COLBENEMID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COLBENEMID (COLBENEMID).
Colchicine inhibits microtubule polymerization, reducing neutrophil chemotaxis and inflammation. Probenecid inhibits renal tubular reabsorption of uric acid, increasing uric acid excretion.
| Metabolism | Colchicine: primarily hepatic via CYP3A4; Probenecid: hepatic metabolism via glucuronidation and oxidation. |
| Excretion | Renal: ~76% as unchanged probenecid and metabolites; biliary/fecal: minor (<5%). Colchicine: ~20% renal, ~80% fecal primarily via biliary excretion. |
| Half-life | Probenecid: 6-12 hours (dose-dependent); colchicine: 20-30 hours (terminal) in renal impairment may prolong. |
| Protein binding | Probenecid: ~85-95% primarily to albumin; colchicine: ~30-50% to albumin and other proteins. |
| Volume of Distribution | Probenecid: 0.15-0.2 L/kg (confined to plasma and extracellular fluid); colchicine: 2-8 L/kg (wide tissue distribution, high in leukocytes). |
| Bioavailability | Probenecid: ~100% oral; colchicine: ~45% oral (range 25-50%) with significant first-pass metabolism. |
| Onset of Action | Probenecid: 30 minutes (oral) for uricosuric effect; colchicine: 12-24 hours (oral) for anti-inflammatory effect. |
| Duration of Action | Probenecid: 8-12 hours for urate lowering; colchicine: 48-72 hours anti-inflammatory; effect may persist after cessation due to slow clearance. |
Adults: 1 tablet (probenecid 500 mg / colchicine 0.5 mg) orally once daily for first week, then twice daily thereafter. May increase to 3-4 tablets daily in divided doses if needed.
| Dosage form | TABLET |
| Renal impairment | CrCl <50 mL/min: contraindicated. CrCl 50-80 mL/min: reduce dose by 50% or extend interval. CrCl >80 mL/min: no adjustment. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% or use with caution. Child-Pugh C: contraindicated (risk of colchicine accumulation). |
| Pediatric use | Not recommended for pediatric use; safety and efficacy not established. |
| Geriatric use | Start at lowest dose (e.g., 1 tablet daily) and titrate slowly; monitor renal function and avoid in CrCl <50 mL/min. Consider reduced doses 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 COLBENEMID (COLBENEMID).
| Breastfeeding | Colchicine is excreted into human milk with a milk-to-plasma ratio (M/P ratio) of approximately 0.9. Probenecid passes into breast milk in small amounts. Due to potential serious adverse effects in nursing infants, including gastrointestinal toxicity and bone marrow suppression, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Colbenemid is a combination of colchicine and probenecid. Colchicine is associated with increased risk of fetal harm when administered during pregnancy, including chromosomal abnormalities and fetal death, particularly in the first trimester. Probenecid should be avoided in pregnancy due to potential teratogenic effects and neonatal toxicity. Overall, use is contraindicated in pregnant women. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to colchicine or probenecid; severe renal impairment (CrCl < 30 mL/min); concurrent use of P-glycoprotein or strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) with colchicine; blood dyscrasias; peptic ulcer disease; acute gout flare treatment with history of uric acid renal calculi.
| Precautions | Severe toxicity with colchicine in renal/hepatic impairment; blood dyscrasias (probenecid); increased risk of colchicine toxicity with CYP3A4 inhibitors; avoid use with NSAIDs due to increased GI toxicity. |
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| Fetal Monitoring | Monitor maternal hepatic and renal function, complete blood count, and serum uric acid levels. Fetal monitoring by ultrasound to assess growth and development is recommended if inadvertent exposure occurs. |
| Fertility Effects | Colchicine may cause reversible azoospermia in males and ovarian dysfunction in females, potentially impairing fertility. Probenecid has no well-documented direct effect on fertility. The combination's impact on human fertility is not well studied. |