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Drug Interactions between ivacaftor / lumacaftor and sunitinib

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

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Interactions between your drugs

Major

SUNItinib lumacaftor

Applies to: sunitinib and ivacaftor / lumacaftor

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of sunitinib and its pharmacologically active metabolite, both of which are substrates of the isoenzyme. In healthy volunteers, administration of a single dose of sunitinib with the potent CYP450 3A4 inducer, rifampin, decreased the combined (i.e., sunitinib plus its primary active metabolite) peak plasma concentration (Cmax) and systemic exposure (AUC) values by 23% and 46%, respectively, compared to administration of sunitinib alone.

MANAGEMENT: Concomitant use of sunitinib with potent CYP450 3A4 inducers should generally be avoided. Alternative therapeutic agents with minimal or no enzyme induction potential should be considered whenever possible. If coadministration with a potent CYP450 3A4 inducer is required, a dose increase for sunitinib in 12.5 mg increments up to a maximum of 87.5 mg daily for gastrointestinal stromal tumor (GIST) and renal cell carcinoma (RCC) or 62.5 mg daily for pancreatic neuroendocrine tumors (pNET) may be considered based on careful monitoring of clinical response and tolerability. (Note: This recommendation is based on pharmacokinetic data from healthy volunteers as described above. The safety and efficacy of sunitinib with concomitant CYP450 3A4 inducers have not been established. In two cytokine-refractory metastatic RCC studies, 33 of the 169 patients received sunitinib with a potent CYP450 3A4 inducer with no modification of the starting dose of sunitinib.)

References

  1. (2006) "Product Information. Sutent (sunitinib)." Pfizer U.S. Pharmaceuticals Group
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."

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Drug and food interactions

Moderate

SUNItinib food

Applies to: sunitinib

GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during sunitinib therapy may increase the plasma concentrations of sunitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of large amounts of grapefruit or grapefruit juice during sunitinib therapy.

References

  1. (2006) "Product Information. Sutent (sunitinib)." Pfizer U.S. Pharmaceuticals Group

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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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