Immunosuppressants/Drugs Used In Rheumatology

Question 1

Notes on leflunomide

Answer 1

• Common adverse effects → diarrhoea, nausea, vomiting, mouth ulcers, skin rash, alopecia, minor infections, mild increase in BP and liver enzymes
• Major adverse events → lung injury, severe infection and cytopaenias
• Risk of adverse events increased with concurrent medications (esp. methotrexate), alcohol consumption and low body weight
• Contraindicated in pregnancy
• Avoid live vaccines including up to six months after treatment

Question 2

Notes on methotrexate

Answer 2

• Structural analogue of folic acid - inhibs binding of dihydrofolic acid to dihydrofolate reductase
• Prodrug → active only when poluglutamated within cells - slow takes 27 weeks - explains time to acheivement of plateau effect of clinical response
• Cleared by kidneys. NSAIDs may decrease excretion (but doses given in RA very low so likely no impact)
• 50% protein bound. Minimal drug interactions
  
  • Caution with folate depleting agents (co-trim BD dosing for infection should be avoided, and probenecid)
• Contraindications
  
  • Pregnant women, those contemplating pregnancy or not on adequate contraception
  • Liver disease or excessive alcohol intake
  • Severe renal impairment (eGFR <30)
• Single weekly dose (can be given PO, SC, IM)
• Toxicities → bone marrow, liver, lung. GI side effects and stomatitis.
• Daily supplementation with folic acid
• Antidote folinic acid/leucovorin

Question 3

Notes on hydroxychloroquine

Answer 3

New warnings for cardiac effects (in relation to use during COVID 19 pandemic)

• QT prolongation
• Cardiomyopathy