Methotrexate with Rolapitant Interaction Details

Brand Names Associated with Methotrexate

Brand Names Associated with Rolapitant

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 17, 2023

Interaction Effect

Increased methotrexate exposure

Interaction Summary

Methotrexate is a substrate of BCRP and oral rolapitant is a BCRP inhibitor that can significantly increase substrate exposure and potential for adverse reactions; if concomitant use cannot be avoided, monitor for adverse reactions related to the substrate . A post hoc safety analysis supports the tolerability of oral rolapitant in a large number of patients as part of an antiemetic triple-drug regimen prior to cycle 1 of emetogenic chemotherapy comprised of BCRP substrates, which included irinotecan, methotrexate, or topotecan (n=44). There were no differences in toxicities experienced in those treated with rolapitant and BCRP substrate drugs compared with control populations .

Severity

Moderate

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Oral rolapitant is a BCRP inhibitor that can significantly increase substrate exposure and potential for adverse reactions; if concomitant use with a substrate cannot be avoided, monitor for adverse reactions related to the substrate. A post-hoc safety analysis of cycle 1 treatment-emergent adverse effects (TEAE) and serious TEAEs showed no difference in frequencies of common toxicities when oral rolapitant was part of an antiemetic triple-drug regimen prior to chemotherapy regimens comprised of substrates of CYP2D6 and BCRP, which included about 40 patients treated with irinotecan, methotrexate, or topotecan .

Mechanism Of Interaction

Inhibition of BCRP-mediated efflux transport of methotrexate by rolapitant

Literature Reports

A) An integrated safety analysis of cycle 1 treatment-emergent adverse effects (TEAE) and serious TEAEs frequencies in patients when oral rolapitant was added to chemotherapy regimens containing CYP2D6 or BCRP substrate drugs compared with non-use of CYP2D6 or BCRP substrate drugs showed no difference in toxicities experienced in those treated with irinotecan, methotrexate, or topotecan and rolapitant (n=44) compared with control (n=42). Common TEAEs and serious TEAEs occurred with comparable frequencies in the rolapitant and control populations when patients were grouped by BCRP substrate drug use (ie, methotrexate, irinotecan, etoposide, epirubicin, docetaxel, DOXOrubicin, fluorouracil, topotecan) vs non-use as well as when grouped by CYP2D6 substrate drug use (ie, ondansetron, metoclopramide, ranitidine) vs non-use. Across 4 phase II and III trials, 53% of patients received CYP2D6 substrate drugs (n=1368) and 63% received BCRP substrate drugs (n=1637) .

B) Coadministration of a single oral dose of rolapitant 180 mg (BCRP inhibitor) with sulfasalazine 500 mg (BCRP substrate) on day 1 and sulfasalazine alone on day 8 showed a significantly increased sulfasalazine Cmax by 140% and AUC by 130% on day 1 and on day 8, sulfasalazine Cmax and AUC were still elevated by 17% and 32% .

Methotrexate Overview

• Methotrexate is used to treat severe psoriasis (a skin disease in which red, scaly patches form on some areas of the body) that cannot be controlled by other treatments. Methotrexate is also used along with rest, physical therapy, and sometimes other medications to treat severe active rheumatoid arthritis (RA; a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) that cannot be controlled by certain other medications. Methotrexate is also used to treat certain types of cancer including cancers that begin in the tissues that form around a fertilized egg in the uterus, breast cancer, lung cancer, certain cancers of the head and neck, certain types of lymphoma, and leukemia (cancer that begins in the white blood cells). Methotrexate is in a class of medications called antimetabolites. Methotrexate treats cancer by slowing the growth of cancer cells. Methotrexate treats psoriasis by slowing the growth of skin cells to stop scales from forming. Methotrexate may treat rheumatoid arthritis by decreasing the activity of the immune system.

Rolapitant Overview

• Rolapitant is used along with other medications to prevent nausea and vomiting that may occur several days after receiving certain chemotherapy medications. Rolapitant is in a class of medications called antiemetics. It works by blocking the action of neurokinin and substance P, natural substances in the brain that cause nausea and vomiting.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.