AZATHIOPRINE

By Gary M. White, MD

Note: This is a summary only. Please consult the latest information when prescribing.

Trade Name

Supplied

Dosing

Precautions

Baseline

Monitor

Contraindications

Thiopurine Methyltransferase Activity

The main catabolic pathway is thioprurine methyltransferase (TPMT). Most patients are homozygous for the normal allele, but 11% in one study had lower levels because they were heterozygous and 0.3% had very low or absent levels. It these patients that are at risk for profound immunosuppression with azathioprine. Homozygotes for the high activity may be inadequately immunosuppressed with traditional doses [AD 1995;131;193].

SIDE EFFECTS

The most common side effects are nausea and epigastric pain. In one report, 12% of patients experienced nausea, vomiting, or diarrhea usually within the first few months although it may be immediate. This can be decreased by decreasing the dose, dividing the dose, or taking it with food. However, some patients must stop it because of this. Bone marrow suppression which is the main side effect of concern is manifested by leukopenia, e.g. < 2500.

Increase risk infection

There is some data to suggest that there is an increased risk of infection by e.g. warts, Herpes etc.

Hypersensitivity syndrome

The acute development within several weeks of starting therapy of fever, hypotension, nausea, vomiting, diarrhea, tachycardia and oliguria may rarely occur [CED 1995;20;353].

Increase Neoplasia

Lymphoma, leukemia, breast cancer, and SCC have been reported. Non-Hodgkin’s lymphoma seems to be the neoplasia patients are at most risk to, but studies where imuran was the only immunosuppressive and analogy with CSA suggest that this risk is low. In one study of 755 patients with IBD treated with azathioprine 2 mg/kg/d for a median of 12.5 months, and a follow up of 9 years, the authors concluded that azathioprine did not significantly increase the risk of neoplasia [Lancet 1995;343;1249].

Hypersensitivity Pancreatitis

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