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Cotrimoxazole: Side Effects, Contraindications and Dosage

Cotrimoxazole is an antibiotic with a fixed combination of trimethoprim (Diaminopyrimidine antibiotic group) and sulfamethoxazole (sulfonamide antibiotic group).

Mechanism of Action of Cotrimoxazole

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

Antibiotic Spectrum of Cotrimoxazole:

Broad spectrum activity against aerobic bacteria in the Gram-negative and Gram-positive range. In urology, the typical pathogens of urinary tract infections such as Enterobacteriaceae or Chlamydia are covered, but with increasing resistance rates. Cotrimoxazole is ineffective against anaerobes, enterococci, Treponema pallidum, Pseudomonas, and mycoplasmas.

Urologic Indications for Cotrimoxazole:

Treatment of urinary tract infection (UTI) with proven sensitivity. Antibiotic prophylaxis of UTI.

Pharmacokinetics of Cotrimoxazole

• Good bioavailability when administered orally
• Elimination half life 10–12 hours
• Partial hepatic metabolism of both components
• Renal excretion 60% (trimethoprim) and 90% (sulfamethoxazole).

Side Effects of Cotrimoxazole

Cotrimoxazole is relatively well tolerated.

• Allergy: Exanthema, very rarely severe skin reactions (Lyell and Stevens-Johnson syndrome).
• Kidney: Crystalluria, worsening of existing renal insufficiency (reversible).
• Blood: Rarely bone marrow depression during long-term therapy, extremely rarely agranulocytosis.

Drug Interactions with Cotrimoxazole

Cotrimoxazole enhances the effect of oral vitamin K antagonists, phenytoin, barbiturates, and sulfonylureas. It increases the toxicity of cyclosporine and methotrexate.

Contraindications of Cotrimoxazole

• Allergy to sulfonamides or trimethoprim
• Folic acid deficiency
• Severe liver disease
• Pregnancy (especially during the first trimester and shortly before birth)
• Premature and newborn infants
• Glucose-6-phosphate dehydrogenase deficiency
• Acute hepatic porphyria
• severe renal insufficiency (GFR below 15 ml/min)
• Bone marrow insufficiency

Dosage of Cotrimoxazole

• The mixing ratio between trimethoprim and sulfamethoxazole is 1:5. Adults receive a standard dosage of 960 mg (160 mg trimethoprim and 800 mg sulfamethoxazole) 1-0-1 p.o.
• Children receive 24 mg/kg body weight of cotrimoxazole 1-0-1 p.o.
• A dose reduction is necessary in cases of renal insufficiency with a GFR of 30–15 ml/min (half the standard dose).
• For uncomplicated cystitis in women, a treatment duration of three days is recommended; for complicated urinary tract infections, choose a treatment duration of 7–10 days.

Monotherapy with Trimethoprim:

Monotherapy with Trimethoprim is an option for uncomplicated or complicated urinary tract infections with proven sensitivity. The daily dose is 200–400 mg, depending on the severity of the disease, and is administered in two separate doses.

Antibiotic Prophylaxis of UTI:

Cotrimoxazole 480 mg (80 mg trimethoprim and 400 mg sulfamethoxazole) or trimethoprim alone 100–150 mg once daily p.o. at bedtime or after sexual intercourse.

References

H. R. Brodt, A. Hörauf, M. Kresken, W. Solbach, and T. Welte, Infektionstherapie: Antibiotika, Virostatika, Antimykotika, Antiparasitäre Wirkstoffe. Thieme, 2023.

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.

  Deutsche Version: Cotrimoxazol

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