TRIMPEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIMPEX (TRIMPEX).
Inhibits dihydrofolate reductase, blocking the conversion of dihydrofolic acid to tetrahydrofolic acid, thereby inhibiting bacterial thymidine synthesis and DNA replication.
| Metabolism | Primarily hepatic via N-oxidation and hydroxylation; not extensively metabolized by cytochrome P450 enzymes. |
| Excretion | Renal: 40-70% as unchanged drug; biliary/fecal: minimal (10-15% as metabolites) |
| Half-life | 8-11 hours; prolonged in renal impairment (creatinine clearance <10 mL/min: 20-40 hours) |
| Protein binding | 42-46% primarily to albumin |
| Volume of Distribution | 1.5-2 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 90-100% |
| Onset of Action | Oral: 2-4 hours; intravenous: 30 minutes to 1 hour |
| Duration of Action | 12-24 hours; extended by renal impairment or concurrent CYP450 inhibition |
5 mg/kg orally every 6 hours for acute infections; 5 mg/kg orally every 12 hours for chronic urinary tract infections.
| Dosage form | TABLET |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: administer every 8-12 hours; CrCl <10 mL/min: administer every 12-24 hours. |
| Liver impairment | No specific adjustment for Child-Pugh A or B; Child-Pugh C: reduce dose by 50% or extend interval to every 12 hours. |
| Pediatric use | 2.5 mg/kg orally every 12 hours for children <2 months; 5 mg/kg orally every 6 hours for children ≥2 months. Maximum 400 mg/day. |
| Geriatric use | Use with caution; consider renal function. Adjust dose based on CrCl; monitor for myelosuppression and folate deficiency. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIMPEX (TRIMPEX).
| Breastfeeding | Trimethoprim is excreted into breast milk in low concentrations; M/P ratio approximately 0.5-1.3. Considered compatible with breastfeeding in healthy term infants, but caution in preterm or jaundiced infants due to potential for bilirubin displacement and kernicterus. |
| Teratogenic Risk | Trimpex (trimethoprim) is a folate antagonist. First trimester: risk of neural tube defects, cardiovascular malformations, and cleft palate due to folate antagonism; contraindicated unless no alternative. Second and third trimesters: risk of megaloblastic anemia, impaired folate metabolism; avoid if possible. Folate supplementation may reduce risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to trimethoprim or any component of the formulation","Megaloblastic anemia due to folate deficiency"]
| Precautions | ["May cause megaloblastic anemia due to folate deficiency, especially in patients with marginal folate levels","Risk of blood dyscrasias (thrombocytopenia, leukopenia, neutropenia); monitor CBCs","Caution in patients with impaired hepatic or renal function","May aggravate porphyria","Geriatric patients may be at increased risk of severe adverse reactions"] |
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| Fetal Monitoring | Monitor maternal complete blood count (CBC) including folate levels, especially in prolonged therapy; fetal ultrasound for structural anomalies if exposed in first trimester; neonatal monitoring for hyperbilirubinemia and anemia. |
| Fertility Effects | No conclusive evidence of adverse effects on fertility in humans. In animal studies, high doses have shown impaired spermatogenesis and ovarian function; clinical significance uncertain. |