Methotrexate: Brands, Price & Uses in Bangladesh

Established / FDA-approved uses

• Oncology (high-dose or intensive regimens): acute lymphoblastic leukemia (including meningeal leukemia, given intrathecally), non-Hodgkin lymphoma, osteosarcoma (high-dose with leucovorin rescue), breast cancer (combination chemotherapy), advanced head and neck squamous cell carcinoma, lung cancer, and gestational trophoblastic neoplasia (choriocarcinoma, invasive mole).
• Rheumatology/Dermatology (low-dose weekly regimen): severe, active rheumatoid arthritis in adults; polyarticular-course juvenile idiopathic arthritis; severe, recalcitrant, disabling psoriasis not adequately responsive to other therapies.

Guideline-supported / commonly used (including off-label) uses

• Psoriatic arthritis and other inflammatory arthritides, as a disease-modifying agent, often in combination with other therapies.
• Maintenance of remission in Crohn's disease, as an adjunct/alternative when other agents are unsuitable.
• Medical management of early, unruptured ectopic pregnancy (single or multi-dose protocol), supported by obstetric practice guidelines, in appropriately selected patients.
• Adjunct treatment for selected autoimmune/inflammatory conditions (e.g. dermatomyositis, certain vasculitides, sarcoidosis) under specialist supervision.

Important: the dose, frequency and monitoring required differ enormously between the low-dose weekly autoimmune/dermatologic regimen and the much higher intermittent oncology regimens. See Dosage and Administration.

CRITICAL SAFETY WARNING — Weekly, NOT daily dosing for autoimmune/dermatologic conditions

For rheumatoid arthritis, psoriasis, juvenile idiopathic arthritis and other non-cancer (autoimmune) indications, Methotrexate is taken as a single dose (or divided over 24 hours) ONCE PER WEEK — on the SAME day every week — never every day. Fatal and serious toxic overdoses have occurred because patients mistakenly took their weekly autoimmune-disease dose of Methotrexate every day instead of once weekly. Patients and caregivers must have the weekly schedule, and the specific day of the week, clearly explained and written down at every prescription and refill. Any pharmacist or physician dispensing or prescribing Methotrexate for a non-cancer indication should confirm the patient understands "once weekly" dosing before dispensing.

Cancer chemotherapy regimens, in contrast, use much higher doses given intermittently on cycles determined by the treating oncologist, and must be administered strictly according to the specific protocol.

Adult dosing by indication

Renal and hepatic impairment

Methotrexate is largely renally eliminated; dose reduction or avoidance is required in renal impairment (contraindicated in severe renal impairment). Use is contraindicated in significant hepatic impairment; liver function should be assessed before and periodically during therapy.

Folic acid supplementation

For the low-dose weekly regimens (rheumatoid arthritis, psoriasis, JIA), the physician commonly co-prescribes folic acid (typically a small daily or weekly dose, on non-Methotrexate days) to reduce mouth ulcers, GI upset, liver enzyme elevation and low blood counts. This is standard practice and patients should not start, stop or change their folic acid dose without medical advice.

Administration

Tablets are taken by mouth, generally with or without food, exactly on the prescribed day(s). Injectable forms are given by a healthcare professional (intramuscular, subcutaneous, intravenous or, for CNS-directed treatment, intrathecal) under appropriate supervision.

Side effects depend heavily on dose. At low weekly doses (autoimmune/dermatologic use) the following are common: nausea, mouth sores/stomatitis, loss of appetite, fatigue, headache, and mild elevation of liver enzymes; these are part of why folic acid is co-prescribed.

Serious adverse effects, which are dose-related but can occur at any dose, include:

• Bone marrow suppression (low white cells, low platelets, anemia) increasing risk of infection and bleeding.
• Liver toxicity, including, with long-term low-dose use, risk of fibrosis or cirrhosis.
• Kidney toxicity, particularly with high doses.
• Serious or opportunistic infections due to immunosuppression.
• Severe gastrointestinal toxicity (mucositis, ulceration, bleeding), especially with concurrent NSAID use.
• Potentially fatal skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Lung toxicity (interstitial pneumonitis/pulmonary fibrosis) — cough, shortness of breath or fever should be reported immediately.
• Rarely, tumor lysis syndrome in high-dose oncology use.

Patients should seek prompt medical attention for fever, unusual bruising/bleeding, mouth ulcers, yellowing of the skin/eyes, persistent cough or breathlessness, or severe skin rash.