Methotrexate is a folate antagonist antimetabolite and immunosuppressive agent. In the 5mg strength, it is primarily used for the long-term management of autoimmune diseases like rheumatoid arthritis and psoriasis. It works by competitively inhibiting dihydrofolate reductase (DHFR), disrupting DNA synthesis and cellular replication, particularly in rapidly dividing cells. In India, it is a cornerstone of disease-modifying antirheumatic drug (DMARD) therapy due to its efficacy and cost-effectiveness.
Adult: Rheumatoid Arthritis/Psoriasis: Initial dose: 7.5 mg once weekly, orally. May be increased gradually by 2.5 mg increments at 4-6 week intervals to a usual effective dose of 10-15 mg/week. Max recommended weekly dose for these conditions is 25 mg. Dose is often split (e.g., 5mg every 12 hours for 3 doses) to improve tolerance.
Note: Take ONCE A WEEK, on the same day each week. For GI tolerance, can be taken with food. Folic acid (5mg) should be taken once daily except on the methotrexate day, OR as a single 5mg dose 24 hours after the methotrexate dose. Avoid alcohol completely. Maintain adequate hydration.
Methotrexate competitively and irreversibly inhibits the enzyme dihydrofolate reductase (DHFR). DHFR is responsible for converting dihydrofolate to tetrahydrofolate (THF), a crucial cofactor in the synthesis of thymidylate, purine nucleotides, and certain amino acids. This inhibition depletes intracellular THF pools, leading to impaired synthesis of DNA, RNA, and proteins, thereby suppressing proliferation of rapidly dividing cells such as activated lymphocytes in autoimmune disorders and hyperproliferative synovial cells.
Pregnancy: CATEGORY X. Contraindicated. High risk of fetal death, congenital abnormalities (craniofacial, limb, CNS defects - 'aminopterin syndrome'), and miscarriage. Pregnancy must be excluded before starting. Effective contraception (two methods) is mandatory for both males and females during and for at least 3 months (some recommend 6 months) after therapy.
Driving: May cause dizziness, fatigue, or blurred vision. Patients should be cautioned about operating machinery or driving until they know how the drug affects them.
| NSAIDs (e.g., Ibuprofen, Naproxen, Diclofenac) | Competitively inhibit renal tubular secretion of methotrexate, potentially increasing serum levels and risk of toxicity (myelosuppression). | Major |
| Trimethoprim-Sulfamethoxazole (Co-trimoxazole) | Synergistic antifolate effect; dramatically increases risk of severe bone marrow suppression. | Major |
| Probenecid | Reduces renal clearance of methotrexate, increasing toxicity risk. | Major |
| Phenytoin | Methotrexate may decrease phenytoin protein binding and clearance, increasing phenytoin toxicity risk. | Moderate |
| Oral Hypoglycemics (e.g., Sulfonylureas) | Methotrexate may potentiate hypoglycemic effect. | Moderate |
| Theophylline | Methotrexate may decrease theophylline clearance. | Moderate |
| Retinoids (e.g., Acitretin) | Increased risk of hepatotoxicity. | Moderate |
| Live Vaccines (MMR, Varicella, Yellow Fever) | Risk of disseminated vaccine-induced infection due to immunosuppression. | Major |
Same composition (Methotrexate (5mg)), different brands: