Plecanatide

Plecanatide is supplied as an oral tablet taken once daily.

Plecanatide closely resembles uroguanylin, a natural hormone that regulates intestinal fluid. Developed as SP-304 and marketed as Trulance, it received US approval in 2017 for chronic idiopathic constipation, with adult IBS-C added later.

Guanylate cyclase-C activation on intestinal lining raises cyclic GMP, promoting chloride, bicarbonate and water secretion. Stool becomes softer and bowel movement is facilitated. Like natural uroguanylin, its signaling is pH sensitive and favors the mildly acidic upper-small-intestinal environment. Developers describe this as closer to regional physiological signaling.

Absorption is minimal and action is mainly local. In a Phase 3 chronic-idiopathic-constipation trial, durable responder rates were about 21% with plecanatide and 10% with placebo. Diarrhea was the most common adverse event.

FDA approval covers adult chronic idiopathic constipation and IBS-C. A boxed warning concerns serious pediatric dehydration: the medicine is contraindicated below age six and should be avoided from age six to under 18.

Adults with the specified constipation conditions take it once a day, with or without food. It is not intended for pediatric use.

Diarrhea is the most frequent adverse effect and can become severe enough to cause dehydration. Contraindications include age under six and known or suspected mechanical bowel obstruction. The pediatric avoidance warning also applies to ages six through 17.