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Azathioprine

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 is reversible if drug withdrawn early 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

  1. Drugs com Azathioprine https://www.drugs.com/cdi/azathioprine-tablets.html
  2. Medicine compendium Azathioprine https://www.medicines.org.uk/emc/product/2541/smpc
  3. CKS NHS DMARDs September 2017 https://cks.nice.org.uk/dmards
  4. 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
  5. Comprehensive Dermatologic Drug Therapy Third Edition Azathioprine , 14, 182-189.e2
  6. Dermatological Pharmacology : systemic drugs Medicine , 2017-06-01, Volume 45 , Issue 6 , Pages 363-367
  7. 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
  8. Gwent Shared Care Protocol Azathioprine ( or Mercaptopurine ) accessed via
http://www.wales.nhs.uk/sites3/Documents/371/Doc%202%20
Defining%20shared%20care.pdf

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