By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a new drug for the treatment of chronic idiopathic constipation (CIC) in adults. Plecanatide is the second guanylate cyclase-C agonist (GC-C; after linaclotide) and is marketed as Trulance.
INDICATIONS
Plecanatide is indicated for the treatment of CIC.1
DOSAGE
The recommended dose is 3 mg taken orally once daily with or without food.1 The tablets can be crushed and mixed with applesauce or administered with water via a nasogastric or gastric feeding tube. Plecanatide is available as 3 mg tablets.
POTENTIAL ADVANTAGES
Plecanatide provides another option for the treatment of CIC.
POTENTIAL DISADVANTAGES
Diarrhea is the most common adverse event (5% vs. 1% for placebo).1 Severe diarrhea was reported in 0.6% (vs. 0.3% for placebo).
COMMENTS
GC-C regulates intestinal fluid and electrolyte homeostasis.2 Stimulation of the GC-C receptor results in fluid movement into the gut lumen and facilitates defecation. Plecanatide’s action is limited to the gastrointestinal tract as the drug is minimally absorbed. The safety and efficacy of plecanatide were evaluated in two randomized, placebo-controlled, 12-week trials.1,5 Subjects experienced constipation in line with the modified Rome III criteria for at least three months. Subjects basically experienced fewer than three complete spontaneous bowel movements (CSBMs) during each of the last weeks prior to randomization, along with straining during defecation, lumpy or hard stools, and sensation of anorectal obstruction/blockage. A CSBM is a bowel movement that occurs in the absence of laxative use within 24 hours and is associated with the feeling of complete evacuation.5 Subjects were randomized to plecanatide 3 mg daily (n = 453 and 430) or placebo (n = 452 and 440). Efficacy was assessed based on CSBMs, with a responder defined as having at least three CSBMs in a given week and an increase of at least one CSBM from baseline in the same week for at least nine weeks out of the 12 treatment weeks and at least three of the last four weeks of the study. Response rates were 21% vs. 10% in study one and 21% vs. 13% for study two, with a treatment difference of 11% (6.1, 15.4) and 8% (2.6, 12.4), respectively. The mean change in CSBMs/week from baseline to week 12 was 1.1 CSBMs/week. Stool frequency, stool consistency, and amount of straining generally improved. When plecanatide was discontinued, subjects generally returned to baseline. There currently are no published comparative studies between linaclotide (Linzess) and plecanatide. Treatment difference for linaclotide were 17% (11, 22.8) and 10% (4.2, 15.7) in two similar studies for the treatment of CIC.4 The cost for plecanatide was not available at the time of this review.
CLINICAL IMPLICATIONS
CIC is persistent constipation for which there is no structural or biochemical explanation.3,6 Plecanatide is the second GC-C agonist to be approved. In contrast to linaclotide, plecanatide currently is not approved for irritable bowel syndrome with constipation.
REFERENCES
- Trulance Prescribing Information. Synergy Pharmaceuticals, Inc. January 2017.
- Jiang C, Xu Q, Wen X, Sun H. Current developments in pharmacological therapeutics for chronic constipation. Acta Pharm Sin B 2015;5:300-309.
- National Institutes of Health. 12-week study of plecanatide for CIC (The CIC3 Study). Available at: http://bit.ly/2lkSakx.
- Linzess Prescribing Information. Allergan USA Inc. and Ironwood Pharmaceuticals Inc. January 2017.
- FDA News Release. FDA approves Trulance for chronic idiopathic constipation. Available at: http://bit.ly/2k5wNlA.
Plecanatide is indicated for the treatment of chronic idiopathic constipation.
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