Everolimus with Fosphenytoin Interaction Details
Brand Names Associated with Everolimus
- Afinitor Disperz®
- Afinitor®
- Everolimus
- RAD001
- Zortress®
Brand Names Associated with Fosphenytoin
- Cerebyx®
- Fosphenytoin Injection
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 20, 2023
Interaction Effect
Reduced everolimus exposure and reduced efficacy of everolimus
Interaction Summary
Everolimus Cmax and AUC decreased and clearance increased after coadministration with rifAMPin, a strong CYP3A4 and PgP inducer. If concomitant use is required in patients with breast cancer, progressive neuroendocrine tumors of pancreatic origin, renal cell carcinoma, or renal angiomyolipoma with tuberous sclerosis complex (TSC), double the daily everolimus dosage using increments of 5 mg or less. Once the inducer is discontinued for 5 days, return to the everolimus dose used prior to initiating the inducer. For patients with TSC-associated subependymal giant cell astrocytoma or partial-onset seizures, double the daily everolimus dosage in increments of 5 mg or less; measure everolimus trough concentrations approximately 2 weeks after initiating the inducer and adjust dosage to maintain trough concentrations of 5 to 15 nanograms/mL. Resume the everolimus dose used prior to initiating an inducer, once all inducers are discontinued for 5 days, and measure trough levels 2 weeks after discontinuation . If concurrent therapy is necessary in transplant recipients, closely monitor everolimus whole blood trough levels .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
If concomitant use of everolimus and a P-glycoprotein and strong CYP3A4 inducer is required in patients with breast cancer, progressive neuroendocrine tumors of pancreatic origin, renal cell carcinoma, or renal angiomyolipoma with tuberous sclerosis complex (TSC), double the daily everolimus dosage using increments of 5 mg or less. Once the inducer is discontinued for 5 days, return to the everolimus dose used prior to initiating the inducer. For patients with TSC-associated subependymal giant cell astrocytoma or partial-onset seizures, double the daily everolimus dosage in increments of 5 mg or less; measure everolimus trough concentrations approximately 2 weeks after initiating the inducer and adjust dose to maintain trough concentrations of 5 to 15 nanograms/mL. Resume the everolimus dose used prior to initiating an inducer, once all inducers are discontinued for 5 days, and measure trough levels 2 weeks after discontinuation. If concurrent therapy is necessary in transplant recipients, closely monitor everolimus whole blood trough levels .
Mechanism Of Interaction
Induction of CYP3A4-mediated metabolism of everolimus; induction of P-gp mediated efflux transport of everolimus
Literature Reports
A) Coadministration of everolimus (a CYP3A4 and P-glycoprotein (PgP) substrate) and rifAMPin (a strong CYP3A4 and PgP inducer) in healthy volunteers increased the everolimus clearance nearly 3-fold, decreased Cmax by 58%, and decreased AUC by 63% .
Everolimus Overview
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Everolimus (Afinitor) is used to treat advanced renal cell carcinoma (RCC; cancer that begins in the kidneys) that has already been treated unsuccessfully with other medications. Everolimus (Afinitor) is also used to treat a certain type of advanced breast cancer that has already been treated with at least one other medication. Everolimus (Afinitor) is also used to treat a certain type of cancer of the pancreas, stomach, intestines, or lungs that has spread or progressed and that cannot be treated with surgery. Everolimus (Afinitor) is also used to treat kidney tumors in people with tuberous sclerosis complex (TSC; a genetic condition that causes tumors to grow in many organs). Everolimus (Afinitor and Afinitor Disperz) is also used to treat subependymal giant cell astrocytoma (SEGA; a type of brain tumor) in adults and children 1 year of age and older who have TSC. Everolimus (Afinitor Disperz) is also used along with other medications to treat certain types of seizures in adults and children 2 years of age and older who have TSC. Everolimus (Zortress) is used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune system of the person who received the organ) in certain adults who have received kidney transplants. Everolimus is in a class of medications called kinase inhibitors. Everolimus treats cancer by stopping cancer cells from reproducing and by decreasing blood supply to the cancer cells. Everolimus prevents transplant rejection by decreasing the activity of the immune system.
Fosphenytoin Overview
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Fosphenytoin injection is used to treat primary generalized tonic-clonic seizures (formerly known as a grand mal seizure; seizure that involves the entire body) and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Fosphenytoin injection may also be used to control certain type of seizures in people who cannot take oral phenytoin. Fosphenytoin 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.