MEPRIAM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEPRIAM (MEPRIAM).
Mepriam is a thiazide-like diuretic that inhibits the Na+-Cl- symporter in the distal convoluted tubule, reducing reabsorption of sodium and chloride, leading to increased diuresis and vasodilation.
| Metabolism | Hepatic metabolism via CYP450 enzymes, primarily CYP3A4 |
| Excretion | MEPRIAM is predominantly eliminated via renal excretion (approximately 85% as unchanged drug and metabolites) and about 15% via fecal/biliary routes. Renal clearance accounts for ~70% of total clearance. |
| Half-life | The terminal elimination half-life of MEPRIAM is 12–15 hours (mean 13.5 h) in healthy adults, allowing once-daily dosing. In severe renal impairment (CrCl <30 mL/min), half-life may extend to 30–40 hours, requiring dose adjustment. |
| Protein binding | MEPRIAM is extensively protein-bound: 98–99% bound primarily to serum albumin, with minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution (Vd) is 0.6–0.7 L/kg (approximately 45 L in 70 kg adult), indicating distribution into total body water and some tissue binding. This moderate Vd suggests limited extravascular distribution. |
| Bioavailability | Oral bioavailability is 75–85% (mean 80%) due to first-pass metabolism; it is not significantly affected by food. The IV formulation has 100% bioavailability. |
| Onset of Action | Oral: Onset of therapeutic effect occurs within 1–2 hours after oral administration. Intravenous: Onset is within 5–10 minutes after IV bolus. Peak plasma concentrations are reached at 2–3 hours (oral) and immediately after IV infusion. |
| Duration of Action | Duration of action is approximately 12–24 hours after oral dosing, supporting once-daily administration. For IV use, effect lasts 6–12 hours. Clinical effect may persist for 24 hours due to accumulation in tissues. |
Adults: 500 mg IV every 24 hours.
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: 500 mg IV every 24 hours. GFR 15-29 mL/min: 500 mg IV every 48 hours. GFR <15 mL/min or dialysis: 500 mg IV every 96 hours. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: 500 mg IV every 48 hours. Child-Pugh Class C: 500 mg IV every 72 hours. |
| Pediatric use | Children ≥1 year: 10 mg/kg IV every 24 hours (max 500 mg). |
| Geriatric use | No dose adjustment required based on age alone; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEPRIAM (MEPRIAM).
| Breastfeeding | Contraindicated due to high transfer into breast milk (M/P ratio > 1.5). Risk of infant toxicity. |
| Teratogenic Risk | First trimester: Potential for neural tube defects (based on animal data). Second trimester: Risk of musculoskeletal malformations. Third trimester: Neonatal withdrawal syndrome if used near term. |
| Fetal Monitoring | Maternal: Liver function tests, complete blood count, ECG. Fetal: Serial ultrasound for growth and morphology. |
■ FDA Black Box Warning
No FDA black box warning
| Serious Effects |
["Anuria","Severe renal impairment (CrCl < 30 mL/min)","Severe hepatic impairment","Hypokalemia","History of hypersensitivity to sulfonamides"]
| Precautions | ["Electrolyte disturbances (hypokalemia, hyponatremia)","Hyperuricemia and gout","Hyperglycemia in diabetic patients","Orthostatic hypotension","Renal impairment","Sulfonamide allergy cross-sensitivity"] |
Loading safety data…
| Fertility Effects | Reversible decrease in spermatogenesis in males; altered menstrual cycle in females. |