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GENERAL: Azathioprine tablets should be administered at least 1 hour before or 3 hours after food or milk (see Pharmacology: Pharmacokinetics under Actions).
POSOLOGY: POPULATIONS: Adults: Transplants: Depending on the immunosuppressive regimen employed, a dosage of up to 5 mg/kg bodyweight/day may be given orally on the first day of therapy.
Maintenance dosage should range from 1 to 4 mg/kg bodyweight/day 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.
Other Indications: In general, starting dosage is from 1 to 3 mg/kg bodyweight/day, and should be adjusted, within these limits, depending on the clinical response (which may not be evident for weeks or months) and haematological tolerance.
When 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 azathioprine.
The maintenance dosage required may range from less than 1 mg/kg bodyweight/day to 3 mg/kg bodyweight/day, depending on the clinical condition being treated and the individual patient response, including haematological tolerance.
Paediatric population: Transplants and Other Indications: See Adults as previously mentioned.
Overweight paediatric population: 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 (see Pharmacology: Pharmacokinetics under Actions).
Elderly: There is limited experience of the administration of azathioprine to elderly patients. Although the available data do not provide evidence that the incidence of side effects among elderly patients is higher than that among other patients treated with azathioprine, it is advisable to monitor renal and hepatic function, and to consider dosage reduction if there is impairment (see Renal Impairment and Hepatic Impairment as follows).
Renal impairment: In patients with renal insufficiency, consideration should be given to reducing the dosage (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: In patients with hepatic insufficiency, consideration should be given to reducing the dosage (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Drug interactions: When xanthine oxidase inhibitors, such as allopurinol, and azathioprine are administered concomitantly it is essential that only 25% of the usual dose of azathioprine is given since allopurinol decreases the rate of catabolism of azathioprine (see Interactions).
TPMT-deficient patients: 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 for homozygous deficient patients has not been established (see Precautions).
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 (see Precautions).
Patients with NUDT15 variant: Patients with inherited mutated NUDT15 gene are at increased risk for severe thiopurine toxicity, such as early leukopenia and alopecia, from conventional doses of thiopurine therapy and generally require substantial dose reduction.
Genotypic and phenotypic testing of NUDT15 variants should be considered before initiating thiopurine therapy.
