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Drug Interactions between avapritinib and siponimod

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

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Interactions between your drugs

Major

siponimod avapritinib

Applies to: siponimod and avapritinib

MONITOR CLOSELY: Coadministration of siponimod with antineoplastic, immunosuppressive, or other immune-modulating therapies may result in additive immune system effects and increased risk of infections. Siponimod causes reversible sequestration of lymphocytes in lymphoid tissues. When administered daily, siponimod produces a dose-dependent reduction in peripheral lymphocyte count to 20% to 30% of baseline values, which may increase the risk of infections. Life-threatening and rare fatal infections have occurred in association with siponimod. Decreased lymphocyte counts persist during chronic daily dosing and generally return to normal within 10 days after stopping the medication. However, residual pharmacodynamic effects, such as decreased peripheral lymphocytes, may persist for up to 3 to 4 weeks after the last dose. Use of other myelo- or immunosuppressive drugs during this time may lead to unintended additive effects on the immune system.

MANAGEMENT: The safety and efficacy of siponimod in combination with antineoplastic, immunosuppressive, or other immune-modulating agents have not been evaluated. Close monitoring for signs and symptoms of infection is advised during coadministration and for 3 to 4 weeks after the last dose of siponimod. When switching from drugs with prolonged immune effects to siponimod, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2022) "Product Information. Mayzent (siponimod)." Novartis Pharmaceuticals

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

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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