Methotrexate is a dihydrofolate reductase (DHFRase) inhibitor which inhibits DNA repair, synthesis and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to its effect.
A convenient regimen for Low Dose Methotrexate (LDMTX) in adults (used in RA, psoriasis, sarcoidosis, Crohn’s disease) is to start therapy with intermittent oral administration of 5–10 mg once a week. If, after 6–8 weeks, the response is not adequate and no adverse effects are present, the weekly dose can be gradually increased to 25 mg.
Clinical uses of Methotrexate
Mnemonic: CANCER
- Choriocarcinoma
- Abortion
- Non-hodgkin lymphoma
- Chron’s disease
- Ectopic pregnancy
- Rheumatoid Arthritis
Adverse effects of Methotrexate
Mnemonic: MTX
- Mucositis/Myelosuppression
- Transaminase increase (i.e., hepatotoxicity)
- X-rays warranted (chest x-ray for varicella pneumonia or pneumonitis)
Once weekly dosing with folate
- Methotrexate for “Monday“.
- Folic acid for “Friday“.
Monitoring on Methotrexate
Mnemonic: 0, 1, 2, 3
- 0 (baseline): CBC, LFT, RFT, Chest X-ray, Pregnancy test (young females)
- 1-2 weeks: CBC and LFT after initial dose or every dose escalation
- 3 months: CBC, LFT, RFT on stable/maintenance dose
References:
- Methotrexate: Update on Pharmacology, Clinical Applications and Warnings – Nova Science Publishers
- Examination Pediatrics by Wayne Harris
- Safer prescribing of high-risk medicines – Methotrexate: potentially fatal in overdose, BPAC NZ