Azathioprine

AZATHIOPRINE

Mechanism of Action

Azathioprine is a synthetic DMARD that acts through its major metabolite, 6-thioguanine. 6-Thioguanine suppresses inosinic acid synthesis, B-cell and T-cell function, immunoglobulin produc-tion, and interleukin-2 secretion .

Pharmacokinetics

The metabolism of azathioprine is bimodal in humans, with rapid metabolizers clearing the drug four times faster than slow metabo-lizers. Production of 6-thioguanine is dependent on thiopurine methyltransferase (TPMT), and patients with low or absent TPMT activity (0.3% of the population) are at particularly high risk of myelosuppression by excess concentrations of the parent drug, if dosage is not adjusted.

Indications

Azathioprine is approved for use in rheumatoid arthritis and is used at a dosage of 2 mg/kg/d. Controlled trials show efficacy in psoriatic arthritis, reactive arthritis, polymyositis, systemic lupus erythematosus, and Behçet’s disease.

Adverse Effects

Azathioprine’s toxicity includes bone marrow suppression, GI disturbances, and some increase in infection risk. As noted, lymphomas may be increased with azathioprine use. Rarely, fever, rash, and hepatotoxicity signal acute allergic reactions.