Drug Interactions between amisulpride and droperidol

GENERALLY AVOID: Amisulpride can cause dose- and concentration-dependent prolongation of the QT interval. Droperidol can also cause dose-dependent QT prolongation and has been associated with torsade de pointes, other serious arrhythmias, and death. Theoretically, coadministration of multiple 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 40 healthy Caucasian and Japanese subjects, the maximum mean difference in QTcF (Fridericia corrected QT interval) for amisulpride compared to placebo after baseline correction was 5.0 ms following a 5 mg IV infusion over 2 minutes and 23.4 ms following a 40 mg IV infusion over 8 minutes. A maximum mean difference of 13.4 ms is predicted for a 10 mg IV infusion over 1 minute based on the exposure-QTcF response relationship identified from the data in the study. In a study of 40 patients without known cardiac disease who underwent extracranial head and neck surgery, significant prolongation of the median corrected QT interval (QTc) by 37, 44, and 59 ms was observed within 10 minutes of 0.1, 0.175, and 0.25 mg/kg droperidol doses, respectively. 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: Coadministration of amisulpride and droperidol should be avoided. Caution and close clinical monitoring (e.g., electrocardiogram, serum electrolytes) are recommended if concomitant use is required. 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.

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