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Drug Interactions between azathioprine and lurbinectedin

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

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Interactions between your drugs

Moderate

azaTHIOprine lurbinectedin

Applies to: azathioprine and lurbinectedin

GENERALLY AVOID: The use of azathioprine with other immunosuppressive or myelosuppressive agents may result in additive hematologic toxicities and increased risk of infections, particularly in transplant patients. Azathioprine alone may cause dose-related and potentially life-threatening bone marrow suppression, although it is usually reversible when managed promptly. Leucopenia, anemia, thrombocytopenia, and rarely, agranulocytosis, pancytopenia, and aplastic anemia have been reported. Dose-related reductions in numbers of circulating total white cells, granulocytes, and lymphocytes may also occur. Treatment with azathioprine alone or in combination with other immunosuppressants, particularly corticosteroids, has been associated with increased susceptibility to infections including severe or atypical infection and reactivation with varicella zoster virus, hepatitis B, cytomegalovirus, and other infectious agents. Very rare cases of JC virus-associated progressive multifocal leukoencephalopathy (PML), a severely disabling and potentially fatal opportunistic viral infection of the brain, have also been reported. In addition, chronic use of azathioprine with other immunosuppressants may increase the risk of lymphoma, skin cancer, and other malignancies. Again, the risk is greatest in transplant patients, with the exception of hepatosplenic T-cell lymphoma (HSTCL), which has occurred primarily in patients with Crohn's disease or ulcerative colitis, especially adolescent and young adult males.

MANAGEMENT: Concomitant use of azathioprine with other immunosuppressive or myelosuppressive agents should be avoided whenever possible. Close clinical and laboratory monitoring for hematologic toxicity is advised if coadministration is required. Since azathioprine is considered a slow-acting drug, delayed myelosuppression may occur, and effects may persist even after the drug has been discontinued. Prompt reduction in dosage or temporary withdrawal of azathioprine may be necessary if a persistently low or rapid decline in leucocyte count occurs, or if there is other evidence of bone marrow depression.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."

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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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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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