What are the recommended colchicine dosing regimens for acute gout, gout prophylaxis, familial Mediterranean fever, and acute pericarditis in adults, and how should doses be adjusted for renal or hepatic impairment, elderly patients, and interacting drugs?

Colchicine Dosing Regimens and Adjustments

Acute Gout Flare Treatment

Administer colchicine 1.2 mg at the first sign of symptoms, followed by 0.6 mg one hour later (total 1.8 mg), then after a 12-hour pause resume 0.6 mg once or twice daily until the attack resolves. 1, 2, 3

Critical Timing Requirements

• Treatment must begin within 36 hours of symptom onset; efficacy drops sharply beyond this window 2, 3
• Maximum benefit occurs when started within 12 hours of symptom onset 1, 2
• Do not initiate colchicine if symptom onset exceeds 36 hours 2, 3

Evidence Supporting Low-Dose Regimen

• This 1.8 mg total regimen is as effective as the obsolete high-dose regimen (4.8 mg over 6 hours) but with significantly fewer gastrointestinal side effects 2, 4
• The AGREE trial demonstrated 50% or greater pain reduction with a number needed to treat of 5 2
• The older regimen of 0.5 mg every 2 hours until relief or toxicity is obsolete and causes severe diarrhea in most patients 2

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Gout Flare Prophylaxis

Prescribe colchicine 0.5–1 mg daily (0.6 mg once or twice daily in the US) for at least 6 months when initiating or adjusting urate-lowering therapy. 1, 2, 3

Duration Guidelines

• Continue prophylaxis for at least 6 months after starting urate-lowering therapy 1, 2
• Alternatively, continue for 3 months after achieving target serum urate (<6 mg/dL) if no tophi are present 2
• Extend to 6 months after achieving target serum urate if tophi are present 2

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Familial Mediterranean Fever (FMF)

The maximum recommended oral dose for FMF is 3 mg daily in adults and 2 mg daily in children, typically divided into 2–3 doses. 1, 5

Initiation and Titration Strategy

• Start at a subtherapeutic dose of 0.5 mg/day and increase gradually by 0.5 mg in divided daily doses to minimize gastrointestinal side effects 1
• Single daily dosing may increase compliance, but divided doses reduce side effects 1
• Patients requiring the maximum tolerated dose for at least 6 months who continue to have one or more attacks monthly are considered colchicine-resistant 1

Monitoring Requirements

• Review patients at 6-monthly intervals to evaluate attack frequency and monitor acute phase reactants between attacks 1
• During the first year, more frequent monitoring is needed to assess tolerability, side effects, and compliance 1

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Acute Pericarditis

Administer colchicine 0.5 mg twice daily for patients >70 kg or 0.5 mg once daily for patients ≤70 kg, in addition to standard anti-inflammatory therapy. 6

Treatment Duration and Efficacy

• Continue for the duration of the pericarditis episode, typically several weeks 6
• Colchicine hastens response to anti-inflammatory therapy and reduces subsequent risk of recurrences 6
• Gastrointestinal intolerance occurs in 5–10% of cases and may be controlled by dose reduction or temporary discontinuation 6

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Dose Adjustments for Renal Impairment

Mild Renal Impairment (eGFR 60–89 mL/min)

• No dose adjustment needed for prophylaxis (0.6 mg daily) 7
• For acute gout, use standard regimen (1.2 mg followed by 0.6 mg one hour later) with close monitoring 2

Moderate Renal Impairment (eGFR 30–59 mL/min)

• For prophylaxis: reduce to 0.48 mg daily (using oral solution) or 0.5 mg daily (where available); the standard 0.6 mg daily tablet or 0.6 mg every-other-day results in subtherapeutic or supratherapeutic levels 7
• For acute gout: use standard regimen with close monitoring 2
• After acute dosing, resume prophylactic dose of 0.5–0.6 mg once daily 2

Severe Renal Impairment (eGFR 15–29 mL/min)

• For prophylaxis: reduce to 0.3 mg daily (using oral solution or by splitting tablets); standard dosing results in plasma levels 36% above maximum tolerated level 3, 7
• Avoid colchicine for acute gout flares; use alternative therapy 1, 2

End-Stage Renal Disease (eGFR <15 mL/min or dialysis)

• Colchicine is contraindicated; select alternative anti-inflammatory therapy 2

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Dose Adjustments for Hepatic Impairment

Colchicine elimination half-life may be up to sevenfold longer in patients with liver cirrhosis; dose reduction is required, though specific dosing is not well-defined in guidelines. 1

