What is the recommended colchicine dosing for an adult acute gout flare, and how should it be adjusted for patients over 65, eGFR <30 mL/min, hepatic impairment, or strong CYP3A4/P‑gp inhibitors?

Colchicine Dosing for Acute Gout Flare

Standard Adult Dosing (Normal Renal & Hepatic Function)

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 after a 12-hour pause resume 0.6 mg once or twice daily until the attack resolves. 1, 2, 3

• This low-dose regimen achieves ≥50% pain reduction with a number needed to treat of 3–5 and is as effective as obsolete high-dose protocols (4.8 mg over 6 hours) while causing significantly fewer gastrointestinal adverse effects (23% vs 77% diarrhea). 1, 4

• Critical timing: Colchicine must be started within 36 hours of symptom onset; efficacy drops sharply after this window, with maximum benefit when initiated within the first 12 hours. 1, 2, 3

---

Dose Adjustments for Age >65 Years

Elderly patients require the same standard loading dose (1.2 mg followed by 0.6 mg one hour later) but demand closer monitoring for adverse effects, particularly when renal function is declining. 1, 5

• In general practice, elderly patients are frequently prescribed excessive doses without adequate consideration of age-related pharmacokinetic changes. 6

• Calculate estimated creatinine clearance using the Cockcroft-Gault formula in all patients over 65 before prescribing colchicine. 3, 6

---

Dose Adjustments for Renal Impairment

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

The standard acute loading dose (1.2 mg followed by 0.6 mg one hour later) does not require adjustment, but close monitoring for adverse effects is mandatory. 1, 3, 5

• After the initial loading doses, reduce the maintenance dose to 0.6 mg once daily (rather than twice daily) in patients with eGFR 30–50 mL/min. 1

• A treatment course should be repeated no more than once every two weeks in patients with moderate renal impairment (eGFR 30–50 mL/min). 5

Severe Renal Impairment (eGFR <30 mL/min) or Dialysis

Colchicine is contraindicated for acute gout flares in patients with severe renal impairment (eGFR <30 mL/min) due to the risk of fatal toxicity. 1, 2, 3

• If colchicine must be used in dialysis patients, the maximum dose is a single 0.6 mg tablet, with no repeat dosing for at least two weeks. 3, 5

• Preferred alternative: Oral prednisone 30–35 mg daily for 5 days (no taper needed) or intra-articular corticosteroid injection for accessible large joints. 1, 3

---

Dose Adjustments for Hepatic Impairment

Mild to Moderate Hepatic Impairment

The standard acute loading dose (1.2 mg followed by 0.6 mg one hour later) does not require adjustment, but patients must be monitored closely for adverse effects. 5

Severe Hepatic Impairment

Dose reduction should be considered; the FDA label recommends close monitoring but does not specify an exact reduced dose. 5

• Colchicine clearance is significantly reduced and plasma half-life prolonged in chronic hepatic impairment. 5

• In practice, consider reducing the maintenance dose to 0.6 mg once daily (rather than twice daily) and extending the interval between treatment courses to at least two weeks. 5

---

Absolute Contraindication: Strong CYP3A4 or P-Glycoprotein Inhibitors

Patients with any degree of renal or hepatic impairment who are concurrently receiving strong CYP3A4 or P-glycoprotein inhibitors must not be given colchicine because the combination markedly raises plasma colchicine concentrations and can cause fatal toxicity. 1, 2, 3, 5

Specific Inhibitors to Avoid

• Macrolide antibiotics: clarithromycin, erythromycin 1, 3, 5, 7
• Antifungals: ketoconazole, itraconazole 3, 5, 7
• Immunosuppressants: cyclosporine 1, 3, 5, 7
• HIV protease inhibitors: ritonavir, indinavir, lopinavir/ritonavir, saquinavir, atazanavir, fosamprenavir, nelfinavir, tipranavir 5
• Calcium channel blockers: verapamil, diltiazem 1, 8
• Tyrosine kinase inhibitors: sunitinib 8

Dose Adjustment in Patients with Normal Renal & Hepatic Function Taking Moderate CYP3A4/P-gp Inhibitors

If renal and hepatic function are both normal, the acute loading dose should be reduced to 0.6 mg × 1 dose, followed by 0.3 mg one hour later, with no repeat treatment for at least 3 days. 5

• Maximum daily prophylactic dose in this setting is 0.6 mg (may be given as 0.3 mg twice daily). 5

---

Alternative Therapies 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; after the full-dose period, either stop abruptly or taper over 7–10 days. 1, 2, 3

• Oral corticosteroids provide Level A evidence of efficacy equivalent to colchicine with fewer adverse events (27% vs 63%). 1

Second-Line Alternative: Intra-Articular Corticosteroid Injection

For involvement of one or two large, accessible joints, administer intra-articular triamcinolone acetonide (40 mg for the knee, 20–30 mg for the ankle). 1, 3

Third-Line Alternative: NSAIDs (Use with Caution)

NSAIDs should be used with extreme caution in patients with moderate renal impairment and are relatively contraindicated in elderly individuals with hepatic disease. 1

• If NSAIDs are selected, employ full FDA-approved dosing (e.g., naproxen 500 mg twice daily, indomethacin 50 mg three times daily) until complete resolution of the gout attack, with close monitoring of renal function. 1, 2

---

Clinical Algorithm for Dose Selection

1. Calculate eGFR using Cockcroft-Gault formula in all patients, especially those >65 years. 3, 6

2. Screen for drug interactions with strong CYP3A4/P-glycoprotein inhibitors. 1, 3, 5

3. If eGFR ≥30 mL/min AND no strong CYP3A4/P-gp inhibitors AND symptom onset ≤36 hours:

   • Give colchicine 1.2 mg followed by 0.6 mg one hour later. 1, 2, 3
   • After 12 hours, resume 0.6 mg once or twice daily until attack resolves. 1, 3

4. If eGFR <30 mL/min OR strong CYP3A4/P-gp inhibitors present OR symptom onset >36 hours:

   • Use oral prednisone 30–35 mg daily for 5 days or intra-articular corticosteroid injection. 1, 2, 3

5. If hepatic impairment is present:

   • Mild-moderate: standard dose with close monitoring. 5
   • Severe: consider dose reduction and avoid if strong CYP3A4/P-gp inhibitors are present. 5

---

Common Pitfalls to Avoid

• Do not attempt dose reduction of colchicine as a "compromise" in patients with renal or hepatic impairment who are taking strong CYP3A4/P-gp inhibitors; even a single 0.6 mg dose carries unacceptable toxicity risk. 1

• Do not use obsolete high-dose colchicine regimens (e.g., 0.5 mg every 2 hours until relief or toxicity); they cause severe diarrhea in most patients without added benefit. 1, 7

• Do not initiate colchicine after 36 hours from symptom onset; efficacy drops dramatically and alternative therapy should be selected. 1, 2, 3

• Do not prescribe colchicine without calculating eGFR, particularly in elderly patients, as excessive doses are frequently prescribed in real-world practice without adequate consideration of renal function. 6