KINGSTON RHEUMORS
Azathioprine
This shared care guideline sets out details for the care of
patients with
rheumatoid arthritis prescribed methotrexate. These guidelines provide
additional limited information necessary to aid in the treatment of
rheumatology patients. As with all shared care guidelines these highlight
significant prescribing issues but should be used in conjunction with the
summary of product characteristics (Data sheet) and do not replace the drug
company information .
Indications for the purposes of this guideline; Treatment of adults with
rheumatoid arthritis, systemic lupus erythematosus and other rheumatological
diseases.
Dosage
The normal dose range is 50mg to 200mg daily. The target dose will be clearly
specified in the clinic letter.
Contraindications – should not be used in:
Patients with known hypersensitivity to Mercaptopurine.
Breastfeeding.
Precautions - caution is advised in:
Pregnancy. Patients of childbearing age should be advised to use a reliable
method of contraception during treatment. When planning a pregnancy it is
important that both men and women on this drug discuss medication with the
Rheumatology Team (at least six months before conception) since all drugs can
potentially affect the unborn child. There have been reports of premature birth
and low birth weight following maternal exposure, particularly in combination
with corticosteroids. There have also been reports of spontaneous abortion
following either maternal or paternal exposure. There have been some reports
of leucopenia and/or thrombocytopenia in neonates following maternal
exposure.
Patients with deficiency in the enzyme thiopurine methyltransferase (TPMT) as
these patients have a higher risk of bone marrow toxicity.
Patients with renal failure, hepatic disease and cardiac failure.
Monitoring
Prior to starting therapy :
Measure baseline LFTs and CBC.
Pre-screening for TPMT deficiency .
Ongoing Monitoring:
CBC and LFTs regularly: fortnightly for the first three months then monthly
thereafter is satisfactory.
In order to monitor the effectiveness of treatment, the CRP measured at least
three-monthly would be helpful.
Stop and refer to the rheumatology team if:
Liver enzymes especially transaminase increased x 3 upper limit of normal.
WCC falls on three successive occasions and/or WCC falls below 3.5 x 109
Platelet count falls on three successive occasions and/or
Platelet count falls below 150 x 109
NB. The MCV may rise. If an isolated MCV rise, check for other causes (B12,
TFT, folate and alcohol consumption). A high MCV is not an indication to stop
treatment.
Side effects
Very common > [1 in 10] > Common > [1 in 100] > Uncommon > [1 in 1000] >
Rare > [1 in 10000] > Very rare
Patients must report mouth ulcers, sore throat, fever, epistaxis, unexpected
bruising or bleeding, and any unexplained illness/infection and should be seen
urgently for full blood count and liver function tests.
Very common/Common:
Nausea – may be relieved by administering tablets after meals.
Uncommon
Anaemia.
Bone marrow depression, leucopenia, thrombocytopenia – in predisposed
patients.
Hypersensitivity reactions.
Hepatitis.
Pancreatitis.
Alopecia.
Susceptibility to viral, fungal and bacterial infections.
Common/Significant Drug Interactions
Allopurinol (or other Xanthine oxidase inhibitors) – increased risk of toxicity,
reduce dose of azathioprine to 25% of original dose.
Warfarin – anticoagulant effect possibly reduced.
Trimethoprim and co-trimoxazole – increased risk of haematological toxicity if
renal function is impaired.
Clozapine may lead to agranulocytosis
Aminosalicylates e.g. mesalazine may inhibit the TPMT enzyme and should be
used only with caution with Azathioprine.
Vaccines - Live attenuated vaccines are contraindicated. For additional
information refer to the British Society of Rheumatology guidance on
vaccinations for immuno-suppressed patients at
http://www.rheumatology.org.uk/guidelines/clinicalguidelines/vaccineguideline
Notes
Passive immunisation should be carried out using Varicella Zoster
Immunoglobulin (VZIG) in non-immune patients if exposed to chickenpox or
shingles.
Flu and Pneumoccal vaccines may be given.
Product information
References
Summary of Product Characteristics Imuran http://emc.medicines.org.uk/: January 2006.
British Society of Rheumatologists Guidelines http://www.rheumatology.org.uk January
2006.
BNF 50
Stockley Drug Interactions 7th ed.
