Drug Interaction Report

MONITOR: Coadministration with vandetanib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein transporter, such as digoxin and dabigatran. The mechanism involves increased absorption and/or decreased clearance due to inhibition of drug efflux mediated by intestinal and renal/hepatic P-glycoprotein, respectively. Vandetanib is a weak P-glycoprotein inhibitor. The clinical significance is unknown. In healthy subjects, coadministration of a single 0.25 mg dose of digoxin with a 300 mg dose of vandetanib increased the mean digoxin Cmax by 29% and the mean AUC by 23%.

MANAGEMENT: Caution is advised if vandetanib must be used concomitantly with medications that are substrates of P-glycoprotein, particularly those with a narrow therapeutic range such as digoxin. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever vandetanib is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including morphine and diamorphine. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of morphine may cause rapid release of the drug, resulting in high systemic levels of morphine that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. The interaction was observed in in vitro studies using a 24-hour morphine formulation (Avinza 30 mg capsule, available in the U.S. from Ligand Pharmaceuticals). When the capsule was mixed with 900 mL of buffer solutions containing ethanol 20% and 40%, the dose of morphine that was released was alcohol concentration-dependent, leading to a more rapid release of morphine. Although the clinical relevance of this finding is unknown, 'dose-dumping' into the bloodstream is conceivable.

MANAGEMENT: Until more information is available, patients taking sustained-release formulations of morphine should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as morphine or diamorphine should not be combined with alcohol.