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Drug Interactions between ivacaftor / lumacaftor and osimertinib

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

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Interactions between your drugs

Major

lumacaftor osimertinib

Applies to: ivacaftor / lumacaftor and osimertinib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of osimertinib, which has been shown in vitro to be primarily metabolized by the isoenzyme. Reduced therapeutic efficacy of osimertinib should be anticipated. In a clinical pharmacokinetic study, the osimertinib systemic exposure (AUC) at steady state was reduced by 78% when given concomitantly with the potent CYP450 3A4 inducer rifampin (600 mg daily for 21 days). In addition, the AUC and peak plasma concentration (Cmax) of the pharmacologically active metabolite of osimertinib, AZ5104, also decreased by 82% and 78%, respectively.

MANAGEMENT: Concomitant use of osimertinib with potent CYP450 3A4 inducers should generally be avoided. However, if concomitant use is required, some authorities recommend increasing the dose of osimertinib to 160 mg daily during treatment with the potent 3A4 inducer and resumed at 80 mg daily, 3 weeks after discontinuation of the potent 3A4 inducer.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2015) "Product Information. Tagrisso (osimertinib)." Astra-Zeneca Pharmaceuticals

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Moderate

ivacaftor osimertinib

Applies to: ivacaftor / lumacaftor and osimertinib

GENERALLY AVOID: Coadministration with osimertinib may alter the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. In vitro, osimertinib has been shown to be a competitive inhibitor as well as inducer of CYP450 3A4. However, no pharmacokinetic data are available from drug interaction studies.

MANAGEMENT: Concomitant use of osimertinib and sensitive CYP450 3A4 substrates or substrates with narrow therapeutic ranges should generally be avoided. These drugs include, but are not limited to: alfentanil, cisapride, colchicine, cyclosporine, fentanyl, ivacaftor, lovastatin, simvastatin, oral midazolam, triazolam, pimozide, quinidine, sildenafil, ergot derivatives, macrolide immunosuppressants, and vinca alkaloids.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2015) "Product Information. Tagrisso (osimertinib)." Astra-Zeneca Pharmaceuticals

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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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