Date of Issue Nov 2006.
Reviewed 10/09
rheumatoid arthritis prescribed methotrexate. These guidelines provide
additional limited information necessary to aid in the treatment of
rheumatology patients. As with all shared care guidelines these highlight
significant prescribing issues but should be used in conjunction with the
summary of product characteristics (Data sheet) and do not replace the drug
company information .
Indications for the purposes of this guideline; Treatment of adults with
rheumatoid arthritis, systemic lupus erythematosus and other rheumatological
diseases.
Dosage
The normal dose range is 50mg to 200mg daily. The target dose will be clearly
specified in the clinic letter.
Contraindications – should not be used in:
Patients with known hypersensitivity to Mercaptopurine.
Breastfeeding.
Precautions - caution is advised in:
Pregnancy. Patients of childbearing age should be advised to use a reliable
method of contraception during treatment. When planning a pregnancy it is
important that both men and women on this drug discuss medication with the
Rheumatology Team (at least six months before conception) since all drugs can
potentially affect the unborn child. There have been reports of premature birth
and low birth weight following maternal exposure, particularly in combination
with corticosteroids. There have also been reports of spontaneous abortion
following either maternal or paternal exposure. There have been some reports
of leucopenia and/or thrombocytopenia in neonates following maternal
exposure.
Patients with deficiency in the enzyme thiopurine methyltransferase (TPMT) as
these patients have a higher risk of bone marrow toxicity.
Patients with renal failure, hepatic disease and cardiac failure.
Monitoring
Prior to starting therapy :
Measure baseline LFTs and CBC.
Pre-screening for TPMT deficiency .
Ongoing Monitoring:
CBC and LFTs regularly: fortnightly for the first three months then monthly
thereafter is satisfactory.
In order to monitor the effectiveness of treatment, the CRP measured at least
three-monthly would be helpful.
Stop and refer to the rheumatology team if:
Liver enzymes especially transaminase increased x 3 upper limit of normal.
WCC falls on three successive occasions and/or WCC falls below 3.5 x 109
Platelet count falls on three successive occasions and/or
Platelet count falls below 150 x 109
NB. The MCV may rise. If an isolated MCV rise, check for other causes (B12,
TFT, folate and alcohol consumption). A high MCV is not an indication to stop
treatment.
Side effects
Very common > [1 in 10] > Common > [1 in 100] > Uncommon > [1 in 1000] >
Rare > [1 in 10000] > Very rare
Patients must report mouth ulcers, sore throat, fever, epistaxis, unexpected
bruising or bleeding, and any unexplained illness/infection and should be seen
urgently for full blood count and liver function tests.
Very common/Common:
Nausea – may be relieved by administering tablets after meals.
Uncommon
Anaemia.
Bone marrow depression, leucopenia, thrombocytopenia – in predisposed
patients.
Hypersensitivity reactions.
Hepatitis.
Pancreatitis.
Alopecia.
Susceptibility to viral, fungal and bacterial infections.
Common/Significant Drug Interactions
Allopurinol (or other Xanthine oxidase inhibitors) – increased risk of toxicity,
reduce dose of azathioprine to 25% of original dose.
Warfarin – anticoagulant effect possibly reduced.
Trimethoprim and co-trimoxazole – increased risk of haematological toxicity if
renal function is impaired.
Clozapine may lead to agranulocytosis
Aminosalicylates e.g. mesalazine may inhibit the TPMT enzyme and should be
used only with caution with Azathioprine.
Vaccines - Live attenuated vaccines are contraindicated. For additional
information refer to the British Society of Rheumatology guidance on
vaccinations for immuno-suppressed patients at
http://www.rheumatology.org.uk/guidelines/clinicalguidelines/vaccineguideline
Notes
Passive immunisation should be carried out using Varicella Zoster
Immunoglobulin (VZIG) in non-immune patients if exposed to chickenpox or
shingles.
Flu and Pneumoccal vaccines may be given.
Product information
References
Summary of Product Characteristics Imuran http://emc.medicines.org.uk/: January 2006.
British Society of Rheumatologists Guidelines http://www.rheumatology.org.uk January
2006.
BNF 50
Stockley Drug Interactions 7th ed.
Date of Issue Nov 2006.
Reviewed 10/09