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Drug Interactions between Imbruvica and siponimod

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

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Interactions between your drugs

Major

ibrutinib siponimod

Applies to: Imbruvica (ibrutinib) and siponimod

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

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

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Drug and food interactions

Major

ibrutinib food

Applies to: Imbruvica (ibrutinib)

GENERALLY AVOID: Coadministration with grapefruit, grapefruit juice, or Seville oranges may significantly increase the plasma concentrations of ibrutinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Pharmacokinetic modeling suggests that other moderate CYP450 3A4 inhibitors such as diltiazem and erythromycin may increase ibrutinib systemic exposure (AUC) by 6- to 9-fold under fasting condition. The safety and efficacy of these exposures are unknown. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 to 1400 mg) given for 28 days, which yielded single dose AUC values that were approximately 50% greater than steady-state exposures seen at the highest indicated dose of 560 mg.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ibrutinib. The mechanism of interaction is unknown. According to the product labeling, administration with food increases ibrutinib exposure approximately 2-fold compared to administration after overnight fasting.

MANAGEMENT: Patients treated with ibrutinib should avoid consumption of Seville oranges, grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ibrutinib should be taken once daily at approximately the same time each day.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Imbruvica (ibrutinib)." Pharmacyclics 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

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