July 31, 2009 — The US Food and Drug Administration (FDA) has approved the first single-ingredient oral colchicine product (Colcrys, Mutual Pharmaceutical Company, Inc) for the treatment of familial Mediterranean fever and acute gout flares.
Oral colchicine has been used for many years as an unapproved drug with no FDA-approved prescribing information, dosage recommendations, or drug interaction warnings, the agency said in a news release, noting the development of new safety concerns.
An FDA analysis of safety data from reported adverse events, published literature, and company-sponsored pharmacokinetic and drug interaction studies has revealed cases of fatal colchicine toxicity in certain patients receiving standard doses of the drug concomitantly with other drugs such as clarithromycin.
These data suggested that drug interactions affecting the gastrointestinal absorption and/or hepatic metabolism of colchicine play a central role in the development of toxicity, the FDA said.
As a result, the new prescribing information for colchicine warns that concomitant use of P-glycoprotein or strong cytochrome P 450 isoenzyme 3A4 inhibitors is contraindicated in patients with renal or hepatic impairment receiving therapy.
Dose reductions or interruption of colchicine therapy should be considered in patients with normal renal and hepatic function who require concomitant treatment with a P-glycoprotein or strong cytochrome P 450 isoenzyme 3A4 inhibitor.
The new prescribing information for colchicine also contains data from clinical studies showing that substantially lower doses than usual provide equal efficacy for the treatment of gout with improved safety parameters. As a result, the FDA-approved dose of colchicine in acute gout flares is 1.2 mg followed by a second dose of 0.6 mg administered 1 hour later (total, 1.8 mg).
Patients should be informed of the risk for potentially fatal colchicine drug interactions that can occur at prescribed doses and with medications that are given for a short time, such as antibiotics. Patients should be instructed to avoid consuming grapefruit and grapefruit juice during treatment and to maintain an index of suspicion for signs of colchicine toxicity such as muscle numbness/pain, numbness/tingling in the extremities, unusual bleeding/bruising, severe diarrhea/vomiting, feeling weak/tired, increased infections, and pale or grey color of the lips, tongue, or palms.
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Cite this: Yael Waknine. FDA Approves Colchicine With Drug Interaction and Dose Warnings - Medscape - Jul 31, 2009.