PROBENECID
Clinical safety rating: safe
Animal studies have demonstrated safety
Inhibits renal tubular reabsorption of uric acid, increasing its excretion and lowering serum urate levels. Also inhibits renal tubular secretion of weak acids (e.g., penicillins, cephalosporins).
| Metabolism | Primarily hepatic via oxidation and glucuronidation; minor renal metabolism. |
| Excretion | Renal excretion of unchanged drug and metabolites; ~77% of dose recovered in urine within 48 hours (50% as glucuronide conjugates, 27% as unchanged probenecid); ~11% excreted in feces via biliary elimination. |
| Half-life | Terminal elimination half-life is approximately 6-12 hours in adults with normal renal function; may be prolonged in renal impairment or older adults. |
| Protein binding | Approximately 75-95% bound to plasma albumin. |
| Volume of Distribution | Apparent volume of distribution is about 9 L (approximately 0.13 L/kg in adults); indicates limited extravascular distribution, primarily confined to plasma and extracellular fluid. |
| Bioavailability | Oral bioavailability is nearly complete (>90%) with peak plasma concentrations achieved within 2-4 hours. |
| Onset of Action | Oral: Onset of uricosuric effect occurs within 30-60 minutes; peak effect at 2-4 hours. |
| Duration of Action | Uricosuric effect lasts approximately 8 hours after a single oral dose; clinical effect on renal tubular transport persists for 6-12 hours. |
Oral: 250 mg twice daily for 1 week, then 500 mg twice daily; for gout prophylaxis, initial 250 mg twice daily for 3-4 weeks then increase to 500 mg twice daily; for hyperuricemia secondary to thiazide diuretics, 250 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: 250 mg once daily or 500 mg every 12-24 hours; GFR <10 mL/min: avoid use; anuria: contraindicated. |
| Liver impairment | No specific adjustment recommended; use caution in severe hepatic impairment. |
| Pediatric use | For gout or hyperuricemia (children >2 years): 25 mg/kg/day (max 2 g/day) divided every 6-8 hours; as adjunct to penicillin/cephalosporin: 25 mg/kg/day (max 2 g/day) divided every 8 hours for infants >3 months and children; neonates: dose not established. |
| Geriatric use | Start at lowest dose (250 mg once daily) due to age-related renal impairment; monitor renal function regularly; avoid if GFR <30 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Increases levels of many drugs by inhibiting their renal secretion (eg penicillins methotrexate) Can cause GI upset and nephrotic syndrome.
| Breastfeeding | Probenecid is excreted into breast milk in low concentrations; M/P ratio not available. Consider benefits of breastfeeding versus potential risk of adverse effects in infant (e.g., rash, gastrointestinal effects). Use with caution. |
| Teratogenic Risk | Probenecid is FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies exist. Use only if clearly needed. First trimester: No known teratogenic effects. Second and third trimesters: No specific fetal risks documented; avoid near term due to potential for neonatal hyperbilirubinemia (displaces bilirubin from albumin). |
■ FDA Black Box Warning
None.
| Common Effects | Hyperuricemia |
| Serious Effects |
["Hypersensitivity to probenecid or any component.","Severe renal impairment (CrCl <50 mL/min) or anuria.","History of uric acid kidney stones.","Concomitant use with methotrexate (increases methotrexate toxicity).","Use during acute gouty attack (unless already on therapy)."]
| Precautions | ["Use with caution in patients with peptic ulcer disease.","May worsen acute gouty arthritis; prophylactic colchicine or NSAIDs recommended during initiation.","Risk of uric acid stone formation; ensure adequate hydration and alkalinize urine if needed.","Avoid use in patients with blood dyscrasias or bone marrow depression.","May interfere with urine glucose and ketone tests."] |
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| Fetal Monitoring | Monitor renal function, uric acid levels, and complete blood count periodically. Observe for signs of hypersensitivity reactions. In pregnancy, monitor fetal growth and well-being as clinically indicated. |
| Fertility Effects | No specific human studies on fertility effects. Animal studies have not shown impaired fertility. Theoretical potential to affect spermatogenesis due to inhibition of prostaglandin synthesis but clinical significance unknown. |