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Drug Interactions between cobicistat / darunavir and rucaparib

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

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Interactions between your drugs

Moderate

darunavir rucaparib

Applies to: cobicistat / darunavir and rucaparib

MONITOR: Coadministration with rucaparib may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is decreased clearance due to rucaparib-mediated inhibition of CYP450 3A4. In a clinical study, rucaparib increased midazolam Cmax and AUC by 1.13- and 1.38-fold, respectively.

MANAGEMENT: Caution is advised if rucaparib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever rucaparib is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

References

  1. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852

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Moderate

cobicistat rucaparib

Applies to: cobicistat / darunavir and rucaparib

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations and the risk of adverse effects of rucaparib, which has been shown in vitro to be a substrate of the isoenzyme. However, the effects on the pharmacokinetics of rucaparib have not been evaluated in vivo.

MANAGEMENT: Caution is advised if rucaparib is used concomitantly with potent CYP450 3A4 inhibitors. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever a potent CYP450 3A4 inhibitor is added to or withdrawn from therapy with rucaparib.

References

  1. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852

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Drug and food interactions

Moderate

darunavir food

Applies to: 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.


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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.