Alerts

Oral Colchicine (Colcrys) – Severe Drug Interactions with Strong CYP3A4 and P-glycoprotein Inhibitors

August 3, 2009

The FDA recently reviewed the safety of oral colchicine (Colcrys). New drug interactions have been identified with this agent. Oral colchicine was linked to 169 cases of fatal toxicity. One-hundred seventeen cases occured in patients taking therapeutic doses, and over half of these 117 cases involved concomitant use of clarithromycin. Colchicine is a substrate of cytochrome P450 3A4 (CYP3A4) in the liver and gastrointestinal (GI) tract, along with P-glycoprotein efflux pumps (P-gp) in the GI tract. Strong CYP3A4 inhibitors (eg, clarithromycin, cyclosporine, diltiazem, erythromycin, grapefruit juice, itraconazole, ketoconazole, verapamil) may increase colchicine levels and the subsequent risk of toxicity. Many CYP3A4 inhibitors also inhibit P-gp, which could further increase this effect. Because colchicine is 10 – 20% cleared by the kidneys, renal impairment may also reduce its clearance.

Whenever possible, avoid prescribing colchicine concomitantly with strong CYP3A4 or P-gp inhibitors in patients with impaired renal or hepatic function. If strong inhibitors are required in patients with normal organ function, consider decreasing the colchicine dose or temporarily discontinuing colchicine. Monitor patients taking colchicine for signs of toxicity, including muscle weakness or pain, tingling in the fingers or toes, pale gray lips and tongue, pale gray palms, and severe nausea or vomiting.

In addition to these warnings, the FDA changed the recommended dose of colchicine for gout flairs to 1.2 mg orally initially, followed by 0.6 mg given 1 hour later. The FDA is also requiring that a Patient Medication Guide be dispensed with colchicine (Colcrys®). Additional information is available at the following links:

The FDA requires the distribution of Medication Guides for drugs determined to be a serious and significant public health concern. This requirement applies primarily to medications dispensed in the outpatient setting (refer to Code of Federal Regulations 21CFR208.1). However, it may be appropriate to educate inpatients about the potential hazards of prescription medications, at the clinician’s discretion. The complete list of drugs that require a Medication Guide as part of the FDA-regulated product labeling is available online at: http://www.fda.gov/cder/Offices/ODS/labeling.htm.

Updated
August 3, 2009; University of Utah, Drug Information Service. Copyright 2009, Drug Information Service, University of Utah, Salt Lake City, UT.