Methotrexate
GoodRxMethotrexate · oral tablet
Misc.
Approved uses
Severe rheumatoid arthritis and polyarticular juvenile idiopathic arthritis
Adults: 7.5 mg ONCE WEEKLY, or 2.5 mg every 12 hours for three doses once weekly, adjusted to response
The once-weekly schedule is the single most dangerous thing on this card: daily dosing by mistake has killed people
Acute lymphoblastic leukaemia and other malignancies, and severe psoriasis
Per the regimen for the specific malignancy; psoriasis 10 to 25 mg once weekly
OFF-LABELNot in the FDA label for this product
Non-infectious uveitis, as a corticosteroid-sparing agent
25 mg orally once weekly in the trial
RCT · n=216 · best posterior
The FAST trial randomised 216 adults with non-infectious uveitis to methotrexate 25 mg weekly or mycophenolate 3 g daily. Treatment success at 6 months was 66.7% on methotrexate against 57.1% on mycophenolate, which did not reach significance overall (odds ratio 1.50, 95% CI 0.81 to 2.81, p=0.20). The useful finding is the split by anatomy: methotrexate was better for posterior uveitis and panuveitis (74.4% against 55.3%, p=0.02) while mycophenolate was better for intermediate uveitis (63.6% against 33.3%, p=0.07), and the interaction between drug and subtype was significant at p=0.004. Raised liver enzymes were the commonest laboratory problem, in 13.0% on methotrexate.
Contraindications
Methotrexate tablets are contraindicated in: Pregnant women receiving methotrexate tablets for treatment of non-neoplastic diseases. Patients with a history of a severe hypersensitivity reactions, including anaphylaxis, to methotrexate.
Available FormsMethotrexate 2.5 mg tablets, plus injectable formulations.
Mechanism of ActionMethotrexate inhibits dihydrofolic acid reductase. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication.
Warnings & Precautions
- Severe and fatal toxicities have been reported, including myelosuppression, serious infection, hepatotoxicity, renal toxicity, pulmonary toxicity, gastrointestinal toxicity and dermatologic reactions. This carries a boxed warning.
- Embryofetal toxicity: methotrexate can cause fetal death and congenital malformations, and is contraindicated in pregnancy for non-malignant indications. This carries a boxed warning.
- Medication errors, including daily rather than weekly dosing, have led to death; the rheumatologic dose is ONCE WEEKLY.
- Folate supplementation reduces some toxicity without abolishing efficacy.
Common Side Effects
Common: stomatitis, nausea, abdominal distress, elevated transaminases, leukopenia and fatigue. Serious: myelosuppression, hepatotoxicity, interstitial pneumonitis, renal impairment and severe dermatologic reactions.
Pregnancy & LactationPregnancy: Contraindicated for non-malignant indications. It causes embryofetal death and congenital malformations. Verify pregnancy status before starting, and use effective contraception during and after treatment.
Lactation: Methotrexate is present in human milk; advise against breastfeeding during treatment.
Pediatric UseSafety and effectiveness have been established in children for acute lymphoblastic leukaemia and polyarticular juvenile idiopathic arthritis. Dosing is by body surface area, and severe neurotoxicity has been reported after high-dose regimens.