NAPLEX Question of the Week: Methotrexate

A drug with many uses is the subject of our question of the week.
NAPLEX Question of the Week: Methotrexate

Share this post

Choose a social network to share with, or copy the shortened URL to share elsewhere

This is a representation of how your post may appear on social media. The actual post will vary between social networks

Which of the following are true regarding methotrexate? Select all that apply.  

A. Methotrexate reversibly binds to and inhibits dihydrofolate reductase 

B. Methotrexate may be administered orally, IM, IV, intrathecally, or subcutaneously

C. Brand names include Otrexup, Rasuvo, RediTrex, Trexall, Xatmep, and Xgeva.  

D. Adverse reactions include alopecia, Stevens-Johnson syndrome, and GI intolerance

E. Doses >500 mg/m2 require leucovorin rescue  


Answers with rationale: 

The correct answers are B, D, and E  

Methotrexate, or MTX, is an antineoplastic agent that can be used as an immunosuppressant in the treatment of various cancers, Crohns disease, psoriasis, and rheumatoid arthritis. It is a folate antimetabolite that irreversibly binds to and inhibits dihydrofolate reductase which interferes with DNA synthesis, repair, and cellular replication, making Answer A incorrect. It is important to note that methotrexate is cell cycle specific for the S phase of the cycle, making actively proliferative tissues in cancer more susceptible to its effects. The mechanism in the treatment for rheumatoid arthritis, psoriasis, and Crohn's disease are not completely understood.  

Methotrexate is administered orally, IM, IV, intrathecally, and subcutaneously, making Answer B correct. When evaluating the administration of methotrexate, it is important to understand why the patient is taking this medication and make sure it is dosed appropriately.  Often when used for rheumatoid arthritis it is dosed orally weekly but misfills have occurred in practice where the dose is given daily, setting the patient up for potential significant toxicity.

Methotrexate is available in many brand names including Otrexup, Rasuvo, RediTrex, Trexall, and Xatmep. Xgeva is a brand name for denosumab and not methotrexate, making Answer C incorrect.  

Methotrexate has a large range of side effects, many of which are dose and route specific. Some adverse reactions include alopecia, Stevens-Johnson syndrome, and GI intolerances such as nausea, vomiting, and diarrhea, making Answer D correct. Others include headache, photosensitivity, stomatitis, and blood dyscrasias which are all important to counsel patients on when starting this medication.  

 The use of methotrexate is limited by its toxicities to normal tissues, particularly the gastrointestinal side effects and bone marrow suppression. To improve the therapeutic index of methotrexate treatment, leucovorin is used to bypass the metabolic block induced by methotrexate. Leucovorin selectively rescues normal but not malignant cells, however the mechanism behind this is not completely understood. In methotrexate doses greater than 500 mg/m2, leucovorin rescue therapy 24-36 hours after methotrexate dose is required as doses of methotrexate of this amount are otherwise fatal, making Answer E correct.  

See everyone next week as we close out 2020! 


Dr. B

Create a Free MyAccess Profile

AccessMedicine Network is the place to keep up on new releases for the Access products, get short form didactic content, read up on practice impacting highlights, and watch video featuring authors of your favorite books in medicine. Create a MyAccess profile and follow our contributors to stay informed via email updates.