Makindo Medical Notes

⚠️ 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.

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• 💉 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.