PROBENECID
Clinical safety rating
safeAnimal 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. |
| Molecular Weight | 285.36 |
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 | Data limited; avoid routine use. May be used for gout prophylaxis if clearly needed. No known teratogenicity in animal studies. |
| 2nd trimester | Use only if benefit outweighs risk; may increase uric acid excretion, theoretical risk of nephrolithiasis. Monitor renal function. |
| 3rd trimester | Use with caution; may compete with bilirubin for albumin binding, theoretical risk of kernicterus in neonates. Avoid near term. |
Clinical note
Increases levels of many drugs by inhibiting their renal secretion (eg penicillins methotrexate) Can cause GI upset and nephrotic syndrome.
| Placental transfer | Crosses placenta in animals; human data limited. Likely crosses due to low molecular weight and protein binding (75-90%). |
| Breastfeeding | Excreted in breast milk in low amounts (estimated 0.5% of maternal dose). Generally considered compatible with breastfeeding. Monitor infant for rash or gastrointestinal effects. |
| Lactation Rating | L2 (Probably Compatible) |
| 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). |
| 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. |
■ FDA Black Box Warning
None.
| Common Effects | Hyperuricemia |
| Serious Effects |
Known hypersensitivity to probenecidBlood dyscrasias (e.g., aplastic anemia, leukopenia)Uric acid renal stones (active or history)Concurrent use of methotrexate (increases methotrexate toxicity)Acute gouty attack (may precipitate exacerbation unless combined with colchicine)Severe renal impairment (CrCl < 30 mL/min)
| 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. |
| Food/Dietary | Avoid high-purine foods (organ meats, sardines, anchovies, shellfish, red meat) as they increase uric acid levels. Limit alcohol, especially beer and spirits, which increase uric acid. Maintain high fluid intake (water, citrus juices) to promote urine flow and prevent stones. Avoid cranberry juice as it may acidify urine. |
| Clinical Pearls | Probenecid inhibits renal tubular secretion of uric acid, increasing its excretion; used for chronic gout, not acute attacks. It also reduces renal excretion of penicillins and cephalosporins, so it is used to increase serum levels of these antibiotics. Ensure adequate hydration (at least 2-3 L daily) to prevent urate nephropathy. Avoid in patients with creatinine clearance <50 mL/min, history of uric acid stones, or acute gout attack. Alkalinization of urine (urine pH 6.5-7) reduces stone risk. Monitor serum uric acid, renal function, and CBC. Drug interactions: potentiates toxicity of methotrexate, NSAIDs, thiazides, salicylates (salicylates antagonize uricosuric effect). |
| Patient Advice | Take probenecid with food or antacids to reduce GI upset. · Drink at least 8-10 glasses of water daily while on this medication. · Do not take aspirin or other salicylates; they can reduce the effect. · This drug may increase bleeding risk if you take blood thinners like warfarin. · Report any signs of allergic reaction, rash, or fever immediately. · Avoid alcohol as it increases uric acid levels. · Tell your doctor before taking other medications, especially antibiotics. · Do not use during an acute gout attack; wait until attack resolves. · May cause dizziness or drowsiness; avoid driving until you know how it affects you. · Store at room temperature, away from moisture and heat. |
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