Increased liver enzyme levels during azathioprine treatment: Beware of concomitant use of proton pump inhibitors

Azathioprine (AZA) is a purine antagonist, which is frequently used off label in chronic inflammatory skin diseases. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) influence the metabolism of AZA. A reduced enzymatic activity of TMPT is associated with increased 6-thioguaninie nucleotide (6-TGN) levels which may cause severe leukopenia. High TPMT activity is associated with increased 6-methylmercaptopurine (6-MMP) levels (toxic 6-MMP >5700 pmol/8x10(8) RBCs), which is associated with liver toxicity.(1) Alanine transaminase (ALT) >3 upper limits of normal has been identified as a sensitive, but not necessarily specific signal of liver toxicity.(2) In daily practice AZA is often started with a test dose of 50 mg/day for 1-2 weeks. If laboratory tests show no abnormalities, the dose is increased to up to 150-200 mg/day. This article is protected by copyright. All rights reserved.