Azathioprine PO, IV
Prevention of rejection in renal transplantation.
Management of severe, active rheumatoid arthritis
Management of Crohns disease
Management of various autoimmune conditions
In patients in the ICU the benefits of continuing immunosuppressive therapy with azathioprine needs to be weighed up against the risks of such therapy. Dose reduction may be appropriate.
50mg vials of powder. Reconstitute in 5-15ml of water for Injection ONLY and swirl vial gently until solution is clear. Dilute the reconstituted solution to 20-200ml in compatible IV fluid and administer over 30-60 minutes
Compatible with the following IV fluids:
0.45% sodium chloride normal saline Glucose and Sodium chloride
Store at room temperature. Reconstituted solution is stable for 24 hrs at room temperature. When diluted in compatible IV fluid, resultant solution is stable for 24 hours at room temperature.
Administration via a central line is preferred if a central line is present
PO / NG:
Azamun 50mg tablets (pale yellow), Imuran 50mg tablets (yellow)
Note: crushing tablets is NOT recommended. See Pharmacist for advice.
IV and Oral:
5mg/kg on the 1st day; maintenance 1-4mg/kg/day; continue indefinitely
Initially 1-3mg/kg/day until response evident then reduce to the lowest effective dose.
Note: the IV route should only be used when the oral route is not available.
Safety and efficacy of azathioprine in children have not been established.
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY
Dose in renal impairment [GFR (ml/min)]
<10 50-75% of usual dose
10-20 75-100% of usual dose
>20-50 dose as in normal renal function
Dose in renal replacement therapy
CAPD 50-75% of usual dose
HD dose as in normal renal function
CVVHDF 75-100% of usual dose
Azathioprine is an immunosuppressive antimetabolite. Azathioprine is well absorbed following oral administration.
Hypersensitivity to Azathioprine.
Azathioprine is cytotoxic and therefore presents a potential occupational hazard to personnel handling the drug. It should be handled accordingly.
Leukopenia and thrombocytopenia:
Severe leukopenia and/or thrombocytopenia may occur in patients on azathioprine. Macrocytic anaemia and severe bone marrow depression may also occur. Hematologic toxicities are dose related and may be more severe in renal transplant patients whose homograft is undergoing rejection.
Serious infections are a constant hazard for patients receiving chronic immunosuppression, especially for homograft recipients. Fungal, viral, bacterial and protozoal infections may be fatal and should be treated vigorously. Reduction of azathioprine dosage and/or use of other drugs should be considered.
Risk of Neoplasia
Renal transplant patients receiving azathioprine are known to have an increased risk of malignancy, predominantly skin cancer and reticulum cell or lymphomatous tumours.
A gastrointestinal hypersensitivity reaction characterised by severe nausea and vomiting has been reported. These symptoms may also be accompanied by diarrhoea, rash, fever, malaise, myalgias, elevations in liver enzymes, and occasionally, hypotension.
No tests additional to routine ICU tests are required.
Drug/Laboratory Test Interactions
Use with Allopurinol:
The principal pathway for detoxification of azathioprine is inhibited by allopurinol. Patients receiving azathioprine and allopurinol concomitantly should have a dose reduction of azathioprine, to approximately 1/3 to 1/4 the usual dose.
Use with Other Agents Effecting Myelopoiesis:
Drugs which may affect leukocyte production, including co-trimoxazole, may lead to exaggerated leukopaenia, especially in renal transplant recipients.
Use with Angiotensin Converting Enzyme Inhibitors:
The use of angiotensin converting enzyme inhibitors to control hypertension in patients on azathioprine has been reported to induce severe leukopaenia.
Use with Warfarin:
Azathioprine may inhibit the anticoagulant effect of warfarin
Body as a Whole:
Fever, neoplasia, infections
Reversible interstitial pneumonitis
Nausea and vomiting, diarrhoea, hepatic veno-occlusive disease, pancreatitis.
Leukopaenia and/or thrombocytopaenia, anaemia, bone marrow suppression.