Trulance

On January 17, 2017, the FDA approved Trulance (plecanatide; Synergy Pharmaceuticals) to treat chronic idiopathic constipation (CIC) in adult patients. CIC is estimated to affect 42 million individuals in the United States and includes features of persistent constipation with no structural or biochemical explanation. Trulance is thought to work in the upper gastrointestinal tract to stimulate intestinal fluid secretion and support bowel function.^1,2

INDICATIONS AND USAGE

Trulance is indicated for adults for the treatment of CIC, carries a black box warning for a serious risk of dehydration in pediatric patients, and is contraindicated for use in patients younger than 6. Use also should be avoided in patients 6 to younger than 18. The safety and effectiveness of Trulance have not been established in patients younger than 18.²

MECHANISM OF ACTION

Trulance is structurally related to an endogenous guanylate cyclase-C agonist known as uroguanylin. Through activation of guanylate cyclase-C, plecanatide and its active metabolite are thought to increase concentrations of cyclic guanosine monophosphate (cGMP) intracellularly and extracellularly within cells lining the luminal surface of within the intestinal epithelium. Elevated levels of cGMP are thought to stimulate secretion of chloride and bicarbonate to the intestinal lumen through activation of the cystic fibrosis transmembrane conductance regulator ion channel, thereby increasing fluid secretion in the gastrointestinal tract and accelerating intestinal transit.²

DOSAGE AND ADMINISTRATION

Trulance should be administered at the recommended adult dosage of 3 mg orally once daily and may be taken with or without food; tablets should be swallowed whole. Trulance is available in 30-tablet bottles and unit-dose blister packs. Bottles of the medication should not be opened prior to dispensing.²

PHARMACOLOGY AND PHARMACOKINETICS

Following oral administration, plecanatide is minimally absorbed systemically. As a result, standard pharmacokinetic parameters could not be assessed for this medication.²

CLINICAL STUDIES

Trulance was studied in a series of two 12-week, double-blind, placebo-controlled, randomized, multicenter clinical studies. Study 1 included 905 patients, and study 2 included 870 patients. Patients were randomized equally to placebo or Trulance 3 mg daily. The mean age in the studies was 45 years, with 80% of participants being female.²

Patients were required to meet Rome III criteria for irritable bowel syndrome with constipation at least 3 months prior to screening and to have experienced symptoms for at least 6 months prior to receiving a diagnosis. Patient outcomes were assessed on changes from baseline in weekly complete spontaneous bowel movements (CSBMs). Response was defined as experiencing at least 3 CSBMs per week, with an increase from baseline of at least 1 CSBM per week in at least 9 weeks of the 12-week study and in at least 3 of the last 4 weeks of the study.²

In study 1, more than one-fifth (21%) of patients receiving Trulance (n = 453) experienced response versus 10% of patients receiving placebo (n = 452). This result was statistically significant, with an 11 percentage-point treatment difference (95% CI, 6.1%- 15.4%). Similarly, in study 2, the same proportion (21%) of patients experienced response with Trulance (n = 430) versus 13% of patients receiving placebo (n = 440). This result was also statistically significant, with an 8 percentage-point treatment difference (95% CI, 2.6%-12.4%).²

WARNINGS AND PRECAUTIONS

In clinical studies, the most common adverse reaction was diarrhea, which occurred in 5% of patients receiving Trulance 3 mg daily across clinical studies versus 1% of patients receiving placebo. Severe diarrhea was reported in 0.6% of patients receiving treatment; in these instances, treatment should be temporarily discontinued and patients should be rehydrated. For a complete listing of potential adverse reactions with Trulance, please consult the product package insert.

Michael R. Page, PharmD, RPh, has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times®.

References

• FDA approves Trulance for chronic idiopathic constipation [news release]. Silver Spring, MD: FDA; January 10, 2017. www.fda.gov/newsevents/newsroom/pressannouncements/ucm537725.htm. Accessed June 2017.
• Trulance [package insert]. New York, NY: Synergy Pharmaceuticals, Inc; 2017.