BENEMID
Clinical safety rating
cautionComprehensive clinical and safety monograph for BENEMID (BENEMID).
Competitive inhibitor of renal tubular secretion of organic acids (urate, penicillin, other drugs), enhancing urate excretion and reducing serum uric acid levels. Also inhibits renal transport of weak organic acids.
| Metabolism | Hepatic metabolism via oxidation and glucuronidation; minimal CYP450 involvement. |
| Excretion | Renal (70-80% as unchanged drug and metabolites), biliary/fecal (20-30%) |
| Half-life | Terminal elimination half-life 6-12 hours in adults; prolonged to 12-24 hours in renal impairment or elderly; clinically significant for twice-daily dosing |
| Protein binding | Approximately 85-95% bound primarily to albumin |
| Volume of Distribution | 0.15-0.30 L/kg; indicates limited extravascular distribution, consistent with high protein binding and renal elimination |
| Bioavailability | Oral: >90% |
| Onset of Action | Oral: 30 minutes; peak effect at 2-4 hours for uricosuric activity |
| Duration of Action | Uricosuric effect persists 8-12 hours; requires twice-daily dosing to maintain therapeutic effect |
| Molecular Weight | 285.36 |
250 mg orally twice daily for 1 week, then 500 mg orally twice daily; maximum 2 g/day.
| Dosage form | TABLET |
| Renal impairment | CrCl <50 mL/min: avoid use; CrCl 50-90 mL/min: reduce dose by 50%. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment. |
| Pediatric use | Not recommended for children under 2 years. For older children: 25 mg/kg/day divided every 6 hours, up to 40 mg/kg/day maximum 2 g/day. |
| Geriatric use | Start at low end of dosing range (250 mg twice daily); monitor renal function and urate levels. |
| 1st trimester | Probenecid crosses the placenta. Limited human data; avoid in first trimester due to potential teratogenic effects in animal studies. |
| 2nd trimester | Use only if clearly needed. No well-controlled human studies; potential risk of neonatal toxicity. |
| 3rd trimester | Avoid near term due to risk of neonatal hyperbilirubinemia and kernicterus (probenecid displaces bilirubin from albumin). |
Clinical note
Comprehensive clinical and safety monograph for BENEMID (BENEMID).
| Placental transfer | Probenecid crosses the placenta; documented in animal studies and limited human data. Extent of transfer is significant enough to achieve fetal plasma concentrations. |
| Breastfeeding | Probenecid is excreted into breast milk in small amounts; however, concentrations are likely low. Caution is advised due to potential for adverse effects in nursing infants, such as gastrointestinal disturbances or hypersensitivity. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category D for second and third trimesters due to risk of neonatal hemolysis and jaundice from sulfonamide component; first trimester use associated with possible neural tube defects based on animal data and limited human reports. |
| Fetal Monitoring | Monitor maternal renal function, uric acid levels, and signs of hypersensitivity; fetal ultrasound for anomaly detection if used in first trimester; neonatal monitoring for hemolysis, jaundice, and kernicterus if used near term. |
| Fertility Effects | No significant adverse effects on fertility reported in humans; animal studies show no impairment. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to probenecid or any component of the formulationHistory of uric acid renal calculi (nephrolithiasis)Acute gouty attack (should not be initiated during an attack)Severe renal impairment (creatinine clearance < 50 mL/min)Concurrent use with high-dose methotrexate (increases methotrexate toxicity)
| Precautions | Risk of acute gouty arthritis upon initiation; use NSAIDs or colchicine prophylactically. Use with caution in patients with peptic ulcer disease, renal impairment (CrCl <50 mL/min), or history of uric acid calculi. May cause aplastic anemia and other blood dyscrasias. Avoid use during acute gout attack. |
| Food/Dietary | Avoid high doses of aspirin or salicylate-containing foods. Maintain adequate fluid intake. No specific food restrictions but alcohol may increase serum uric acid and reduce efficacy. Avoid large doses of vitamin C (may acidify urine and increase urate stone risk). |
| Clinical Pearls | BENEMID (probenecid) inhibits renal tubular secretion of penicillins and cephalosporins, increasing their serum levels. Use with caution in patients with G6PD deficiency due to risk of hemolytic anemia. Avoid in patients with blood dyscrasias or peptic ulcer disease. Ensure adequate hydration to prevent urate nephropathy during gout therapy. |
| Patient Advice | Take with food or milk to reduce gastrointestinal upset. · Drink plenty of fluids (at least 2 liters daily) to prevent kidney stones. · Do not take with aspirin or other salicylates as they may reduce effectiveness. · This medication may increase the effects of other drugs like penicillins and methotrexate. · Report any signs of allergic reaction, severe skin rash, or joint pain immediately. |
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