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Drug Interactions between deutetrabenazine and emtricitabine / rilpivirine / tenofovir alafenamide

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

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Interactions between your drugs

Moderate

rilpivirine deutetrabenazine

Applies to: emtricitabine / rilpivirine / tenofovir alafenamide and deutetrabenazine

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

Moderate

rilpivirine food

Applies to: emtricitabine / rilpivirine / tenofovir alafenamide

GENERALLY AVOID: Coadministration with grapefruit or grapefruit juice may increase the plasma concentrations of rilpivirine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. In 15 study subjects given rilpivirine (150 mg once daily) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily), mean rilpivirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) were increased by 30%, 49% and 76%, respectively. In 16 study subjects given a single 500 mg dose of a less potent CYP450 3A4 inhibitor chlorzoxazone two hours after rilpivirine (150 mg once daily), mean rilpivirine Cmax, AUC, and Cmin were increased by 17%, 25%, and 18%, respectively. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

ADJUST DOSING INTERVAL: The administration of rilpivirine in a fasting state may decrease its oral absorption. Under fasted conditions, the systemic exposure to rilpivirine was 40% lower compared to normal or high-fat caloric meals (533 to 928 Kcal). The systemic exposure was 50% lower when rilpivirine was taken with a protein-rich nutritional beverage.

MANAGEMENT: Coadministration of grapefruit or grapefruit juice with rilpivirine should preferably be avoided. For optimal absorption, it is recommended to take rilpivirine on a regular schedule with a meal.

References

  1. (2011) "Product Information. Edurant (rilpivirine)." Tibotec Pharmaceuticals
  2. Cerner Multum, Inc. (2015) "Canadian Product Information."

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Minor

tenofovir food

Applies to: emtricitabine / rilpivirine / tenofovir alafenamide

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.

References

  1. (2001) "Product Information. Viread (tenofovir)." Gilead Sciences

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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.

See also

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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

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