Tenapanor: A Phosphate Blocker for Dialysis and a Treatment for IBS With Constipation

Table of Contents

1. What Tenapanor Is
2. How Tenapanor Works in the Gut
3. How It Differs From Phosphate Binders
4. Approvals and Doses on the Two Labels
5. Safety Facts on the Labels
6. Why High Phosphate Matters in Dialysis
7. The Phosphate Trials
8. What the Pooled Phosphate Evidence Shows
9. The Irritable Bowel Syndrome Trials
10. What Is Not Known
11. Key Research Papers
12. Connections
13. Featured Videos

What Tenapanor Is

Tenapanor is a small-molecule drug taken by mouth twice a day, just before meals. Its target is the sodium/hydrogen exchanger 3 (NHE3), a pump on the inner surface of the small intestine and colon that the labels describe as primarily responsible for absorbing sodium from food. The drug was the first of its kind: the trial reports call it a first-in-class, minimally absorbed inhibitor of this exchanger.

“Minimally absorbed” is meant literally. According to both U.S. labels, blood levels of tenapanor stayed below the laboratory’s detection limit (less than 0.5 ng/mL) in most samples after single and repeated doses. When healthy volunteers swallowed a single radiolabelled dose, about 70% of the label came out in the stool within 120 hours, mostly as the unchanged drug, and about 9% appeared in the urine, mainly as breakdown products. Its main breakdown product, called M1, is described on the labels as inactive against the sodium/hydrogen exchanger 3.

The same molecule is sold under two different product labels by the manufacturer: one for irritable bowel syndrome with constipation (50 mg tablets) and one for phosphate control in dialysis (10, 20 and 30 mg tablets). A 2019 review of the drug’s first approval traces how it was developed for both conditions (Markham 2019).

How Tenapanor Works in the Gut

Sodium and water. By blocking the sodium/hydrogen exchanger 3, tenapanor leaves more sodium in the gut. The irritable bowel syndrome label states that this increases water secretion into the bowel, which speeds the passage of stool and makes it softer. That is the basis of its use in constipation, and it is also the reason diarrhea is its most common side effect in every trial.

Phosphate. Phosphate from food is absorbed in two ways: actively, through carrier proteins inside the gut-lining cells, and passively, by seeping through the tight seals (“tight junctions”) between those cells — the paracellular route. The phosphate label states that blocking the exchanger reduces phosphate absorption by reducing phosphate permeability through this paracellular pathway. The main laboratory study behind that statement (King 2018) worked in rats and mice and in layers of human gut-lining cells grown from stem cells. In those cell layers, tenapanor changed the tight junctions so that electrical resistance across the layer rose and phosphate leaked through less; cell layers lacking the exchanger behaved the same way, and the drug had no effect without it. The authors also report that the drug lowered the amount of the main active phosphate carrier, NaPi2b, which they describe as preventing the gut from compensating through the active route. In healthy volunteers, 15 mg twice a day for 4 days raised the phosphorus in stool and lowered it in urine.

A competing explanation. The exact mechanism is still debated. A 2025 review (Nakanishi 2025) states that the site of action and the precise way blocking the exchanger reduces phosphate uptake “remain incompletely understood”. It proposes, as a hypothesis, that the drug makes the contents of the colon more alkaline, which shifts phosphate into a form that passes less easily through the negatively charged pores between cells. The authors note earlier findings that tenapanor does not change the amount of tight-junction proteins, and suggest the effect is physical and chemical rather than structural. This has not been tested directly.

Gut barrier and pain. The irritable bowel syndrome label adds that, in animal models, tenapanor reduced abdominal pain by lowering visceral hypersensitivity (an over-sensitive gut) and by decreasing intestinal permeability; in a rat model it normalised the excitability of the colon’s sensory nerves. A 2024 review describes the same idea — that the drug may restore the gut barrier through its effect on tight junctions — as resting on preclinical studies (Lacy 2024). How it relieves pain in people has not been shown directly.

How It Differs From Phosphate Binders

Phosphate binders are the standard medicines for high phosphate in dialysis. They are taken with meals and bind phosphate inside the gut so that it leaves in the stool; the types (calcium-based, calcium-free and iron-based) are described on the Hyperphosphatemia page. Tenapanor does not bind anything. It reduces how much phosphate the gut wall lets through, so the trial authors describe it as a “phosphate absorption inhibitor” and its pairing with binders as a “dual-mechanism” treatment (Pergola 2021).

The practical difference the trials stress is the number of pills. Binders are taken with meals, often several at a time. In a 2009 survey of 233 people on dialysis at three U.S. centres, the median person took 19 pills a day, a quarter took more than 25, and phosphate binders made up about half of the total; 62% did not take their binders as prescribed. A higher binder pill count was linked to lower quality of life, and the authors found no relationship between adherence and blood phosphate (Chiu 2009). Tenapanor is one small tablet twice a day.

Several trials measured pill burden directly:

• Japan, 26 weeks (67 patients). With tenapanor 30 mg twice a day added and binders cut back, binder tablets fell from a mean of 14.7 a day to 3.0. 71.6% of patients cut their combined tablet count by at least 30%, and 28.4% stopped binders altogether. Diarrhea, the most frequent drug-related side effect, affected 74.6% (Akizawa 2021).
• Japan, 52 weeks (212 patients). 77.5% reached at least a 30% cut in the daily number of binder tablets plus tenapanor tablets; 51.9% had switched completely from binders by week 50. Diarrhea affected 63.7%, mostly mild (Koiwa 2023).
• United States, 10 weeks (OPTIMIZE, 333 patients). Patients who switched straight from binders to tenapanor cut a median of 4 pills a day; those who halved their binders and added tenapanor cut a median of 1 pill a day (Sprague 2024).

