Azathioprine Amber Drug Guidance

Leeds
Drug Azathioprine: Amber Drug Guidance for the
treatment of children with autoimmune hepatitis (AIH)
Amber Drug Level 3 (amber drug with monitoring requirements)
We have started your patient on azathioprine. We will continue to see
the patient and prescribe azathioprine until the patient (and their
condition) is stable which would usually be 1 month. After this period the
GP will be asked to take over prescribing and monitoring responsibilities
under this amber drug protocol. This drug requires monitoring.
This guideline outlines the specific responsibilities of the Specialist, GP,
and patient when azathioprine is prescribed. The general responsibilities
for prescribing and monitoring amber drugs can be found here.
Prescribing
Information
Indication for therapy (including licensing information):
1. Steroid sparing treatment in children (from birth to 18 years) with
autoimmune hepatitis.
2.
Licensing Information
Azathioprine is licensed as an immunosuppressant for use in
transplantation and auto-immune diseases including auto-immune chronic
active hepatitis.
Classification: Amber Level 3
Monitoring: Required
Baseline Tests:
 U&E
 LFT including gamma GT
 FBC
 TPMT (thiopurine methyltransferase) activity (optional blood test to
assess potential risk for myelotoxicity)
 Varicella zoster antibodies.
Routine Tests/Monitoring:
 Monitor FBC 2 weekly for the first 4 weeks, once monthly for next 2
months, then 3 monthly.
 If dose altered, increased or decreased, check FBC weekly for at least
one month or until stable.
 Monitor LFT, amylase (and CRP for disease activity) 3 monthly
Disease Monitoring:
The specialist will assess and monitor the patient’s response to
treatment – usually 3 monthly depending on patient’s condition.
Azathioprine Amber Drug Guidance
Date approved: February 2013
Review due: February 2016
1
The following is a summary of prescribing information only.
Consult the BNF and SPC for full and current prescribing
information.
Dose: 1-3mg/kg/day in one or two divided doses for AIH in children,
usually starting at 1mg/kg/day increasing as tolerated, depending on
response. See clinic referral letter for recommended dose for particular
patient.
Formulation: 25mg and 50mg tablets (licensed). 10mg capsules
(unlicensed). Suspension (unlicensed special)
Adverse drug reactions:
1. Hypersensitivity reactions, including malaise, fever, vomiting,
diarrhoea, skin rash, arthralgia, headache, dizziness, hypotension,
interstitial nephritis – calls for immediate withdrawal of drug.
2. Flu-like symptoms (myalgia, fever, headache) that
characteristically occur after 2–3 weeks and cease rapidly when the
drug is withdrawn.
3. GI symptoms such as nausea, vomiting and diarrhoea
occasionally severe and responds to dose reduction.
4. Bone marrow suppression - usually dose related and generally
reversible. Profound leucopenia (< 3.5 x 109 /L), neutropenia (< 1.50
x109 /L) and thrombocytopenia (platelets < 150x109 /L) can
develop suddenly and unpredictably in between blood tests and this
responds well to dose reduction and rarely drug withdrawal.
Discuss with the consultant.
5. Hepatotoxicity is rare. If liver transaminases are twice the normal
levels then inform the consultant.
6. Pancreatitis is uncommon and usually mild. Serum amylase should
be checked in any patient complaining of abdominal pain.
7. Hair loss – usually insignificant and reversible
8. Lymphoma: There is a slightly increased risk of lymphoma
however the benefits of azathioprine outweigh any risk of lymphoma
in inflammatory bowel disease and auto immune hepatitis.
Advise the patient or carer to report promptly should a sore throat
or other signs of infection occur.
Cautions/Contra-indications:
1. Patients with no immunity to varicella zoster will require Varicella
Zoster Immunoglobulin if exposed to chicken pox or herpes zoster.
If chicken pox develops they will need treatment with aciclovir.
2. Live vaccines (MMR, BCG, varicella zoster and yellow fever) are
contraindicated
Interactions:

Warfarin (reduced anticoagulant effect)

Co-trimoxazole and trimethoprim ( increased risk of haematological
toxicity)

Aminosalicylates (possible increased risk of leucopenia)

Allopurinol (increases the effects and toxicity of azathioprine)
Azathioprine Amber Drug Guidance
Date approved: February 2013
Review due: February 2016
2
Pregnancy/breast-feeding:
Treatment should not be initiated during pregnancy. If the patient
becomes pregnant on treatment then consideration should be given to
stopping treatment in consultation with the Specialist. There have been
reports of premature birth and low birth-weight following exposure to
azathioprine in transplant recipients, especially in combination with
corticosteroids.
Azathioprine is only present in breast milk in low concentrations. Small
studies have shown no evidence of harm in infants, suggesting it is
acceptable to use if the potential benefit outweighs the risk
Communication
Contact Names and Details
Medicines Information:
0113 2065377
[email protected]
Medicines Information Patient Helpline:
Prepared by:
0113 2064376
Penny North Lewis, Advanced Clinical Pharmacist
Dr S Rajwal, Consultant Paediatric Hepatologist
Responsibilities Specific to azathioprine for the treatment of AIH in
children
The general guidelines for Amber level 3 drugs can be found here.
Responsibilities
of Specialist
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Responsibilities
of GP
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Responsibilities
Responsibilities
of Patient/Carer
of Patient/Carer
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
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
To perform any baseline tests, initial routine tests and disease
monitoring; and prescribe azathioprine for first 4 weeks.
To communicate baseline and routine test results to GP.
Provide continuing clinical support to patient and GP.
To continue monitoring as agreed with secondary care and as
outlined in the primary care LES for Monitoring Amber Drugs.
To refer patient back to the Specialist if concerned about any
monitoring results.
To take responsibility for taking azathioprine as prescribed.
To attend for blood tests/disease monitoring on time (if appropriate).
To ensure that Disease Monitoring Booklet is taken to all Specialist
and GP appointments (if appropriate).
To understand potential for adverse events and report these to the
Specialist and/or GP.
To check with community pharmacist that there are no interactions
with azathioprine, when buying any over the counter medicines or
herbal/homoeopathic products.
To contact the GP, Specialist or Medicines Information patient
helpline if further information or advice is needed about
azathioprine.
Azathioprine Amber Drug Guidance
Date approved: February 2013
Review due: February 2016
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