Drug Interactions between propafenone and ziprasidone

CONTRAINDICATED: Ziprasidone can cause dose-related prolongation of the QT 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 placebo-controlled trials in adults, oral ziprasidone increased the QTc interval by approximately 10 msec at the highest recommended daily dosage of 160 mg compared to placebo. In a study comparing the QT prolonging effect of several antipsychotic drugs at the maximum plasma concentration following administration alone in patient volunteers, the mean increase in QTc (QT interval corrected for heart rate) from baseline for ziprasidone ranged from approximately 9 to 14 msec greater than for four of the comparator drugs (haloperidol, olanzapine, quetiapine, and risperidone), but was approximately 14 msec less than the prolongation observed for thioridazine. In another study evaluating the QT prolonging effect of intramuscular ziprasidone versus intramuscular haloperidol (control) at the maximum plasma concentration following administration in patient volunteers, the mean increase in QTc from baseline for ziprasidone (20 mg and 30 mg doses given 4 hours apart) was 4.6 msec after the first injection and 12.8 msec after the second injection, which at 30 mg is 1.5 times the highest recommended dose. The mean increase in QTc from baseline for haloperidol (7.5 mg and 10 mg doses given 4 hours apart) was 6.0 msec following the first injection and 14.7 msec following the second injection. No patients had a QTc interval exceeding 500 msec. 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).

MONITOR CLOSELY: Central nervous system depressant or toxic effects may be additively or synergistically increased in patients taking ziprasidone with certain other drugs (such as other CNS-active agents or efavirenz) that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: Coadministration of ziprasidone with other drugs that can prolong the QT interval is considered contraindicated. Additionally, patients treated with any medication that can cause CNS toxicity symptoms should be advised to seek prompt medical attention if they experience symptoms. Patients should be advised to avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them.