What is the recommended dosing regimen for colchicine (Colcrys) in an adult patient with an acute flare of gout, considering potential renal impairment and other comorbidities?

Colchicine Dosing for Acute Gout Flares

Standard Dosing Regimen

For acute gout flares in adults with normal renal function, give colchicine 1.2 mg (two tablets) at the first sign of symptoms, followed by 0.6 mg (one tablet) one hour later, for a total of 1.8 mg over one hour. 1, 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, 3
• The number needed to treat (NNT) for achieving 50% or greater pain reduction at 24 hours is 5 1
• Treatment must be initiated within 36 hours of symptom onset for optimal effectiveness, ideally within 12 hours 1, 4

Critical Timing and Continuation

• After the initial loading doses (1.2 mg + 0.6 mg), wait 12 hours, then resume prophylactic dosing of 0.6 mg once or twice daily until the acute attack completely resolves 4
• If already taking prophylactic colchicine when the attack occurs, take the loading dose as above, then wait 12 hours before resuming the regular prophylactic dose 4
• Treatment delayed beyond 36 hours has significantly reduced effectiveness 1, 4

Dosing Adjustments for Renal Impairment

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

• No dose adjustment required for the acute treatment regimen (1.2 mg followed by 0.6 mg one hour later) 2
• Monitor closely for adverse effects of colchicine 2

Severe Renal Impairment (CrCl <30 mL/min):

• The standard acute dose does not need adjustment, but treatment courses should be repeated no more than once every two weeks 2
• Consider alternative therapy for patients requiring repeated courses 2
• Colchicine should be avoided entirely in severe renal impairment; strongly consider alternative therapy 1, 4

Dialysis Patients:

• Reduce the total dose to a single dose of 0.6 mg (one tablet) 2
• Treatment course should not be repeated more than once every two weeks 2

Dosing Adjustments for Hepatic Impairment

Mild to Moderate Hepatic Impairment:

• No dose adjustment required for acute treatment 2
• Monitor closely for adverse effects 2

Severe Hepatic Impairment:

• The dose does not need adjustment, but treatment courses should be repeated no more than once every two weeks 2
• Consider alternative therapy for patients requiring repeated courses 2

Absolute Contraindications

Never prescribe colchicine to patients with renal or hepatic impairment who are taking strong CYP3A4 or P-glycoprotein inhibitors due to risk of fatal colchicine toxicity: 1, 4, 2

• Clarithromycin, erythromycin
• Cyclosporine
• Ketoconazole
• Ritonavir, indinavir, lopinavir/ritonavir, and other protease inhibitors
• This combination is absolutely contraindicated and can be fatal 1, 2

Alternative Treatment Options When Colchicine is Contraindicated

Oral Corticosteroids (First-Line Alternative):

• Prednisone 30-35 mg daily for 5 days (no taper), OR 1, 5
• Prednisone 0.5 mg/kg/day for 2-5 days at full dose, then taper over 7-10 days 5
• Corticosteroids are generally safer and lower cost compared to colchicine, with fewer adverse effects than NSAIDs 5
• Preferred in patients with severe renal impairment, cardiovascular disease, heart failure, cirrhosis, or peptic ulcer disease 5

NSAIDs (Alternative Option):

• Naproxen 500 mg twice daily OR indomethacin 50 mg three times daily until attack resolves 1, 4
• Use full FDA-approved doses until complete resolution 4
• Avoid in severe renal impairment (CrCl <30 mL/min) 1, 4

Intra-articular Corticosteroid Injection:

• Excellent option for monoarticular or oligoarticular gout involving accessible large joints 1, 4, 5
• Dose varies by joint size 5

Intramuscular Corticosteroids:

• Triamcinolone acetonide 60 mg IM for patients unable to take oral medications 5
• Particularly indicated when patient is NPO or oral medications cannot be tolerated 5

Combination Therapy for Severe Attacks

For severe acute gout with polyarticular involvement or multiple large joints, consider initial combination therapy: 4

• Colchicine + NSAIDs (provides synergistic anti-inflammatory effects) 4
• Oral corticosteroids + colchicine 4
• Intra-articular steroids + any oral modality 4
• Avoid combining NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 4

Common Pitfalls to Avoid

• Never use the older high-dose regimen (0.5 mg every 2 hours until relief or toxicity)—it is obsolete and causes severe diarrhea in most patients 1, 4
• The maximum total dose in the first hour should not exceed 1.8 mg 1
• Higher doses provide no additional benefit but substantially increase gastrointestinal toxicity 1, 3
• Patients on statins with renal impairment are at high risk for colchicine-induced myopathy and neuromuscular toxicity 1
• Treatment of gout flares with colchicine is not recommended in patients with renal impairment who are already receiving colchicine for prophylaxis 2
• Do not interrupt ongoing urate-lowering therapy during an acute gout attack 5

Special Populations

Elderly Patients:

• Use standard dosing but monitor closely for adverse effects 1
• Consider renal function carefully as elderly patients often have reduced creatinine clearance 2

Patients on Statins:

• Monitor closely for myopathy and neuromuscular toxicity, especially with concurrent renal impairment 1

Patients with Diabetes:

• Corticosteroids are still appropriate but monitor glucose closely and adjust diabetic medications proactively 5