Over the past decade, new therapies for IBS-C have emerged, but treatment options remain limited for patients unresponsive to secretagogues. Tenapanor, a sodium/hydrogen exchanger 3 (NHE3) inhibitor, offers a novel mechanism of action by reducing sodium absorption in the intestines, leading to increased intestinal fluid and softer stools. Initially developed for hyperphosphatemia, tenapanor demonstrated GI benefits and minimal systemic availability. Preclinical studies showed tenapanor reduced intestinal permeability and visceral hypersensitivity. Early-phase clinical trials confirmed its safety, tolerability, and favorable pharmacodynamics, with mild GI-related adverse events.

Tenapanor’s efficacy was further validated in Phase II and III trials, where it significantly improved both bowel function and abdominal symptoms in patients with IBS-C. The drug met FDA responder endpoints, improved quality of life scores, and was well tolerated aside from diarrhea being the most frequent side effect. Approved by the FDA in 2019, tenapanor is now a recommended option for patients with IBS-C who are unresponsive to first-line treatments like fiber or PEG. Unlike serotonin agonists, tenapanor has no cardiovascular restrictions and presents a distinct, safe alternative. However, treatment decisions will likely continue to be shaped by cost and comparative safety data across available pharmacologic agents.

Reference: Herekar A, Shimoga D, Jehangir A, et al. Tenapanor in the Treatment of Irritable Bowel Syndrome with Constipation: Discovery, Efficacy, and Role in Management. Clin Exp Gastroenterol. 2023 Jun 7;16:79-85. doi: 10.2147/CEG.S384251. PMID: 37309470; PMCID: PMC10257918.