Azathioprine

If eGFR <29 dose reductions up to 50% may be required

• Initiation: 1mg/kg/day increasing after 4-6 weeks to:
• Maintenance: 2-2.5mg/kg/day
• Maximum dose: 3mg/kg/day

• The dose may be divided or given in one dose immediately after food.
• When maximum benefit has been obtained for several months, the dose should be reduced to the lowest effective dose.
• Pneumovax and annual flu vaccine should be given and Varicella-zoster IgM if exposed to chickenpox/shingles and non-immune.
• If co-prescribed with Allopurinol, the Azathioprine dose must be reduced to one quarter.

• Pre-Treatment – Check TPMT level (await result before prescribing - may need significantly reduced dose or alternative to Azathioprine if TPMT is reduced/absent), FBC, U+E, CRP, LFT inc. Albumin, Hepatitis and HIV serology

• FBC, U+E , CRP, LFT inc. Albumin-      At week 2, then monthly for 3 months, then according to directions of Rheumatologist- (likely 3-6 monthly dependent on co-morbidities/risk factors).

  Stop during Infection, restart when well

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
• Neutrophils < 1.6
• Platelets < 140 withhold and inform Rheumatology Department
• AST or ALT >100
• Creatinine >30% rise over 12 months
• Unexplained Albumin <30g/l
• Unexplained Eosinophilia >0.5  
• Rash or oral ulceration             
• MCV > 105fl - investigate with TSH and B12+ folate and treat any abnormality - if normal, discuss
• Abnormal bruising or sore throat - withhold until FBC available

• Treatment is continued indefinitely providing it remains effective and there are no significant side effects. 
• Azathioprine takes about six weeks to become effective, but may take up to three 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 steroids are still required after three months, discuss alternative with the Rheumatologist.

Pregnancy (except special circumstances), breast feeding, known hypertension, live vaccines.

Caution in:

• renal and liver dysfunction
• TPMT deficiency and infection especially hepatitis B, C and TB
• reduce sun exposure using clothing and sunscreen

• Allopurinol – If must be co-prescribed with Allopurinol, the Azathioprine dose must be reduced to one quarter.
• Caution with other myelosuppressives
• Increased risk of serious haematological toxicity with Co-trimoxazole and Trimethoprim
• Possible risk of leukopenia with ACE inhibitors
• Possible inhibition of anticoagulation with Warfarin
• Reduced absorption phenytoin, sodium valproate, carbamazepine
• Risk of bone marrow toxicity with sulfasalazine, mesalazine, olsalazine, balsalazide

Common effects are in bold type.

Mucocutaneous

• urticaria
• erythematous pruritis

Haematological

• neutropenia
• thrombocytopenia
• anaemia
• macrocytosis

Gastrointestinal

• nausea
• anorexia

Other

• myalgia
• arthralgia
• allergic drug
• fevers
• dose related cholestatic hepatitis
• pancreatitis

Secretaries 01387 241776

Helpline 01387 241095 (answering machine)

Department of Rheumatology doctors via Switchboard 01387 246246/RMS advice request