M Toronto Myositis Centreat St. Michael's Hospital
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Methotrexate

Trexall, Rheumatrex · say “METH-o-TREX-ate”
DMARD
iUsed in myositis based on specialist experience and evidence, not a formal Canadian myositis approval.
i
Once a week, not daily.

Taking methotrexate every day is a dangerous overdose. Pick one day as your “Methotrexate Day” and take it on the same day each week.

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What it is

The most widely used medication in rheumatology.

Methotrexate is a disease-modifying antirheumatic drug (DMARD). At the low doses used in rheumatology, it calms an overactive immune system and reduces the inflammation that drives muscle and joint disease. It is one of the most studied and most effective medications in the field, used safely in millions of patients since the 1980s.

How to take it
  • Available as tablets (2.5 mg) or as an injection. Usual dose is 7.5 to 25 mg once weekly.
  • Tablets: take all of them together on the same day, with or without food.
  • Injection: self-injected under the skin as taught, and often causes fewer stomach effects.
  • Missed dose: take it within 1 to 2 days of your usual day; if longer, skip it and resume the next week.
  • Store in a cool, dry place, away from children and light.
What to expect
  • Full effect takes 6 to 8 weeks, though some people notice improvement sooner.
  • Mild tiredness or nausea for 24 to 48 hours after each dose is common. Folic acid and switching to injections often help.
  • Do not stop because it feels slow, since consistency is what makes it work.
  • Your folic acid is taken on the days you do NOT take methotrexate, or as directed.
Benefits

How it helps you.

Reduces pain and swelling

Effectively settles the inflammation behind painful, swollen, stiff joints and active muscle disease.

Slows structural damage

Controls inflammation to slow the joint damage that leads to deformity over time.

The gold-standard DMARD

The most studied and prescribed DMARD worldwide, with decades of evidence when monitored.

Works with other therapies

Combines well with biologics and other DMARDs, and boosts the effect of many biologics.

Reduces morning stiffness

Many people report easier, less stiff mornings.

Affordable and available

A generic medication, making it one of the most cost-effective treatments available.

Risks & side effects

What you should know.

Your doctor prescribed this because the expected benefits outweigh the risks for your situation. Here is the honest, full picture.

Common side effects
Nausea and fatigue
Most common. Feeling tired or queasy for 24 to 48 hours after each dose. Folic acid and injections often help.
Mouth sores
Small ulcers can occur. Folic acid reduces them; report severe or persistent sores.
Mild hair thinning
Usually mild and reversible with folic acid or a dose change.
Higher infection risk
Mildly suppresses the immune system. Stop for any fever or active infection.
Serious but uncommon
Lung reaction
Rarely causes lung inflammation. Report a new dry cough or breathlessness at rest, stop, and call your doctor.
Liver effects
Long-term use can affect the liver, especially with alcohol. Monitored by blood tests; avoid alcohol.
Low blood counts
Detected by routine blood work. Never take sulfa antibiotics (Septra, trimethoprim) with methotrexate.
Serious infection
Can rarely occur. Stop methotrexate for any fever or signs of infection.
!
Pregnancy warning.

Methotrexate causes serious birth defects and miscarriage. Both women and men must stop it before trying to conceive, at least 3 months ahead. Use reliable contraception while taking it, and contact your doctor immediately if pregnancy occurs.

Staying safe

Monitoring and precautions.

Regular monitoring
  • Blood tests every 4 to 8 weeks: your doctor checks CBC, liver enzymes, and kidney function to catch problems early.
  • Liver health is followed over time, with dose adjustments if needed.
  • Blood counts (white cells, red cells, platelets) are watched, since low counts may need a dose change.
  • Folic acid (1 to 5 mg) is prescribed to reduce nausea, mouth sores, and fatigue.
Daily precautions
  • Avoid alcohol. Both alcohol and methotrexate stress the liver, and together the risk of liver damage rises sharply.
  • Never take Septra (co-trimoxazole) or trimethoprim with methotrexate. Tell every doctor you take it.
  • Flu and COVID vaccines are safe. Avoid live vaccines (live MMR, varicella, yellow fever, nasal flu spray).
  • Use SPF 30+ sunscreen, since methotrexate can increase sun sensitivity.
  • Wash hands often and avoid close contact with people who are actively sick.
When to call your doctor

Contact the clinic if you notice:

Fever or signs of infection
Any fever, chills, persistent sore throat, or painful urination. Stop methotrexate and call before the next dose.
New cough or breathlessness
A new dry cough for weeks, or breathlessness at rest without a cold, may signal a rare lung reaction. Stop and call.
Severe mouth sores
Painful ulcers may mean the dose is too high or folic acid needs adjusting.
Severe nausea or vomiting
Mild nausea is common, but severe or persistent nausea or belly pain should be reported.
Unusual bleeding or bruising
Easy bruising, prolonged bleeding, or blood in urine or stool may signal low blood counts.
Taking sulfa antibiotics
Never take Septra or trimethoprim with methotrexate. This can be life-threatening.

Pregnancy & breastfeeding

Methotrexate must be stopped well before conception by both women and men, since it causes serious birth defects and miscarriage. Talk with your doctor about timing and contraception, and about switching to a pregnancy-safe medication if you are planning a family.

!

This guide is for education, not medical advice. Myositis treatment is individual, and many of these medications are used based on specialist experience and research rather than a single approval for myositis. Never start, stop, or change a medication without your own doctor. Your doses and choices are decided with your care team at the Centre.

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