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Drug Interactions between darunavir and lurbinectedin

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

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Interactions between your drugs

Major

darunavir lurbinectedin

Applies to: darunavir and lurbinectedin

GENERALLY AVOID: Coadministration with a moderate CYP450 3A4 inhibitor may increase the systemic exposure (AUC) of lurbinectedin, which is metabolized by the isoenzyme in vitro. In a Phase 1 study, coadministration of aprepitant, a moderate CYP450 3A4 inhibitor, decreased lurbinectedin plasma clearance by 33% compared to lurbinectedin alone. Increased exposure may increase the incidence and severity of adverse reactions of lurbinectedin, such as myelosuppression and hepatotoxicity.

MANAGEMENT: Concomitant use of lurbinectedin and moderate CYP450 3A4 inhibitors should generally be avoided. If the coadministration of lurbinectedin with a moderate CYP450 3A4 inhibitor cannot be avoided, a dose reduction for lurbinectedin may be considered. Close clinical and laboratory monitoring is advised whenever a moderate inhibitor is added to or withdrawn from therapy. Patients should be advised to contact their physician if they experience symptoms suggestive of myelosuppression or hepatotoxicity, such as fever or any other signs of infection, unusual bruising or bleeding; nausea or vomiting, or pain on the right side of the abdomen.

References

  1. (2020) "Product Information. Zepzelca (lurbinectedin)." Jazz Pharmaceuticals
  2. (2021) "Product Information. Zepzelca (lurbinectedin)." Specialised Therapeutics Pharma Pty Ltd

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Drug and food interactions

Major

lurbinectedin food

Applies to: lurbinectedin

GENERALLY AVOID: Grapefruit and Seville oranges may increase the plasma concentrations of lurbinectedin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit and Seville oranges. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit or Seville oranges, but pharmacokinetic data are available for potent and moderate CYP450 3A4 inhibitors. In a clinical drug interaction study, coadministration of itraconazole, a potent CYP450 3A4 inhibitor, increased the systemic exposure (AUC) of total lurbinectedin by 2.7-fold and unbound lurbinectedin by 2.4-fold. In a Phase 1 study, coadministration of aprepitant, a moderate CYP450 3A4 inhibitor, decreased lurbinectedin plasma clearance by 33% compared to lurbinectedin alone. In general, the effect of grapefruit and Seville oranges is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice and Seville oranges (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 may increase the incidence and severity of adverse reactions of lurbinectedin, such as myelosuppression and hepatotoxicity.

MANAGEMENT: Patients should avoid consumption of grapefruit, grapefruit juice, and Seville oranges during treatment with lurbinectedin.

References

  1. (2020) "Product Information. Zepzelca (lurbinectedin)." Jazz Pharmaceuticals

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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.

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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