Plecanatide (Trulance): how it works, uses and side effects
Clinical review pending
In the US, plecanatide is used in adults with chronic idiopathic constipation or irritable bowel syndrome with constipation. How it works, what the trial data show and which risks to keep in mind.
In the US, plecanatide is used in adults with chronic idiopathic constipation and irritable bowel syndrome with constipation. The drug draws more fluid into the intestine. That softens the stool and makes it easier to move through the gut. The most common side effect is diarrhea. Severe diarrhea can cause the body to lose a substantial amount of fluid.
What is plecanatide?
Plecanatide is sold under the brand name Trulance. It is a peptide that resembles uroguanylin, a hormone the body makes to regulate fluid balance in the intestine. It is used for chronic idiopathic constipation, meaning ongoing constipation with no known cause, and for irritable bowel syndrome with constipation. The drug was developed under the name SP-304 and approved in the US in 2017.
How does plecanatide work?
Plecanatide activates guanylate cyclase C in the lining of the intestine. This raises the level of a messenger molecule there called cyclic GMP. Cyclic GMP promotes the release of chloride, bicarbonate and water into the gut. The extra fluid softens the stool and helps it move along.
As with the body’s own uroguanylin, plecanatide’s activity depends on pH: the slightly acidic environment of the upper small intestine favors its action. According to the developers, this property resembles the body’s natural signaling, which differs from one section of the intestine to the next.
Like other drugs in this class, plecanatide stays largely in the gut. Only very small amounts reach the rest of the body, so the drug acts locally.
In a phase 3 trial in chronic idiopathic constipation, a larger share of participants had a sustained response to plecanatide than to placebo:
| Group | Share with a sustained response |
|---|---|
| Plecanatide | About 21 percent 1 |
| Placebo | Around 10 percent |
To put these numbers in context, we would need the criteria for a “sustained response,” the dose, the follow-up period and measures of statistical uncertainty, none of which are given here. So the figures do not yet tell us how much symptoms improved or for how long. Diarrhea was the most common side effect in this trial.
Is plecanatide FDA-approved?
Yes. The US Food and Drug Administration (FDA) approved plecanatide in 2017 for the treatment of chronic idiopathic constipation in adults. Approval for adults with irritable bowel syndrome with constipation followed later. 2
The US prescribing information carries a prominent warning about severe dehydration in children, meaning a serious loss of body fluid. In the US, this kind of warning is called a “Boxed Warning.” Children under 6 must not be given plecanatide. In children and adolescents aged 6 to under 18, its use should be avoided.
What is plecanatide prescribed for?
Doctors prescribe plecanatide to adults with chronic idiopathic constipation or irritable bowel syndrome with constipation. It is taken once a day, with or without food. The drug is not intended for children.
What are the side effects?
According to the prescribing information, diarrhea is the most common side effect. Severe diarrhea can lead to dehydration, a serious loss of body fluid.
Children under 6 must not take plecanatide. The same applies to people with a known or suspected mechanical bowel obstruction.