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Azathioprine is an immunosuppressive antimetabolite. Imidazolyl derivative of 6- mercaptopurine. Widely used due to its immunosuppresant and anti-inflammatory properties Interferes with nucleic acid synthesis ( Purine antagonist ) Used either alone or in combination ( usually corticosteroids) Azathioprine is a pro-drug- rapidly converted to 6-MP which is then metabolized by purine salvage pathway It may take weeks to months for significant response to be achieved Usually started @ 50 mg/ day ( available in 25 ,50 , 100 mg ) Typical maintenance dose may be 2 to 2.5 mg/kg
Indications- Following organ transplant Reduce steroid requirement of renal transplant patients Psoariatic arthritis Severe rheumatoid arthritis SLE Dermatomyositis Polymyositis Autoimmune chronic active hepatitis Pemphigus vulgaris Polyarteritis nodosa Auto-immune haemolytic anaemia Chronic idiopathic thrombocytopenic purpura
Adverse effects- Nausea Dose-dependent Usually resolves after few weeks Gradual dose escalation may help Divided daily dose Antiemetics Hypersensitivity Idiosyncratic immunologically mediated reaction Can present with a distinct symptoms within few weeks Generalised or organ specific symptoms as ○ fever ○ myalgia ○ arthralgia ○ nausea
Myelotoxicity Bone marrow suppression –> Neutropenia Dose dependent Can be seen in up to 5-30 % Susceptibility to infection Even in absence of neutropenia Mild lymphopenia may contribute to this VZV ( Varicell zoster ) is particularly seen more commonly Hepatotoxicity Mild derangement common- usually with no serious complication Two patterns of liver injury Risk of developing nonmelanoma skin cancer ( NMSC ) increases by long term use of azathioprine to solid- organ transplant recipients Advice about sun -protection Increased risk of non-Hodgkins’s lymphoma Bone marrow suppression is reversible if drug withdrawn early enough Ask about any evidence of infection eg sore throat / oral ulceration , unexplained rash or unusual bruising at every consultation
References
- Drugs com Azathioprine https://www.drugs.com/cdi/azathioprine-tablets.html
- Medicine compendium Azathioprine https://www.medicines.org.uk/emc/product/2541/smpc
- CKS NHS DMARDs September 2017 https://cks.nice.org.uk/dmards
- Meggitt, S., Anstey, A., Mohd Mustapa, M., Reynolds, N. and Wakelin, S. (2011), British Association of Dermatologists’ guidelines for the safe and effective prescribing of azathioprine 2011. British Journal of Dermatology, 165: 711-734. doi:10.1111/j.1365-2133.2011.10575.x
- Comprehensive Dermatologic Drug Therapy Third Edition Azathioprine , 14, 182-189.e2
- Dermatological Pharmacology : systemic drugs Medicine , 2017-06-01, Volume 45 , Issue 6 , Pages 363-367
- Shropshire Clinical Commissioning Group Azathioprine Rheumatology Local Safety Monitoring Schedule March 2015 https://www.sath.nhs.uk/wp-content/uploads/2016/12/Azathioprine-SCA-v10-FINAL.pdf
- Gwent Shared Care Protocol Azathioprine ( or Mercaptopurine ) accessed via http://www.wales.nhs.uk/sites3/Documents/371/Doc%202%20 Defining%20shared%20care.pdf