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 |
| Molecular Weight | 290.32 |
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 | Avoid; risk of folate antagonism and potential teratogenicity, especially neural tube defects. |
| 2nd trimester | Use only if benefit outweighs risk; monitor for folate deficiency. |
| 3rd trimester | Avoid near term due to risk of kernicterus in neonate. |
Clinical note
Comprehensive clinical and safety monograph for PRIMSOL (PRIMSOL).
| Placental transfer | Trimethoprim crosses the placenta extensively, achieving fetal serum concentrations approximately 50-100% of maternal levels. |
| Breastfeeding | Trimethoprim is excreted into breast milk in low levels; may interfere with folate metabolism in infants. Use with caution in neonates with G6PD deficiency or hyperbilirubinemia. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to trimethoprim or any componentMegaloblastic 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 |
| Food/Dietary | No significant food interactions. Avoid excessive potassium-rich foods (e.g., bananas, oranges, potatoes) if taking other medications that raise potassium. Can be taken with or without food. Maintain adequate hydration. |
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| L2 (Safer) |
| 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. |
| 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. |
| Clinical Pearls | Primsol (trimethoprim) is a folate antagonist used primarily for urinary tract infections. Monitor for hyperkalemia, especially in elderly, renal impairment, or those on ACE inhibitors/ARBs. Do not use in pregnancy (folate antagonist). Dose adjust for renal function (CrCl <15 mL/min: contraindicated; CrCl 15-30 mL/min: reduce dose). Can cause megaloblastic anemia with prolonged use; consider folate supplementation. Interactions with methotrexate (increased toxicity) and warfarin (enhanced anticoagulation). |
| Patient Advice | Take this medication exactly as prescribed, with a full glass of water. · Complete the entire course even if you feel better. · Avoid prolonged sun exposure; use sunscreen (photosensitivity). · Report signs of allergic reaction: rash, itching, difficulty breathing. · May cause dizziness; avoid driving if affected. · Inform your doctor if you have kidney disease, electrolyte imbalances, or take diuretics or ACE inhibitors (risk of high potassium). · Not recommended if pregnant or breastfeeding; discuss contraception options. |