Drug Interactions between doxepin topical and propafenone

MONITOR: Coadministration with Class IC antiarrhythmic agents may increase the plasma concentrations of some tricyclic antidepressants (TCAs). The proposed mechanism is inhibition of CYP450 2D6, the isoenzyme primarily or partially responsible for the metabolism of most TCAs. In one case report, a patient developed dry mouth, dizziness, sedation, and tremors in association with increased desipramine serum concentrations when digoxin and propafenone were added to his medication regimen. The symptoms resolved following cessation of desipramine for 5 days. However, when desipramine was restarted at one-half the previous dosage, desipramine levels were still elevated compared to before propafenone was added.

MONITOR: Class IC antiarrhythmic agents can cause prolongation of the QT interval. Theoretically, coadministration with other agents such as TCAs that can prolong the QT interval may increase the risk of ventricular arrhythmias, including ventricular tachycardia and torsade de pointes, because of additive arrhythmogenic potential related to their effects on cardiac conduction. In general, the risk of an individual agent or combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution and clinical monitoring are recommended if a class IC antiarrhythmic agent is prescribed in combination with a tricyclic antidepressant. Pharmacologic response and serum TCA levels should be monitored more closely whenever a class IC antiarrhythmic agent is added to or withdrawn from therapy, and the TCA dosage adjusted as necessary. Patients should be advised to notify their physician if they experience possible signs and symptoms of TCA toxicity such as excessive sedation, dry mouth, blurred vision, urinary retention, constipation, tachycardia, arrhythmia, and seizures. Patients should seek medical attention if they experience symptoms that could indicate the occurrence of torsades de pointes such as dizziness, palpitations, or syncope.