Methotrexate
TREXALL
Pronunciation: meth-oe-TREX-ayt
“Metal Treks eight”
What it isDHFR inhibitor that depletes folate; rheumatoid arthritis, psoriasis, and malignancy.
Why this oneIt is the inexpensive anchor DMARD in rheumatoid arthritis and improves response when combined with biologics.
What limits itA daily-for-weekly dosing error can be fatal; supplement folate, monitor counts and organ function, and avoid trimethoprim.
FDA-approved for
- cancer/RA/psoriasis (~1953)
Off-label
- ectopic pregnancy
- inflammatory bowel disease
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Acute lymphoblastic leukemia (maintenance) | adult | 20 mg/m2 PO once weekly | adjust to ANC/platelets | |
| Mycosis fungoides | adult | 25-75 mg PO once weekly (monotherapy) or 10 mg/m2 PO twice weekly (combination) | ||
| Relapsed/refractory non-Hodgkin lymphoma | adult | 2.5 mg PO 2-4x/week (metronomic combination) | 10 mg/week | |
| Rheumatoid arthritis | adult | 7.5 mg PO once weekly | adjust to response | >20 mg/week increases serious adverse reaction risk |
| Polyarticular juvenile idiopathic arthritis | pediatric | 10 mg/m2 PO once weekly | adjust to response | >30 mg/m2/week increases serious adverse reaction risk |
| Psoriasis | adult | 10-25 mg PO once weekly | lowest effective dose | 30 mg/week |
Renal CLcr <90 mL/min: increased risk of adverse reactions; monitor closely and reduce dose or discontinue
Hepatic Undefined (PK/safety unknown; may be at increased risk of adverse reactions)
Once-weekly dosing; medication errors with daily dosing have been fatal
Instructions
- Dose ONCE WEEKLY (not daily) — daily dosing has caused death; verify regimen
- Verify pregnancy status in females of reproductive potential before starting
- Administer folic or folinic acid to reduce adverse reactions
- Do not give to patients unable to swallow a tablet
- Cytotoxic drug — follow special handling/disposal
Available strengths
- tab 2.5, 5, 7.5, 10, 15 mg
- sol 2, 2.5 mg/mL
- inj 50, 100, 250, 1000 mg
Contraindications
- Pregnancy (for non-neoplastic diseases)
- History of severe hypersensitivity reactions (incl. anaphylaxis) to methotrexate
Cautions
- Myelosuppression
- Gastrointestinal toxicity
- Hepatotoxicity
- Pulmonary toxicity
- Dermatologic reactions
- Renal toxicity
- Serious infections
- Neurotoxicity
- Secondary malignancies
- Tumor lysis syndrome
- Increased risk with third-space fluid accumulation
Adverse reactions
- Ulcerative stomatitis
- Leukopenia
- Nausea
- Abdominal distress
- Infection, malaise, fatigue, chills, fever, dizziness
Pregnancy Contraindicated (non-neoplastic disease); causes embryo-fetal toxicity and fetal death; skull/CNS/limb anomalies with first-trimester exposure
Lactation Undefined
Cost
| Strength | #/mo | generic $/mo | CostPlus | |
|---|---|---|---|---|
| 2.5 mg | tab | 4 q-wk | $0.63 | offered |
| 5 mg | tab | 4 q-wk | $96.35 | not offered |
| 7.5 mg | tab | 4 q-wk | $144.84 | not offered |
| 10 mg | tab | 4 q-wk | $192.54 | not offered |
| 15 mg | tab | 4 q-wk | not offered |
Generic entry2035 est.
⚠ BOXED WARNING
- Serious toxic reactions and embryo-fetal toxicity
Classes and tags
Clinical profile
Legacy pregnancy categoryX
Defining liabilityPotentially fatal myelosuppression, hepatotoxicity, pneumonitis and dosing-error toxicity; weekly dosing errors are especially dangerous.
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