COLBENEMID
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | Probenecid: 285.36 Da; Colchicine: 399.44 Da |
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 | Colbenemid (probenecid and colchicine) is generally avoided in the first trimester due to potential teratogenic effects associated with colchicine and limited safety data. Use only if clearly needed. |
| 2nd trimester | May be used if benefit outweighs risk, but colchicine can cause fetal harm; probenecid is generally considered low risk. Monitor closely. |
| 3rd trimester | Avoid near term due to risk of colchicine toxicity in the neonate and potential interactions with labor drugs. |
Clinical note
Comprehensive clinical and safety monograph for COLBENEMID (COLBENEMID).
| Placental transfer | Colchicine crosses the placenta; probenecid also crosses but to a lesser extent. Evidence suggests moderate transfer of both components. |
| Breastfeeding | Colchicine is excreted into breast milk in small amounts and may cause gastrointestinal effects in the infant. Probenecid is also excreted but in low concentrations. The manufacturer recommends caution and monitoring for diarrhea in the infant. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to probenecid, colchicine, or any componentSevere renal impairment (CrCl <30 mL/min)History of blood dyscrasias (e.g., aplastic anemia, agranulocytosis) from probenecid or colchicineConcurrent use of high-dose methotrexate or other nephrotoxic drugs that require probenecid inhibition? (actually probenecid is used with methotrexate; contraindicated if colchicine components cause issues)Active peptic ulcer disease (relative but consider absolute)Concurrent use of P-glycoprotein inhibitors (e.g., clarithromycin, ketoconazole) or CYP3A4 inhibitors with colchicine due to risk of colchicine toxicity
| 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. |
| Food/Dietary | Alcohol reduces efficacy and increases hyperuricemia; avoid completely. High-purine foods (e.g., red meat, organ meats, sardines, mussels) may exacerbate gout. Grapefruit juice may increase colchicine toxicity via CYP3A4 inhibition. Acidic foods (e.g., cranberries, prunes) can decrease urine pH and increase uric acid crystallization risk. Maintain adequate hydration with water. |
| Clinical Pearls | Colbenemid is a fixed-dose combination of colchicine (0.5 mg) and probenecid (500 mg). Probenecid increases uric acid excretion by inhibiting renal tubular reabsorption; colchicine reduces gout flare inflammation. Avoid in patients with severe renal impairment (CrCl <30 mL/min) or peptic ulcer disease. Probenecid can increase serum levels of penicillins, cephalosporins, and NSAIDs. Colchicine toxicity risk increases with concurrent P-glycoprotein or CYP3A4 inhibitors (e.g., clarithromycin, cyclosporine). Monitor for myopathy and neuropathy. May cause a false-positive urinary glucose test. |
| Patient Advice | Take with food or milk to reduce gastrointestinal upset. · Drink at least 2-3 liters of fluid daily to prevent kidney stones. · Avoid alcohol and high-purine foods (organ meats, shellfish) during therapy. · Report signs of toxicity: muscle weakness, numbness, tingling, severe diarrhea, or vomiting. · Do not take with macrolide antibiotics or antifungal medications without consulting your doctor. · Store at room temperature away from moisture and heat. |
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