Azathioprine is administered orally at the dose of 2 mg/kg/day in 1, 2, or 3 daily doses, without exceeding 200 mg/day (based on the therapeutic tests published) and with rounding to the higher multiple dose of 25 mg (e.g., for a 70 kg patient, the dose will be of 150 mg/day). This dose may be increased to 3 mg/kg/day by the physician if he or she judges this to be appropriate (in cases of partial response at 2 mg/kg/day), in the absence of a study having proven a better effectiveness of azathioprine at the dose of 3 mg/kg/day, however. The maximum dosage must not exceed 200 mg/day, whatever the weight of the patient. On the other hand, the physician may reduce the daily dose by 25 mg to 50 mg in case of a minor side effect to improve the digestive or hematological tolerance of the treatment. If this is not sufficient and/or if the side effect noted is serious, the treatment must be discontinued immediately. When making the decision to introduce azathioprine, the physician currently can use the recommendations of the Network National of Pharmacogenetics (RNGx) published in 2017. Caution concerning genetic deficiency in TPMT (thiopurine methyltransferase) and the risk of rapid development of a myelosuppression is present in the RCP of azathioprine. There has not, however, been any pharmacogenetic recommendation in the RCP, contrary to the case of the American RCP.

The Clinical Pharmacogenetics Implementation Consortium and the RNGx recommend searching for a TPMT deficiency based on the identification of the allelic variants TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C or on the phenotyping of the TPMT, making possible the classification of individuals as a function of their metabolic capacity and proposing adaptation of doses as a function of TPMT status.

No studies, however, have indicated that an adaptation of doses based on the genotypic study would allow reducing the risk of hematological events, particularly during the course of chronic inflammatory diseases of the intestine. Thus, performing this test does not preclude strict hematological monitoring, particularly during the first weeks of treatment.

The concomitant prescription of a treatment for hypouricemia by allopurinol or febuxostat is contraindicated (it increases the medullary toxicity). If allopurinol or febuxostat cannot be discontinued, then another immunosuppressant must be chosen.

Azathioprine is usually prescribed for a duration of 12–24 months (optimal length not defined).

Biological monitoring will include the regular performance of a hemogram of the platelets and of the transaminases (ASAT or ALAT) every week during the first month, then every month for 3 months, and then every 3 months up to cessation.