Phthalates in 5-Aminosalicylates: Informing Therapeutic Choice and Minimizing Risk

Geoffrey C. Nguyen, MD, PhD, Associate Professor of Medicine, Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, Toronto, ON.

Abstract
5-Aminosalicylates (5-ASAs) are considered first-line therapy for mild to moderate ulcerative colitis because of their proven effectiveness and safety profile, even in pregnancy. One formulation, however, contains dibutyl phthalate (DBP) in its coating. Though DBP may cause disruptions in utero reproductive development and other congenital abnormalities in rodents, it is unclear whether it leads to physiologically significant fetal abnormalities in humans. The US Food and Drug Administration has changed its classification for DBP-containing 5-ASAs from pregnancy category B to pregnancy category C to reflect a greater degree of uncertainty regarding its effect in humans. For pregnant women with ulcerative colitis, the most important message is to take their inflammatory bowel disease (IBD) medications to prevent disease relapse, which may have the most adverse effects on pregnancy. Physicians should, however, discuss with young women who are taking 5-ASA with DBP the benefits and risks of switching to another formulation of 5-ASA without the DBP compound.
Key words: phthalates, 5-aminosalicylate, ulcerative colitis, dibutyl phthalate, pregnancy.

Introduction
Ulcerative colitis (UC) is a chronically relapsing condition involving inflammation of the colon that may lead to substantially impaired quality of life and colectomy in up to one-third of patients. The goals of medical management are to achieve and maintain clinical remission and to prevent long-term complications of long-standing disease. 5-Aminosalicylates (5-ASAs) are the first-line therapy for mild to moderate UC given their excellent safety profile, even during pregnancy.¹ There are various formulations of 5-ASA that enable them to be released at different sites of the gastrointestinal tract (Figure 1). One of these delivery mechanisms is pH dependent, with a release at a pH of 7; this assures that the release occurs predominantly in the colon, which is most effective in UC. Under the trade name Asacol a type of mesalazine, this formulation uses Eudragit S enteric coating, which also contains dibutyl phthalate (DBP).² The use of phthalates as excipients, which are inactive carriers for the active ingredients of a medication, has recently undergone scrutiny because certain phthalates may be associated with endocrine and reproductive toxicities.