Tucatinib with Gemfibrozil Interaction Details
Brand Names Associated with Tucatinib
- Tucatinib
- Tukysa®
Brand Names Associated with Gemfibrozil
- Gemfibrozil
- Lopid®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Increased tucatinib exposure and risk of toxicity
Interaction Summary
Avoid concomitant use of tucatinib (CYP2C8 substrate) with a strong CYP2C8 inhibitor because increased tucatinib exposure may increase risk of toxicities. In a clinical study, concomitant use of tucatinib with gemfibrozil, a strong CYP2C8 inhibitor, resulted in a significant increase in tucatinib AUC and Cmax. If coadministration with a strong CYP2C8 inhibitor is required, reduce tucatinib to 100 mg orally twice daily. After discontinuation of the strong CYP2C8 inhibitor for 3 elimination half-lives, resume tucatinib dose that was taken prior to concomitant use.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of tucatinib (CYP2C8 substrate) with a strong CYP2C8 inhibitor because increased tucatinib exposure may increase risk of toxicities. If coadministration with a strong CYP2C8 inhibitor is required, reduce tucatinib to 100 mg orally twice daily. After discontinuation of the strong CYP2C8 inhibitor for 3 elimination half-lives, resume tucatinib dose that was taken prior to concomitant use.
Mechanism Of Interaction
Inhibition of CYP2C8-mediated metabolism of tucatinib
Literature Reports
A) In a clinical study, coadministration of a single tucatinib 300 mg dose with steady-state gemfibrozil 600 mg twice daily (a strong CYP2C8 inhibitor) resulted in a ratio of tucatinib exposure with and without concomitant drug for AUC of 3 and Cmax of 1.6 .
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.
Gemfibrozil Overview
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Gemfibrozil is used with diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and triglycerides (other fatty substances) in the blood in certain people with very high triglycerides who are at risk of pancreatic disease (conditions affecting the pancreas, a gland that produces fluid to break down food and hormones to control blood sugar). Gemfibrozil is also used in people with a combination of low high-density lipoprotein (HDL; 'good cholesterol') levels and high low-density lipoprotein (LDL; 'bad cholesterol') and triglyceride levels to reduce the risk of heart disease. Gemfibrozil is in a class of lipid-regulating medications called fibrates. It works by reducing the production of triglycerides in the liver.
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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.