Basic Information
ID DDInter2012 and DDInter1770
Interaction Elevated terfenadine plasma concentrations have been reported in healthy subjects coadministered mibefradil and terfenadine. QTc prolongation, a known risk factor for terfenadine induced cardiac arrhythmias, was reported to be 12%. The mechanism is inhibition of the metabolism of terfenadine by mibefradil.
Management The concomitant use of terfenadine and mibefradil is contraindicated due to the risk for life threatening cardiac arrhythmias. Cetirizine, fexofenadine or loratadine may be safer antihistamine alternatives.
References [1] "Product Information. Posicor (mibefradil)." Roche Laboratories (2001):
Alternative for Mibefradil C08C
Felodipine Amlodipine Nisoldipine Nicardipine Isradipine Clevidipine
Levamlodipine Nifedipine Celecoxib Nimodipine
Alternative for Terfenadine R06A
Ketotifen Levocetirizine Chlorcyclizine Cetirizine Acrivastine Triprolidine
Tripelennamine Azelastine Dexbrompheniramine Clemastine Fexofenadine
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.