Colchicine dose does not require dose adjustments when co-administered with azithromycin
Novel Evidence-Based Colchicine Dose-Reduction Algorithm to Predict and Prevent Colchicine Toxicity in the Presence of Cytochrome P450 3A4/P-glycoprotein Inhibitors
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Study Design
All studies were open-label, non-randomized, single-center, one-sequence, two-period DDI experiments, using two 0.6-mg doses of colchicine, separated by a minimum 14-day washout period, followed by administration of the approved on-label regimen of known CYP3A4/P-glycoprotein inhibitors. Plasma concentrations of colchicine, but not the reference CYP3A4/P-glycoprotein inhibitors, were determined, and the pharmacokinetic parameters were calculated.
Study Results
The ratios of the maximum concentration and area under the curve from time 0 to infinity for colchicine plus CYP3A4/P-glycoprotein inhibitors versus colchicine alone were 125 across all studies, with the exception of studies involving azithromycin. Significant DDIs were present when single doses of colchicine were coadministered with most of the selected CYP3A4/P-glycoprotein inhibitors. Recommended colchicine dose reductions of 33-66 for the treatment of acute gout and 50-75 for prophylaxis were calculated for concomitant therapy with each agent, with the exception of no dose adjustment when colchicine is used in combination with azithromycin.
Study Conclusions
We demonstrated the need for specific reductions in the dose of colchicine when it is used in combination with 2 broadly prescribed calcium channel blockers (verapamil ER and diltiazem ER) and that the dose of colchicine does not need to be adjusted when it is used in combination with azithromycin.
References
Terkeltaub RA. Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome p450 3a4/p-glycoprotein inhibitors. Arthritis Rheum. 2011; 8: 2226-37.
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