Methotrexate — Uses, Dosage, Side Effects & Safety

Drug class: Antimetabolite; Disease-Modifying Antirheumatic Drug (DMARD); Antineoplastic agent

At a glance: Methotrexate, an antimetabolite and Disease-Modifying Antirheumatic Drug (DMARD), is utilized in various conditions including autoimmune diseases and certain cancers. Its mechanism involves inhibiting dihydrofolate reductase, thereby interfering with DNA synthesis and cell proliferation. Common side effects can include gastrointestinal disturbances and myelosuppression. Regular monitoring of complete blood counts and liver function tests is crucial during treatment.

Overview

Methotrexate is a medication used to treat several conditions, including certain cancers (such as leukemia, lymphoma, and breast cancer), autoimmune diseases like rheumatoid arthritis, and severe psoriasis. It works by interfering with the growth of rapidly dividing cells, including cancer cells and immune cells that cause inflammation. For autoimmune diseases, methotrexate helps reduce inflammation and slow disease progression. It is usually taken once a week, not daily, to minimize side effects. Patients should be aware that regular blood tests are needed to monitor for potential side effects, and folic acid supplementation is often recommended to reduce toxicity.

Clinical information

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Therapeutic uses

• Rheumatoid arthritis
• Psoriasis
• Psoriatic arthritis
• Certain cancers (e.g., acute lymphoblastic leukemia, breast cancer, osteosarcoma)
• Ectopic pregnancy

Common side effects

• Nausea
• Vomiting
• Diarrhea
• Mouth sores
• Hair loss
• Liver damage
• Bone marrow suppression
• Lung problems

Drug interactions

• NSAIDs can reduce methotrexate clearance and increase toxicity, particularly at higher (oncologic) doses
• Trimethoprim-sulfamethoxazole increases risk of severe bone marrow suppression
• Alcohol increases risk of hepatotoxicity
• Proton pump inhibitors may reduce methotrexate elimination

Contraindications

• Breastfeeding
• Active serious infection
• Pre-existing severe blood disorders such as bone marrow hypoplasia
• Significant hepatic or renal impairment (dose-dependent)
• Pregnancy

Missed dose

If you miss a dose, contact your healthcare provider for instructions. Do not double the next dose to make up for the missed one.

Overdose

Methotrexate overdose can be life-threatening. Symptoms include mouth sores, vomiting, bleeding, and severe bone marrow suppression. Seek emergency medical attention immediately. Leucovorin (folinic acid) may be used as an antidote.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Precautions & warnings

Carries boxed warnings for severe toxicity including bone marrow suppression, hepatotoxicity, and, at oncologic doses, severe skin reactions and renal failure. Regular monitoring of complete blood count, liver function, and renal function is required. Folic acid supplementation is commonly used to reduce side effects in rheumatologic dosing.

Pregnancy

Contraindicated in pregnancy due to well-established teratogenic and abortifacient effects; effective contraception is required during and for a defined period after treatment for both patients who could become pregnant and male partners.

When to seek emergency help

Seek urgent medical attention for fever, unusual bleeding or bruising, severe mouth sores, shortness of breath, or yellowing of the skin or eyes.

Key safety information

• Requires regular blood test monitoring
• Never take extra doses without checking the intended dosing schedule — rheumatologic dosing is typically once weekly, not daily

Clinical Pearls

• Methotrexate can cause serious or fatal toxicity, especially to the liver, lungs, and bone marrow.
• Not for use during pregnancy or breastfeeding.
• Requires regular blood monitoring for safety.
• May increase risk of infections.
• Can interact with many other medications.
• Avoid alcohol due to increased risk of liver toxicity.
• Avoid live vaccines while using methotrexate.
• Avoid NSAIDs and certain antibiotics unless approved by your doctor.

Frequently Asked Questions about Methotrexate

How long does methotrexate take to work for arthritis?

It may take 4–12 weeks to notice improvement in symptoms of rheumatoid arthritis. Continue taking as prescribed and attend all follow-up appointments.

Can I drink alcohol while taking methotrexate?

Alcohol should be avoided, as it increases the risk of liver damage when combined with methotrexate.

Why is methotrexate given once a week?

Weekly dosing helps reduce the risk of serious side effects and toxicity. Daily dosing can be dangerous and should only be done under strict medical supervision for certain cancers.

Do I need to take folic acid with methotrexate?

Yes, folic acid is often prescribed to reduce side effects such as mouth sores and liver toxicity.

What monitoring is required while on methotrexate?

Regular blood tests to check liver function, kidney function, and blood cell counts are essential.

Is methotrexate safe in pregnancy?

No, methotrexate is contraindicated in pregnancy due to risk of birth defects and fetal harm.

What should I do if I develop a cough or shortness of breath?

Contact your healthcare provider immediately, as these could be signs of lung toxicity.

Educational information only. Always consult a qualified healthcare professional before starting, stopping, or changing any medication.