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Drug Interactions between Austedo and Braftovi

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

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Interactions between your drugs

Moderate

deutetrabenazine encorafenib

Applies to: Austedo (deutetrabenazine) and Braftovi (encorafenib)

GENERALLY AVOID: Deutetrabenazine has been associated with modest QT interval prolongation. A single 24 mg dose has been shown to increase the QTc by approximately 4.5 msec in a study in healthy male and female subjects. The risk of clinically significant QT prolongation may be increased in patients treated in combination with a strong CYP450 2D6 inhibitor or in patients who are poor metabolizers of CYP450 2D6 (approximately 7% of Caucasians and 2% of Asians and those of African descent). However, data evaluating the effects at higher exposures to deutetrabenazine or its active metabolites are lacking. 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 drugs involved and dosages of the drugs. In addition, central nervous system (CNS)-depressant effects may be additively or synergistically increased in patients taking deutetrabenazine with certain other drugs that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: Coadministration of deutetrabenazine with other drugs that can prolong the QT interval should generally be avoided. Deutetrabenazine is not recommended for use in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. If concomitant use is required, assessment of baseline QT interval and periodic monitoring during therapy may be considered. In addition, dosage reduction may be considered in patients on concurrent therapy with a strong CYP450 2D6 inhibitor, or in patients who are poor metabolizers of CYP450 2D6. The maximum recommended dosage of deutetrabenazine is 18 mg per dose and 36 mg per day during coadministration with a potent CYP450 2D6 inhibitor or in patients who are poor metabolizers of CYP450 2D6. Patients and their caregivers should be advised to notify their physician if they experience new or worsening depression, suicidal thoughts, parkinsonism, restlessness, agitation, dysphagia, and/or excessive sedation while taking deutetrabenazine. Patients should also 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.

References

  1. (2017) "Product Information. Austedo (deutetrabenazine)." Teva Pharmaceuticals USA

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Drug and food interactions

Major

encorafenib food

Applies to: Braftovi (encorafenib)

GENERALLY AVOID: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of encorafenib, which is primarily metabolized by the isoenzyme. When a single 50 mg dose of encorafenib (equivalent to 0.1 times the recommended dose) was administered with posaconazole, a potent CYP450 3A4 inhibitor, encorafenib peak plasma concentration (Cmax) increased by 68% and systemic exposure (AUC) increased by 3-fold. When the same dose of encorafenib was administered with diltiazem, a moderate CYP450 3A4 inhibitor, encorafenib Cmax increased by 45% and AUC increased by 2-fold. Increased exposure to encorafenib may increase the risk of serious and life-threatening adverse effects such as hemorrhage, uveitis, QT prolongation, hepatotoxicity, dermatologic reactions, and new malignancies.

MANAGEMENT: Concomitant use of encorafenib with grapefruit or grapefruit juice should generally be avoided. If coadministration is required, the manufacturer recommends reducing the encorafenib dose to one-third of the dose used prior to addition of a potent CYP450 3A4 inhibitor or one-half of the dose used prior to addition of a moderate CYP450 3A4 inhibitor. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, the encorafenib dose that was taken prior to initiating the inhibitor may be resumed.

References

  1. (2018) "Product Information. Braftovi (encorafenib)." Array BioPharma Inc.

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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.