What is the recommended colchicine (Colchicine) regimen for the management of acute gout and prophylaxis?

Colchicine Regimen in Gout

For acute gout flares, administer colchicine 1.2 mg at the first sign of flare followed by 0.6 mg one hour later (total 1.8 mg), but only if started within 36 hours of symptom onset; for prophylaxis, use 0.6 mg once or twice daily starting with urate-lowering therapy and continue for at least 6 months. 1, 2, 3

Acute Gout Flare Treatment

Standard Dosing Regimen

• Loading dose: 1.2 mg followed by 0.6 mg one hour later (total 1.8 mg over 1 hour) 1, 2, 3
• This low-dose regimen is as effective as higher doses with significantly fewer gastrointestinal side effects 1, 4, 5
• After initial doses, continue with 0.6 mg once or twice daily (beginning 12 hours after initial doses) until the attack resolves 1, 4, 3

Critical Timing Window

• Colchicine must be started within 12-36 hours of symptom onset for maximum effectiveness 1, 2, 4
• Delaying treatment beyond 36 hours significantly reduces efficacy and is not recommended 1, 2

Efficacy Data

• At 24 hours post-treatment, 38% of patients achieved ≥50% pain reduction with the low-dose regimen versus 16% with placebo (NNT = 3) 3, 6
• The recommended low-dose regimen (1.8 mg total) showed similar efficacy to high-dose regimens (4.8 mg) but with substantially better tolerability 3, 5

Prophylaxis Regimen

Standard Dosing

• 0.6 mg once or twice daily (maximum 1.2 mg/day) 7, 1, 2, 3
• Initiate prophylaxis with or just prior to starting urate-lowering therapy (allopurinol, febuxostat, pegloticase) 1, 2, 3

Duration of Prophylaxis

The duration should be the greater of the following 7, 2:

• At least 6 months from initiation of urate-lowering therapy 7, 1, 2
• OR 3 months after achieving target serum urate (if no tophi detected on physical exam) 7, 2
• OR 6 months after achieving target serum urate (if tophi are present on physical exam) 7, 2

Prophylaxis During Acute Flare

• If a flare occurs while on prophylaxis, administer the acute treatment regimen (1.2 mg followed by 0.6 mg one hour later), then wait 12 hours before resuming the prophylactic dose 3

Dose Adjustments for Renal Impairment

Severe Renal Impairment (eGFR <30 mL/min)

• Reduce to a single dose of 0.6 mg with no repeat treatment for at least two weeks 1, 2, 4
• Consider avoiding colchicine entirely and use glucocorticoids as first-line treatment instead 2, 4

Moderate Renal Impairment (eGFR 30-60 mL/min)

• Use standard dosing with caution and monitor closely for toxicity 1

Dialysis Patients

• Single dose of 0.6 mg; do not repeat before two weeks 4

Critical Drug Interactions

Absolute Contraindications

Do not use colchicine with strong CYP3A4 and/or P-glycoprotein inhibitors 1, 2, 4, 3:

• Clarithromycin
• Erythromycin
• Cyclosporine
• Ketoconazole/itraconazole
• Ritonavir/nirmatrelvir (Paxlovid)
• Verapamil/diltiazem

These combinations significantly increase colchicine levels and risk of life-threatening toxicity 4, 3

Dose Reduction Required

• When moderate CYP3A4/P-gp inhibitors cannot be avoided, reduce colchicine dose by 50% or more 2, 3

Alternative Prophylaxis Options

When Colchicine is Contraindicated or Not Tolerated

First-line alternatives 7, 2:

• Low-dose NSAIDs with proton pump inhibitor 7, 2
• Low-dose prednisone or prednisolone (<10 mg/day) 7, 2

Acute Flare Alternatives

When colchicine cannot be used for acute flares 4:

• NSAIDs at full FDA-approved doses until complete resolution 4
• Prednisone 0.5 mg/kg/day for 5-10 days, then stopped or tapered over 7-10 days 4
• Intra-articular corticosteroid injection for involvement of 1-2 large joints 7, 4

Combination Therapy for Severe Acute Gout

When to Consider Combination Therapy

• Severe acute gout with multiple large joints involved 7
• Polyarticular arthritis 7
• Inadequate response to initial monotherapy 7

Acceptable Combinations

Simultaneous use of full doses (or prophylaxis doses) of 7:

• Colchicine and NSAIDs
• Oral corticosteroids and colchicine
• Intra-articular steroids with any other modality

Avoid combining NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 7

Common Pitfalls to Avoid

Timing Errors

• Starting colchicine beyond 36 hours of symptom onset dramatically reduces effectiveness and should be avoided 1, 2, 4

Premature Discontinuation

• Stopping prophylaxis too early leads to increased flare rates during urate-lowering therapy 2
• Continue for the full recommended duration based on tophi status and serum urate goals 2

Dosing Errors

• Using high-dose colchicine regimens (>1.8 mg in first hour) increases toxicity without improving efficacy 1, 4, 5
• Not adjusting dose in renal impairment can lead to severe toxicity including neuromyopathy and bone marrow suppression 1, 2

Drug Interaction Oversights

• Failing to screen for CYP3A4/P-gp inhibitors before prescribing colchicine can result in life-threatening toxicity 4, 3
• Calculate eGFR and review medication list before every colchicine prescription 4

Monitoring Failures

• Monitor for neurotoxicity and myotoxicity, especially in patients with renal impairment or concurrent statin therapy 2