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Drug Interactions between darunavir and ibrutinib

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

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Interactions between your drugs

Major

darunavir ibrutinib

Applies to: darunavir and ibrutinib

ADJUST DOSE: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ibrutinib, which is primarily metabolized by the isoenzyme. In 18 healthy volunteers administered a single 120 mg dose of ibrutinib alone on day 1 and a single 40 mg dose of ibrutinib on day 7 in combination with ketoconazole 400 mg daily on days 4 thru 9, there was a 29-fold increase in dose-normalized ibrutinib peak plasma concentration (Cmax) and 24-fold increase in dose-normalized systemic exposure (AUC) during treatment with ketoconazole compared to administration alone. Pharmacokinetic modeling suggests that moderate CYP450 3A4 inhibitors such as diltiazem and erythromycin may increase the AUC of ibrutinib by 6- to 9-fold under fasting condition. The safety and efficacy of these exposures are unknown. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 to 1400 mg) given for 28 days, which yielded single dose AUC values that were approximately 50% greater than steady-state exposures seen at the highest indicated dose of 560 mg.

MANAGEMENT: The dosage of ibrutinib should be adjusted according to the indication in the product labeling whenever it is used in combination with a moderate CYP450 3A4 inhibitor such as amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir, diltiazem, dronedarone, erythromycin, fluconazole, fosamprenavir, fosaprepitant, imatinib, or verapamil. All patients should be closely monitored for signs of ibrutinib toxicity such as myelosuppression, bleeding, infection, and renal impairment.

References

  1. (2013) "Product Information. Imbruvica (ibrutinib)." Pharmacyclics Inc

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Drug and food interactions

Major

ibrutinib food

Applies to: ibrutinib

GENERALLY AVOID: Coadministration with grapefruit, grapefruit juice, or Seville oranges may significantly increase the plasma concentrations of ibrutinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Pharmacokinetic modeling suggests that other moderate CYP450 3A4 inhibitors such as diltiazem and erythromycin may increase ibrutinib systemic exposure (AUC) by 6- to 9-fold under fasting condition. The safety and efficacy of these exposures are unknown. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 to 1400 mg) given for 28 days, which yielded single dose AUC values that were approximately 50% greater than steady-state exposures seen at the highest indicated dose of 560 mg.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ibrutinib. The mechanism of interaction is unknown. According to the product labeling, administration with food increases ibrutinib exposure approximately 2-fold compared to administration after overnight fasting.

MANAGEMENT: Patients treated with ibrutinib should avoid consumption of Seville oranges, grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ibrutinib should be taken once daily at approximately the same time each day.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Imbruvica (ibrutinib)." Pharmacyclics Inc

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Moderate

darunavir food

Applies to: 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.

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