What is the recommended dosing of colchicine (Colcrys) for an adult patient with gout, considering their medical history, including impaired renal function or liver disease?

Colchicine Dosing for Gout

For acute gout flares in adults with normal renal and hepatic function, administer colchicine 1.2 mg 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. 1, 2

Standard Dosing for Acute Gout Flares

Timing is critical: Treatment must be initiated within 36 hours of symptom onset for optimal effectiveness, ideally within 12 hours. 1, 3 Beyond this window, efficacy drops significantly. 1

Initial loading dose:

• 1.2 mg (two 0.6 mg tablets) at first sign of flare 2
• Followed by 0.6 mg (one tablet) one hour later 2
• Maximum total dose in first hour: 1.8 mg 1, 2

Continuation dosing:

• Wait 12 hours after the loading doses 3
• Resume 0.6 mg once or twice daily until attack completely resolves 3, 2

This low-dose regimen is as effective as the older high-dose regimen (4.8 mg over 6 hours) but with significantly fewer gastrointestinal side effects. 1, 4, 5 The number needed to treat for 50% pain reduction is 5. 3

Prophylaxis Dosing

Standard prophylaxis: 0.6 mg once or twice daily (maximum 1.2 mg/day) 6, 2

Duration: Continue for at least 6 months when initiating urate-lowering therapy, or for the greater of 6 months OR 3 months after achieving target serum urate with no tophi detected. 7, 2

Dosing Adjustments for Renal Impairment

Mild Renal Impairment (CrCl 50-80 mL/min or eGFR 60-89 mL/min)

Acute flares: No dose adjustment required, but monitor closely for adverse effects. 2, 8

Prophylaxis: 0.6 mg once or twice daily with close monitoring. 2, 8

Moderate Renal Impairment (CrCl 30-50 mL/min or eGFR 30-59 mL/min)

Acute flares:

• Use standard loading dose (1.2 mg followed by 0.6 mg one hour later) 2
• Monitor closely for adverse effects 2
• Do not repeat treatment course more frequently than every 2 weeks 2

Prophylaxis:

• Start with 0.3 mg once daily 2
• Alternatively, 0.48 mg daily provides more optimal plasma levels than splitting tablets 8
• Monitor closely and increase dose cautiously if needed 2

Severe Renal Impairment (CrCl <30 mL/min or eGFR 15-29 mL/min)

Acute flares:

• Reduce to single dose of 0.6 mg (one tablet) 2
• Do not repeat more than once every 2 weeks 2
• Consider alternative therapy strongly 7

Prophylaxis:

• Start with 0.3 mg once daily 6, 2
• For optimal plasma levels, 0.3 mg (2.5 mL oral solution) is preferred over tablet splitting 8
• Increase dose cautiously with close monitoring 2

Dialysis Patients

Acute flares: Single dose of 0.6 mg only; do not repeat more than once every 2 weeks. 2

Prophylaxis: 0.3 mg twice weekly with close monitoring. 2

Absolute Contraindications

Do NOT prescribe colchicine to patients with renal OR hepatic impairment who are concurrently taking: 1, 7, 2

Strong CYP3A4 inhibitors:

• Clarithromycin (fatal toxicity reported) 2
• Erythromycin 1
• Ketoconazole 1, 2
• Itraconazole 2
• Ritonavir 2
• Other protease inhibitors 2

Strong P-glycoprotein inhibitors:

• Cyclosporine (fatal toxicity reported) 1, 2
• Ranolazine 2

Dosing Adjustments for Drug Interactions (in patients WITHOUT renal/hepatic impairment)

With Strong CYP3A4 or P-gp Inhibitors

Acute flares:

• Reduce to 0.6 mg × 1 dose, followed by 0.3 mg one hour later 2
• Do not repeat for at least 3 days 2

Prophylaxis:

• Reduce to 0.3 mg once daily (or 0.3 mg every other day if baseline dose was 0.6 mg once daily) 2

With Moderate CYP3A4 Inhibitors (diltiazem, verapamil, erythromycin, fluconazole, grapefruit juice)

Acute flares:

• 1.2 mg × 1 dose (do not give second 0.6 mg dose) 2
• Do not repeat for at least 3 days 2

Prophylaxis:

• Reduce to 0.3 mg twice daily or 0.6 mg once daily 2

Dosing Adjustments for Hepatic Impairment

The FDA label recommends caution and dose reduction in hepatic impairment, with the same absolute contraindication when combined with CYP3A4 or P-gp inhibitors. 2 Monitor closely for adverse effects and consider starting with lower prophylactic doses (0.3 mg daily). 2

Alternative Treatment Options When Colchicine is Contraindicated

Oral corticosteroids: Prednisone 30-35 mg daily for 3-5 days 1, 3, 7

NSAIDs at full FDA-approved doses: 1, 3

• Naproxen 500 mg twice daily until attack resolves 1, 7
• Indomethacin 50 mg three times daily until attack resolves 1, 7
• Avoid in severe renal impairment (CrCl <30 mL/min) 3

Intra-articular corticosteroids: Excellent option for monoarticular gout 1, 3, 7

Critical Pitfalls to Avoid

The older high-dose regimen (0.5 mg every 2 hours until relief or toxicity) is obsolete and should never be used - it causes severe diarrhea in most patients with no additional benefit. 1, 3

Do not exceed 1.8 mg total dose in the first hour for acute treatment. 1, 2 Higher doses provide no additional benefit but substantially increase gastrointestinal toxicity. 3

Patients on statins with renal impairment are at high risk for colchicine-induced myopathy and neuromuscular toxicity. 1, 7 Monitor for muscle weakness, elevated creatine kinase, or neuropathy symptoms. 7

Treatment delayed beyond 36 hours has significantly reduced effectiveness. 1, 3 Educate patients on "pill in the pocket" approach for self-medication at first warning symptoms. 3

If patient is already taking prophylactic colchicine when acute attack occurs: Give the loading dose (1.2 mg followed by 0.6 mg one hour later), then wait 12 hours before resuming regular prophylactic dose. 3, 2