Azathioprine

ADMINISTRATION ROUTES:

PO, IV

ALTERNATIVE NAMES:

Imuran, Azamun

ICU INDICATIONS:

1. Prevention of rejection in renal transplantation

2. Management of severe, active rheumatoid arthritis

3. Management of Crohns disease

4. Management of various autoimmune conditions

In patients in the ICU the benefits of continuing immunosuppressive therapy with azathioprine must be weighed up against the risks of such therapy. Dose reduction may be appropriate.

PRESENTATION AND ADMINISTRATION:

IV:

50 mg vials of powder. Reconstitute in 5-15 mL of water for Injection ONLY and swirl vial gently until solution is clear. Dilute the reconstituted solution to 20-200 mL in compatible IV fluid and administer over 30-60 minutes

Compatible with the following IV fluids:

0.45% sodium chloride, 0.9% sodium chloride, glucose and sodium chloride, 5% dextrose

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 50 mg tablets (pale yellow)

Imuran 50 mg tablets (yellow)

Note: crushing tablets is NOT recommended. See ICU Pharmacist for advice.

DOSAGE:

IV and Oral:

Transplant survival:

5 mg/kg on the 1st day; maintenance 1-4 mg/kg/day. Continue indefinitely

Other indications:

Initially 1-3 mg/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.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose in renal impairment

Dose in renal replacement therapy

DOSAGE IN PAEDIATRICS:

Safety and efficacy of azathioprine in children have not been established

CLINICAL PHARMACOLOGY:

Azathioprine is an immunosuppressive antimetabolite. Azathioprine is well absorbed following oral administration.

CONTRAINDICATIONS:

1. Hypersensitivity to azathioprine.

WARNINGS:

Cytotoxicity:

Azathioprine is cytotoxic and therefore presents a potential occupational hazard to personnel handling the drug. Pregnant staff should not be involved in its preparation or administration. Please consult the ICU Pharmacist.

Leukopaenia and thrombocytopaenia:

Severe leukopaenia and/or thrombocytopaenia may occur in patients on azathioprine. Macrocytic anaemia and severe bone marrow depression may also occur. Haematologic toxicities are dose related and may be more severe in renal transplant patients whose homograft is undergoing rejection.

Serious Infections:

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.

PRECAUTIONS:

General:

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.

Laboratory Tests:

No tests additional to routine ICU tests are required.

Drug/Laboratory Test Interactions:

None known.

IMPORTANT DRUG INTERACTIONS IN ICU:

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.

ADVERSE REACTIONS:

Body as a Whole:

Fever, neoplasia, infections

Respiratory System:

Reversible interstitial pneumonitis

Digestive System:

Nausea and vomiting, diarrhoea, hepatic veno-occlusive disease, pancreatitis

Musculoskeletal Systemc:

Myalgias, arthralgias

Haematological system:

Leukopaenia and/or thrombocytopaenia, anaemia, bone marrow suppression