Take orally, usually once weekly for autoimmune conditions. It is crucial to adhere to the prescribed weekly schedule to avoid serious side effects. May be taken with or without food. Folic acid supplementation is often co-prescribed, but not on the same day as methotrexate.

Methotrexate inhibits dihydrofolate reductase (DHFR), an enzyme that catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF). THF is essential for purine and pyrimidine synthesis, which are crucial for DNA and RNA synthesis. By inhibiting DHFR, methotrexate depletes THF, thereby inhibiting nucleic acid synthesis and cell division. This mechanism contributes to its cytotoxic, immunosuppressive, and anti-inflammatory effects.

• •Pregnancy and Breastfeeding (Category X)
• •Severe renal or hepatic impairment
• •Pre-existing blood dyscrasias (e.g., bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)
• •Active infection, immunodeficiency syndromes
• •Alcoholism or alcoholic liver disease

Store below 30°C in a dry place, away from light and moisture. Keep out of reach of children.

Symptoms of overdose include severe bone marrow suppression, mucositis, stomatitis, and gastrointestinal toxicity. The primary antidote for methotrexate overdose is leucovorin (folinic acid) rescue, administered as soon as possible, ideally within the first hour. Hydration and urinary alkalinization may also be used to enhance methotrexate excretion.

Methotrexate is contraindicated in pregnancy (Category X) due to its teratogenic and embryotoxic effects. Effective contraception must be used by both male and female patients during therapy and for a specified period after discontinuation (at least 3 months for females and males after the last dose). It is also contraindicated during breastfeeding as it is excreted in breast milk and can cause serious adverse reactions in nursing infants.