Leflunomide

Use with caution in CKD 4/5 (eGFR <29)

• Initiation: 10-20mg once daily orally
• Maintenance: 20 mg once daily, reducing to 10mg if poorly tolerated, or used in combination with methotrexate
• If diarrhoeal side effect is predicted, Loperamide can be co-prescribed for 2 weeks, or loading dose can be omitted
• Pneumococcal vaccine and annual flu vaccine should be given and VZIG if exposed to chicken pox

• Pre-Treatment: Hepatitis and HIV serology, FBC, U+E, CRP, LFT inc albumin, BP (should be <140/90 – if not treat), weight (to allow assessment of weight loss)

then 

• FBC, U+E, CRP and LFT, BP and weight fortnightly until stable dose for 6 weeks then monthly for 3 months then 3 monthly (monthly if on other immunosuppressant or hepatotoxic drug)

Entering the results into a monitoring booklet will ensure that trends are not missed. Patients who do not attend for monitoring should be warned of the risk that serious adverse effects may go unnoticed. In the event of persistent failure to attend for monitoring please inform the Rheumatology department.

• WBC < 3.5 withhold and inform rheumatology         
• Neutrophils <1.6
• Platelets <140
• AST or ALT >100    
• MCV>105- check TSH, haematinics and contact us if normal
• Albumin <30g/l - if unexplained
• Creatinine >30% rise in 12 months
• Eosinophilia >0.5 – if unexplained
• Hair loss, headache, GI upset, rash/itch– reduce dose, treat symptoms, washout if severe
• Weight loss – if >10% and no cause found, reduce dose or consider washout
• Hypertension – treat, if remains high, stop and consider washout
• Breathlessness – stop and consider washout

• Treatment is continued indefinitely providing it remains effective and there are no significant side effects
• Leflunomide takes about 8 weeks to become effective but may take up to 6 months
• During this period there are likely to be continued symptoms or signs of disease activity
• It is reasonable to use IM Depo steroid (Kenalog 40 mg or Depo Medrone 80 mg) up to monthly, depending on the requirements of the individual patient
• The dose required is small (eg monthly Kenalog 40 mg = 1.6 mg Prednisolone daily)
• If IM Depo steroids are still required 6 months after starting treatment, an alternative should be discussed with the rheumatologist
• If a decision is made to stop Leflunomide and start another DMARD, Leflunomide should be washed out as below

• Disease modifying drugs will not prevent all flares
• Flares can be managed with IM Depo steroid as outlined above
• If flares become more frequent, or the disease fails to settle between flares, an alternative should be discussed with the rheumatologist

• pregnancy and breast feeding
• severe immunodeficiency
• impaired liver function
• moderate to severe renal impairment
• severe unexplained hypoproteinaemia
• serious infection
• bone marrow impairment (anaemia and cytopenias not caused by RA or PsA)
• Live vaccines are contraindicated

• Caution with combination with haemotoxic or hepatotoxic drugs e.g. methotrexate
• Contraception is required for 2 years after treatment in women, and 3 months in men (unless washed out and levels confirmed)
• If pregnancy occurs whilst on treatment, the drug must be stopped immediately, and a full wash out procedure followed as desrcribed below
• Contact rheumatologist so that blood testing can be organised by the company

• Cholestyramine should not be co-prescribed

If diarrhoea is persistent and severe despite discontinuation of the drug, or if the patient becomes pregnant, or if severe infection develops, the drug should be washed out with Cholestyramine 8gm three times a day for 11 days.

Common effects are in bold type.

Mucocutaneous

• mouth ulcers
• rashes 
• pruritis

Haematological

• blood dyscrasias

Gastrointestinal

• nausea
• diarrhoea
• abdominal pain
• gastritis
• gastroenteritis
• mouth ulcers

Other

• headaches
• respiratory infection and bronchitis
• alopecia
• Raised LFTs
• anorexia
• hypertension
• dizziness
• UTI

Secretaries 01387 241776

• Iseabail Graham
• Caron Cowen

Helpline 01387 241095 (answering machine)

Nurse Specialists:

• Petra Cannon
• Ingrid Crane
• Andrew Wilson 

Department of Rheumatology doctors via Switchboard 01387 246246

• Dr A Russell - Consultant
• Dr R Akintayo - Locum Consultant
• Dr A Drever - Associate Specialist
• Dr L Moran - Associate Specialist