Drug interactions between adenosine and iloperidone

GENERALLY AVOID: Iloperidone may cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in elevated risk of ventricular arrhythmias, including ventricular tachycardia and torsade de pointes, because of additive arrhythmogenic potential related to their effects on cardiac conduction. In an open-label study in patients with schizophrenia or schizoaffective disorder, an iloperidone dosage of 12 mg twice daily was associated with QTc prolongation of 9 msec. The effect on the QT interval is augmented by the presence of CYP450 2D6 and/or 3A4 inhibitors. Under conditions of metabolic inhibition for both CYP450 2D6 and 3A4 using paroxetine 20 mg once daily and ketoconazole 200 mg twice daily, a mean QTcF (Fridericia-corrected QT interval) increase from baseline of approximately 19 msec was observed. No cases of torsade de pointes or other severe cardiac arrhythmias were reported during the premarketing period. 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: The use of iloperidone in combination with other medications that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is unavoidable. Patients should have regular ECGs and be monitored for arrhythmias when QT interval is prolonged. Persistent QTc measurements exceeding 500 msec will require suspension of iloperidone therapy and immediate action to correct any concomitant risk factors before resuming treatment. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.