Lapatinib with Afatinib Interaction Details
Brand Names Associated with Lapatinib
- Lapatinib
- Tykerb®
Brand Names Associated with Afatinib
- Afatinib
- Gilotrif®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 26, 2024
Interaction Effect
Increased exposure of afatinib
Interaction Summary
Concurrent use of afatinib, a P-glycoprotein (P-gp) substrate, and a P-gp inhibitor may increase afatinib exposure and increase the risk of afatinib adverse effects. When coadministration of afatinib with ritonavir 200 mg twice daily for 3 days (a P-gp inhibitor) was evaluated in healthy volunteers, afatinib AUC and Cmax increased by 19% and 4%, respectively; when ritonavir was administered 1 hour before a single afatinib 20-mg dose, afatinib AUC and Cmax increased by 48% and 39%, respectively; when ritonavir was administered 6 hours after afatinib, the afatinib AUC and Cmax increased by 11% and 5%, respectively. Therefore, if coadministration of afatinib and a P-gp inhibitor is necessary and not tolerated, decrease the afatinib daily dose by 10 mg. Resume the original afatinib dose, as tolerated, if concurrent P-gp inhibitor therapy is discontinued[1].
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Coadministration of afatinib, a P-glycoprotein (P-gp) substrate, and a P-gp inhibitor may increase afatinib exposure and increase the risk of adverse effects. If concurrent use of afatinib and a P-gp inhibitor is necessary and not well-tolerated, decrease the afatinib daily dose by 10 mg. Resume previous afatinib dose, as tolerated, if concurrent P-gp inhibitor is discontinued[1].
Mechanism Of Interaction
Inhibition of P-glycoprotein-mediated efflux transport of afatinib
Literature Reports
A) The concurrent use of ritonavir and afatinib resulted in increased afatinib exposure in 2 pharmacokinetic studies in healthy subjects, with varied amount of elevation dependent upon the timing of dosing of the individual agents. Compared with oral administration of afatinib alone, coadministration of ritonavir 200 mg twice daily for 3 days resulted in increased afatinib AUC(0 to infinity) and Cmax by 19% and 4%, respectively, and when ritonavir administration time was moved to 6 hours after afatinib, the afatinib AUC(0 to infinity) and Cmax increased by 11% and 5%, respectively. In the second study, when ritonavir (200 mg twice daily for 3 days) was administered 1 hour before a single afatinib 20-mg dose, afatinib AUC(0 to infinity) and Cmax increased by 48% and 39%, respectively [1].
References
1 ) Product Information: GILOTRIF(TM) oral tablets, afatinib oral tablets. Boehringer Ingelheim Pharmaceuticals, Inc. (per FDA), Ridgefield, CT, 2013.
Lapatinib Overview
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Lapatinib is used with capecitabine (Xeloda) to treat a certain type of advanced breast cancer in people who have already been treated with other chemotherapy medications. Lapatinib is also used with letrozole (Femara) to treat a certain type of breast cancer in postmenopausal women (women who have experienced a change of life; end of menstrual periods) that has spread to other parts of the body. Lapatinib 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 or slow the spread of cancer cells.
Afatinib Overview
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Afatinib is used to treat certain types of non-small cell lung cancer that has spread to nearby tissues or to other parts of the body. Afatinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply.
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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.