Drug Interaction Report

MONITOR: Amide-type local anesthetics (e.g., lidocaine, bupivacaine, ropivacaine) may have additive cardiac effects when coadministered with class I antiarrhythmic agents. In general, the toxic effects of amide-type anesthetics when coadministered with structurally related antiarrhythmic agents are additive and potentially synergistic which may lead to bradycardia, chest pain, heart block, arrhythmias, ECG abnormalities, and cardiac arrest. The clinical significance of the interaction has not been established.

MANAGEMENT: If coadministration of amide-type local anesthetics with class I antiarrhythmic agents (e.g., procainamide, mexiletine, disopyramide) is required, caution and clinical monitoring are recommended for additive cardiac effects. Advise patients to contact their physician if they experience adverse effects such as chest pain, palpitations, nausea, vomiting, lightheadedness, nervousness, dizziness, or tremors.

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.