Adagrasib with Topotecan Interaction Details


Brand Names Associated with Adagrasib

  • Adagrasib
  • Krazati®

Brand Names Associated with Topotecan

  • Hycamtin®
  • Topotecan

Medical Content Editor
Last updated Feb 26, 2024


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Interaction Effect

Increased exposure to P-gp substrates


Interaction Summary

Avoid concomitant use of adagrasib with P-gp substrates, where minimal concentration changes may lead to serious adverse reactions, unless otherwise recommended in the prescribing information for these substrates. Concomitant use of P-gp substrates with adagrasib increases exposure of P-gp substrates, which may increase the risk of adverse reactions related to these substrates. Concomitant use of 600 mg twice daily dose of adagrasib with digoxin (a P-gp substrate), the predicted increase in AUC and Cmax of digoxin is by 1.5-fold and 1.9-fold respectively[1].


Severity

Major


Onset

Unspecified


Evidence

Theoretical


How To Manage Interaction

Avoid concomitant use of adagrasib with P-gp substrates, where minimal concentration changes may lead to serious adverse reactions, unless otherwise recommended in the prescribing information for these substrates. Concomitant use of P-gp substrates with adagrasib increases exposure of P-gp substrates, which may increase the risk of adverse reactions related to these substrates[1].


Mechanism Of Interaction

Inhibition of P-gp-mediated efflux transport by adagrasib


Literature Reports

A) Concomitant use of 600 mg twice daily dose of adagrasib with digoxin (a P-gp substrate), the predicted increase in AUC and Cmax of digoxin is by 1.5-fold and 1.9-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

  • 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.

See More information Regarding Adagrasib

Topotecan Overview

  • Topotecan is used to treat small cell lung cancer (a type of cancer that begins in the lungs) that was successfully treated with a different chemotherapy medication but has returned no sooner than 45 days after the last dose of the first chemotherapy medication was taken. Topotecan is in a class of medications called topoisomerase I inhibitors. It works by killing cancer cells.

See More information Regarding Topotecan

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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.