Gemfibrozil with Imatinib Interaction Details
Brand Names Associated with Gemfibrozil
- Gemfibrozil
- Lopid®
Brand Names Associated with Imatinib
- Gleevec®
- Imatinib
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 25, 2023
Interaction Effect
Increased imatinib trough level or reduced imatinib exposure
Interaction Summary
Repeated coadministration of gemfibrozil, an inhibitor of CYP2C8 with imatinib, a CYP2C8 substrate, may increase imatinib exposure. However in a randomized crossover study in healthy subjects (n=10) who received gemfibrozil 600 mg or placebo twice daily for 6 days, coadministration of a single dose of imatinib 200 mg on day 3 resulted in reduced imatinib exposure in subjects who received gemfibrozil. Impairment in the formation of imatinib's main metabolite, N-desmethylimatinib, was also seen and was reflected in decreased N-desmethylimatinib exposure. However, the CYP2C8-inhibiting action of gemfibrozil may increase imatinib trough levels above the 1000 ng/mL therapeutic threshold with ongoing exposure. Imatinib dose reduction may be necessary with higher or multiple imatinib doses. Caution is warranted if these drugs are concurrently administered.
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Use caution with concurrent administration of gemfibrozil and imatinib. Ongoing coadministration of gemfibrozil and imatinib may increase imatinib trough levels and may require an imatinib dose reduction, or may result in reduced imatinib exposure due to impaired absorption and decreased formation of the active metabolite.
Mechanism Of Interaction
Inhibition of CYP2C8-mediated metabolism of imatinib by gemfibrozil; reduced imatinib absorption and impaired CYP2C8-mediated conversion of imatinib to its active metabolite
Literature Reports
A) In a randomized crossover study of 10 healthy subjects administered gemfibrozil 600 mg or placebo twice daily for 6 days and imatinib 200 mg on day 3, imatinib peak plasma concentrations (Cmax) and 0-to-12-hour AUC were reduced by 35% and 23%, respectively, compared with placebo (p less than 0.001). Impaired imatinib absorption was seen in all subjects, with the peak plasma concentration/plasma concentration at 24 hours ratio (Cmax/C24h) reduced by 44% (p less than 0.001). Cmax and 0-to-12-hour AUC of imatinib's main metabolite, N-desmethylimatinib, were reduced by 56% and 48%, respectively, compared with placebo (p less than 0.001). Gemfibrozil also reduced the Cmax/C24h ratio of N-desmethylimatinib by 17% (p=0.222). However, imatinib dose reduction may be necessary with higher or multiple imatinib doses, as the CYP2C8-inhibiting action of gemfibrozil may increase imatinib trough levels above the 1000 ng/mL therapeutic threshold with ongoing exposure. Caution is warranted if these drugs are concurrently administered .
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.
Imatinib Overview
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Imatinib is used to treat certain types of leukemia (cancer that begins in the white blood cells) and other cancers and disorders of the blood cells. Imatinib is also used to treat certain types of gastrointestinal stromal tumors (GIST; a type of tumor that grows in the walls of the digestive passages and may spread to other parts of the body). Imatinib is also used to treat dermatofibrosarcoma protuberans (a tumor that forms under the top layer of skin) when the tumor cannot be removed surgically, has spread to other parts of the body, or has come back after surgery. Imatinib 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 the spread of cancer cells.
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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.