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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROLOPRIM (PROLOPRIM).
| Breastfeeding | Trimethoprim is excreted into breast milk with a milk-to-plasma ratio (M/P) of approximately 0.5. Concentrations are low, but theoretical risk of interference with infant folate metabolism, especially in premature or ill infants. Caution advised; consider alternative agents. |
| 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. |
■ 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 trimethoprim or any component of the formulation; megaloblastic anemia due to folate deficiency; concomitant use with dofetilide or ticagrelor.
| 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. |
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| 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. |