What is the mechanism of action of Trulance (Plecanatide)?

From the Guidelines

Trulance (plecanatide) is recommended as a treatment option for chronic idiopathic constipation (CIC) in adults, with a standard dosage of 3 mg taken orally once daily, as supported by recent clinical practice guidelines 1. The medication works by activating guanylate cyclase-C receptors in the intestines, which increases intestinal fluid secretion and accelerates transit through the gut, thereby relieving constipation. Some key points to consider when prescribing Trulance include:

• The medication typically begins working within the first week of treatment, though some patients may require several weeks to experience full benefits.
• Common side effects include diarrhea, abdominal pain, and bloating.
• Trulance is contraindicated in children under 6 years due to risks of severe dehydration, and in patients with known or suspected mechanical gastrointestinal obstruction.
• Patients should maintain adequate hydration while taking this medication and contact their healthcare provider if they experience severe diarrhea or persistent abdominal pain. The use of plecanatide for the management of CIC has been evaluated in three 12-week randomized double-blinded placebo-controlled trials, which demonstrated its efficacy in increasing intestinal fluid and accelerating GI transit 1. Key considerations for patient management include:
• Monitoring for adverse effects, such as diarrhea and abdominal pain.
• Adjusting the dosage or discontinuing the medication if severe side effects occur.
• Counseling patients on the importance of maintaining adequate hydration and seeking medical attention if they experience severe diarrhea or persistent abdominal pain.

From the FDA Drug Label

Because of increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop diarrhea and its potentially serious consequences. TRULANCE is contraindicated in patients less than 6 years of age Given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of TRULANCE in patients 6 years to less than 18 years of age.

• Contraindication: TRULANCE is contraindicated in patients less than 6 years of age.
• Precaution: Avoid the use of TRULANCE in patients 6 years to less than 18 years of age due to the lack of clinical safety and efficacy data in pediatric patients 2.

From the Research

Overview of Trulance

• Trulance, also known as plecanatide, is a medication used to treat chronic idiopathic constipation and irritable bowel syndrome with constipation 3, 4.
• It works by stimulating guanylate cyclase-C receptors to increase chloride and bicarbonate secretion into the intestine, preventing the absorption of sodium ions, and increasing the secretion of water into the lumen 4.

Efficacy of Trulance

• Studies have shown that plecanatide is effective in increasing complete spontaneous bowel movements (CSBMs) and improving symptoms of constipation in patients with chronic idiopathic constipation and irritable bowel syndrome with constipation 5, 6.
• A phase 2 trial found that plecanatide significantly increased overall CSBM responder rates compared to placebo, and was associated with decreased time to first CSBM and significant increases in CSBM and spontaneous bowel movement (SBM) frequency rates 5.
• Post hoc analyses of placebo-controlled trials found that plecanatide was effective in treating severe constipation in adults with chronic idiopathic constipation and irritable bowel syndrome with constipation 6.

Safety and Tolerability of Trulance

• Plecanatide has been shown to be well-tolerated, with the most frequently reported treatment-emergent adverse event being diarrhea 5.
• Experimental studies have found that plecanatide is significantly better than placebo in reducing constipation severity, straining, stool consistency, bowel movements, and quality of life, with limited cases of diarrhea and no serious adverse events reported 7.
• However, long-term safety data are limited, and patients' affordability of plecanatide may be limited by its costs 7.