Drug Interactions of Antiarrhythmic Drugs

Drug-drug interactions (DDIs) of the antiarrhythmic drugsAntiarrhythmic drugs (AADs) defined as the modification of their efficacy and/or safety when coadministered with other drugs are common in daily practice. DDIs may result in a decrease in drug plasma levels leading to treatment failure, or an increase in drug plasma levels which, because of the narrow therapeutic window of AADs, increases the risk of serious adverse drug effects, mainly proarrhythmia and cardiac death. The risk of DDIs increases in elderly, patients on polypharmacy, with multimorbidity, hepatic and/or renal impairment, when coadministered with strong inducers or inhibitors of cytochrome P450 enzymes (CYPs) and efflux transporter P-glycoprotein (P-gp) and in carriers of genetic variants in genes encoding CYP450 (CYP450) and P-gp (ABCB1). Pharmacokinetic drug interactions frequently result from changes in the biotransformation and/or excretion of the AAD, leading to an increase or decrease in drug exposure. Pharmacodynamic drug interactions of AADs commonly result from additive QT prolongation between AADs and many drugs commonly prescribed. Interestingly, almost half of the DDIs are predictable and avoidable by monitoring the ECG and drug plasma levels, dose adjustment or use of an alternative drugs. Therefore, the aim of this chapter is to increase the awareness of DDIs among prescribers and to improve the understanding of the mechanisms involved in their appearance, their clinical relevance and ways to circumvent the interaction.