Ingrezza and Zykadia

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer information for this interaction is not currently available.ADJUST DOSE: Coadministration with a strong CYP450 3A4 inhibitor may increase the systemic exposure and risk of adverse effects of valbenazine, including somnolence and QT interval prolongation. The proposed mechanism is decreased clearance due to inhibition of CYP450 3A4 activity. Increased concentrations of valbenazine and its active metabolite, (+)-alfa-dihydrotetrabenazine, may lead to clinically significant prolongation of the QT interval. 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 may show QTc prolongation of an average of 11.7 msec, compared to an average increase of 6.7 msec in otherwise healthy volunteers. 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. In addition, central nervous system-depressant effects may be additively or synergistically increased in patients taking valbenazine with certain other drugs that cause these effects, especially in elderly or debilitated patients. MANAGEMENT: Pharmacologic response to valbenazine should be monitored more closely whenever a strong inhibitor of CYP450 3A4 (e.g., itraconazole, ketoconazole, clarithromycin) is added to or withdrawn from therapy. Valbenazine is not recommended for use in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. Assessment of baseline QT interval and periodic monitoring during therapy may be considered. The manufacturer recommends reducing the dose of valbenazine to 40 mg once daily during concomitant administration with strong CYP450 3A4 inhibitors. Valbenazine dosage may be increased accordingly if these agents are discontinued. 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. When valbenazine is used in combination with other drugs that cause CNS depression, patients should be monitored for potentially excessive or prolonged CNS depression. 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. References "Product Information. Ingrezza (valbenazine)." Neurocrine Biosciences, Inc., San Diego, CA.

ADJUST DOSE: Coadministration with a strong CYP450 3A4 inhibitor may increase the systemic exposure and risk of adverse effects of valbenazine, including somnolence and QT interval prolongation. The proposed mechanism is decreased clearance due to inhibition of CYP450 3A4 activity. Increased concentrations of valbenazine and its active metabolite, (+)-alfa-dihydrotetrabenazine, may lead to clinically significant prolongation of the QT interval. 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 may show QTc prolongation of an average of 11.7 msec, compared to an average increase of 6.7 msec in otherwise healthy volunteers. 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. In addition, central nervous system-depressant effects may be additively or synergistically increased in patients taking valbenazine with certain other drugs that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: Pharmacologic response to valbenazine should be monitored more closely whenever a strong inhibitor of CYP450 3A4 (e.g., itraconazole, ketoconazole, clarithromycin) is added to or withdrawn from therapy. Valbenazine is not recommended for use in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. Assessment of baseline QT interval and periodic monitoring during therapy may be considered. The manufacturer recommends reducing the dose of valbenazine to 40 mg once daily during concomitant administration with strong CYP450 3A4 inhibitors. Valbenazine dosage may be increased accordingly if these agents are discontinued. 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. When valbenazine is used in combination with other drugs that cause CNS depression, patients should be monitored for potentially excessive or prolonged CNS depression. 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.

Ingrezza

Generic Name: valbenazine

Brand name: Ingrezza

Synonyms: n.a.

What is Ingrezza?

Zykadia

Generic Name: ceritinib

Brand name: Zykadia

Synonyms: n.a.

What is Zykadia?