What is the recommended dosing and duration of colchicine (Colchicine) for acute gout and familial Mediterranean fever (FMF)?

Colchicine Dosing and Duration

Acute Gout Treatment

For acute gout flares, administer colchicine 1.2 mg at the first sign of symptoms, followed by 0.6 mg one hour later (total 1.8 mg over 1 hour), but only if treatment can be initiated within 36 hours of symptom onset. 1, 2, 3

Initial Dosing Regimen

• Loading dose: 1.2 mg (two 0.6 mg tablets) at first sign of flare 1, 3
• Second dose: 0.6 mg (one tablet) exactly one hour later 1, 3
• Maximum initial treatment: 1.8 mg total over one hour period 1, 2, 3
• Critical timing: Colchicine is only effective if started within 36 hours of symptom onset; delaying beyond this window significantly reduces effectiveness 1, 2, 4

Continuation After Initial Doses

• Wait 12 hours after the initial loading doses before resuming any colchicine 1, 2
• Then continue with prophylactic dosing of 0.6 mg once or twice daily until the gout attack completely resolves 1, 2, 3

Critical Pitfall to Avoid

Higher doses (the old regimen of 0.6 mg hourly for multiple doses) are not more effective and cause significantly more gastrointestinal side effects 1, 5, 6. The low-dose regimen (1.8 mg total) is as effective as higher doses with far better tolerability 1, 5, 6.

---

Gout Flare Prophylaxis

For prophylaxis of gout flares, use colchicine 0.6 mg once or twice daily, with a maximum dose of 1.2 mg/day. 1, 2, 3

Standard Prophylactic Dosing

• Dose: 0.6 mg once or twice daily 1, 2, 3
• Maximum: 1.2 mg per day 3
• Timing: Initiate prophylaxis with or just prior to starting urate-lowering therapy (allopurinol, febuxostat, pegloticase) 2, 3

Duration of Prophylaxis

The American College of Rheumatology recommends continuing prophylaxis based on the following algorithm: 1, 2

• Minimum duration: At least 6 months after initiating urate-lowering therapy 1, 2
• If no tophi present: Continue for 3 months after achieving target serum urate level 1, 2
• If tophi are present: Continue for 6 months after achieving target serum urate level AND resolution of tophi on physical examination 1, 2

---

Familial Mediterranean Fever (FMF)

For FMF in adults, the recommended dose is 1.2 to 2.4 mg daily, adjusted in 0.3 mg increments based on disease control and tolerability. 3

Adult Dosing

• Starting range: 1.2 to 2.4 mg daily 3
• Dose adjustment: Increase in 0.3 mg/day increments as needed to control disease 3
• Maximum: 2.4 mg/day 3
• Administration: May be given as single dose or divided into two doses daily 3
• If side effects occur: Decrease in 0.3 mg/day increments 3

Pediatric FMF Dosing (Age 4 and Older)

The FDA-approved dosing is age-based and may be given as single or divided dose twice daily: 3

• Ages 4-6 years: 0.3 to 1.8 mg daily 3
• Ages 6-12 years: 0.9 to 1.8 mg daily 3
• Adolescents >12 years: 1.2 to 2.4 mg daily 3

---

Dose Adjustments for Drug Interactions

Colchicine requires significant dose reduction when coadministered with CYP3A4 or P-glycoprotein inhibitors due to risk of fatal toxicity. 1, 3

Strong CYP3A4 Inhibitors (Contraindicated in Renal/Hepatic Impairment)

For drugs including clarithromycin, ketoconazole, itraconazole, ritonavir, atazanavir: 1, 3

• Acute gout treatment: 0.6 mg × 1 dose, followed by 0.3 mg one hour later; do not repeat for at least 3 days 3
• Prophylaxis: 0.3 mg once daily OR 0.6 mg once every other day 3
• FMF: Maximum 0.6 mg daily (may give as 0.3 mg twice daily) 3

Moderate CYP3A4 Inhibitors

For drugs including diltiazem, verapamil, erythromycin, fluconazole, grapefruit juice: 3

• Acute gout treatment: 1.2 mg × 1 dose only; do not repeat for at least 3 days 3
• Prophylaxis: 0.3 mg twice daily OR 0.6 mg once daily 3
• FMF: Maximum 1.2 mg daily (may give as 0.6 mg twice daily) 3

P-glycoprotein Inhibitors

For cyclosporine and ranolazine (fatal toxicity reported with cyclosporine): 1, 3

• Same dose reductions as strong CYP3A4 inhibitors 3

---

Dose Adjustments for Renal Impairment

Patients with severe renal impairment or on dialysis require dramatic dose reduction to prevent fatal toxicity. 4, 3

Dialysis Patients

• Acute gout: Single dose of 0.6 mg; do not repeat for at least 2 weeks 4
• Prophylaxis/FMF: Requires significant reduction per FDA labeling 3

Moderate to Severe Chronic Kidney Disease

• Dose reduction is required per FDA labeling 1, 3
• Consult FDA-approved prescribing information for specific adjustments 1

---

Key Clinical Pearls

Common Pitfalls

• Do NOT use the old "hourly dosing" regimen - it increases toxicity without improving efficacy 1, 5, 6
• Do NOT start colchicine >36 hours after symptom onset - effectiveness drops dramatically 1, 2, 4
• Do NOT ignore drug interactions - fatal colchicine toxicity has been reported with clarithromycin and cyclosporine 1, 3, 7
• Do NOT use full doses with renal impairment - colchicine has a narrow therapeutic index and toxicity can be fatal 7, 6

Toxicity Recognition

Colchicine poisoning presents in three phases: 7

1. 0-24 hours: Gastrointestinal symptoms (may be absent with IV administration)
2. 24 hours to 7 days: Multi-organ dysfunction, sepsis, potential death
3. Recovery phase: Occurs over weeks if patient survives

The lowest reported lethal oral doses are 7-26 mg, with high fatality after acute ingestions exceeding 0.5 mg/kg 7.