PROBEN-C
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROBEN-C (PROBEN-C).
Probenecid inhibits tubular reabsorption of uric acid in the kidney, increasing uric acid excretion and lowering serum urate levels. It also competitively inhibits organic anion transport (OAT) at the proximal tubule, reducing renal excretion of penicillin and other beta-lactam antibiotics.
| Metabolism | Hepatic metabolism via glucuronidation and oxidation (CYP450 involvement minimal). |
| Excretion | PROBEN-C (probenecid and colchicine) excretion: Probenecid is primarily excreted renally (75% as unchanged drug and metabolites), with a small amount excreted in bile (5-10%). Colchicine is eliminated mainly via feces (about 60% as unchanged drug and metabolites) and renal excretion (20-30%). |
| Half-life | Terminal elimination half-life of probenecid is approximately 6-12 hours in healthy adults; colchicine's terminal half-life ranges from 20-30 hours in normal renal function. Clinical context: Dosing interval adjustments are recommended in renal impairment (CrCl <50 mL/min) for colchicine accumulation risk. |
| Protein binding | Probenecid: 85-95% bound to albumin. Colchicine: approximately 30-50% bound to albumin. |
| Volume of Distribution | Probenecid: Vd approximately 0.15-0.2 L/kg, primarily confining to plasma and extracellular fluid. Colchicine: Vd large, approximately 2-10 L/kg, indicating extensive tissue distribution (e.g., leukocytes). |
| Bioavailability | Probenecid: oral bioavailability is 100% after oral administration (completely absorbed). Colchicine: oral bioavailability is approximately 45% (range 30-60%) due to first-pass metabolism. |
| Onset of Action | Onset of action: Probenecid – oral: onset of uricosuric effect within 30-60 minutes. Colchicine – oral: onset of anti-inflammatory effect within 24-48 hours. |
| Duration of Action | Duration of action: Probenecid – uricosuric effect persists for 8-12 hours after a single dose. Colchicine – anti-inflammatory effect lasts for several days; however, GI side effects may limit duration of therapy. |
Oral, 500 mg twice daily. Each tablet contains probenecid 500 mg and colchicine 0.5 mg.
| Dosage form | TABLET |
| Renal impairment | CrCl >50 mL/min: No adjustment. CrCl 35-50 mL/min: Reduce dose to 500 mg once daily. CrCl <35 mL/min: Contraindicated. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Use with caution; reduce dose by 50% (500 mg once daily). Child-Pugh C: Avoid use; contraindicated. |
| Pediatric use | Not recommended for use in children; safety and efficacy not established. |
| Geriatric use | Start at 500 mg once daily; monitor renal function and avoid in CrCl <35 mL/min due to increased risk of toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROBEN-C (PROBEN-C).
| Breastfeeding | Probenecid is excreted into breast milk in small amounts; M/P ratio unknown. Caution is advised. Consider risk-benefit; monitor infant for potential adverse effects. |
| Teratogenic Risk | No adequate studies in pregnant women. Animal studies have not shown teratogenic effects. However, because probenecid can inhibit renal excretion of many drugs, caution is warranted. Risk cannot be ruled out; should be used only if clearly needed. Trimester 1: Unknown risk; Trimester 2 and 3: Unknown risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to probenecid","Acute gouty attack","Uric acid nephrolithiasis (history of uric acid kidney stones)","Severe renal impairment (CrCl < 50 mL/min)","Concurrent use of high-dose methotrexate","Blood dyscrasias (e.g., aplastic anemia)"]
| Precautions | ["Avoid use with aspirin or other salicylates as they antagonize uricosuric effect","May precipitate acute gouty attacks during initial therapy","Use with caution in patients with peptic ulcer disease","Monitor renal function regularly","Contraindicated in patients with uric acid kidney stones due to risk of stone formation","Caution in patients with blood dyscrasias"] |
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| Monitor renal function and uric acid levels. Adjust concomitant medications (e.g., penicillins, cephalosporins) as needed. In pregnancy, monitor for signs of uric acid nephropathy and adverse effects of decreased renal clearance. |
| Fertility Effects | No specific data on human fertility effects. Animal studies have not shown impaired fertility. Probenecid may interfere with testicular function in animal models, but clinical relevance is unknown. |