Antibacterial, dihydrofolate reductase inhibitor
ATC code: J01EA01 (Trimethoprim)
Brand names
Proloprim, Primsol
Inhibits bacterial dihydrofolate reductase, the enzyme converting dihydrofolate to tetrahydrofolate needed for nucleotide synthesis. Active against most Enterobacteriaceae and Pneumocystis. In co-trimoxazole, potentiates the antibacterial effect of sulfamethoxazole. Blocks ENaC in distal renal tubules by the same mechanism as amiloride, causing potassium retention.
Second line
Trimethoprim is used for uncomplicated urinary tract infection in adults when fosfomycin or nitrofurantoin are unsuitable. SEIMC restricts empirical use because of growing E. coli resistance in Spain (above 25% in most regions). Long-term use requires potassium and creatinine monitoring.
3 pairs found. Sorted from critical to minor.
Mechanism
Trimethoprim inhibits renal OCT2 transporter clearing dofetilide. Levels double. Tikosyn Section 4.3 strict contraindication.
Symptoms
Torsades de pointes.
Management
Combination contraindicated.
Mechanism
Trimethoprim blocks ENaC in collecting ducts – potassium retention. With spironolactone dual aldosterone blockade. Sudden death increase reported in the elderly.
Symptoms
Hyperkalaemia within 3-7 days.
Management
Combination contraindicated in patients over 65. In younger patients check K+ at 3-5 days.
Mechanism
Dual K+-sparing effect: enalapril suppresses aldosterone, trimethoprim blocks ENaC. Hyperkalaemia.
Symptoms
Hyperkalaemia within 5 days.
Management
Check K+ and creatinine on day 5. Alternative – fosfomycin or nitrofurantoin for UTI.
Sources
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Folate antagonist – neural tube defect risk in first trimester. Use only when necessary with folic acid 5 mg/day.
Passes into milk. Breastfeeding possible in term infants older than 1 month.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Trimethoprim is evaluated for the following indications with varying evidence strength: Urinary tract infection (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Trimethoprim (≥ 1 in 100): Nausea, vomiting, Rash, Pruritus, Creatinine rise (artefactual). See the Safety section for uncommon and serious reactions.
FDA category C. Folate antagonist – neural tube defect risk in first trimester. Use only when necessary with folic acid 5 mg/day.
Passes into milk. Breastfeeding possible in term infants older than 1 month.
Trimethoprim is contraindicated in: Severe renal impairment (eGFR below 15 mL/min); Megaloblastic anaemia from folate deficiency; Combination with dofetilide (FDA Tikosyn 4.3); Combination with methotrexate; Hyperkalaemia. Full list in the Safety section.