Methotrexate

Methotrexate (Oncology Use)

🔴 Red Flag (Important) Information

• NEVER take methotrexate daily when prescribed weekly → fatal dosing errors have occurred.

• Severe myelosuppression risk → regular FBC monitoring is essential.

• Hepatotoxicity → avoid alcohol; monitor liver function closely.

• Pulmonary toxicity → stop immediately if new cough or dyspnoea develops.

• Teratogenic → contraindicated in pregnancy; strict contraception required.

• Renal impairment increases toxicity → dose adjustment and hydration required.

• Multiple serious drug interactions (NSAIDs, antibiotics, PPIs).

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🔹 1. Basic Information

Generic name: Methotrexate
Drug class: Antimetabolite (antifolate)
Formulation: Oral tablets (oncology doses may also be IV/IM in other formulations)
Tablet strength: 2.5 mg

Mechanism of Action:
Inhibits dihydrofolate reductase (DHFR) → blocks DNA synthesis and cell replication, particularly in rapidly dividing cells such as cancer cells.

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🔹 2. Oncology Indications (FULL – per PI)

Methotrexate is indicated for the treatment of the following malignancies in adults and children:

• Breast cancer

• Non-Hodgkin’s lymphoma

• Leukaemia

Methotrexate is commonly used:

• As part of combination chemotherapy regimens

• In high-dose or low-dose schedules, depending on cancer type, protocol, and patient factors

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🔹 3. Dosing & Administration (Oncology)

• Dose: Individualised based on:

  • Cancer type

  • Body surface area

  • Age

  • Renal function

• Route: Oral or parenteral (protocol-dependent)

• Schedule:

  • Given daily for several days, followed by a rest period, or

  • As part of cyclical combination chemotherapy

⚠️ Exact dosing and schedule must be explained to the patient clearly
⚠️ Regular blood tests are mandatory

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🔹 4. Contraindications

• Hypersensitivity to methotrexate

• Pregnancy or breastfeeding

• Severe hepatic disease

• Severe renal impairment (unless dose adjusted and closely monitored)

• Pre-existing severe blood dyscrasias

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🔹 5. Monitoring Requirements

Baseline and ongoing:

• FBC: Monitor for anaemia, neutropenia, thrombocytopenia

• Liver function tests: ALT, AST, bilirubin

• Renal function: Creatinine, eGFR

• Clinical monitoring:

  • Signs of infection

  • Mucositis

  • Pulmonary symptoms

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🔹 6. Common & Serious Side Effects

Common:

• Nausea, vomiting

• Mouth ulcers (mucositis)

• Fatigue

• Hair loss

• Diarrhoea

• Rash

Serious / Life-threatening:

• Severe myelosuppression

• Hepatotoxicity

• Pulmonary toxicity (pneumonitis)

• Severe infections

• Gastrointestinal ulceration

• Secondary malignancies (rare, delayed)

• Tumour lysis syndrome (in high-dose settings)

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🔹 7. Drug Interactions (Clinically Important)

Avoid or use with extreme caution:

• NSAIDs (e.g. ibuprofen, aspirin)

• Certain antibiotics (e.g. trimethoprim, penicillins)

• Proton pump inhibitors

• Phenytoin

• Probenecid

• Alcohol (↑ hepatotoxicity)

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🔹 8. Use in Special Populations

• Pregnancy: Contraindicated (highly teratogenic)

• Breastfeeding: Contraindicated

• Renal impairment: Dose reduction required

• Hepatic impairment: Avoid or use with caution

• Paediatrics: Used in oncology under specialist supervision

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🔹 9. Duration of Use / When to Stop

Continue according to oncology protocol until:

• Completion of planned cycles, or

• Disease progression, or

• Unacceptable toxicity

Discontinue immediately if:

• Severe bone marrow suppression

• Pulmonary toxicity

• Severe hepatotoxicity

• Life-threatening infection

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🔹 10. Key Clinical Reminder

Methotrexate dosing errors are a known cause of preventable death.
Always confirm dose, frequency, and indication, especially when switching between oncology and non-oncology use.

 

 

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2022/09/Final-approved-PIL.pdf