Adagrasib with Vardenafil Interaction Details
Brand Names Associated with Adagrasib
- Adagrasib
- Krazati®
Brand Names Associated with Vardenafil
- Levitra®
- Staxyn®
- Vardenafil
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 26, 2024
Interaction Effect
An increased risk of QT interval prolongation, increased exposure to CYP3A4 substrates
Interaction Summary
Avoid concomitant use of adagrasib with QT prolonging sensitive CYP3A substrates unless otherwise recommended in the prescribing information for these substrates. Concomitant use of these drugs will increase the concentrations of these drugs, which may increase the risk of adverse reactions of these drugs and QTc interval prolongation. Concomitant use of adagrasib with other products that prolong the QTc interval may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including torsade de pointes, other serious arrhythmias, and sudden death. Monitor electrocardiogram and electrolytes prior to starting adagrasib, during concomitant use, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and in patients who are unable to avoid concomitant medications that are known to prolong the QT interval. Withhold adagrasib if the QTc interval is greater than 500 msec or the change from baseline is greater than 60 msec until QTc interval is less than 481 msec or return to baseline. Resume adagrasib at the next lower dose level. Permanently discontinue adagrasib incase of torsade de pointes, polymorphic ventricular tachycardia or signs or symptoms of serious or life-threatening arrhythmia[1].
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Avoid concomitant use of adagrasib with QT prolonging sensitive CYP3A substrates unless otherwise recommended in the prescribing information for these substrates. Concomitant use of these drugs will increase the concentrations of these drugs, which may increase the risk of adverse reactions of these drugs and QTc interval prolongation. Concomitant use of adagrasib with other products that prolong the QTc interval may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including torsade de pointes, other serious arrhythmias, and sudden death. If concomitant use cannot be avoided, monitor electrocardiogram and electrolytes prior to starting adagrasib, during concomitant use, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and in patients who are unable to avoid concomitant medications that are known to prolong the QT interval. Withhold adagrasib if the QTc interval is greater than 500 msec or the change from baseline is greater than 60 msec until QTc interval is less than 481 msec or return to baseline. Resume adagrasib at the next lower dose level. Permanently discontinue adagrasib if torsade de pointes, polymorphic ventricular tachycardia, or signs or symptoms of serious or life-threatening arrhythmia occur[1].
Mechanism Of Interaction
Additive QT interval prolongation; 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].
B) In the pooled safety population, exposure to adagrasib as a single agent at 600 mg orally twice daily in 366 patients with NSCLC and other solid tumors enrolled in KRYSTAL-1 and KRYSTAL-12, 6% of 366 patients with at least one post-baseline electrocardiogram (ECG) assessment had an average QTc greater than or equal to 501 msec and 11% of patients had an increase from baseline of QTc greater than 60 msec. Adagrasib causes concentration-dependent increases in the QTc interval [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.
Vardenafil Overview
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Vardenafil is used to treat erectile dysfunction (impotence; inability to get or keep an erection) in men. Vardenafil is in a class of medications called phosphodiesterase (PDE) inhibitors. It works by increasing blood flow to the penis during sexual stimulation. This increased blood flow can cause an erection. Vardenafil does not cure erectile dysfunction or increase sexual desire. Vardenafil does not prevent pregnancy or the spread of sexually transmitted diseases such as human immunodeficiency virus (HIV).
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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.