Drug Interactions between asenapine and Rybix ODT

GENERALLY AVOID: Asenapine may cause dose-related prolongation of the QT interval. Tramadol may also prolong the QT interval, and 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. The effects of asenapine on the QT/QTc interval were evaluated in a dedicated QT study using dosages of 5, 10, 15, and 20 mg twice a day in 151 clinically stable patients with schizophrenia. At these dosages, asenapine was associated with QTc interval increases ranging from 2 to 5 msec compared to placebo. No patient treated with asenapine experienced QTc increases of 60 msec or more from baseline or a QTc of 500 msec or more. In short-term clinical trials using 5 or 10 mg twice a day, post-baseline QT prolongations exceeding 500 msec were reported at comparable rates for asenapine and placebo. There were no reports of torsade de pointes arrhythmia or any other adverse reactions associated with delayed ventricular repolarization. The effect of tramadol on the QT interval was evaluated in a randomized, double-blind, 4-way crossover, placebo- and positive-controlled, multiple-dose ECG study of 62 healthy subjects. The maximum placebo-adjusted mean change from baseline in the Fridericia-corrected QT interval (QTcF) was 5.5 msec in the 400 mg/day treatment arm (100 mg every 6 hours on days 1 through 3 with a single 100 mg dose on day 4) and 6.5 msec in the 600 mg/day treatment arm (150 mg every 6 hours on days 1 through 3 with a single 150 mg dose on day 4), both occurring at the 8-hour time point. 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). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

GENERALLY AVOID: Concomitant use of opioids such as tramadol with other central nervous system (CNS) depressants such as asenapine may result in hypotension, profound sedation, respiratory depression, coma, and death.

MANAGEMENT: Coadministration of asenapine with tramadol should generally be avoided. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve the desired clinical effect. Patients should have regular ECGs and be monitored for arrhythmias when the QT interval is prolonged. Persistent QTc measurements exceeding 500 msec will require suspension of asenapine therapy and immediate action to correct any concomitant risk factors before resuming treatment. Particular care should be exercised in patients suspected to be at an increased risk of torsade de pointes. 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. In addition, patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them.

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