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Drug Interactions between Talzenna and valbenazine

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

valbenazine talazoparib

Applies to: valbenazine and Talzenna (talazoparib)

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of talazoparib, which has been shown in vitro to be a substrate of both efflux membrane transporters. In clinical studies, administration of talazoparib with the P-gp inhibitors amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil resulted in an approximate 45% increase in talazoparib exposure and an increase in the rate of talazoparib dose reduction. In contrast, coadministration with the P-gp inhibitors azithromycin, atorvastatin, diltiazem, felodipine, fluvoxamine, and quercetin increased talazoparib exposure by just 8%. The effect of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied.

MANAGEMENT: No initial dosage adjustment is recommended by the manufacturer when talazoparib is coadministered with inhibitors of BCRP and/or P-gp other than amiodarone, carvedilol, clarithromycin, itraconazole, or verapamil. However, patients should be closely monitored for adverse effects such as myelosuppression and myelodysplastic syndrome/acute myeloid leukemia, and dosage adjustments made or treatment withheld as needed in accordance with the product labeling.

References

  1. "Product Information. Talzenna (talazoparib)." Pfizer U.S. Pharmaceuticals Group (2018):

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Drug and food interactions

Major

valbenazine food

Applies to: valbenazine

ADJUST DOSE: Coadministration with grapefruit juice may increase the plasma concentration of valbenazine. The mechanism is inhibition of CYP450 3A4-mediated first-metabolism in the gut wall by certain compounds present in grapefruits. The use of valbenazine has been associated with modest prolongation of the QT interval. However, clinically significant QT prolongation may occur in patients taking a strong CYP450 3A4 inhibitor due to increased concentrations of valbenazine and its active metabolite (+)-alfa-dihydrotetrabenazine. 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: Pharmacologic response to valbenazine should be monitored more closely whenever a strong inhibitor of CYP450 3A4 is added to or withdrawn from therapy. 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. 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 receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. "Product Information. Ingrezza (valbenazine)." Neurocrine Biosciences, Inc. (2017):

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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