Adagrasib with Felodipine Interaction Details
Brand Names Associated with Adagrasib
- Adagrasib
- Krazati®
Brand Names Associated with Felodipine
- Felodipine
- Lexxel® (as a combination product containing Enalapril, Felodipine)
- Plendil®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 26, 2024
Interaction Effect
Increased exposure to CYP3A substrates
Interaction Summary
Avoid concomitant use of adagrasib with sensitive CYP3A substrates unless otherwise recommended in the prescribing information for these substrates. Concomitant use of sensitive CYP3A substrates with adagrasib increases exposure of CYP3A substrates, which may increase the risk of adverse reactions related to these substrates. In studies, concomitant use of 400 mg twice daily dose of adagrasib with midazolam (a sensitive CYP3A substrate) increased the AUC and Cmax of midazolam by 4.8-fold and 21-fold respectively. With 600 mg twice daily dose of adagrasib, the predicted increase in AUC and Cmax of midazolam is by 3.1-fold and 31-fold respectively[1].
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of adagrasib with sensitive CYP3A substrates unless otherwise recommended in the prescribing information for these substrates. Concomitant use of sensitive CYP3A substrates with adagrasib increases exposure of CYP3A substrates, which may increase the risk of adverse reactions related to these substrates[1].
Mechanism Of Interaction
Inhibition of CYP3A substrate metabolism by adagrasib
Literature Reports
A) Concomitant use of 400 mg twice daily dose of adagrasib with midazolam (a sensitive CYP3A substrate) increased the AUC and Cmax of midazolam by 4.8-fold and 21-fold respectively. With 600 mg twice daily dose of midazolam, the predicted increase in AUC and Cmax of midazolam is by 3.1-fold and 31-fold respectively [1].
References
1 ) Product Information: KRAZATI(TM) oral tablets, adagrasib oral tablets. Mirati Therapeutics Inc (per FDA), San Diego, CA, 2022.
Adagrasib Overview
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Adagrasib is used to treat certain types of non-small cell lung cancer (NSCLC) that has spread to nearby tissues or to other parts of the body or cannot be removed by surgery in adults who have received at least one other treatment.Adagrasib is in a class of medications called KRAS 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.
Felodipine Overview
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Felodipine is used to treat high blood pressure. Felodipine is in a class of medications called calcium channel blockers. It works by relaxing the blood vessels so your heart does not have to pump as hard.
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High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.
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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.