Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: Douglas Pharmaceuticals Ltd, P O Box 45 027, Auckland 0651, New Zealand Phone: (09) 835 0660
Azamun is used as an immunosuppressant anti-metabolite either alone, or more commonly in combination with other agents (usually corticosteroids) and procedures that influence the immune response. The therapeutic effect of Azamun may be evident only after weeks or months and can include a steroid-sparing effect, thereby reducing the toxicity associated with high dosage and the prolonged use of corticosteroids.
Azamun, in combination with corticosteroids and/or other immunosuppressive agents and procedures, is indicated to enhance the survival of organ transplants, such as renal, cardiac and hepatic transplants; and to reduce the corticosteroid requirements of renal transplant recipients.
Azamun is indicated for the treatment of moderate to severe Crohn’s disease in patients in whom corticosteroid therapy is required, in patients who cannot tolerate corticosteroid therapy or patients whose disease is refractory to other standard first-line therapy.
Azamun, either alone or in combination with corticosteroids and/or other medicines and procedures has been used with clinical benefit (which may result in a dose reduction to/or the discontinuation of corticosteroid therapy) in a proportion of patients suffering from:
Azathioprine is a potent immunosuppressive agent and should be used under the direction of a physician familiar with the risk associated with this type of therapy. The patient should be evaluated carefully and monitored adequately during treatment.
Children considered to be overweight may require doses at the higher end of the dose range and therefore close monitoring of response to treatment is recommended.
Depending on the immuno-suppressive regimen adopted, a loading dose of up to 5 mg/kg/day is usually given.
Maintenance dosage may range from 1-4 mg/kg/day orally and must be adjusted according to clinical requirements and haematological tolerance.
Evidence indicates that azathioprine therapy should be maintained indefinitely, even if only low doses are necessary, because of the risk of graft rejection.
In general, starting dosage rarely exceeds 3 mg/kg/day, and should be reduced depending on the clinical response (which may not be evident for weeks or months) and haematological tolerance.
When a therapeutic response is evident, consideration should be given to reducing the maintenance dosage to the lowest level compatible with the maintenance of that response. If no improvement occurs in the patient’s condition within three months, consideration should be given to withdrawing Azamun. However, for patients with Crohn’s disease, a treatment duration of at least 12 months should be considered and response to treatment may not be clinically apparent until after 3-4 months of treatment.
The maintenance dosage required may range from less than 1 mg/kg/day to 3 mg/kg/day, depending on the clinical condition being treated and the individual patient response, including haematological tolerance.
Children considered to be overweight may require doses at the higher end of the dose range and therefore close monitoring of response to treatment is recommended.
Particular care should be taken to monitor haematological response and to reduce the maintenance dosage to the minimum required for clinical response (refer to, renal and/or hepatic impairments).
In patients with renal/or hepatic insufficiency, dosages should be given at the lower end of the normal range (refer to section 4.4).
Patients with inherited little or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe azathioprine toxicity from conventional doses of azathioprine and generally require substantial dose reduction. The optimal starting dose of heterozygous deficient patients has not been established.
Most patients with heterozygous TPMT deficiency can tolerate recommended azathioprine doses, but some may require dose reduction. Genotypic and phenotypic tests of TPMT are available, refer to section 4.4 for further information.
When xanthine oxidase inhibitors, such as allopurinol, and azathioprine are administered concomitantly it is essential that only one quarter of the usual dose of azathioprine is given since allopurinol decreases the rate of ch4. atabolism of azathioprine e.g., an azathioprine dose of 100 mg should be reduced to 25 mg (refer to section 4.5).
Azamun tablets should be administered at least 1 hour before or 3 hours after food or milk.
Azamun tablets should be swallowed whole with liquid and must not be divided or chewed.
Unexplained infection, ulceration of the throat, bruising and bleeding are the main signs of overdosage with azathioprine and result from bone marrow depression which may be maximal after 9-14 days. These signs are more likely to be manifest following chronic overdosage, rather than after a single acute overdose. There has been a report of a patient who ingested a single overdose of 7.5 g of azathioprine. The immediate toxic effects of the overdose were nausea, vomiting and diarrhoea, followed by mild leucopenia and mild abnormalities in liver function. Recovery was uneventful.
There is no specific antidote. The value of dialysis in patients who have taken an overdose of azathioprine is not known, though azathioprine is partially dialysable.
For advice on the management of overdose please contact the National Poisons Centre on 0800 POISON (0800 764766).
36 months.
Azamun 25 mg and 50 mg: Store at or below 30°C and protect from light and moisture.
Azamun 75 mg and 100 mg: Store at or below 25°C and protect from light and moisture.
Azamun 25 mg: 30, 60 and 100 tablets in PVC/PVDC-Aluminium foil blister strips.
Azamun 50 mg, 75 mg, 100 mg: 100 tablets in PVC/PVDC-Aluminium foil blister strips.
Not all strengths or pack sizes may be marketed.
Any unused medicine or waste material should be disposed of in accordance with local requirements.
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