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Drug Interactions between isavuconazonium and Prezcobix

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

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Interactions between your drugs

Major

cobicistat isavuconazonium

Applies to: Prezcobix (cobicistat / darunavir) and isavuconazonium

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of isavuconazole, which is primarily metabolized by CYP450 3A4 and 3A5 and subsequently by uridine diphosphate glucuronosyltransferases (UGT). When a single dose of isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) was administered to healthy volunteers following multiple dosing of the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 24 days), isavuconazole peak plasma concentration (Cmax) increased by 9% and systemic exposure (AUC) increased by 422%.

MANAGEMENT: Concomitant use of isavuconazonium sulfate with potent CYP450 3A4 inhibitors is considered contraindicated. Ritonavir given at low dosages as a pharmacokinetic booster may be used with caution, but is contraindicated at high dosages (e.g., 400 mg every 12 hours).

References

  1. (2015) "Product Information. Cresemba (isavuconazonium)." Astellas Pharma US, Inc

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Moderate

darunavir isavuconazonium

Applies to: Prezcobix (cobicistat / darunavir) and isavuconazonium

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of isavuconazole, which is primarily metabolized by CYP450 3A4 and 3A5 and subsequently by uridine diphosphate glucuronosyltransferases (UGT). When a single dose of isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) was administered to healthy volunteers following multiple dosing of the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 24 days), isavuconazole peak plasma concentration (Cmax) increased by 9% and systemic exposure (AUC) increased by 422%. Lopinavir-ritonavir (400 mg-100 mg twice daily) increased the Cmax and AUC of isavuconazole by 74% and 96%, respectively.

MANAGEMENT: Caution is advised when isavuconazonium sulfate is prescribed with CYP450 3A4 inhibitors. Patients should be monitored for adverse effects such as nausea, vomiting, diarrhea, peripheral edema, hypokalemia, hypomagnesemia, and hepatotoxicity. In addition, many CYP450 3A4 inhibitors are also substrates of the isoenzyme, thus pharmacologic response to these agents should also be monitored, as isavuconazole itself is reportedly a moderate CYP450 3A4 inhibitor.

References

  1. (2015) "Product Information. Cresemba (isavuconazonium)." Astellas Pharma US, Inc

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Drug and food interactions

Moderate

darunavir food

Applies to: Prezcobix (cobicistat / darunavir)

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

References

  1. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech 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.

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

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

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