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Drug Interactions between netupitant / palonosetron and Orkambi

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

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Interactions between your drugs

Major

ivacaftor netupitant

Applies to: Orkambi (ivacaftor / lumacaftor) and netupitant / palonosetron

ADJUST DOSE: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ivacaftor, which is primarily metabolized by the isoenzyme. In study subjects, ivacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.5- and 3.0-fold when it was administered concomitantly with fluconazole, a moderate CYP450 3A4 inhibitor. When lumacaftor/ivacaftor was coadministered with ciprofloxacin, another moderate CYP450 3A4 inhibitor, lumacaftor Cmax and AUC decreased by 12% and 14%, respectively, while ivacaftor Cmax and AUC increased by 29% each. These changes are not considered clinically significant. Physiologically based pharmacokinetic (PBPK) simulations suggest that coadministration with moderate CYP450 3A4 inhibitors may increase elexacaftor AUC by 1.9- to 2.3-fold and tezacaftor AUC by approximately 2.1-fold.

MANAGEMENT: Please consult manufacturer's product labeling for complete dosing information.
For ivacaftor - For patients aged 6 months and older the frequency of dosing should be reduced to 1 tablet or packet once a day when coadministered with moderate CYP450 3A4 inhibitors. Patients should continue to receive the same tablet or oral granule packet strength, but instead of dosing twice a day, the frequency should be reduced to once a day. For example, ivacaftor 150 mg twice a day should be 150 mg once a day, ivacaftor 50 mg twice a day should be 50 mg once a day, etc. Use of ivacaftor with moderate or strong CYP450 3A4 inhibitors is not recommended in patients less than 6 months of age.
For lumacaftor/ivacaftor - No dosage adjustment is necessary when coadministered with moderate CYP450 3A4 inhibitors.
For tezacaftor/ivacaftor - The frequency of dosing should be reduced to a single morning dose of one tezacaftor/ivacaftor tablet alternating with one ivacaftor tablet every other morning during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.
For elexacaftor/tezacaftor/ivacaftor - The frequency of dosing should be reduced to a single morning dose of two elexacaftor /tezacaftor /ivacaftor tablets alternating with one ivacaftor tablet every other day during treatment with moderate CYP450 3A4 inhibitors. The evening dose of ivacaftor should not be taken.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals (2012):
  3. "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals (2015):
  4. "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals (2022):
  5. "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (2019):
View all 5 references

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Major

netupitant lumacaftor

Applies to: netupitant / palonosetron and Orkambi (ivacaftor / lumacaftor)

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of netupitant. When a single 300 mg-0.5 mg dose of netupitant-palonosetron was administered following 600 mg once daily administration of the potent CYP450 3A4 inducer rifampin for 17 days, mean netupitant peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 62% and 82%, respectively, while mean Cmax and AUC of palonosetron decreased by 15% and 19%, respectively.

MANAGEMENT: Concomitant use of netupitant or its prodrug, fosnetupitant, should generally be avoided during chronic administration of potent CYP450 3A4 inducers due to the potential for reduced efficacy of netupitant.

References

  1. Cerner Multum, Inc. "Australian Product Information." O 0
  2. "Product Information. Akynzeo (netupitant-palonosetron)." Eisai Inc (2014):
  3. "Product Information. Akynzeo for Injection (fosnetupitant-palonosetron)." Helsinn Therapeutics Inc (2018):

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Drug and food interactions

Moderate

ivacaftor food

Applies to: Orkambi (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. "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals (2012):
  2. "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals (2015):
  3. "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals (2022):
  4. "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (2019):
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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