in creatinine levels, may be observed.

With simultaneous use with ACE inhibitors, especially in elderly patients, the development of hyperkalemia is possible.

Trimethoprim, by inhibiting the renal transport system, increases the AUC of dofetilide by 103% and the C_max of dofetilide by 93%. With increased concentration, dofetilide can cause ventricular arrhythmias with QT interval prolongation, including torsades de pointes arrhythmia. Simultaneous use is contraindicated.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.