Imuran Dosage/Direction for Use

Imuran should be administered at least 1 hour before or 3 hours after food or milk (see Pharmacology: Pharmacokinetics: Absorption under Actions).
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 Imuran therapy should be maintained indefinitely, even if only low doses are necessary, because of the risk of graft rejection.
Multiple Sclerosis: The dose recommended for the treatment of relapsing remittent multiple sclerosis is 2 to 3 mg/kg bodyweight/day. Treatment duration in excess of one year may be required to establish efficacy. Control of disease progression may not be apparent until after two years of therapy.
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 Imuran. However, for patients with IBD, a treatment duration of at least 12 months should be considered and a response to treatment may not be clinically apparent until after three to four months of treatment.
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.
Children: Multiple Sclerosis: Multiple sclerosis is not a commonly diagnosed disease in children. The use of Imuran is not recommended.
Other Indications: 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: Special Patient Populations: Overweight children under Actions).
Elderly: 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 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: Special Patient Populations: Renal Impairment under Actions).
Hepatic Impairment: In patients with hepatic insufficiency, consideration should be given to reducing the dosage (see Precautions and Pharmacology: Pharmacokinetics: Special Patient Populations: Hepatic Impairment under Actions).
Drug Interactions: When xanthine oxidase inhibitors, such as allopurinol, and Imuran are administered concomitantly it is essential that only 25% of the usual dose of Imuran is given since allopurinol decreases the rate of catabolism of Imuran (see Interactions).
Patients with Thiopurine S-Methyltransferase (TPMT) Deficiency: Patients with inherited little or no TPMT activity are at increased risk for severe Imuran toxicity from conventional doses of Imuran and generally require substantial dose reduction. The optimal starting dose for homozygous deficient patients has not been established (see Monitoring under Precautions and Pharmacology: Pharmacokinetics under Actions).
Most patients with heterozygous TPMT deficiency can tolerate recommended Imuran doses, but some may require dose reduction. Genotypic and phenotypic tests of TPMT are available (see Monitoring under Precautions and Pharmacology: Pharmacokinetics under Actions).
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. Patients of Asian ethnicity are particularly at risk, due to the increased frequency of the mutation in this population. The optimal starting dose for heterozygous or homozygous deficient patients has not been established. Genotypic and phenotypic testing of NUDT15 variants should be considered before initiating thiopurine therapy in all patients (including paediatric patients) to reduce the risk of thiopurine-related severe leukocytopenia and alopecia, especially in Asian populations (see Pharmacology: Pharmacokinetics under Actions).