Methotrexate is a folate antagonist antimetabolite and immunosuppressive agent. In the 20mg strength, it is primarily used for the treatment of severe, active rheumatoid arthritis (RA) and psoriasis that is not adequately responsive to other forms of therapy. It is also a cornerstone chemotherapeutic agent for various malignancies. It works by competitively inhibiting dihydrofolate reductase (DHFR), disrupting DNA, RNA, and protein synthesis, leading to anti-inflammatory, immunosuppressive, and cytotoxic effects.
Adult: Rheumatoid Arthritis/Psoriasis: Initial: 7.5 mg once weekly, as a single oral dose. May be increased gradually to a maximum of 20-25 mg/week based on response and tolerability. Dose is often split (e.g., 2.5 mg every 12 hours for 3 doses) to improve GI tolerance. Oncology: Varies widely by protocol (e.g., 40 mg/m² weekly for ALL maintenance).
Note: ORAL: Take ONCE A WEEK on the same designated day. Can be taken with or after food to reduce GI upset. Do not take folic acid on the same day; take it at least 24 hours after Methotrexate dose. Maintain adequate hydration. Avoid alcohol completely.
Methotrexate competitively and irreversibly inhibits the enzyme dihydrofolate reductase (DHFR). DHFR is responsible for converting dihydrofolate to tetrahydrofolate, a crucial cofactor in the synthesis of thymidylate, purine nucleotides, and amino acids (serine, methionine). This inhibition depletes intracellular tetrahydrofolate pools, leading to impaired synthesis of DNA, RNA, and proteins. In autoimmune conditions, it also promotes adenosine release, which has potent anti-inflammatory effects, and induces apoptosis of activated T-lymphocytes.
Pregnancy: CATEGORY X. Absolutely contraindicated. Causes fetal death, craniofacial abnormalities, limb defects, CNS anomalies (aminopterin syndrome). Pregnancy must be excluded before initiation. Effective contraception (two reliable methods) is mandatory for both males and females during and for at least 3 months (some protocols recommend 6 months) after therapy.
Driving: May cause dizziness or fatigue. Patients should be cautioned about operating machinery or driving if affected.
| NSAIDs (e.g., Ibuprofen, Naproxen) | Competes for renal tubular secretion, increasing Methotrexate levels and risk of myelosuppression. | Major |
| Probenecid | Decreases renal clearance of Methotrexate, increasing toxicity. | Major |
| Trimethoprim-Sulfamethoxazole (Co-trimoxazole) | Additive antifolate effect, dramatically increasing risk of myelosuppression and megaloblastic anemia. | Major |
| Phenytoin | Methotrexate may decrease Phenytoin levels; Phenytoin may increase Methotrexate toxicity. | Moderate |
| Retinoids (e.g., Acitretin) | Increased risk of hepatotoxicity. | Moderate |
| Theophylline | Methotrexate may increase Theophylline levels. | Moderate |
| Live Vaccines (MMR, Varicella, OPV) | Risk of disseminated vaccine-induced infection due to immunosuppression. | Major |
Same composition (Methotrexate (20mg)), different brands: