COL-PROBENECID
Clinical safety rating: safe
Increases levels of many drugs by inhibiting their renal secretion (eg penicillins methotrexate) Can cause GI upset and nephrotic syndrome.
Colchicine binds to tubulin, inhibiting microtubule polymerization and reducing inflammatory cell chemotaxis. Probenecid inhibits renal tubular reabsorption of uric acid, increasing uric acid excretion and lowering serum urate levels.
| Metabolism | Colchicine is metabolized primarily by CYP3A4 and to a lesser extent by CYP2D6. Probenecid is metabolized via glucuronidation and oxidation; it inhibits renal tubular secretion of many drugs and inhibits the metabolism of some drugs. |
| Excretion | Colchicine: ~65% renal excretion as unchanged drug and metabolites; 10-20% biliary excretion. Probenecid: ~77-88% renal excretion (primarily as glucuronide conjugate); <15% biliary/fecal. |
| Half-life | Colchicine: terminal half-life 20-30 hours (up to 40-60 hours in renal impairment). Probenecid: 6-12 hours (dose-dependent, prolonged in renal disease). |
| Protein binding | Colchicine: 30-50% bound to albumin. Probenecid: 85-95% bound to albumin. |
| Volume of Distribution | Colchicine: Vd 2-4 L/kg (extensive tissue distribution, high affinity for tubulin). Probenecid: Vd 0.2-0.4 L/kg (limited extravascular distribution). |
| Bioavailability | Colchicine: Oral bioavailability ~50% (wide interindividual variability). Probenecid: Oral bioavailability ~100%. |
| Onset of Action | Colchicine: Oral onset 1-2 hours (therapeutic effect in acute gout). Probenecid: Oral onset 2-4 hours (inhibition of renal tubular transport). |
| Duration of Action | Colchicine: Duration of therapeutic effect 12-24 hours (for acute gout). Probenecid: Duration of action 6-12 hours (tubular transport inhibition). |
Each tablet contains 0.5 mg colchicine and 500 mg probenecid. For gout prophylaxis, 1 tablet orally once daily, increasing to 1 tablet twice daily if needed. For acute gout flares, 2 tablets initially, then 1 tablet every 2 hours until relief or gastrointestinal symptoms occur, with a maximum of 8 tablets per flare.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with CrCl < 50 mL/min. Use not recommended in severe renal impairment. |
| Liver impairment | Avoid use in Child-Pugh class B or C due to risk of colchicine accumulation. Use with caution in mild hepatic impairment, consider reducing dose. |
| Pediatric use | Not recommended for use in children (safety and efficacy not established). |
| Geriatric use | Use with caution due to increased risk of renal impairment and accumulation. Start at lower doses (e.g., 1 tablet daily). Monitor renal function and for myelosuppression. |
| 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.
| FDA category | Animal |
| Breastfeeding | Colchicine: M/P ratio 0.93; small amounts excreted, monitor infant for gastrointestinal effects. Probenecid: Not recommended; M/P ratio unknown; avoid due to potential renal effects in infant. |
| Teratogenic Risk | Pregnancy Category D (probenecid) and C (colchicine). First trimester: Colchicine associated with increased risk of chromosomal abnormalities and neural tube defects. Second and third trimesters: Probenecid may cause fetal harm including nephrotoxicity and growth restriction. Colchicine may cause fetal toxicity at high doses. |
■ FDA Black Box Warning
None
| Common Effects | Hyperuricemia |
| Serious Effects |
["Hypersensitivity to colchicine or probenecid","Severe renal impairment (CrCl <10 mL/min)","Hepatic impairment (colchicine)","Blood dyscrasias (probenecid)","Concurrent use of P-glycoprotein or CYP3A4 strong inhibitors (e.g., clarithromycin, ketoconazole) with colchicine"]
| Precautions | ["Fatal overdoses have been reported with colchicine; do not exceed recommended dose.","Severe toxicity can occur with concomitant use of CYP3A4 or P-glycoprotein inhibitors.","Monitor renal function; dose adjustment required in renal impairment.","Hematologic toxicity (bone marrow suppression) with probenecid.","Uric acid stone formation; ensure adequate hydration and alkalinization of urine.","Drug interactions: colchicine with statins, macrolides, antifungals; probenecid with NSAIDs, penicillins, methotrexate."] |
Loading safety data…
| Fetal Monitoring | Maternal: Serum uric acid, renal function, liver enzymes, CBC, colchicine levels if toxicity suspected. Fetal: Ultrasound for growth and anatomy (colchicine), monitoring for oligohydramnios (probenecid). |
| Fertility Effects | Colchicine: May reduce spermatogenesis and cause azoospermia; reversible. Probenecid: No known fertility effects. Both: Limited human data. |