Adagrasib with Phenytoin Interaction Details
Brand Names Associated with Adagrasib
- Adagrasib
- Krazati®
Brand Names Associated with Phenytoin
- Dilantin®
- Phenytek®
- Phenytoin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 26, 2024
Interaction Effect
Increased phenytoin exposure, reduced adagrasib exposure and reduced efficacy of adagrasib
Interaction Summary
Avoid concomitant use of adagrasib with phenytoin (a strong CYP3A4 inducer and a sensitive CYP2C9 substrate), where minimal concentration changes may lead to serious adverse reactions. Concomitant use of sensitive CYP2C9 substrates with adagrasib increases exposure of CYP2C9 substrates, which may increase the risk of adverse reactions related to these substrates. Additionally, Concomitant use of adagrasib with strong CYP3A4 inducers, reduces adagrasib exposure which may reduce the effectiveness of adagrasib[1].
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of adagrasib with phenytoin (a strong CYP3A4 inducer and a sensitive CYP2C9 substrate), where minimal concentration changes may lead to serious adverse reactions. Concomitant use of sensitive CYP2C9 substrates with adagrasib increases exposure of CYP2C9 substrates, which may increase the risk of adverse reactions related to these substrates. Additionally, Concomitant use of adagrasib with strong CYP3A4 inducers, reduces adagrasib exposure which may reduce the effectiveness of adagrasib[1].
Mechanism Of Interaction
Inhibition of CYP2C9 substrate metabolism by adagrasib; induction of CYP3A4-mediated metabolism of adagrasib
Literature Reports
A) Concomitant use of single 600 mg dose of adagrasib with rifampin (a strong CYP3A inducer) decreased the AUC and Cmax of adagrasib by 95% and 88% respectively. With multiple 600 mg doses of adagrasib, the predicted decrease in AUC and Cmax of adagrasib is greater than 66% and 61% respectively [1].
B) Concomitant use of 600 mg twice daily dose of adagrasib with warfarin (a sensitive CYP2C9 substrate), the predicted increase in AUC and Cmax of warfarin is by 2.9-fold and 1.1-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.
Phenytoin Overview
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Phenytoin is used to control certain type of seizures, and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Phenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
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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.