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Drug Interactions between avapritinib and ropeginterferon alfa-2b

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

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Interactions between your drugs

Moderate

avapritinib ropeginterferon alfa-2b

Applies to: avapritinib and ropeginterferon alfa-2b

GENERALLY AVOID: Coadministration with other myelosuppressive agents may potentiate the hematologic toxicities of ropeginterferon alfa-2b. Decreased peripheral blood counts have been reported in patients receiving interferon alfa products, including ropeginterferon alfa-2b. In two open label trials consisting of 178 patients receiving ropeginterferon alfa-2b monotherapy (dosed every 2 to 4 weeks) for the treatment of polycythemia vera, 80% of whom were exposed for 12 months or longer, leukopenia occurred in 20% of patients and thrombocytopenia in 19% of patients. Leukopenia, thrombocytopenia and anemia of grade 3 or higher occurred in 2%, 2% and 1% of patients, respectively. Moreover, infections occurred in 48% of patients, while serious infections occurred in 8% of patients.

MANAGEMENT: Concomitant use of ropeginterferon alfa-2b with other myelosuppressive agents should be avoided when possible. Otherwise, close clinical and laboratory monitoring are advised. Complete blood counts should be performed at baseline, during titration, and every 3 to 6 months or more frequently as clinically indicated during the maintenance phase.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2021) "Product Information. BESREMi (ropeginterferon alfa-2b)." PharmaEssentia USA Corp

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Drug and food interactions

Major

avapritinib food

Applies to: avapritinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of avapritinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. Based on pharmacokinetic modeling, administration of avapritinib (300 mg once daily) in combination with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 600% at steady state, while administration with the moderate CYP450 3A4 inhibitor fluconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 210% at steady state. 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. Increased exposure to avapritinib may increase the risk and/or severity of serious adverse effects such as intracranial hemorrhage, cognitive impairment, mood disorders, hallucinations, edema, and decreases in hemoglobin, leukocytes, neutrophils, and platelets.

ADJUST DOSING INTERVAL: Food may increase the oral absorption of avapritinib. When avapritinib was administered with a high-calorie, high-fat meal (approximately 909 calories; 58 g carbohydrate, 56 g fat, 43 g protein), avapritinib Cmax and AUC increased by 59% and 29%, respectively, compared to administration in the fasted state.

MANAGEMENT: Avapritinib should be administered on an empty stomach at least 1 hour before or 2 hours after a meal. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with avapritinib.

References

  1. (2020) "Product Information. Ayvakit (avapritinib)." Blueprint Medicines Corporation

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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

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