Methotrexate
A weekly steroid-sparing immunosuppressant for inflammatory and autoimmune eye disease; carries FDA Boxed Warnings and is dosed once weekly - never daily.
Drug Class: Immunosuppressants
Methotrexate is an immunosuppressant medication used to reduce reliance on steroids in various inflammatory and autoimmune conditions affecting the visual system. For autoimmune indications it is dosed once a week, never daily.
Critical safety: methotrexate is dosed ONCE WEEKLY for autoimmune disease
Daily dosing - even by accident, even for a few days - has caused fatal toxicity. The Institute for Safe Medication Practices (ISMP) lists methotrexate as a high-alert medication for this reason.
- Confirm the day of the week with your prescriber and write it on the bottle.
- Never "catch up" a missed dose without calling your prescriber.
- If you accidentally take methotrexate on more than one day in a week, call your prescriber or poison control immediately - do not wait for symptoms.
FDA Boxed Warnings - methotrexate
The FDA label for methotrexate carries boxed warnings for:
- Embryo-fetal toxicity - methotrexate causes miscarriage and major birth defects (see Pregnancy section).
- Severe bone marrow suppression - life-threatening cytopenias can occur, especially with kidney impairment.
- Hepatotoxicity - risk of cirrhosis with long-term use; alcohol greatly increases this risk.
- Pulmonary toxicity - interstitial pneumonitis can develop acutely or chronically and can be fatal. Report any new cough or shortness of breath.
- Serious infection - including opportunistic infections.
- Renal toxicity and tumor lysis at high doses (oncology dosing); plus severe skin reactions, GI toxicity, and lymphoma.
Key Takeaways
- Dosed once weekly - never daily - for autoimmune disease
- Steroid-sparing immunosuppressant that builds effect over weeks
- Multiple FDA boxed warnings including hepatotoxicity, pneumonitis, and embryo-fetal toxicity
- Folic acid supplementation reduces side effects
- Strictly avoid in pregnancy; both partners need reliable contraception and a washout before conceiving
- Regular CBC, LFTs, and renal function monitoring is required
Common Uses
- Giant cell arteritis (steroid-sparing)
- Optic perineuritis (recurrent or steroid-dependent)
- Inflammatory eye disease (uveitis, scleritis)
- Thyroid eye disease (in some cases)
- Orbital inflammation (idiopathic orbital inflammatory disease)
- Sarcoidosis affecting vision
- Various autoimmune conditions affecting the visual system
How It Works
- Inhibits folic acid metabolism
- Reduces immune cell activity
- Anti-inflammatory effects
- Effects build over weeks to months
Dosing
Important
- Once weekly dosing (NOT daily)
- Starting: 7.5-15 mg weekly
- May increase to 25 mg weekly
- Oral or injectable
Folic Acid
- Take folic acid daily (except methotrexate day)
- Reduces side effects
- Usually 1 mg daily
Side Effects
Common
- Nausea (especially on dosing day)
- Fatigue
- Mouth sores
- Hair thinning
Serious
- Liver damage
- Bone marrow suppression
- Lung problems
- Infection risk
Precautions
Pregnancy and contraception - methotrexate is teratogenic
Methotrexate causes miscarriage and severe birth defects. It also affects sperm. Both partners must use reliable contraception while on it, and both need a washout before trying to conceive.
- Women: the current FDA label recommends reliable contraception during treatment and for 6 months after the final dose. Some rheumatology bodies (ACR, EULAR) consider a shorter washout (one menstrual cycle to ~3 months) acceptable in low-dose autoimmune use; discuss the right plan with your prescriber.
- Men: the FDA label recommends stopping methotrexate at least 3 months before attempting to conceive. The 2020 ACR Reproductive Health Guideline now conditionally permits men to continue methotrexate during conception attempts based on more recent paternal-exposure safety data - discuss the right approach with your prescriber.
- If you think you may be pregnant on methotrexate, contact your doctor the same day - do not simply stop the medication alone; a coordinated plan is needed
- Breastfeeding is not recommended while on methotrexate
Alcohol
- Avoid or minimize
- Increases liver toxicity risk
Immunizations
- Avoid live vaccines
- Get flu and pneumonia vaccines
Monitoring
- CBC (blood counts) every 2-4 weeks during titration, then every 2-3 months
- Liver function tests (LFTs) on the same schedule; persistent elevation triggers a hold or dose change
- Kidney function (creatinine, eGFR) at baseline and periodically - methotrexate is renally cleared and toxicity rises sharply when eGFR is <30
- Baseline chest imaging in patients with prior lung disease; report any new cough, fever, or shortness of breath promptly (possible pneumonitis)
- Hepatitis B and C screening, and latent TB screening, before starting
- Symptoms of infection or toxicity at every visit
- Visual acuity and exam to monitor disease activity
Related Medications
- Prednisone-often used initially, methotrexate allows tapering
- Mycophenolate mofetil-alternative steroid-sparing agent
- Azathioprine-another option for immunosuppression
When to Contact Your Doctor
- Fever or signs of infection
- Severe nausea or vomiting
- Mouth sores that don't heal
- Unusual bruising or bleeding
- Vision changes or new eye pain
- Shortness of breath or persistent cough
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.
References
For current U.S. drug labeling, contraindications, boxed warnings, pregnancy/lactation language, and formulation-specific dosing, check the official label databases and your prescriber's instructions.