Drug Interaction Report

GENERALLY AVOID: Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of most calcium channel blockers (CCBs), as CYP450 3A4 is the primary isoenzyme responsible for their metabolism. Some drug interaction studies have reported a significant reduction in plasma levels for certain CCBs. For example, when a single dose of nimodipine (60 mg) was administered to patients with epilepsy (n=8) who were also receiving chronic treatment with a potent CYP450 3A4-inducing antiepileptic agent (phenytoin, phenobarbital and/or carbamazepine), the mean areas under the plasma nimodipine concentration curve (AUC) were lowered by about 7-fold compared to the control group. In another drug interaction study comparing nisoldipine pharmacokinetics in epileptic patients on concurrent phenytoin therapy (n=12) to healthy controls (n=12), the AUC of nisoldipine was approximately 90% lower (1.6 vs 15.2 mcg/L/h) in patients on concomitant phenytoin therapy. Clinical data for all calcium channel blockers with potent CYP450 3A4 inducers are not available.

MANAGEMENT: Concomitant use of calcium channel blockers (CCBs) primarily metabolized by CYP450 3A4 with potent CYP450 3A4 inducers should generally be avoided. Additional monitoring and dose adjustments may be required if coadministration is necessary, particularly during initiation, titration, or discontinuation of the CYP450 3A4 inducer. Individual product labeling for the CCB should be consulted for further guidance.