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Cotrimoxazole: Side Effects, Contraindications and Dosage

Co-trimoxazole is an antibiotic with a fixed combination of trimethoprim (dihydrofolate reductase inhibitor) and sulfamethoxazole (sulfonamide).

Mechanism of Action of Cotrimoxazole

Cotrimoxazole is bactericidal due to the double inhibition of bacterial folic acid synthesis.

Antibiotic Spectrum of Cotrimoxazole:

Bacteria causing urinary tract infection such as E. coli, Enterococci, Mycoplasma, Klebsiella, Serratia, Enterobacter (KES group), but with increasing resistance rates.

Urologic Indications for Cotrimoxazole:

Treatment or prevention of urinary tract infection (UTI).

Pharmacokinetics of Cotrimoxazole

• Elimination half life 10–12 hours.
• Renal elimination 60% (trimethoprim) to 90% (sulfamethoxazole)

Side Effects of Cotrimoxazole

Allergy:

Skin rash, rarely severe skin reactions (Stevens-Johnson and Lyell syndrome).

Kidney:

Exacerbation of renal failure (reversible).

Blood:

Bone marrow depression in case of long-term therapy, rarely agranulocytosis.

Drug Interactions with Co-trimoxazole

Co-trimoxazole enhances the effect of phenytoin and sulfonylureas. Increased toxicity of cyclosporine, barbiturates, p-aminosalicylic acid and methotrexate.

Contraindications of Cotrimoxazole

• Folic acid deficiency
• Severe liver disease
• Renal failure
• Pregnancy, newborns
• Glucose-6-phosphate dehydrogenase deficiency
• Acute hepatic porphyria
• Bone marrow insufficiency

Dosage of Co-trimoxazole

The ratio between trimethoprim and sulfamethoxazole is 1:5. The dosage for adults is 480 mg (80 mg trimethoprim and 400 mg sulfamethoxazole) 1-0-1 p.o. to 960 mg p.o. 1-0-1. The dosage for children is 24 mg/kg p.o. co-trimoxazole 1-0-1.

In uncomplicated UTI of women, co-trimoxazole is given for three days. In any other urinary tract infection, the recommended treatment duration is at least seven days.

References

Drekonja DM, Trautner B, Amundson C, Kuskowski M, Johnson JR. Effect of 7 vs 14 Days of Antibiotic Therapy on Resolution of Symptoms Among Afebrile Men With Urinary Tract Infection: A Randomized Clinical Trial. JAMA. 2021 Jul 27;326(4):324-331. doi: 10.1001/jama.2021.9899.

Simon und Stille 1997 SIMON, C. ; STILLE, W.: Antibiotika-Therapie in Klinik und Praxis.
9. Auflage.
Stuttgart New York : Schattauer, 1997

  Deutsche Version: Cotrimoxazol