Methotrexate 💊
⚠️ If overdose ➝ potentially lethal myelosuppression.
💊 Dose for rheumatic disease is 10–25 mg once per week.
❌ If given daily by accident, the patient may die.
👀 Advise to seek medical help urgently if any fever, sore throat, bruising, or mouth ulcers.
💉 Methotrexate toxicity ➝ consider Folinic acid 15 mg IV OD.
- 💉 Cytotoxic agent and DMARD.
- ☠️ Potentially lethal if taken or prescribed daily or dosed wrongly.
Actions
- 🔬 Structural analogue of folate.
- ⛔ Inhibits dihydrofolic acid reductase ➝ blocks DNA synthesis.
- 🧩 DMARD effect mechanism unclear.
- 🛡️ Folinic acid reverses effects of methotrexate.
Indications
- 🤲 Rheumatoid arthritis (DMARD, onset 4–6 wks).
- 🎗️ Cancer chemotherapy (ALL, NHL, choriocarcinoma, Burkitt’s lymphoma, cutaneous T-cell lymphoma).
- 🧴 Severe psoriasis.
- 🤰 Ectopic pregnancy (specialist use).
Dose
- 💊 Rheumatoid disease: Start 7.5 mg once weekly, ↑ by 2.5 mg every 6 wks to 15–25 mg once weekly.
➕ Give folic acid 5 mg the day after MTX. Reduce dose in elderly/renal impairment.
- 🎗️ Oncology: Daily high-dose regimens, specialist use only.
- 🤰 Ectopic pregnancy: Single IM dose 50 mg/m² or 1 mg/kg (≈ 75–100 mg). Follow local protocols.
Dose Range (non-oncology weekly regimens)
| Name | Dose | Frequency | Route |
|---|
| Methotrexate (Rheumatoid disease) | 7.5–25 mg | Weekly | PO |
| Methotrexate (Severe Crohn’s disease) | 10–25 mg | Weekly | PO |
| Methotrexate (Severe Psoriasis) | 2.5–25 mg | Weekly | PO |
Interactions
- ❌ Acitretin ➝ ↑ MTX toxicity.
- ❌ NSAIDs/Aspirin/Probenecid ➝ ↑ MTX toxicity.
- ❌ Ciclosporin ➝ ↑ MTX toxicity.
Cautions
- 💧 Effusions (ascites, pleural) ➝ drain before MTX or risk toxicity.
- 🍷 Avoid hepatotoxic drugs, alcohol, porphyria.
- 👩🍼 Women must use contraception during and 3 months after MTX.
Contraindications
- 🚫 eGFR <30 mL/min.
- 🚫 Active infection (shingles, HSV, bacterial, varicella).
- 🚫 Pregnancy, breastfeeding, large effusion, liver/renal dysfunction.
- 🚫 Immunodeficiency, bone marrow failure (anaemia, leukopenia, thrombocytopenia).
- 🚫 Alcoholism, chronic liver disease.
Side Effects
- 🤢 GI upset: nausea, vomiting, anorexia.
- 🩸 Haematological: bone marrow suppression, cytopenias.
- 😷 Hypersensitivity pneumonitis (2–5%, reversible).
- 🦠 Opportunistic infections (e.g. Pneumocystis jirovecii).
- 🧑⚕️ Hepatic: transaminase rise, fibrosis, cirrhosis with long-term use.
- 👄 Oral ulcers (reduced with folate 5 mg).
- 💇 Hair loss, stomatitis, diarrhoea, tumour lysis syndrome.
Toxicity
- Folic acid (given on non-MTX days) reduces toxicity.
- 🚨 Severe MTX toxicity ➝ Folinic acid 15 mg IV OD.
