COLCHICINE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Colchicine binds to tubulin, preventing microtubule polymerization and thereby inhibiting neutrophil chemotaxis, adhesion, and superoxide anion production, as well as reducing inflammatory cytokine release.
| Metabolism | Primarily metabolized by CYP3A4; also a substrate for P-glycoprotein (P-gp). Demethylation and glucuronidation also occur. |
| Excretion | Primarily fecal (via biliary excretion, ~65%) and renal (~20% unchanged). Enterohepatic recirculation occurs. |
| Half-life | Terminal elimination half-life is 20–40 hours in healthy individuals; prolonged in renal or hepatic impairment. Clinical context: steady-state achieved in 3–5 days. |
| Protein binding | 30–50% bound to albumin; slightly higher in hepatic disease. |
| Volume of Distribution | 2–7 L/kg (extensive tissue binding, especially in leukocytes and kidneys). Reflects high intracellular accumulation. |
| Bioavailability | Oral: 25–50% (first-pass metabolism and efflux transporters). |
| Onset of Action | Oral: 12–24 hours for acute gout; IV: 6–12 hours. For gout prophylaxis, effect begins within 24 hours. |
| Duration of Action | 2–4 days for acute gout; for prophylaxis, duration extends with continued dosing. Clinical note: effects persist beyond plasma levels due to tissue binding. |
1.2 mg orally at first sign of gout flare, followed by 0.6 mg one hour later; for prophylaxis, 0.6 mg orally once or twice daily. Maximum dose: 1.8 mg per treatment course.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-50 mL/min: reduce dose or frequency; for GFR <30 mL/min: contraindicated or use with extreme caution, maximum 0.6 mg per day; not recommended in dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | For familial Mediterranean fever: 0.5-2 mg/day orally divided into 1-2 doses, weight-based: 0.02-0.03 mg/kg/day; not recommended for gout in children. |
| Geriatric use | Start at lower dose (0.3 mg once or twice daily) due to increased sensitivity and higher risk of toxicity; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 or P-gp inhibitors (eg clarithromycin) dramatically increase levels and risk of fatal toxicity Can cause myelosuppression with chronic use.
| Breastfeeding | Colchicine is excreted into breast milk in low amounts. Milk-to-plasma ratio is approximately 1.1. Based on limited data, a breastfeeding infant would receive a low dose (estimated 0.01 mg/kg/day for a maternal dose of 1.2 mg/day). No adverse effects have been reported in infants. However, caution is advised; monitor infant for signs of toxicity (e.g., diarrhea, nausea). The benefits of breastfeeding likely outweigh risks if maternal doses are therapeutic. |
| Teratogenic Risk | Colchicine is associated with an increased risk of fetal harm, particularly in the first trimester, due to its antimitotic effects. Fetal exposure may cause chromosomal abnormalities, spontaneous abortion, and malformations. The drug crosses the placenta. Risk is dose-dependent; therapeutic doses are associated with low absolute risk but higher than background. Use only if clearly needed and after counseling. |
■ FDA Black Box Warning
Colchicine can cause fatal toxicity when administered with potent P-glycoprotein and/or CYP3A4 inhibitors. Use with these drugs requires dose adjustment or avoidance.
| Common Effects | Diarrhea |
| Serious Effects |
["Hypersensitivity to colchicine","Concurrent use of potent CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, ritonavir) and P-glycoprotein inhibitors (e.g., cyclosporine) in patients with renal or hepatic impairment"]
| Precautions | ["Hematologic toxicity (bone marrow suppression)","Neuromuscular toxicity (myopathy, rhabdomyolysis), especially with concurrent statin use or renal impairment","Renal and hepatic impairment require dose reduction","Monitor for toxicities in elderly or debilitated patients"] |
| Food/Dietary |
Loading safety data…
| Fetal Monitoring | Monitor maternal complete blood count (CBC) and liver and renal function periodically due to potential myelosuppression and hepatotoxicity. During pregnancy, fetal monitoring should include routine ultrasound for anatomy and growth, with increased surveillance if signs of toxicity or high doses are used. Monitor for maternal gastrointestinal adverse effects (nausea, vomiting, diarrhea) as early signs of toxicity. |
| Fertility Effects | Colchicine can cause reversible suppression of spermatogenesis and may reduce sperm count and motility. In women, it may interfere with ovulation due to antimitotic effects, but data are limited. Fertility may be impaired during therapy but typically returns after discontinuation. Use with caution in patients attempting conception. |
| Grapefruit and grapefruit juice: increase colchicine serum concentration via CYP3A4 inhibition; avoid concurrent use. Alcohol: may increase risk of gastrointestinal adverse effects and reduce efficacy; limit or avoid alcohol. |
| Clinical Pearls | Colchicine has a narrow therapeutic index; toxicity is dose-dependent and cumulative. Use lowest effective dose, especially in renal impairment. Avoid concurrent use with P-glycoprotein or CYP3A4 inhibitors (e.g., clarithromycin, cyclosporine) as they increase colchicine levels and risk of severe myotoxicity or rhabdomyolysis. Monitor for gastrointestinal symptoms (nausea, vomiting, diarrhea) as early signs of toxicity. For acute gout, initiate within 12-36 hours of symptom onset; use a loading dose of 1.2 mg followed by 0.6 mg one hour later (not repeat within 3 days). For familial Mediterranean fever, start with 0.6 mg BID and titrate. Colchicine is contraindicated in patients with renal or hepatic impairment receiving concurrent strong CYP3A4 or P-gp inhibitors. |
| Patient Advice | Take colchicine exactly as prescribed; do not take extra doses or increase frequency. · For acute gout flare: take 1.2 mg (2 tablets) at first sign of pain, then 0.6 mg (1 tablet) one hour later. Do not repeat this regimen for at least 3 days. · For daily prophylaxis: take the prescribed dose (usually 0.6 mg once or twice daily) at the same time each day. · Call your doctor immediately if you experience severe diarrhea, vomiting, abdominal pain, muscle pain, weakness, numbness/tingling, unusual bleeding or bruising, or signs of infection (fever, sore throat). · Avoid grapefruit juice and grapefruit products while taking colchicine, as they can increase the drug level and risk of side effects. · Avoid alcohol, as it may increase the risk of side effects and reduce drug effectiveness. · Inform your doctor of all medications you take, especially antibiotics (clarithromycin, erythromycin), antifungals (ketoconazole, itraconazole), HIV medications (ritonavir), and heart medications (amiodarone, verapamil, diltiazem). · Do not take colchicine if you have severe kidney or liver disease without consulting your doctor. |