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Drug Interactions between inotersen and tazemetostat

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

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Interactions between your drugs

Major

inotersen tazemetostat

Applies to: inotersen and tazemetostat

MONITOR CLOSELY: Coadministration of inotersen and drugs that interfere with platelet function or coagulation may potentiate the risk of serious, potentially life-threatening bleeding complications, including spontaneous intracranial and intrapulmonary hemorrhage. Inotersen causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia. In a premarketing clinical trial, platelet counts below 100 x 10^9/L and 75 x 10^9/L occurred in 25% and 14% of patients receiving inotersen, respectively, versus 2% and none of the patients receiving placebo, respectively. Thirty-nine percent of inotersen-treated patients with a baseline platelet count below 200 x10^9/L had a nadir platelet count below 75 x 10^9/L, compared to 6% of patients with baseline platelet counts 200 x10^9/L or higher. Three inotersen-treated patients (3%) developed sudden severe thrombocytopenia (i.e., platelet count below 25 x 10^9/L), all of whom had treatment-emergent antiplatelet IgG antibodies detected shortly before or at the time of the severe thrombocytopenia. In 2 patients, platelet clumping caused uninterpretable platelet measurements that delayed the diagnosis and treatment of severe thrombocytopenia. Platelet clumping can be caused by a reaction between antiplatelet antibodies and ethylenediaminetetraacetic acid (EDTA). In the clinical trial, 23% of inotersen-treated patients had at least one uninterpretable platelet count caused by platelet clumping, compared to 13% of placebo-treated patients.

MANAGEMENT: Caution is advised when inotersen is prescribed with antiplatelet agents, anticoagulants, or other medications that commonly cause thrombocytopenia or bleeding. A platelet count should be obtained prior to initiation of inotersen and regularly during and for at least 8 weeks after treatment in accordance with the product labeling. Inotersen should not be administered in patients with a platelet count below 100 x 10^9/L or in patients who are unable to adhere to the recommended laboratory monitoring and management guidelines. Patients or their caregivers should be apprised of the signs and symptoms of thrombocytopenia and to seek medical attention if they occur, including any unusual or prolonged bleeding (e.g., petechiae, easy bruising, hematoma, subconjunctival bleeding, gingival bleeding, epistaxis, hemoptysis, irregular or heavier than normal menstrual bleeding, hematemesis, hematuria, hematochezia, melena), neck stiffness, or atypical severe headache. If thrombocytopenia is suspected, obtain a platelet count as soon as possible and withhold further inotersen dosing until platelet count is confirmed to be acceptable. A prompt recheck of the platelet count is necessary if a platelet measurement is not interpretable (e.g., clumped sample). The manufacturer recommends glucocorticoid therapy in patients with a platelet count below 50 x 10^9/L and in patients with suspected immune-mediated thrombocytopenia. Additionally, consideration should be given to discontinuing any concomitant medications that may be contributing to the thrombocytopenia and/or bleeding complication, if clinically feasible.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2018) "Product Information. Tegsedi (inotersen)." Akcea Therapeutics

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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.