Drug Interactions between Quinaglute Dura-Tabs and valbenazine

GENERALLY AVOID: Coadministration with a strong CYP450 2D6 inhibitor may increase the exposure of (+)-alfa-dihydrotetrabenazine, the active metabolite of valbenazine, which may increase the risk of adverse effects, including somnolence and QT interval prolongation. The proposed mechanism is decreased clearance due to inhibition of CYP450 2D6 activity. Increased concentrations of valbenazine and (+)-alfa-dihydrotetrabenazine may lead to clinically significant prolongation of the QT interval. Poor CYP450 2D6 metabolizer status (approximately 7% of Caucasians and 2% of Asians and those of African descent) is also predicted to increase exposure to (+)-alfa-dihydrotetrabenazine. Analysis of clinical data from two studies in healthy volunteers showed increased QTc intervals at higher plasma concentrations of (+)-alfa-dihydrotetrabenazine. Based on an 80 mg dose of valbenazine, patients with increased exposure to (+)-alfa-dihydrotetrabenazine (e.g., due to poor CYP450 2D6 metabolizer status or coadministration of a strong CYP450 2D6 inhibitor) may show QTc prolongation of an average of 11.7 msec, compared to an average increase of 6.7 msec in otherwise healthy volunteers. Pharmacodynamically, valbenazine and quinidine, a class IA antiarrhythmic, may also have additive effects on the QT interval. 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 drugs involved and dosages of the drugs.

MANAGEMENT: Due to increased risk of QT prolongation and torsade de pointes arrhythmia, concomitant use of valbenazine with quinidine should generally be avoided. Valbenazine is also not recommended for use in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. If coadministration is required, assessment of baseline QT interval and periodic monitoring during therapy may be considered. The manufacturer recommends a dosage reduction for valbenazine during concomitant administration with strong CYP450 2D6 inhibitors or in patients who are poor metabolizers of CYP450 2D6. Patients and their caregivers 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. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their doctor if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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