Newly-Published Colchicine Safety Data Provide First Evidence-Based Dosing Guidance to Avoid Potentially Serious Interactions With Commonly Prescribed Drugs
PHILADELPHIA, Aug. 11, 2011 /PRNewswire/ -- Newly-published results from a series of colchicine safety studies provide physicians with the first evidence-based dosing guidance for colchicine when co-administered with certain commonly prescribed drugs, helping doctors and patients avoid serious and potentially life-threatening drug-drug interactions.
The study results, published in a paper titled "Evidence Basis of a Novel Colchicine Dose Reduction Algorithm to Predict and Prevent Colchicine Toxicity in the Presence of P-gp/CYP450 3A4 Inhibitors," appear in the August issue of Arthritis & Rheumatism, the journal of the American College of Rheumatology. The paper recommends colchicine dose reductions when used with medications such as immunosuppressants, antibiotics, hypertension drugs, anti-fungals and protease inhibitors.
The seven studies highlighted in the paper formed part of the basis for URL Pharma's New Drug Application (NDA) for Colcrys® (colchicine, USP). Colcrys is the only single-ingredient colchicine product to be reviewed and approved by the U.S. Food and Drug Administration, and is indicated for the prophylaxis and treatment of gout flares, and for the treatment of Familial Mediterranean Fever (FMF).
The studies assessed cyclosporine, an immunosuppressant; clarithromycin and azithromycin, two antibiotics; diltiazem and verapamil, two hypertension drugs; ketoconazole, an anti-fungal drug; and ritonavir, a protease inhibitor. Each of these drugs is known to inhibit cytochrome P450 3A4 (CYP3A4) and/or P-glycoprotein (P-gp).
Each of these drugs, except for azithromycin, was found to interact significantly with standard colchicine dosing regimens, in some cases more than doubling levels of colchicine in the blood and increasing the risk of serious toxicities. Cyclosporine and clarithromycin in particular increased peak colchicine blood levels by nearly 300 percent. The authors recommended that colchicine doses