Posology : מינונים

4.2 Posology and method of administration
Specialist medical literature should be consulted for guidance as to clinical experience in particular conditions.
General
When the oral route is impractical azathioprine injection may be administered by the i.v. route only, however, this route should be discontinued as soon as oral therapy can be tolerated once more.

Imuran tablets should be administered at least 1 hour before or 3 hours after food or milk (see Section 5.2 Pharmacokinetics: Absorption).


Dosage in transplantation - adultsDepending on the immunosuppressive regimen employed, a dosage of up to 5mg/kg bodyweight/day may be given on the first day of therapy, either orally or intravenously.
Maintenance dosage should range from 1-4mg/kg bodyweight/day and must be adjusted according to clinical requirements and haematological tolerance.

Corticosteroid therapy is usually given concomitantly with Imuran.

Evidence indicates that Imuran therapy should be maintained indefinitely, even if only low doses are necessary, because of the risk of graft rejection.

Dosage in other conditions - adults:
In general, starting dosage is from 1-3mg/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.

In general, starting dosage rarely exceeds 3mg/kg bodyweight/day, and should be reduced, 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 3 months, consideration should be given to withdrawing Imuran.

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
See Dosage in transplantation - adults.

Other Indications:

Overweight children
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 Section 5.2 Pharmacokinetics: Special Patient Populations: Overweight children).

Use in the elderly
The rapid in vivo cleavage of the azathioprine molecule followed by tissue fixation makes it impossible to relate plasma drug levels to toxicity. There are no specific data as to the tolerance of Imuran in elderly patients. There is limited experience of the administration of Imuran 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 Imuran, it is advisable to monitor renal and hepatic function, and to consider dosage reduction if there is impairment (see Section 4.2 Posology and method of administration - Renal and/or hepatic impairment).

The dosage is adjusted on the basis of the clinical state and the response of the individual patient. If no improvement has occurred after 3 months, consideration should be given to discontinuing the drug.

Renal and/or hepatic impairment
In patients with renal and/or hepatic insufficiency, consideration should be given to reducing the dosage (see Section 4.4 Special warnings and precautions for use).

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 Section 4.5 Interaction with other medicinal products and other forms of interaction).

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 Section 4.4 Special warnings and Precautions for Use: Monitoring and Section 5.2 Pharmacokinetics).
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 Section 4.4 Special warnings and precautions for use: Monitoring and Section 5.2 Pharmacokinetics).