What colchicine dosing should be used for an acute gout flare and for prophylaxis, and how should the dose be adjusted in renal or hepatic impairment or when the patient is taking strong CYP3A4/P‑glycoprotein inhibitors?

Colchicine Dosing for Acute Gout Flares and Prophylaxis

Acute Gout Flare Dosing

For an acute gout flare, administer colchicine 1.2 mg orally at the first sign of symptoms, followed by 0.6 mg one hour later (total 1.8 mg over one hour), then continue 0.6 mg once or twice daily until the attack resolves—but only if treatment begins within 36 hours of symptom onset. 1

Critical Timing Window

• Colchicine must be initiated within 36 hours of symptom onset; efficacy drops sharply beyond this window and treatment should not be started after this timeframe. 1
• Maximum benefit occurs when treatment begins within 12–24 hours of symptom onset. 1
• After the initial loading doses (1.2 mg + 0.6 mg), wait 12 hours before resuming prophylactic dosing of 0.6 mg once or twice daily until complete resolution. 1

Evidence Supporting Low-Dose Regimen

• The AGREE trial demonstrated that this low-dose regimen (1.8 mg total) is equally effective as high-dose colchicine (4.8 mg over 6 hours) for pain reduction at 24 hours, with a number needed to treat of 5 for achieving 50% or greater pain reduction, but with significantly fewer gastrointestinal side effects. 1
• The older high-dose regimen of 0.5 mg every 2 hours until relief or toxicity is obsolete and causes severe diarrhea in most patients. 1

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Prophylaxis Dosing

For prophylaxis of gout flares (particularly when initiating urate-lowering therapy), prescribe colchicine 0.6 mg once or twice daily for at least 6 months, or until 3 months after achieving target serum urate (<6 mg/dL) if no tophi are present. 1

• In patients weighing <70 kg, use 0.6 mg once daily rather than twice daily. 2
• Continue prophylaxis for 6 months after achieving target serum urate if tophi are present. 1
• If already taking prophylactic colchicine when an acute attack occurs, take the loading dose (1.2 mg + 0.6 mg), then wait 12 hours before resuming the regular prophylactic dose. 1

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Dose Adjustments in Renal Impairment

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

• Acute flare treatment: Use the standard regimen (1.2 mg followed by 0.6 mg one hour later) with close monitoring for adverse effects; after 12 hours, continue 0.6 mg once or twice daily until resolution. 1, 3
• Prophylaxis: Reduce to 0.6 mg once daily (or 0.3 mg once daily in moderate impairment) with close monitoring. 3

Severe Renal Impairment (CrCl <30 mL/min)

• Acute flare treatment: The loading dose does not require adjustment, but treatment courses should be repeated no more than once every two weeks. 3
• Prophylaxis: Start with 0.3 mg once daily; any dose increase requires close monitoring. 3
• Absolute contraindication: Colchicine should be avoided entirely in severe renal impairment, and alternative therapy (corticosteroids or NSAIDs) should be strongly considered. 1

Dialysis Patients

• Acute flare treatment: Reduce to a single dose of 0.6 mg; do not repeat more than once every two weeks. 3
• Prophylaxis: Start with 0.3 mg twice weekly with close monitoring. 3

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Dose Adjustments in Hepatic Impairment

Mild to Moderate Hepatic Impairment

• Acute flare and prophylaxis: No dose adjustment required, but monitor closely for adverse effects. 3

Severe Hepatic Impairment

• Prophylaxis: Dose reduction should be considered; start with 0.3 mg once daily or every other day. 3
• Acute flare: Use with extreme caution and close monitoring. 3

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Dose Adjustments with Strong CYP3A4/P-Glycoprotein Inhibitors

Absolute Contraindications

Patients with any degree of renal or hepatic impairment who are concurrently receiving strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, verapamil, or other protease inhibitors) must NOT be given colchicine because this combination markedly raises plasma colchicine concentrations and can cause fatal toxicity. 1, 3

• Case reports document severe colchicine toxicity—including cardiovascular collapse, profuse diarrhea, metabolic acidosis, and hematologic abnormalities—when combined with P-glycoprotein inhibitors in patients with renal impairment. 1, 4
• Verapamil inhibits both CYP3A4 and P-glycoprotein, raising colchicine plasma concentrations by approximately 93–103%; the combination is explicitly contraindicated by ACC/AHA/HRS guidelines. 1

Dose Adjustments in Patients WITHOUT Renal or Hepatic Impairment

If the patient has normal renal and hepatic function but is taking a strong CYP3A4/P-glycoprotein inhibitor:

• Acute flare treatment: Reduce to 0.6 mg × 1 dose, followed by 0.3 mg one hour later; do not repeat for at least 3 days. Maximum daily prophylactic dose is 0.6 mg (may be given as 0.3 mg twice daily). 3
• Prophylaxis: Reduce from 0.6 mg twice daily to 0.3 mg once daily, or from 0.6 mg once daily to 0.3 mg every other day. 3

Specific Inhibitors and Adjustments

The FDA label provides detailed dose-reduction tables for protease inhibitors (ritonavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, saquinavir, tipranavir), macrolides (clarithromycin, erythromycin), and azole antifungals (ketoconazole, itraconazole). 3

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Alternative Treatments When Colchicine Is Contraindicated

First-Line Alternative: Oral Corticosteroids

• Prescribe prednisone 0.5 mg/kg per day (approximately 30–35 mg daily) for 5–10 days at full dose, then stop abruptly or taper over 7–10 days. 1
• Oral corticosteroids are equally effective as colchicine for acute gout flares (Level A evidence). 1

Second-Line Alternative: Intra-Articular Corticosteroid Injection

• For monoarticular or oligoarticular involvement of large, accessible joints, inject triamcinolone acetonide (40 mg for the knee, 20–30 mg for the ankle). 1

Third-Line Alternative: NSAIDs

• Use full FDA-approved anti-inflammatory doses (naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily) until complete resolution. 1
• NSAIDs should be used with extreme caution in patients with moderate renal impairment, hepatic disease, heart failure, or cirrhosis. 1
• NSAIDs are relatively contraindicated in elderly patients with hepatic disease. 1

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Common Pitfalls to Avoid

• Never attempt dose reduction of colchicine as a "compromise" in patients with renal/hepatic impairment taking strong CYP3A4/P-glycoprotein inhibitors; even a single 0.6 mg dose carries unacceptable toxicity risk. 1
• Do not start colchicine after 36 hours from symptom onset; switch to corticosteroids or NSAIDs instead. 1
• Do not use high-dose colchicine regimens (>1.8 mg in the first hour); they provide no additional benefit but substantially increase gastrointestinal toxicity. 1
• Do not discontinue urate-lowering therapy (allopurinol, febuxostat) during an acute gout flare if the patient is already on it. 1
• Do not combine NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity. 1
• When colchicine is co-prescribed with statins, heightened monitoring for neuro- and muscular toxicity is advised, especially in renal impairment. 1