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Drug Interactions between ivacaftor / lumacaftor and siponimod

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

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Interactions between your drugs

Major

lumacaftor siponimod

Applies to: ivacaftor / lumacaftor and siponimod

GENERALLY AVOID: Coadministration with drugs that cause moderate induction of CYP450 2C9 and strong induction of CYP450 3A4 may decrease the plasma concentrations of siponimod, which is primarily metabolized by these isoenzymes. This interaction includes concomitant use of siponimod with a moderate CYP450 2C9/strong CYP450 3A4 dual inducer or a moderate CYP450 2C9 inducer in combination with a separate strong CYP450 3A4 inducer. In CYP450 2C9*1/*1 genotype subjects, coadministration of a moderate CYP450 2C9/strong CYP450 3A4 dual inducer (rifampin 600 mg daily) and siponimod (2 mg daily) resulted in 57% and 45% decreases in siponimod steady-state AUC and Cmax, respectively. According to in silico (computer-based) evaluation, use of rifampin and efavirenz (moderate CYP450 3A4 inducer) resulted in decreases up to 78% and up to 52%, respectively, of siponimod steady-state AUC across CYP450 2C9 genotypes. The CYP450 2C9 genotype influences the fractional contributions of CYP450 2C9 and 3A4 to overall elimination. If the metabolic activity of CYP450 2C9 is decreased, a larger contribution of CYP450 3A4 can be anticipated.

MANAGEMENT: Concomitant use of siponimod and drugs that cause moderate induction of CYP450 2C9 and strong induction of CYP450 3A4 (e.g., carbamazepine, enzalutamide, rifampin) is not recommended for all patients. Concomitant use of siponimod and moderate or strong CYP450 3A4 inducers (e.g., apalutamide, bosentan, dabrafenib, dexamethasone, efavirenz, eslicarbazepine, etravirine, fosphenytoin, lorlatinib, lumacaftor, mitotane, modafinil, nafcillin, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifapentine, sotorasib, St. John's wort) is not recommended for patients with CYP450 2C9*1/*3 and *2/*3 genotypes.

References

  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2019) "Product Information. Mayzent (siponimod)." Novartis Pharmaceuticals

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Moderate

ivacaftor siponimod

Applies to: ivacaftor / lumacaftor and siponimod

MONITOR: Coadministration with ivacaftor may increase the plasma concentrations of drugs that are substrates of the CYP450 2C9 isoenzyme. The proposed mechanism, based on in vitro data, involves decreased metabolic clearance due to inhibition of CYP450 2C9 by ivacaftor. The clinical relevance is unknown.

MANAGEMENT: Caution is advised when ivacaftor is used concurrently with drugs that are known CYP450 2C9 substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ivacaftor is added to or withdrawn from therapy.

References

  1. (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
  2. (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
  3. (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
  4. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
View all 4 references

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Drug and food interactions

Moderate

ivacaftor food

Applies to: ivacaftor / lumacaftor

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Elexacaftor and tezacaftor are also CYP450 3A4 substrates in vitro and may interact similarly with grapefruit juice, whereas lumacaftor is not expected to interact.

ADJUST DOSING INTERVAL: According to prescribing information, systemic exposure to ivacaftor increased approximately 2.5- to 4-fold, systemic exposure to elexacaftor increased approximately 1.9- to 2.5-fold, and systemic exposure to lumacaftor increased approximately 2-fold following administration with fat-containing foods relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with ivacaftor-containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit or Seville oranges. All ivacaftor-containing medications should be administered with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products. A typical cystic fibrosis diet will satisfy this requirement.

References

  1. (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
  2. (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
  3. (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
  4. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
View all 4 references

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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.

See also

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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.

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