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Drug Interactions between niraparib and tazemetostat

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

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Interactions between your drugs

Moderate

niraparib tazemetostat

Applies to: niraparib and tazemetostat

MONITOR: Coadministration of niraparib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. In pooled safety population data of patients (n=1,314) with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with niraparib monotherapy, thrombocytopenia was reported in 60% of patients. Two niraparib clinical trials reported greater than or equal to Grade 3 thrombocytopenia in 29% to 39% of patients with niraparib discontinuation due to thrombocytopenia occurring in approximately 3% to 4% of patients. The MAGNITUDE study, which included an evaluation of niraparib in combination with abiraterone for breast cancer gene (BRCA)-mutated metastatic castration-resistant prostate cancer (mCRPC) reported Grade 3 or more thrombocytopenia in 8% of patients.

MANAGEMENT: Concomitant use of anticoagulants or other medications known to reduce platelet count should be approached with caution. Recommendations for holding, adjusting the dose of, or discontinuing niraparib can be found in the manufacturer's labeling. If the patient has additional risk factors for bleeding, such as coadministration with an anticoagulant or antiplatelet, it may be advisable to consider a platelet transfusion at a higher platelet count. For hematologic adverse reactions requiring transfusion, withhold niraparib and consider interrupting any drugs that interfere with platelet function or coagulation. Niraparib may be resumed at a reduced dose per manufacturer recommendations. If hematologic toxicity does not resolve within 28 days following interruption, discontinue niraparib and consider referral to a hematologist. Blood counts should be monitored as recommended by the manufacturer. Patients should be advised to promptly report any signs or symptoms of bleeding to their primary care provider.

References

  1. (2023) "Product Information. Akeega (abiraterone-niraparib)." Janssen Biotech, Inc.
  2. (2023) "Product Information. Zejula (niraparib)." GlaxoSmithKline
  3. (2023) "Product Information. Zejula (niraparib)." GlaxoSmithKline Inc
  4. (2023) "Product Information. Akeega (abiraterone-niraparib)." Janssen Inc
  5. (2023) "Product Information. Zejula (niraparib)." GlaxoSmithKline Australia Pty Ltd
  6. (2023) "Product Information. Zejula (niraparib)." GlaxoSmithKline UK Ltd
View all 6 references

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Drug and food interactions

Major

tazemetostat food

Applies to: tazemetostat

GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during tazemetostat therapy may significantly increase the plasma concentrations of tazemetostat. The proposed mechanism is inhibition of the CYP450 3A4-mediated metabolism of tazemetostat by certain compounds in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). According to the product labeling, coadministration of tazemetostat (400 mg twice daily) with the moderate CYP450 3A4 inhibitor fluconazole increased the tazemetostat steady state exposure (AUC 0 to 8 hours) by 3.1-fold and peak plasma concentration by 2.3-fold. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. Clinically, this interaction may result in an increased risk of the frequency or severity of adverse reactions due to tazemetostat such as hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress.

MANAGEMENT: The manufacturer advises that patients treated with tazemetostat should avoid consumption of grapefruit or grapefruit juice.

References

  1. (2020) "Product Information. Tazverik (tazemetostat)." Epizyme, 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.