Colchicine for acute gout: updated information about dosing and drug interactions

Vomiting and diarrhoea commonly occur when colchicine is repeatedly dosed at 1-hour or 2-hour intervals for acute gout.1,3 These are the first signs of colchicine toxicity, and may precede rare adverse effects including muscle damage, neuropathy, multiple organ failure and bone marrow suppression.4 Patients with renal or hepatic impairment may be particularly susceptible to severe colchicine toxicity (Box 2).2,5-7

Increasing awareness of toxicity led prescribing guidelines to recommend lower colchicine doses and extended dosing intervals.8-10 Case reports and expert opinion suggested that the treatment benefit could be maintained at lower colchicine doses, but no data from controlled trials were available until recently.1,11

Recent trial evidence demonstrates that low-dose colchicine (2 tablets followed by 1 tablet 1 hour later) is effective when prescribed within 12 hours of onset of an acute gout flare, with a low incidence of gastrointestinal adverse effects (Table 1).1 A higher dose (2 tablets followed by 1 tablet every hour for 6 hours) offered no additional clinical benefit, but increased the risk of gastrointestinal toxicity. This study was conducted in the United States, where colchicine is available as 0.6 mg tablets rather than the 0.5 mg tablets available in Australia.

Concurrently prescribing colchicine and inhibitors of cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (P-gp) increases the potential for colchicine toxicity (Box 1).2,5 The US Food and Drug Administration reported that of 117 cases of fatal colchicine toxicity at therapeutic doses (≤ 2 mg/day), more than half occurred in patients who were taking clarithromycin at the same time.2 However, a possible role for renal impairment or prolonged colchicine dosing cannot be excluded in these cases.

Fatal and non-fatal colchicine toxicity has occurred in patients taking colchicine and concomitant erythromycin, cyclosporin, statins and calcium-channel blockers, including verapamil and diltiazem.2,12

Concurrently prescribing colchicine and inhibitors of cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (P-gp) increases the potential for colchicine toxicity (Box 1).2,5 The US Food and Drug Administration reported that of 117 cases of fatal colchicine toxicity at therapeutic doses (≤ 2 mg/day), more than half occurred in patients who were taking clarithromycin at the same time.2 However, a possible role for renal impairment or prolonged colchicine dosing cannot be excluded in these cases.

Fatal and non-fatal colchicine toxicity has occurred in patients taking colchicine and concomitant erythromycin, cyclosporin, statins and calcium-channel blockers, including verapamil and diltiazem.2,12

A smaller colchicine pack size of 30 tablets will replace the existing 100-tablet pack later this year.19 Prescribers should consider prescribing the number of colchicine tablets sufficient for the patient's needs (see Provide patients with clear instructions about colchicine use).

Inform patients that colchicine can effectively relieve the pain of acute gout at doses lower than those they may have used in the past. An analgesic such as paracetamol can be taken while waiting for colchicine to take effect during an acute gout flare.15

Self-care strategies include placing an ice pack on the affected joint and using a simple device such as a cardboard box to keep bedclothes off it at night.10,20 Advise patients to elevate the limb and avoid unnecessary clothing such as socks and shoes, when possible.20

Counsel patients experiencing an acute gout flare on the revised colchicine dosing regimen:15

• take 2 colchicine tablets initially, followed by 1 colchicine tablet 1 hour later
• do not take more than 3 colchicine tablets (1.5 mg) during a course of treatment for an acute gout flare
• do not repeat the course of treatment for at least 3 days.

Discuss the safe and effective use of colchicine in acute gout. Advise patients to:2,15

• tell their doctor and pharmacist about all the medicines they take, and to check before taking any new medicines
• stop taking colchicine and see their doctor if they develop nausea, vomiting or diarrhoea; unusual bleeding or bruising; muscle pain or weakness; or numbness or tingling in the fingers or toes
• avoid eating grapefruit and drinking grapefruit juice when taking colchicine
• be aware that colchicine is not a painkiller and should not be used for other causes or types of pain.