A fixed-dose combination of a folate antagonist antimetabolite (Methotrexate) and a B-vitamin (Folic Acid). Methotrexate inhibits dihydrofolate reductase, disrupting DNA synthesis and cellular replication, which provides anti-inflammatory and immunosuppressive effects. Folic acid is co-administered to reduce the incidence and severity of methotrexate-related side effects, particularly mucositis and hematological toxicity, without significantly compromising its therapeutic efficacy in autoimmune conditions.
Adult: For RA/Psoriasis: Initial dose typically 7.5 mg once weekly. May be increased gradually to a maximum of 20-25 mg/week based on response and tolerability. The folic acid 1mg tablet is taken once daily, except on the day of methotrexate dose (commonly taken the next day).
Note: TAKE METHOTREXATE ONCE A WEEK ONLY, on the same designated day each week. Folic acid is taken daily or weekly on non-methotrexate days as prescribed. Can be taken with or without food, but food may reduce GI upset. Maintain adequate hydration.
Methotrexate competitively and irreversibly inhibits dihydrofolate reductase (DHFR), the enzyme that converts dihydrofolate to tetrahydrofolate (THF). THF is essential for the synthesis of thymidylate, purines, and amino acids (serine, methionine), thereby inhibiting DNA, RNA, and protein synthesis. In autoimmune diseases, low-dose methotrexate promotes adenosine release, which has potent anti-inflammatory effects, and induces apoptosis of activated T-lymphocytes. Folic acid (as folinic acid or folic acid) provides a reduced folate source that bypasses the blocked DHFR step, 'rescuing' normal cells from the metabolic effects of methotrexate, thus reducing toxicity.
Pregnancy: CATEGORY X. Methotrexate is a potent teratogen and abortifacient. Causes fetal death, craniofacial abnormalities, limb defects, and CNS abnormalities. Contraindicated. Women of childbearing potential must use two reliable forms of contraception. Discontinue at least 3 months (one ovulatory cycle) before conception. Men should also avoid fathering a child during and for at least 3 months after therapy.
Driving: May cause dizziness, fatigue, or blurred vision. Patients should not drive or operate machinery if they experience these effects.
| NSAIDs (e.g., Diclofenac, Naproxen) | Competition for renal tubular secretion; increased methotrexate levels and toxicity risk. | Major |
| Trimethoprim/Sulfamethoxazole (Co-trimoxazole) | Additive antifolate effect; severe risk of myelosuppression. | Major |
| Probenecid | Decreases renal clearance of methotrexate, increasing toxicity. | Major |
| Phenytoin | Methotrexate may decrease phenytoin protein binding and clearance; increased phenytoin toxicity. | Moderate |
| Oral Hypoglycemics (e.g., Sulfonylureas) | Methotrexate may potentiate hypoglycemic effect. | Moderate |
| Live Vaccines (e.g., MMR, Varicella, Yellow Fever) | Risk of disseminated vaccine-induced infection due to immunosuppression. | Major |
| Other DMARDs (e.g., Leflunomide) | Increased risk of hepatotoxicity and pancytopenia. | Major |
Same composition (Methotrexate (7.5mg) + Folic Acid (1mg)), different brands: