Generic
Methotrexate
22 brands available in the market
At a glance
Methotrexate is an immunosuppressant and chemotherapy drug used for rheumatoid arthritis, psoriasis, and various cancers. It inhibits DNA synthesis to prevent cell division.
Description
Methotrexate is a folic acid antagonist that irreversibly binds to dihydrofolate reductase, inhibiting the formation of reduced folates, and thymidylate synthetase, resulting in inhibition of purine and thymidylic acid synthesis. It affects actively proliferating tissues such as malignant cells, bone marrow, fetal cells, mucosa, and bladder cells. In psoriasis, the rate of epithelial cell production in the skin is greatly increased; this difference in proliferation rates is the basis for using methotrexate to control the psoriatic process.
Indications
- Neoplastic diseases: Gestational choriocarcinoma, chorioadenoma destruens, hydatidiform mole, acute lymphoblastic leukemia, non-Hodgkin's lymphoma, breast cancer, head and neck cancer, mycosis fungoides, lung cancer
- Rheumatoid arthritis (adult and juvenile)
- Severe psoriasis (not adequately responsive to other therapies)
Therapeutic class
Antidote Preparations, Immunosuppressant
Pharmacological class
Antimetabolite (Folic Acid Antagonist)
Pharmacology
Methotrexate inhibits dihydrofolate reductase to prevent tetrahydrofolate formation, which is required for purine nucleotide and thymidylate synthesis, thereby inhibiting DNA synthesis, repair, and cellular replication.
Mechanism of action
Inhibits DNA synthesis and cell division to prevent growth of cancer cells and hyperactive cells.
Dosage
Rheumatoid Arthritis (Adult): 7.5 mg/week (max 20 mg/week)
Psoriasis: 10-25 mg/week (max 30 mg/week)
ALL (Induction): 3.3 mg/m² + prednisone; Maintenance: 30 mg/m² twice weekly OR 2.5 mg/kg IV every 14 days
Choriocarcinoma: 15-30 mg/day for 5 days (3-5 courses)
Osteosarcoma (IV): 12-15 g/m² infusion + folinic acid
Administration
- Swallow tablet whole; do not chew, crush or break
- Take on an empty stomach (may be taken with meals to reduce GI discomfort)
- Avoid taking with milk-rich products
- Take once weekly on the same day each week
Missed dose
If you miss a dose, take it as soon as you remember; skip if it's almost time for next dose; do not double the dose.
Side effects
Common Side Effects:
- Abdominal pain
- Indigestion
- Loss of appetite
- Nausea, vomiting
- Fatigue
- Mouth sores (ulcerative stomatitis)
- Leukopenia
Precautions & warnings
- Regular blood tests (blood counts, liver and kidney function) required
- Avoid alcohol (risk of liver damage)
- Contraindicated during pregnancy and lactation
- Take folic acid supplements (to reduce side effects)
- Inform doctor if signs of infection occur
- Avoid pregnancy during and for 6 months after treatment
Contraindications
- Severe renal or hepatic impairment
- Pre-existing bone marrow suppression
- Alcoholic liver disease
- AIDS
- Pre-existing blood dyscrasias
- Pregnancy (in psoriasis or RA patients)
- Breastfeeding
Drug interactions
- NSAIDs and salicylates: Increased toxicity
- Probenecid: Increased toxicity
- Sulfonamides, trimethoprim: Bone marrow suppression
- Cisplatin: Nephrotoxicity
- Folic acid: Decreased effectiveness
- Mercaptopurine: Increased plasma levels
Food interactions
Caution with alcohol; consult your doctor (increased risk of liver damage).
Use in pregnancy
Use in Pregnancy: Methotrexate is highly unsafe during pregnancy (Category X); definite evidence of severe fetal harm. Completely contraindicated.
Pregnancy Category: X — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Methotrexate is unsafe during breastfeeding; may cause toxicity to the baby. Do not use.
Pediatric use
Pediatric doses are established (ALL, JRA, etc.); weigh benefits against potential risks in children and young adults.
Geriatric use
Elderly patients require close monitoring for hepatic, bone marrow, and renal toxicity.
Renal / hepatic impairment
Renal Impairment: Caution in kidney disease; dose adjustment based on CrCl; avoid if CrCl <10 mL/min.
Hepatic Impairment: Caution in liver disease; bilirubin 3.1-5.0 mg/dL or AST >3x ULN: give 75% of dose; bilirubin >5.0 mg/dL: avoid use.
Overdose effects
Leucovorin is indicated to diminish toxicity in overdose; symptomatic treatment.
Storage conditions
Store below 30°C in a dry place, protected from light and moisture; keep out of reach of children.
Chemical structure
Methotrexate