Methotrexate (MTX) is the most-used “steroid-sparing” medicine in polymyalgia rheumatica (PMR). This guide explains how it’s used alongside prednisone, how to take folic acid correctly, which labs to check (and when), and the high-value drug and vaccine interactions to know about.
The role of methotrexate in PMR (big picture)
- Why MTX? It can lower relapse risk and reduce total steroid exposure in PMR — most helpful if you’re likely to need steroids for a long time or you’re at high risk of steroid side effects. Trials and reviews in PMR commonly used 7.5–10 mg/week (some programs now explore 15–25 mg/week in trials).
- When to consider it: Early, if relapse risk or steroid toxicity is a concern; otherwise during taper if flares recur. This fits with international PMR guidance. \
How to take methotrexate (and avoid common errors)
- Once weekly, not daily. Choose one weekday (e.g., “MTX Monday”) and stick to it. Daily use is dangerous and has caused fatal overdoses—make sure the prescription and label show the day of the week.
- Dose and route: Typical PMR starting doses are 7.5–15 mg once weekly (tablet or injection). If nausea or absorption issues occur—especially at >15 mg—a switch to subcutaneous MTX can help. Your clinician adjusts based on response and labs.
Folic acid: why, how much, and when
- Why folic acid? MTX blocks folate pathways; folic acid lowers the risk of mouth sores, nausea, liver enzyme rises, and cytopenias without reducing MTX’s benefit.
- Most-used regimen: Folic acid 5 mg once weekly on a different day than MTX; increase to 10 mg/week if side effects persist. (Some clinicians use 1 mg daily except on MTX day — both are acceptable approaches.)
Lab monitoring: baseline, early phase, and long-term
Before starting
- CBC, LFTs, creatinine/eGFR, albumin, hepatitis B/C and HIV screening as indicated; check blood pressure/weight/height; chest X-ray or lung assessment when clinically appropriate; consider TB and varicella status.
After starting or changing the dose
- Every 2 weeks for ≥6 weeks, then monthly for 3–12 months: CBC, LFTs, creatinine/eGFR (albumin often included). Increase frequency if higher-risk.
Once stable
- Every 2–3 months (at least every 12 weeks in rheumatology practice): CBC, LFTs, creatinine/eGFR; watch trends even inside the “normal” range.
Stop & contact your team for specific abnormal thresholds (e.g., neutrophils <1.6×10⁹/L, platelets <140×10⁹/L, AST/ALT >100 U/L), or if symptoms suggest toxicity (see below).
Side effects: what’s common vs. what’s urgent
- Common/usually manageable: Nausea, fatigue the day after dosing, mild mouth sores, reversible liver enzyme bumps—often improved by folic acid, dose split, switch to subcutaneous route, or dose adjustment.
- Urgent “red flags”: New dry cough, breathlessness, or fever (possible MTX pneumonitis); severe mouth ulcers; easy bruising/bleeding; jaundice; high fevers. Hold MTX and seek urgent evaluation.
High-value drug interactions
- Trimethoprim or TMP-SMX (Bactrim/Septra): Avoid with MTX — can cause life-threatening marrow suppression and nephrotoxicity, even at low MTX doses. If absolutely necessary, this requires close specialist oversight.
- Penicillins (e.g., amoxicillin): May raise MTX levels by reducing renal clearance — use caution and monitor if needed, especially with renal impairment or higher MTX doses.
- Proton-pump inhibitors (omeprazole, etc.): Possible reduction in MTX clearance; risk is clearer at high-dose MTX, but use caution (consider H2 blocker if appropriate).
- NSAIDs: Data are mixed; at low-dose MTX many patients still use NSAIDs, but risk of adverse events is higher in some studies — use cautiously, especially with kidney disease or dehydration.
- Nitrous oxide anesthesia: Avoid if possible—potentiates antifolate toxicity; if inadvertently used, clinicians may consider leucovorin rescue.
- Alcohol: In RA cohorts, ≤14 units/week did not raise hepatotoxic risk; above that, risk climbs. Discuss a personalized limit — many programs still advise minimizing alcohol.
Vaccines while on methotrexate
- Non-live vaccines (flu shot, COVID-19, pneumococcal, Shingrix, etc.) are safe with immunosuppression.
- To improve influenza vaccine response, ACR conditionally recommends holding MTX for 2 weeks after the flu shot if disease allows (some data suggest 1 week may be nearly as good). Continue MTX for other non-live vaccines. Avoid live vaccines while immunosuppressed.
Fertility, pregnancy, and breastfeeding (plan ahead)
- Teratogenic: MTX must be stopped before conception; use effective contraception and follow specialist guidance. The ACR 2020 reproductive health guideline provides detailed recommendations and emphasizes pre-pregnancy planning with compatible meds.
Practical setup checklist (patient and clinic)
- Pick a weekly MTX day; verify the label says once weekly.
- Start folic acid 5 mg weekly (different day), adjust to 10 mg if needed.
- Schedule labs: baseline, q2 weeks (6+ weeks), monthly (3–12 mo) and then every 2–3 mo once stable.
- Review and avoid TMP-SMX; flag penicillins/PPIs/NSAIDs/nitrous oxide.
- Vaccines: get up-to-date; plan the flu-shot MTX hold if feasible.
Bottom line
Methotrexate is a proven, practical steroid-sparing option in PMR when used once weekly with folic acid, structured lab monitoring, and attention to a small set of high-risk interactions. Done right, it can cut flares and lower your steroid burden while staying safe.
Medical disclaimer: Educational content only. Not medical advice. Always follow your clinician’s instructions and local protocols.
