PROLOPRIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROLOPRIM (PROLOPRIM).
Inhibits bacterial dihydrofolate reductase (DHFR), blocking the conversion of dihydrofolic acid to tetrahydrofolic acid, thereby inhibiting bacterial DNA, RNA, and protein synthesis.
| Metabolism | Metabolized by the liver to trimethoprim and inactive metabolites (e.g., N-oxide, N-demethylated derivatives). |
| Excretion | Primarily renal (80-90% as unchanged drug); less than 5% as metabolites; fecal excretion negligible. |
| Half-life | Terminal elimination half-life is 8-10 hours in normal renal function; prolonged (>20 hours) in significant renal impairment. |
| Protein binding | Approximately 80-90% bound, primarily to albumin. |
| Volume of Distribution | 1.2-1.5 L/kg; indicates extensive extravascular distribution. |
| Bioavailability | Oral: 80-90% (due to slight first-pass metabolism). |
| Onset of Action | Oral: 2-4 hours; Intravenous: immediately upon administration. |
| Duration of Action | 6-12 hours post-oral dose; longer in renal impairment. |
| Molecular Weight | 290.32 |
100 mg orally twice daily or 200 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | For CrCl 15-30 mL/min: 50-100 mg orally every 24 hours; for CrCl <15 mL/min: not recommended. |
| Liver impairment | No specific Child-Pugh based dose adjustments; use with caution in severe hepatic impairment. |
| Pediatric use | Children <12 years: 4-6 mg/kg/day orally divided every 12 hours; maximum dose 200 mg/day. |
| Geriatric use | Start at low end of dosing range (e.g., 100 mg once daily) due to potential age-related renal impairment; monitor renal function. |
| 1st trimester | Avoid use in first trimester; folate antagonist may increase risk of neural tube defects. |
| 2nd trimester | Use only if clearly needed; potential risk of kernicterus in neonates. |
| 3rd trimester | Avoid near term due to risk of hemolytic anemia and kernicterus in newborns. |
Clinical note
Comprehensive clinical and safety monograph for PROLOPRIM (PROLOPRIM).
| Placental transfer | Trimethoprim crosses the placenta; achieves fetal serum concentrations approximately 50-100% of maternal levels. |
| Breastfeeding | Trimethoprim is excreted into breast milk in small amounts; may interfere with infant folate metabolism, especially in G6PD deficiency or preterm infants. Caution advised. |
| Lactation Rating |
■ FDA Black Box Warning
Trimethoprim (the active component) should not be used in patients with megaloblastic anemia due to folate deficiency.
| Serious Effects |
Hypersensitivity to trimethoprimMegaloblastic anemia due to folate deficiency
| Precautions | May cause hyperkalemia, especially with high doses or in patients with renal impairment, concomitant use of potassium-sparing diuretics, or with certain disease states (e.g., diabetes, sepsis, adrenal insufficiency). Use with caution in patients with renal impairment, megaloblastic anemia, or folate deficiency. Monitor serum potassium levels. Photosensitivity may occur. |
| Food/Dietary | No significant food interactions. However, ensure adequate fluid intake to prevent crystalluria. Avoid excessive intake of foods high in potassium (e.g., bananas, oranges, potatoes) as trimethoprim can increase serum potassium. |
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| L3 (Moderate Safety) |
| Teratogenic Risk | Proloprim (trimethoprim) is a folate antagonist. First trimester: Associated with increased risk of neural tube defects, cardiovascular malformations, and oral clefts due to folate antagonism. Second and third trimesters: Risk of folate deficiency, megaloblastic anemia, and potential for adverse fetal outcomes; avoid use especially in folate-deficient patients. |
| Fetal Monitoring | Monitor maternal folate levels, complete blood count (CBC) with platelets, and renal function. Fetal ultrasound for neural tube defects if used in first trimester. Assess for signs of megaloblastic anemia in mother and infant. |
| Fertility Effects | Trimethoprim may reduce folic acid absorption or metabolism, potentially affecting fertility by interfering with folate-dependent processes. No direct evidence of impaired fertility in humans, but folate supplementation is recommended for women planning pregnancy. |
| Clinical Pearls | Proloprim (trimethoprim) is a dihydrofolate reductase inhibitor, effective for uncomplicated UTIs. Monitor for hyperkalemia in elderly or renal impairment; avoid in G6PD deficiency except at recommended doses. Use cautiously with methotrexate due to additive antifolate effects. Adjust dose for creatinine clearance <30 mL/min. |
| Patient Advice | Take exactly as prescribed; finish the full course even if symptoms improve. · Drink plenty of fluids to prevent crystalluria. · Notify your doctor if you develop rash, sore throat, or unusual bleeding/bruising. · Avoid prolonged sun exposure; use sunscreen as photosensitivity may occur. · If you miss a dose, take it as soon as you remember unless it is near the next dose; do not double the dose. |