Antibacterial, dihydrofolate reductase inhibitor
Brand names: Proloprim, Primsol
Updated · Methodology
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.
ICD-10: N39.0 · ICD-11: GC08
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.
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.
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
Verbatim lines from the interaction sections, in the language of the label
«Drug Interactions: Trimethoprim may inhibit the hepatic metabolism of phenytoin. Trimethoprim, given at a common clinical dosage, increased the phenytoin half-life by 51% and decreased the phenytoin…»FDA, section 7 · Open on DailyMed
«Alteración del equilibrio electrolítico: No se recomienda el uso concomitante de losartán junto con diuréticos ahorradores de potasio, suplementos de potasio y sustitutos de la sal que contengan…»AEMPS, section 4.4 · Open on CIMA
«Medicamentos que producen reacciones adversas en la médula ósea: En el caso de los tratamientos con medicamentos que pueden producir reacciones adversas en la médula ósea (p. ej., sulfonamidas…»AEMPS, section 4.5 · Open on CIMA
«La co-administración de trimetoprim (160 mg dos veces al día), un inhibidor moderado de CYP2C8 y repaglinida (una dosis única de 0,25 mg) aumentó el valor AUC de repaglinida, Cmax y t1/AEMPS, section 4.5 · Open on CIMA
«Combinaciones con mayor riesgo de nefrotoxicidad: Deberá tenerse precaución cuando se utilice ciclosporina junto con otros fármacos que presentan sinergia nefrotóxica como son: aminoglucósidos…»AEMPS, section 4.5 · Open on CIMA
«Fármacos que pueden causar una hiperpotasemia : El tratamiento concomitante con fármacos ahorradores de potasio, ciclosporina, tacrolimus o trimetoprim puede asociarse con un aumento de los niveles…»AEMPS, section 4.5 · Open on CIMA
«Trimetoprim: La administración concomitante de trimetoprim con eplerenona incrementa el riesgo de hiperpotasemia. Se debe realizar la monitorización del potasio sérico y de la función renal…»AEMPS, section 4.5 · Open on CIMA
«Los fármacos que pueden promover hipercalemia como diuréticos ahorradores de potasio, inhibidores de la ECA, antagonistas de angiotensina II, sales de potasio, AINEs, heparinas (de bajo peso…»AEMPS, section 4.5 · Open on CIMA
«Interacciones que aumentan los niveles de litio: Antibióticos (nitroimidazoles (ej. Metronidazol)): el uso concomitante puede aumentar las concentraciones séricas de litio debido a la reducción del…»AEMPS, section 4.5 · Open on CIMA
«Trimetoprim/AEMPS, section 4.5 · Open on CIMA
«Sales de potasio, heparina, diuréticos que retienen potasio y otros principios activos que elevan el potasio plasmático (por ejemplo, antagonistas de la angiotensina II, trimetoprim y en combinación…»AEMPS, section 4.5 · Open on CIMA
«Recomendación relativa a la administración conjunta: No se observaron cambios clínicamente significativos en la exposición de azitromicina o de los medicamentos administrados conjuntamente en los…»AEMPS, section 4.5 · Open on CIMA
«Pharmacokinetic Drug Interactions: Trimethoprim 22 to 28% NA»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Fármacos que influyen en los niveles de ácido fólico: Los anticonceptivos orales, anticonvulsivos, fármacos antituberculosos, el alcohol, la glucarpidasa y los antagonistas del ácido fólico como el…»AEMPS, section 4.5 · Open on CIMA
«En base a los datos in vitro , no se esperan interacciones medicamentosas clínicamente importantes con inhibidores menos potentes de CYP 2C8 (p. ej., trimetoprim). La administración conjunta de…»AEMPS, section 4.5 · Open on CIMA
«Effect of Other Drugs on Mycophenolate Mofetil: Examples Cyclosporine A, trimethoprim/FDA, section 7 · Open on DailyMed
«Drugs that Affect Phenytoin Concentrations: Sulfonamides Sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole-trimethoprim»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Drugs that are known to inhibit CYP3A4 include antifungal agents (ketoconazole, itraconazole) and antibacterial agents (clarithromycin, erythromycin). Drugs that are…»FDA, section 7 · Open on DailyMed
«Effect of Other Drugs on Rifabutin Pharmacokinetics: Sulfamethoxazole-Trimethoprim 800/FDA, section 7 · Open on DailyMed
«Antiinfecciosos: Sulfametoxazol/AEMPS, section 4.5 · Open on CIMA
«No se han observado interacciones farmacocinéticas clínicamente significativas entre sirolimus y ninguna de las siguientes sustancias: aciclovir, atorvastatina, digoxina, glibenclamida…»AEMPS, section 4.5 · Open on CIMA
«Drugs and Supplements Increasing Serum Potassium: trimethoprim»FDA, section 7 · Open on DailyMed
«Drug Interactions:: co-trimoxazole (trimethoprim and sulfamethoxazole) norfloxacin»FDA, section 7 · Open on DailyMed
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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.
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.
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Amoxicillin + Clavulanic Acid, Amoxicillin, Azithromycin, Cefalexin, Cefditoren pivoxil, Clarithromycin, Erythromycin, Linezolid