Azathioprine

Azathioprine

[1 tablet 25 cents; 1 vial for injection $47.72]

ADMINISTRATION ROUTES:

  • IV, PO

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 needs to be weighed up against the risks of such therapy. Dose reduction may be appropriate.

PRESENTATION AND ADMINISTRATION:

  • IV:
    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, D5W
    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.

DOSAGE:

  • IV and Oral:
    Transplant survival:
    5mg/kg on the 1st day; maintenance 1-4mg/kg/day; continue indefinitely
    Other indications:
    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.

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

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. It should be handled accordingly.
    Leukopenia and thrombocytopenia:

    Severe leukopenia and/or thrombocytopenia may occur in patients on azathioprine. Macrocytic anemia 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
    :
    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 characterized by severe nausea and vomiting has been reported. These symptoms may also be accompanied by diarrhea, 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 FOR THE 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 leukopenia, 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 leukopenia.
  • 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
  • Hematological system:
    Leukopaenia and/or thrombocytopaenia, anaemia, bone marrow suppression.

Critical Care Drug Manual

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