Methotrexate (and Other DMARDs)

Side Effects

Short-Term

• GI Symptoms: Nausea, vomiting, diarrhoea, headaches

• Mucocutaneous: Stomatitis, mucositis (mouth ulcers)

Long-Term

• Bone Marrow Suppression: Neutropenia, agranulocytosis (risk of infection)

• Hepatotoxicity, nephrotoxicity (rare but possible), and nephrogenic diabetes insipidus

• Increased Malignancy Risk (e.g. skin cancer) with prolonged immunosuppression

Monitoring

Routine Tests

• FBC: Check WCC, neutrophils, platelets

• UEC (renal function)

• LFTs (baseline and regular)

• Urinalysis: Periodically assess renal/hepatic compromise signs

Chest X-Ray

• Baseline to exclude pre-existing lung disease (MTX can cause pneumonitis)

CMP (Calcium, etc.)

• Monitor for calcium changes; hyperparathyroidism is rare but can occur in chronic inflammatory states

Pre-Initiation Steps

• Infectious Screening: Hepatitis A/B/C, HIV

• Ensure vaccinations are up to date (avoid live vaccines within 4 weeks)

• Advise abstinence from alcohol or strict minimisation to reduce hepatotoxic risk

• Patient Education:

  • Regular Monitoring: Importance of FBC, LFTs

  • Contraception: Methotrexate is teratogenic (both men and women advised to use effective contraception)

  • Review Potential Interactions: e.g. NSAIDs can exacerbate toxicity

GP Review Points

• Check adherence to weekly dosing (common to take once weekly)

• Screen alcohol use (reinforce minimal intake)

• Assess disease activity improvement in conditions like rheumatoid arthritis

• Monitor side effects:

  • Infection risk (dry cough, fever, neutropenia)

  • Bleeding or bruising (bone marrow suppression)

• Vaccination Status: Particularly influenza, pneumococcal

• Patient education on signs of toxicity (mucositis, unusual fatigue, lab changes)

Antidote for Methotrexate Poisoning

• Calcium Folinate (Leucovorin): Replenishes folate and counters MTX’s antimetabolite effect

Normal Renal Function

• 15 mg orally every 6 hrs for 24 hrs

Impaired Renal Function (eGFR <45 mL/min)

• Initial: 15 mg orally, then 15 mg IV every 6 hrs for 3 days

• Continue oral dosing 6-hourly for 1 week or until resolution

Additional Measures

• IV fluids to ensure good hydration and renal perfusion

• Activated charcoal is generally ineffective for MTX because absorption is often complete by the time toxicity is recognised

Key Investigations for Methotrexate Toxicity

1. Renal Function: Serum creatinine, urea, electrolytes

2. FBC: Detect bone marrow suppression (WCC, neutrophils, platelets)

3. Liver Biochemistry: Hepatotoxicity

4. Serum Methotrexate Levels: Not routinely helpful in acute management, but sometimes used in high-dose MTX protocols in oncology

Note

• Monitor calcium levels (CMP) to detect hyperparathyroidism or metabolic disturbances.

• Early detection of toxicity and close patient education are critical for preventing severe complications.

• For other DMARDs (e.g. leflunomide, sulfasalazine), similar monitoring (LFTs, FBC) and vigilance for side effects is essential.

• Regular follow-up with a multidisciplinary team (GP, rheumatologist, allied health) is vital for safe, effective long-term management.