COLCRYS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COLCRYS (COLCRYS).
Colchicine binds to tubulin, inhibiting microtubule polymerization and thus disrupting cellular functions such as mitosis and neutrophil motility. It also reduces the release of chemotactic factors and decreases the activity of the NLRP3 inflammasome, thereby inhibiting the inflammatory response in gout.
| Metabolism | Colchicine is primarily metabolized by CYP3A4 and is also a substrate for P-glycoprotein (P-gp). It undergoes hepatic metabolism and enterohepatic recirculation. Approximately 10-20% is excreted unchanged in the urine. |
| Excretion | Approximately 40-65% of the dose is excreted unchanged in urine (renal excretion) and 10-20% in feces (biliary/fecal elimination). The remainder undergoes hepatic metabolism. |
| Half-life | Terminal elimination half-life is approximately 26-31 hours in healthy subjects. In patients with renal impairment, half-life is prolonged (up to 10-13 days in severe impairment), necessitating dose adjustment. |
| Protein binding | Approximately 39% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Mean Vd is 2-4 L/kg, indicating extensive tissue distribution (e.g., liver, kidney, spleen, gastrointestinal tract). |
| Bioavailability | Oral bioavailability is approximately 45% (range 24-88%). Food does not significantly affect absorption. |
| Onset of Action | Oral: 12-24 hours for acute gout flare (onset of pain relief). IV (historical): 6-12 hours; note that IV colchicine is no longer available in the US due to safety concerns. |
| Duration of Action | Duration of anti-inflammatory effect is 24-72 hours after a single oral dose. For prophylaxis, dosing every 12-24 hours maintains effect; accumulation occurs with repeated dosing. |
For acute gout flares: 1.2 mg orally at first sign of flare, followed by 0.6 mg 1 hour later. Maximum: 1.8 mg per treatment course. For prophylaxis: 0.6 mg orally once or twice daily. Maximum: 1.2 mg/day.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-50 mL/min: reduce dose, avoid repeated courses. For GFR <30 mL/min or dialysis: do not use with P-glycoprotein or CYP3A4 inhibitors; for acute gout, dose 0.6 mg initially, no repeat within 2 weeks. For prophylaxis, 0.3 mg/day. Avoid in dialysis patients. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose or consider alternative. Child-Pugh Class C: avoid use. Severe hepatic impairment: contraindicated. |
| Pediatric use | Safety and efficacy not established in children; not recommended for pediatric use. |
| Geriatric use | Initiate at lowest dose (0.6 mg/day for prophylaxis; for acute gout, 1.2 mg followed by 0.6 mg 1 hour later). Monitor renal function closely; increased sensitivity and risk of toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COLCRYS (COLCRYS).
| Breastfeeding | Colchicine excreted into breast milk; M/P ratio approximately 0.89; infant serum levels low (<5% therapeutic dose), but no adverse effects reported in small studies; caution in neonates with G6PD deficiency; discontinue breastfeeding if infant diarrhea occurs. |
| Teratogenic Risk | Colchicine (COLCRYS) is classified as FDA Pregnancy Category C. First trimester: Crosses placenta; associated with increased risk of spontaneous abortion and chromosomal abnormalities in animal studies; limited human data shows no consistent evidence of major malformations. Second and third trimesters: Possible association with low birth weight and preterm delivery; use only if benefit outweighs risk. Periconceptional use: May reduce risk of familial Mediterranean fever-related pregnancy complications. |
■ FDA Black Box Warning
Fatal overdoses have occurred with Colchicine in adults and children. Keep this medication out of reach of children. Do not exceed recommended doses. Concomitant use of P-glycoprotein inhibitors (e.g., cyclosporine) or strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) can lead to life-threatening toxicity due to increased colchicine levels. Dose adjustments are required in patients with renal or hepatic impairment.
| Serious Effects |
["Hypersensitivity to colchicine or any component of the formulation.","Concurrent use of a P-glycoprotein inhibitor (e.g., cyclosporine) in patients with renal or hepatic impairment.","Concurrent use of a strong CYP3A4 inhibitor (e.g., clarithromycin, ketoconazole) in patients with renal or hepatic impairment."]
| Precautions | ["Fatal overdoses have occurred; strict adherence to dosing guidelines is essential.","Drug interactions with CYP3A4 and P-gp inhibitors can cause severe toxicity; avoid concomitant use or reduce dose as appropriate.","Monitor for myelosuppression (bone marrow depression), particularly with prolonged therapy.","Use with caution in patients with renal or hepatic impairment; dose reduction may be necessary.","Neuromuscular toxicity (e.g., rhabdomyolysis) has been reported, especially in combination with statins or other myotoxic drugs.","Gastrointestinal effects (e.g., diarrhea, nausea) are common and may indicate toxicity."] |
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| Fetal Monitoring | Monitor maternal CBC, liver function, and renal function every 2-4 weeks; fetal ultrasound for growth and anatomy; monitor for preterm labor and preeclampsia; assess for signs of colchicine toxicity (neuromuscular, gastrointestinal). |
| Fertility Effects | Reversible oligospermia and azoospermia reported in males at high doses; no clear evidence of female fertility impairment; may reduce miscarriage risk in familial Mediterranean fever. |