Drug Interactions between apomorphine and nortriptyline

MONITOR: Apomorphine may cause modest dose-related prolongation of the QTc interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In addition, some of these agents (e.g., phenothiazines, tricyclic antidepressants) may cause additive sedative and hypotensive effects with apomorphine. In a thorough QT study where apomorphine exposures were comparable to those of the recommended subcutaneous dosage (6 mg), apomorphine was found to prolong the QTcF interval by 10 msec, with the 90% upper confidence interval reaching 16 msec. The study also established a significant exposure-response relationship between apomorphine concentration and QTcF. Torsade de pointes has not been reported with apomorphine alone at recommended doses. In general, the risk of an individual agent or a 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 is recommended if apomorphine is used in combination with other drugs that can prolong the QT interval. Doses of subcutaneous apomorphine above 6 mg are not recommended. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. If taking drugs that also cause CNS or orthostatic effects (e.g., psychotropic drugs like tricyclic antidepressants, phenothiazines, and neuroleptics), patients should be made aware of the possibility of additive effects with apomorphine and counseled to avoid activities requiring mental alertness until they know how these agents affect them.