What is the recommended colchicine dosing for acute gout attacks, gout prophylaxis, and familial Mediterranean fever, including adjustments for renal or hepatic impairment and interactions with strong CYP3A4 or P‑glycoprotein inhibitors?

Colchicine Dosing Recommendations

Acute Gout Flare 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), but only if treatment can be initiated within 36 hours of symptom onset. 1, 2, 3

Timing Considerations

• Colchicine must be started within 36 hours of symptom onset; efficacy declines sharply after this window and treatment should not be initiated beyond this timeframe. 1, 2, 3
• Maximum therapeutic benefit occurs when treatment begins within 12 hours of symptom onset. 1

Continuation After Loading Dose

• After the initial loading doses (1.2 mg followed by 0.6 mg one hour later), wait 12 hours, then resume prophylactic dosing of 0.6 mg once or twice daily until the acute attack completely resolves. 1, 3

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Gout Flare Prophylaxis (When Starting Urate-Lowering Therapy)

Prescribe colchicine 0.6 mg once or twice daily for at least 6 months when initiating or adjusting urate-lowering therapy to prevent acute flares triggered by urate mobilization. 4, 1, 2, 3

Duration of Prophylaxis

• Continue for at least 6 months, OR 4, 1, 3
• Continue for 3 months after achieving target serum urate < 6 mg/dL if no tophi are present, OR 4, 1, 3
• Continue for 6 months after achieving target serum urate < 6 mg/dL if tophi are present. 4, 1, 3

Alternative Prophylaxis Options

• If colchicine is contraindicated: use low-dose NSAID (e.g., naproxen 250 mg twice daily) with a proton pump inhibitor, OR 4, 1
• Low-dose prednisone ≤10 mg/day as second-line prophylaxis. 4, 1, 3

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Dose Adjustments for Renal Impairment

Mild to Moderate Renal Impairment (CrCl 30–80 mL/min)

• Acute gout treatment: Use standard loading dose (1.2 mg followed by 0.6 mg one hour later) with close monitoring; no dose adjustment required for the acute regimen, but treatment courses should be repeated no more than once every two weeks in patients with CrCl 30–50 mL/min. 1, 5
• Prophylaxis: 0.6 mg once daily (reduce from twice daily) with close monitoring. 4, 5

Severe Renal Impairment (CrCl < 30 mL/min)

• Acute gout treatment: Single dose of 0.6 mg only; do not repeat for at least two weeks. 3, 5
• Prophylaxis: Start with 0.3 mg once daily; any dose increase requires close monitoring. 4, 3, 5
• Colchicine is contraindicated in severe renal impairment (eGFR < 30 mL/min) according to some guidelines due to risk of fatal toxicity. 1, 3

Dialysis Patients

• Acute gout treatment: Single dose of 0.6 mg; do not repeat for at least two weeks. 5
• Prophylaxis: 0.3 mg twice weekly with close monitoring. 5

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Dose Adjustments for Hepatic Impairment

Mild to Moderate Hepatic Impairment

• No dose adjustment required, but monitor closely for adverse effects. 5

Severe Hepatic Impairment

• Dose reduction should be considered for prophylaxis; specific dosing not defined but close monitoring is mandatory. 5

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Critical Drug Interactions: CYP3A4 and P-glycoprotein Inhibitors

Patients with any degree of renal or hepatic impairment who are receiving strong CYP3A4 or P-glycoprotein inhibitors must NOT be given colchicine due to risk of fatal toxicity. 1, 2, 5

Strong Inhibitors (Absolute Contraindication with Renal/Hepatic Impairment)

• Clarithromycin, erythromycin 1, 2, 5, 6
• Cyclosporine 1, 2, 5, 6
• Ketoconazole and other azole antifungals 1, 5, 6
• Ritonavir and other protease inhibitors 1, 5, 6
• Verapamil 1, 5, 6

Dose Reductions for Patients with Normal Renal/Hepatic Function Taking Strong Inhibitors

Acute Gout Treatment:

• Original dose: 1.2 mg × 1, followed by 0.6 mg one hour later
• Adjusted dose: 0.6 mg × 1 dose only; do not repeat for at least 3 days 5, 6

Prophylaxis:

• Original dose: 0.6 mg twice daily → Adjusted: 0.3 mg once daily 5, 6
• Original dose: 0.6 mg once daily → Adjusted: 0.3 mg every other day 5, 6

Moderate Inhibitors (Dose Reduction Required)

• Diltiazem ER: Reduce colchicine dose by 50% for prophylaxis and 33% for acute treatment. 6
• Verapamil ER: Reduce colchicine dose by 50% for prophylaxis and 33% for acute treatment. 6

No Dose Adjustment Required

• Azithromycin: No significant interaction; standard colchicine dosing may be used. 6

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Familial Mediterranean Fever (FMF)

Standard Dosing

• Adults: 1.2–2.4 mg/day in divided doses 7
• Adjust dose based on disease severity and patient response 5

Renal Impairment in FMF

• Mild to moderate (CrCl 30–80 mL/min): Monitor closely; dose reduction may be necessary. 5
• Severe (CrCl < 30 mL/min): Start with 0.3 mg/day; increase only with adequate monitoring. 5
• Dialysis: Start with 0.3 mg/day; increase only with close monitoring. 5

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Common Pitfalls to Avoid

• Do not use the obsolete high-dose regimen (0.5 mg every 2 hours until relief or toxicity); it causes severe diarrhea in most patients without additional benefit. 1, 2
• Do not initiate colchicine after 36 hours from symptom onset; effectiveness drops dramatically. 1, 2, 3
• Do not combine colchicine with strong CYP3A4/P-gp inhibitors in patients with any renal or hepatic impairment due to risk of fatal toxicity. 1, 2, 5
• Do not stop prophylaxis prematurely (before 3–6 months) when initiating urate-lowering therapy; flare rates double without adequate prophylaxis. 1
• Always calculate creatinine clearance before prescribing colchicine, especially in elderly patients. 2
• Do not treat acute gout flares with colchicine in patients already receiving prophylactic colchicine AND taking CYP3A4 inhibitors. 5

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Safety Monitoring

Adverse Effects

• Gastrointestinal toxicity occurs in 23–26% of patients on the low-dose regimen (1.8 mg total) versus 77–100% on obsolete high-dose protocols. 1
• Diarrhea is the most common adverse effect (23% with low-dose regimen). 1
• Monitor for neurotoxicity and myotoxicity, especially in patients with renal impairment or concurrent statin therapy. 3

Drug Interactions Beyond CYP3A4/P-gp

• Statins: Co-administration increases risk of myopathy; heightened monitoring is required, especially with renal impairment. 1, 7
• Grapefruit juice: Can increase colchicine concentrations; advise patients to avoid. 7

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Efficacy Data

• The low-dose regimen (1.8 mg total over one hour) achieves ≥50% pain reduction with a number needed to treat of 3–5 and is as effective as high-dose colchicine (4.8 mg) but with significantly fewer gastrointestinal adverse effects (23% vs 77% diarrhea). 1
• Colchicine prophylaxis reduces the proportion of patients experiencing flares during allopurinol initiation from 77% to 33%. 1