PRIMSOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRIMSOL (PRIMSOL).
Trimethoprim selectively inhibits bacterial dihydrofolate reductase (DHFR), blocking the conversion of dihydrofolate to tetrahydrofolate, thereby inhibiting bacterial DNA synthesis.
| Metabolism | Trimethoprim is metabolized primarily in the liver via oxidation and glucuronide conjugation; CYP450 enzymes are minimally involved, with CYP3A4 contributing to a minor extent. |
| Excretion | Renal: 80-90% as unchanged drug via tubular secretion and glomerular filtration; biliary/fecal: <5% |
| Half-life | Terminal elimination half-life: 8-10 hours in adults with normal renal function (CrCl >30 mL/min); prolonged to 18-24 hours in renal impairment (CrCl <10 mL/min); neonates: 30-50 hours |
| Protein binding | 42-46% bound, primarily to albumin |
| Volume of Distribution | 1.2-1.5 L/kg; indicates extensive tissue penetration, including CSF and prostate |
| Bioavailability | Oral: 90-100% |
| Onset of Action | Oral: 2-4 hours to therapeutic plasma concentrations; IV: immediate |
| Duration of Action | 12-24 hours with twice-daily dosing; clinically effective for treatment of urinary tract infections with dosing every 12 hours |
For Pneumocystis jirovecii pneumonia (PCP) treatment: 15-20 mg/kg/day of trimethoprim component (equivalent to 75-100 mg/kg/day of PRIMSOL) divided every 6 hours, administered orally. For PCP prophylaxis: 5 mg/kg/day or 160 mg of trimethoprim component orally daily or three times weekly.
| Dosage form | SOLUTION |
| Renal impairment | CrCl >30 mL/min: No adjustment. CrCl 15-30 mL/min: Reduce dose by 50% or extend interval to every 12 hours. CrCl <15 mL/min: Use not recommended unless hemodialysis is available; if used, decrease dose by 50% with extended interval. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Monitor closely; consider dose reduction due to potential accumulation. Child-Pugh C: Avoid use due to risk of toxicity. |
| Pediatric use | For PCP treatment: 15-20 mg/kg/day of trimethoprim component divided every 6 hours orally. For PCP prophylaxis: 5 mg/kg/day or 150 mg/m2/day of trimethoprim component orally in divided doses twice daily three times per week. |
| Geriatric use | Increased risk of renal impairment; adjust dose based on creatinine clearance. Monitor for hyperkalemia and folate deficiency. Avoid in elderly with CrCl <15 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRIMSOL (PRIMSOL).
| Breastfeeding | Trimethoprim is excreted into breast milk with an M/P ratio of 0.5-1.5. Concentrations in milk are approximately 50% of maternal serum levels. Theoretical risk of hemolytic anemia in G6PD-deficient infants and interference with folate metabolism in neonates. Use caution, especially in infants with hyperbilirubinemia or G6PD deficiency. |
| Teratogenic Risk | FDA Pregnancy Category C. Trimethoprim is a folate antagonist. First trimester: associated with neural tube defects, cardiovascular malformations, and oral clefts; risk increases with folate deficiency. Second trimester: potential for folate-dependent fetal development disruption. Third trimester: risk of neonatal hyperbilirubinemia and kernicterus due to displacement of bilirubin from albumin. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to trimethoprim or any component of the formulation","Severe hepatic impairment","Creatinine clearance <15 mL/min (unless renal function is monitored closely)","Megaloblastic anemia due to folate deficiency"]
| Precautions | ["Hyperkalemia: risk increased in elderly, renal impairment, or concurrent use of potassium-sparing diuretics, ACE inhibitors, or NSAIDs","Hematologic toxicity: megaloblastic anemia, leukopenia, neutropenia, thrombocytopenia; monitor CBC in patients with folate deficiency or long-term therapy","Hepatotoxicity: rare cases of hepatic injury; monitor hepatic function","Renal impairment: dose adjustment required for CrCl <30 mL/min","Photosensitivity: avoid prolonged sun exposure","Folate deficiency: consider folate supplementation in patients at risk"] |
Loading safety data…
| Fetal Monitoring | Maternal monitoring: CBC, renal and hepatic function tests periodically; folate levels if prolonged therapy. Fetal monitoring: ultrasound for neural tube defects and cardiac anomalies if exposed in first trimester; neonatal monitoring for hyperbilirubinemia and kernicterus if used near term. |
| Fertility Effects | No significant adverse effects on fertility reported in humans. In animal studies, high doses of trimethoprim impaired fertility, but relevance to humans is uncertain. May interfere with folate metabolism, potentially affecting spermatogenesis and ovulation, though clinical significance is low. |