COL-PROBENECID
Clinical safety rating
safeIncreases 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). |
| Molecular Weight | Colchicine: 399.44 Da; Probenecid: 285.36 Da |
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 | Contraindicated due to teratogenic effects (colchicine and probenecid both carry risks; colchicine associated with fetal harm; probenecid not recommended). |
| 2nd trimester | Avoid; risk outweighs benefit. Probenecid may interfere with fetal renal development; colchicine has embryotoxic potential. |
| 3rd trimester | Avoid; colchicine may cause neonatal toxicity; probenecid may accumulate in fetal tissues. |
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 |
| Placental transfer | Both colchicine and probenecid cross the placenta (colchicine: extensive; probenecid: moderate). |
| Breastfeeding | Both components are excreted into breast milk. Colchicine may cause diarrhea in infants; probenecid may interfere with neonatal renal function. Avoid breastfeeding during therapy. |
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Common Effects | Hyperuricemia |
| Serious Effects |
Hypersensitivity to colchicine, probenecid, or any componentSevere renal impairment (CrCl < 10 mL/min)Concurrent use of nephrotoxic drugsBlood dyscrasias (e.g., aplastic anemia, leukopenia)Active peptic ulcerPregnancy (all trimesters)
| 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. |
| Food/Dietary | Avoid or limit intake of high-purine foods (organ meats, anchovies, sardines, mussels, yeast extracts) as they may precipitate gout attacks. Alcohol (especially beer and spirits) increases urate production and decreases urate excretion, raising gout risk. Take with food to minimize gastrointestinal irritation. |
| Clinical Pearls | Colchicine and probenecid combination is used for gout prophylaxis and treatment. Monitor renal function closely; probenecid is contraindicated in CrCl <50 mL/min. Colchicine has a narrow therapeutic index and is contraindicated in patients with hepatic or renal impairment unless dose-adjusted. Avoid concurrent use of strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) which increase colchicine toxicity. Probenecid inhibits tubular secretion of many drugs (e.g., penicillins, methotrexate), increasing their levels. |
| Patient Advice | Take with food to reduce GI upset. · Drink plenty of fluids (at least 2-3 liters daily) to prevent kidney stones. · Report unusual bruising, bleeding, or signs of infection immediately. · Avoid alcohol as it increases serum urate levels and GI irritation. · Do not use this medication during a gout flare; wait until flare resolves. · Colchicine overdose can be fatal; seek emergency care if more than prescribed dose is taken. · Probenecid may cause false-positive urine glucose test with Clinitest. |
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