Drug Interaction Report

MONITOR: Based on in vitro inhibition data, coadministration with mibefradil may increase the plasma concentrations of drugs that are substrates of CYP450 2D6 and/or 3A4. The mechanism is decreased clearance due to inhibition of these isoenzymes by mibefradil.

MANAGEMENT: Caution is advised when mibefradil is used concomitantly with drugs that undergo metabolism by CYP450 2D6 and/or 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever mibefradil is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse.

MANAGEMENT: The use of alcohol during propoxyphene therapy should be avoided. Patients should be warned not to exceed the recommended dosage of propoxyphene and to avoid activities requiring mental alertness until they know how these agents affect them.