Methotrexate Drug Profile

What is Methotrexate?

Methotrexate is an antimetabolite medication that belongs to the class of drugs called folate antagonists. Originally developed as a chemotherapy agent for cancer treatment, it is now widely used at lower doses to treat autoimmune and inflammatory conditions such as rheumatoid arthritis and psoriasis. The medication works by interfering with cellular processes that drive both cancer cell growth and inflammatory responses.

Uses

Methotrexate has several approved medical uses:

• Rheumatoid arthritis: Used as a disease-modifying antirheumatic drug (DMARD) to reduce joint inflammation and slow disease progression
• Psoriasis: Treats severe forms of this skin condition by reducing the rapid growth of skin cells and inflammation
• Cancer treatment: Used in higher doses to treat various cancers including leukemia, lymphoma, breast cancer, and lung cancer
• Juvenile idiopathic arthritis: Helps manage this inflammatory joint condition in children
• Ectopic pregnancy: Used to dissolve abnormal pregnancies that develop outside the uterus

How it works

Methotrexate blocks the action of an enzyme called dihydrofolate reductase, which cells need to produce DNA and RNA. By interfering with this process, the drug prevents rapidly dividing cells from growing and reproducing effectively. In cancer treatment, this targets malignant cells, while in autoimmune conditions, it reduces the activity of overactive immune cells causing inflammation.

Side effects

Common side effects include:

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• Nausea and vomiting
• Mouth sores or ulcers
• Fatigue and weakness
• Loss of appetite
• Stomach upset or abdominal pain
• Headache
• Hair thinning
• Increased sensitivity to sunlight

Serious side effects to watch for:

• Signs of infection (fever, chills, persistent sore throat)
• Unusual bleeding or bruising
• Persistent cough or difficulty breathing
• Yellowing of skin or eyes (jaundice)
• Severe stomach pain or black, tarry stools

Warnings and precautions

• Pregnancy: Methotrexate can cause severe birth defects and is contraindicated during pregnancy. Both men and women should use effective contraception during treatment and for at least three months after stopping the medication.
• Liver function: The drug can cause liver damage, requiring regular blood tests to monitor liver enzymes. Patients with existing liver disease may need dose adjustments or alternative treatments.
• Kidney function: Reduced kidney function can lead to dangerous accumulation of the drug, necessitating dose modifications and careful monitoring in patients with kidney disease.
• Infections: Methotrexate suppresses the immune system, increasing susceptibility to serious infections. Live vaccines should be avoided during treatment.
• Blood cell counts: Regular monitoring is essential as the medication can cause dangerous drops in white blood cells, red blood cells, and platelets.

Interactions

Several important drug and supplement interactions can occur with methotrexate:

• Nonsteroidal anti-inflammatory drugs (NSAIDs): Can increase methotrexate levels and toxicity risk
• Trimethoprim-sulfamethoxazole: May increase bone marrow suppression when combined with methotrexate
• Proton pump inhibitors: Can delay methotrexate elimination, potentially increasing toxicity
• Penicillins: May reduce methotrexate clearance from the body
• Folic acid supplements: May reduce methotrexate effectiveness but are often prescribed to minimize side effects
• Alcohol: Increases risk of liver damage and should be limited or avoided
• Live vaccines: Should not be given due to increased infection risk
• Vitamin supplements with folate: May interfere with methotrexate’s mechanism of action

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Dosage

Methotrexate dosing varies significantly based on the condition being treated. For rheumatoid arthritis, typical starting doses range from 7.5 to 15 mg once weekly, which may be adjusted based on response and tolerance. Psoriasis treatment often begins with 10 to 25 mg weekly. Cancer treatment involves much higher doses and different scheduling protocols determined by oncology specialists. Folic acid supplementation is commonly prescribed alongside methotrexate to reduce side effects. All dosing decisions should be made by a qualified healthcare provider who will consider individual patient factors, kidney and liver function, and the specific condition being treated.

Sources: FDA DailyMed drug labels (public domain), BNF, WHO Essential Medicines List. This article is for informational purposes only and does not constitute medical advice. Always consult your healthcare provider before starting or stopping any medication.

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