Tucatinib with Ivacaftor Interaction Details
Brand Names Associated with Tucatinib
- Tucatinib
- Tukysa®
Brand Names Associated with Ivacaftor
- Ivacaftor
- Kalydeco®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased ivacaftor exposure
Interaction Summary
Concomitant administration of ivacaftor with strong CYP3A4 inhibitors may increase ivacaftor exposure. For Kalydeco(R), reduce dose to 150 mg twice weekly (6 years or older), or 25 mg (wt, 5 kg to less than 7 kg), 50 mg (7 kg to less than 14 kg) or 75 mg (14 kg or greater) of oral granules twice weekly in patients 6 months to 6 years; concomitant use is not recommended in patients less than 6 months. For Orkambi(R), give lumacaftor 100 mg/ivacaftor 125 mg (6 to 11 years) or lumacaftor 200 mg/ivacaftor 125 mg (12 years or older) once daily for first week, then continue the usual dose . For Symdeko(TM), give tezacaftor 100 mg/ivacaftor 150 mg , for Trikafta(TM), give 2 tablets (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet) orally in the morning on day 1 and 4 then continue this dose twice weekly . Use of lumacaftor/ivacaftor is not recommended 2 weeks before, during and 2 weeks after itraconazole treatment .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant administration of ivacaftor with strong CYP3A4 inhibitors may increase ivacaftor exposure. For Kalydeco(R), reduce dose to 150 mg twice weekly (6 years or older), or 25 mg (wt, 5 kg to less than 7 kg), 50 mg (7 kg to less than 14 kg) or 75 mg (14 kg or greater) of oral granules twice weekly in patients 6 months to 6 years; concomitant use is not recommended in patients less than 6 months. For Orkambi(R), give lumacaftor 100 mg/ivacaftor 125 mg (6 to 11 years) or lumacaftor 200 mg/ivacaftor 125 mg (12 years or older) once daily for first week, then continue the usual dose . For Symdeko(TM), give tezacaftor 100 mg/ivacaftor 150 mg , for Trikafta(TM), give 2 tablets (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg per tablet) orally in the morning on day 1 and 4 then continue this dose twice weekly . Use of lumacaftor/ivacaftor is not recommended 2 weeks before, during and 2 weeks after itraconazole treatment .
Mechanism Of Interaction
Inhibition of CYP3A-mediated ivacaftor metabolism
Literature Reports
A) Coadministration of a single dose of ivacaftor 150 mg with strong CYP3A inhibitor ketoconazole 400 mg daily significantly increased ivacaftor AUC by 8.45-fold and Cmax by 2.65-fold .
B) Coadministration of tezacaftor 25 mg and ivacaftor 50 mg orally once daily with strong CYP3A inhibitor itraconazole 200 mg orally twice daily on day 1, followed by 200 mg once daily increased ivacaftor exposure by 15.6-fold and Cmax by 8.6-fold .
Tucatinib Overview
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Tucatinib is used with trastuzumab (Herceptin) and capecitabine (Xeloda) to treat a certain type of hormone receptor–positive breast cancer that has spread to other parts of the body and cannot be treated with surgery in adults who have already been treated with at least one other chemotherapy medication. Tucatinib is also used with trastuzumab to treat a certain type of colorectal cancer (cancer that begins in the large intestine) that has spread to other parts of the body and cannot be treated with surgery in adults who have already been treated with other chemotherapy medications and have not improved or worsened. Tucatinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells.
Ivacaftor Overview
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Ivacaftor is used to treat certain types of cystic fibrosis (an inborn disease that causes problems with breathing, digestion, and reproduction) in adults and children 4 months of age and older. Ivacaftor should be used only in people with a certain genetic make-up. Your doctor may order a blood test to help decide if this medication is right for you. Ivacaftor is in a class of medications called cystic fibrosis transmembrane conductance regulator (CFTR) potentiators. It works by improving the function of a protein in the body to decrease the build-up of thick mucus in the lungs and improving other symptoms of cystic fibrosis.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.