OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Tenapanor – Ibsrela®

DRUG CLASS

Gastrointestinal Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Tenapanor	1234365-97-9	C50-H66-Cl4-N8-O10-S2

ANNOTATED BIBLIOGRAPHY

References updated: 30 April 2023

Abbreviations: IBS, irritable bowel syndrome; NHE3, sodium-hydrogen exchanger isoform 3.

• Zimmerman HJ. Hepatotoxic effects of oncotherapeutic and immunosuppressive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 673-708.

  (Expert review of hepatotoxicity of cancer chemotherapeutic agents published in 1999 before the availability of tenapanor).
• Sharkey KA, MacNaughton WK. Gastrointestinal motility and water flux, emesis, and biliary and pancreatic disease. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 921-44.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2021/211801Orig1s003.pdf.

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA scientific review of the new drug application for safety and efficacy; provides results from pharmacokinetic studies that demonstrated minimal or no detectable serum tenapanor levels after oral administration even in patients with significant hepatic and renal dysfunction or when given with strong inhibitors and inducers of cytochrome P450 [CYP] enzymes).
• Chey WD, Lembo AJ, Rosenbaum DP. Tenapanor treatment of patients with constipation-predominant irritable bowel syndrome: a phase 2, randomized, placebo-controlled efficacy and safety trial. Am J Gastroenterol. 2017;112:763–774. [PMC free article: PMC5418559] [PubMed: 28244495]

  (Among 356 adults with constipation-predominant irritable bowel syndrome treated with tenapanor [5, 20 or 50 mg] twice daily for 12 weeks, response rates were highest with the 50 mg dose [61% vs 34% with placebo] while diarrhea arose in 11% of subjects, “There were no clinically meaningful changes from baseline in laboratory parameters”).
• Block GA, Rosenbaum DP, Yan A, Chertow GM. Efficacy and safety of tenapanor in patients with hyperphosphatemia receiving maintenance hemodialysis: a randomized phase 3 trial. J Am Soc Nephrol. 2019;30:641–652. [PMC free article: PMC6442342] [PubMed: 30846557]

  (Among 219 adults with chronic renal failure on maintenance hemodialysis treated with 3, 10 or 30 mg of tenapanor twice daily for 8 weeks, serum phosphate levels fell in all three groups, but diarrhea was a frequent side effect [30%-50%]; no mention of ALT elevations or hepatotoxicity).
• Markham A. Tenapanor: first approval. Drugs. 2019;79:1897–1903. [PubMed: 31677150]

  (Review of the mechanism of action, history of development, pharmacology, clinical efficacy, and safety of tenapanor shortly after its approval for use in the US, discusses the gastrointestinal side effects but does not mention ALT elevations or hepatotoxicity).
• Chey WD, Lembo AJ. Rosenbaum aDP. Efficacy of tenapanor in treating patients with irritable bowel syndrome with constipation: a 12-week, placebo-controlled phase 3 trial (T3MPO-1). Am J Gastroenterol. 2020;115:281–293. [PMC free article: PMC7771640] [PubMed: 31934897]

  (Among 606 adults with constipation-predominant IBS treated with tenapanor [50 mg] or placebo twice daily for 12 weeks, tenapanor treated patients had greater increases in complete spontaneous bowel movements and more reductions in abdominal symptoms, while adverse events included diarrhea [15% vs 2%] and nausea [2.6% vs 1.7%], discontinuation rates were 7.4% vs <1%, and there were no drug related deaths or serious adverse events and “no notable changes from baseline were observed in laboratory parameters”).
• Block GA, Bleyer AJ, Silva AL, Weiner DE, Lynn RI, Yang Y, Rosenbaum DP, et al. Safety and efficacy of tenapanor for long-term serum phosphate control in maintenance dialysis: a 52-week randomized phase 3 trial (PHREEDOM). Kidney360. 2021;2:1600-1610. [PMC free article: PMC8785778] [PubMed: 35372979]

  (Among 564 patients with chronic renal failure on maintenance dialysis with hyperphosphatemia treated with either tenapanor or sevelamer carbonate for 26 weeks, those on tenapanor with improvements in serum phosphate levels being later re-randomized to continue therapy or stop tenapanor, side effects during therapy were predominantly gastrointestinal with diarrhea arising in 52% taking tenapanor, being severe in 6% and resulting in withdrawal in 16%; no mention of ALT levels or hepatotoxicity).
• Chey WD, Lembo AJ, Yang Y, Rosenbaum DP. Efficacy of tenapanor in treating patients with irritable bowel syndrome with constipation: a 26-week, placebo-controlled phase 3 trial (T3MPO-2). Am J Gastroenterol. 2021;116:1294–1303. [PMC free article: PMC8183489] [PubMed: 33337659]

  (Among 593 adults with constipation-predominant IBS treated with tenapanor [50 mg] or placebo twice daily for 26 weeks, response rates were higher for tenapanor [37% vs 24%] and the main side effect was diarrhea [16% vs 4%], which led to early discontinuation in 6.5% vs 0.7%, and “Generally, there was no evidence of clinically significant differences between treatment groups in electrolytes and other laboratory parameters”).
• Tenapanor (Ibsrela) for irritable bowel syndrome with constipation. Med Lett Drugs Ther. 2022;64(1652):91–94. [PubMed: 35657365]

  (Concise review of the mechanism of action, clinical efficacy, safety, and costs of tenapanor shortly after its approval for use in adults with constipation-predominant IBS, discusses the side effects of diarrhea, abdominal distension, flatulence, and dehydration, but does not mention ALT elevations or hepatotoxicity).