azathioprine Flashcards
what is Azathioprine?
immunosupressive antimetabolite pro-drug and an imidazolyl derivative of 6-mercaptopurine
What class of drugs does Azathioprine belong to?
immunomodifiers
What are examples of other drugs in the same class as Azathioprine?
tocilizumab
leflunomide
interferon beta -1b
etanercept
What is Azathioprine indicated for?
- Crohn’s disease, ulcerative colitis
- Severe Rheumatoid arhtirits,
- auto immune conditions
- suppression of transplant rejection
- severe refractory ezcema
What is the role of Azathioprine in the therapy of CD and UC?
2nd line for fistulating crohn’s disease and continued for maintenance.
What is the dose of Azathioprine given for Crohn’s disease?
adult: 1-3mg/kg daily adjusted according to response max 3mg/kg daily. Use lowest effective dose and consider withdrawal if there is no improvement within 3 months
What is the mechanism of action of Azathioprine?
Structure is similar to thiopurine analoges, enabling it to antagonise purine metabolism and may inhibit synthesis of DNA, RNA and proteins.
may also interfere with cellular metabolism and inhibit mitosis
What are the relevant PD/PK parameters with Azathioprine?
PD: Azathioprine is a chemotherapy drug now used for immunosupression
It is a pro-drug and converted in the body to 6-mercaptopurine
It inhibits purine synthesis which is necessary for proliferation of cells (esp. leukocytes and lymphocytes)
PK: well absorbed following oral admin moderately bound to serum proteins (30%) converted into active form by non enzymatical process and glutathione transferases activation occurs via HGPRT rapidly eliminated from urine. half life- 8 hours?
What are the precautions associated with Azathioprine use?
different formulations may vary in bioavailability
low or no thiopurine methyltransferase
monitor for toxicity throughout treatment
monitor FBC weekly (and more frequently with high doses)
Bone marrow suppressed patients should be warned to immediately report inexplicable bruising, bleeding or infection
pregnancy class D
hepatic and renal impairment
What are the contraindications with Azathioprine?
hypersensitivity to mercaptopurine
low TPMT
Pregnancy
What are the adverse effects with Azathioprine?
hypersensitivity reactions (malaise, dizziness, vomiting, diarrhoea, fever, rigors, myalgia, arthralgia, rash, hypotension, interstial nephritis, dose related bone marrow suppression, liver impairment, cholestatic jaundice, hair loss, increased susceptibility to infections and colitis
What are the relevant drug interactions with Azathioprine?
immunity of body suppressed. do not administer BCG, live influenza, poliomyelitis, rubella, typhoid, varicella-zoster, yellow fever vaccines
haematological effects of Azathioprine increased with allopurinol
Anaemia/leucopenia reported when given with ace inhibitors,
What are the alarm bells associated with Azathioprine use?
watch out for bone marrow suppression, infection status, and TPMT status as well as hepatic and renal function