• Patients with hepatic impairment taking strong CYP3A4 or P-glycoprotein inhibitors must not receive colchicine due to risk of fatal toxicity 1, 2

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Adjustments for Elderly Patients

Elderly patients are at increased risk of adverse effects with colchicine, particularly when combined with renal impairment or interacting drugs. 2

• Use lower prophylactic doses (0.5–0.6 mg once daily) and monitor closely for neurotoxicity and muscular toxicity 1
• Consider alternative therapy (oral corticosteroids or intra-articular injection) for acute gout in elderly patients with multiple comorbidities 2, 8

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Drug Interactions Requiring Dose Adjustment or Avoidance

Absolute Contraindications (Do Not Use Colchicine)

Colchicine must not be given to patients receiving strong P-glycoprotein and/or CYP3A4 inhibitors, especially in the presence of any renal or hepatic impairment. 1, 2, 3

These inhibitors include:

• Clarithromycin, erythromycin (macrolides) 1, 2, 5
• Cyclosporine 1, 2, 5
• Ketoconazole 1, 2, 5
• Ritonavir 1, 2
• Verapamil 1, 2

Mechanism and Risk

• These inhibitors increase colchicine blood levels by 200–300% 1
• Verapamil raises colchicine plasma concentrations by approximately 93–103% 2
• The combination can cause life-threatening toxicity, multiorgan failure, cardiovascular collapse, and death 1, 2

Statin Co-Administration

Patients on statins with renal impairment are at high risk for colchicine-induced myopathy and neuromuscular toxicity; monitor closely for muscle pain, weakness, or elevated creatine kinase. 1, 3, 5, 9

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Alternative Therapies When Colchicine is Contraindicated

For Acute Gout Flares

• Oral corticosteroids: Prednisone 0.5 mg/kg/day (or prednisolone 30–35 mg/day) for 5–10 days, then stop or taper over 7–10 days 1, 2, 3, 8
• NSAIDs: Full FDA-approved doses (naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily) until complete resolution 1, 2, 3, 8
• Intra-articular corticosteroid injection: Triamcinolone acetonide 40 mg for knee, 20–30 mg for ankle (for monoarticular or oligoarticular involvement) 2, 3, 8

For Gout Prophylaxis

• Low-dose NSAIDs: Naproxen 250 mg twice daily with proton pump inhibitor where indicated 1, 2, 8
• Low-dose prednisone: <10 mg/day 2, 8

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Critical Safety Warnings

Toxicity Risk Factors

Conditions that lead to colchicine toxicity include exceeding recommended doses, liver or renal failure, and concomitant administration of CYP3A4/P-glycoprotein inhibitors. 1

• The lowest reported lethal oral doses are 7–26 mg 5
• High fatality rate reported after acute ingestions exceeding 0.5 mg/kg 5
• Maximum recommended dose for FMF is 3 mg daily in adults; exceeding this increases toxicity risk 1

Clinical Presentation of Toxicity

Colchicine toxicity presents in three phases:

1. First 10–24 hours: Gastrointestinal symptoms (cramping, vomiting, diarrhea, cholera-like syndrome) with dehydration, shock, acute renal failure, seizures 1, 5
2. 24 hours to 7 days: Multiorgan failure including bone marrow suppression, renal insufficiency, ARDS, arrhythmias, DIC, neurological disturbances, coma, and death 1, 5
3. Recovery phase (if survived): Rebound leukocytosis, resolution of organ failure, alopecia 1, 5

Management of Toxicity

• Clinical management is essentially supportive; there is no effective means to remove colchicine from tissues and blood 1, 5
• Timely gastrointestinal decontamination with activated charcoal should be considered 5
• F(ab) fragment antibodies have been used successfully in single cases but are not generally available 1

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Common Pitfalls to Avoid

• Never use the obsolete high-dose regimen (0.5 mg every 2 hours until relief or toxicity); it causes severe diarrhea in most patients 2, 3
• Do not start colchicine beyond 36 hours after symptom onset for acute gout; efficacy is negligible 2, 3
• Do not attempt dose reduction as a "compromise" in patients with renal/hepatic impairment taking CYP3A4/P-glycoprotein inhibitors; even a single 0.6 mg dose carries unacceptable toxicity risk 2
• Do not discontinue urate-lowering therapy (allopurinol, febuxostat) during an acute gout flare if the patient is already on it 2
• Do not combine NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 2