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Drug Interactions between Tybost and Vraylar

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

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Interactions between your drugs

Major

cobicistat cariprazine

Applies to: Tybost (cobicistat) and Vraylar (cariprazine)

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of cariprazine and its major active metabolite, didesmethyl cariprazine (DDCAR), both of which are primarily metabolized by the isoenzyme. When cariprazine (0.5 mg/day) was coadministered with the potent CYP450 3A4 inhibitor, ketoconazole (400 mg/day), cariprazine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 3.5- and 4-fold, respectively, while Cmax and AUC of DDCAR increased by approximately 1.5-fold each. The Cmax and AUC of another active metabolite, desmethyl cariprazine (DCAR), decreased by approximately one-third.

MANAGEMENT: The dosage of cariprazine should be reduced in the presence of a potent CYP450 3A4 inhibitor. When initiating a potent CYP450 3A4 inhibitor during stable treatment with cariprazine, the manufacturer recommends reducing the current dosage of cariprazine by one-half. For patients taking 4.5 mg daily, the dosage should be reduced to 1.5 mg or 3 mg daily. For patients taking 1.5 mg daily, the dosing interval should be adjusted to every other day. Conversely, if cariprazine therapy is initiated during treatment with a potent CYP450 3A4 inhibitor, the recommended starting dosage of cariprazine is 1.5 mg on day 1 and day 3, with no dose administered on day 2. From day 4 onward, the dosage should be 1.5 mg daily, then increased to a maximum dosage of 3 mg daily. Following withdrawal of the CYP450 3A4 inhibitor, the dosage of cariprazine may need to be increased.

References

  1. (2015) "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc.

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Drug and food interactions

Moderate

cariprazine food

Applies to: Vraylar (cariprazine)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of cariprazine. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of cariprazine by certain compounds present in grapefruit. When cariprazine (0.5 mg/day) was coadministered with the potent CYP450 3A4 inhibitor, ketoconazole (400 mg/day), cariprazine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 3.5- and 4-fold, respectively, while Cmax and AUC of DDCAR increased by approximately 1.5-fold each. The Cmax and AUC of another active metabolite, desmethyl cariprazine (DCAR), decreased by approximately one-third. The interaction has not been studied with grapefruit juice. 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. Increased exposure to cariprazine may increase the risk of adverse effects such as extrapyramidal symptoms, cognitive and motor impairment, hyperglycemia, dyslipidemia, weight gain, orthostatic hypotension, leucopenia, neutropenia, seizures, and dysphagia.

MANAGEMENT: Patients should avoid the consumption of grapefruit and grapefruit juice during treatment with cariprazine.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2015) "Product Information. Vraylar (cariprazine)." Actavis Pharma, 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.

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