Methotrexate
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Methotrexate
Trexall, Otrexup, Rasuvo, Xatmep, Rheumatrex (discontinued)
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Summary
Classes
Common uses
Rheumatoid arthritis0, Psoriasis and psoriatic arthritis0, Crohn's disease maintenance0, Unruptured ectopic pregnancy0, Medical abortion (in some regimens)0, Leukemia and lymphoma (high-dose oncology regimens)0, CNS prophylaxis in hematologic malignancy (intrathecal)0
Pharmacy
Starting dose
Rheumatologic: 7.5-15 mg PO or SC once weekly (not daily — daily dosing is a recognized fatal error); folic acid 1 mg PO daily on non-MTX days; oncology dosing is far higher and indication-specific
Preparations
2.5 mg tablets; 10-50 mg/mL injection; pre-filled subcutaneous autoinjectors (Otrexup, Rasuvo); 2.5 mg/mL oral solution (Xatmep)
US FDA Max
Rheumatologic ~25 mg/week; oncology indication-specific
Pharmacology
Routes
Oral, subcutaneous, intramuscular, IV, intrathecal
Onset
Rheumatologic effect at 4-8 weeks; ectopic resolution over 2-3 weeks
Duration
Once-weekly dosing in rheumatology
Half-life
3-10 hours (low dose); 8-15 hours (high dose); much longer in third-space accumulation (pleural effusion, ascites)[1]
Bioavailability
60-70% PO at low doses; saturable at high doses (parenteral routes preferred above 15-25 mg/week)[1]
Pregnancy
Contraindicated in pregnancy (Category X); abortifacient and teratogenic. Discontinuation 3-6 months before conception is standard.[citation needed]
Legal status
Rx-only in US
Purported mechanism
Methotrexate competitively inhibits dihydrofolate reductase, depleting tetrahydrofolate and blocking thymidylate, purine, and amino acid synthesis; in rheumatologic doses the immunomodulatory effect appears mediated less by DHFR inhibition and more by AICAR transformylase inhibition with subsequent adenosine accumulation and anti-inflammatory adenosine A2A signaling.0 Folic acid co-supplementation reduces stomatitis, GI, and hepatic toxicity without compromising efficacy. Bone marrow suppression, hepatotoxicity, pneumonitis, and nephrotoxicity (especially with high-dose oncology regimens) are the major adverse effects. Glucarpidase rescues high-dose methotrexate toxicity by cleaving extracellular drug[1].
References
- ↑ 1.0 1.1 1.2 FDA Prescribing Information, methotrexate, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/008085s074lbl.pdf