None of these pill-burden studies had a placebo group, and those in Japan were open-label, so every patient knew what they were taking.

Approvals and Doses on the Two Labels

The U.S. Food and Drug Administration (FDA) approval records list two applications for tenapanor:

• Irritable bowel syndrome with constipation — approved 12 September 2019 as a new molecular entity. Indication: treatment of irritable bowel syndrome with constipation in adults. The label dose is 50 mg by mouth twice a day, taken immediately before breakfast (or the first meal of the day) and immediately before dinner. A missed dose is skipped, not doubled.
• High phosphate in dialysis — approved 17 October 2023 as a new indication submitted as a separate application. Indication: to reduce serum phosphorus in adults with chronic kidney disease on dialysis, as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. The label dose is 30 mg by mouth twice a day, just before the first and last meals of the day, with the dose adjusted according to blood phosphorus and stomach and bowel tolerance. The label states that it is not taken right before a hemodialysis session but before the next meal after dialysis, because diarrhea can follow a dose.

Both labels report that taking the drug 5 to 10 minutes before a meal raised the sodium (irritable bowel syndrome label) or phosphorus (phosphate label) lost in the stool compared with taking it with food or on an empty stomach.

The phosphate approval is narrower than the trials that supported it. Two of the three trials named on the label tested tenapanor on its own after binders had been stopped, but the approved use is as an add-on for people whose binders are not enough or not tolerated.

Safety Facts on the Labels

Children. The irritable bowel syndrome label carries a boxed warning, the FDA’s strongest, titled “Risk of serious dehydration in pediatric patients”. Tenapanor is contraindicated (not to be used) in children under 6. In very young rats (under 1 week old, roughly equal to a child under 2) the drug caused weight loss and deaths presumed to be from dehydration. The label states that use is to be avoided from age 6 to under 12, because there are no data in older young rats and no safety or effectiveness data in children, and that safety and effectiveness have not been established under 18. The phosphate label has no boxed warning, but it lists the same contraindication under age 6 “because of the risk of diarrhea and serious dehydration”, and its animal section reports deaths in juvenile rats up to an age roughly equal to a 2-year-old child.

Bowel blockage. Both labels list known or suspected mechanical blockage of the gut as a contraindication.

Diarrhea. Diarrhea is the main side effect on both labels, at different rates:

• In the two irritable bowel syndrome trials, diarrhea affected 16% on tenapanor versus 4% on placebo over 26 weeks, and 15% versus 2% over 12 weeks. Severe diarrhea affected 2.5% on tenapanor versus 0.2% on placebo across both trials. Bloating of the abdomen, gas and dizziness were the other reactions reported in at least 2%. Side effects led 7.6% of tenapanor-treated patients to stop, versus 0.8% on placebo; diarrhea alone accounted for 6.5% versus 0.7%. Among trial patients with reduced kidney function, diarrhea was reported in 20% on tenapanor versus 0.6% on placebo; the label states that the rate did not track the severity of kidney impairment.
• In the dialysis trials, diarrhea affected 43% to 53% of patients and was the only side effect reported in at least 5%. It was severe in 5%, and was linked to dehydration and low blood sodium in fewer than 1%. Most cases were mild to moderate and settled over time or with a lower dose; it was usually reported soon after starting but could appear at any time. The label states that treatment is to be stopped in patients who develop severe diarrhea. In use after approval, itching, rash and hives have been reported.

Interactions. Tenapanor blocks a gut transporter called OATP2B1 that some other drugs use to enter the body. With the blood-pressure drug enalapril, peak levels of enalapril and its active form fell by about 70% and total exposure by 50% to 65%. The phosphate label adds that tenapanor and the potassium binder sodium polystyrene sulfonate are taken at least 3 hours apart.

Pregnancy and breastfeeding. Because almost none of the drug reaches the blood, both labels state that the mother’s use is not expected to expose the fetus, and tenapanor was not detected in breast milk. Data from pregnant women are limited to a small number.

Why High Phosphate Matters in Dialysis

Healthy kidneys clear extra phosphate easily; failed kidneys cannot, and dialysis removes only part of it. The Hyperphosphatemia page explains the effects on blood vessels, bone and skin in detail. The evidence that high phosphate harms people on dialysis comes mainly from large observational studies. In the best known, of 40,538 people on hemodialysis in the United States, phosphorus above 5.0 mg/dL was linked to a higher risk of death after adjustment for other factors, rising step by step from a relative risk of 1.07 at 5.0 to 6.0 mg/dL to 2.02 at 9.0 mg/dL or more. High phosphorus was also linked to hospital stays for heart disease and for fractures (Block 2004).

Such studies show a link, not that lowering phosphate with a drug prevents those harms. The authors of the HiLo trial state that phosphate targets in hemodialysis are based on observational studies. HiLo set out to test a higher target (6.5 mg/dL or more) against a lower one (below 5.5 mg/dL) in 4,400 patients, with death and hospital stays as the outcome. It enrolled 793, was stopped early because enrolment was too low and the two groups’ phosphate levels did not separate enough, and its authors state that no conclusion about the effect of phosphate targets on clinical outcomes can be drawn (Edmonston 2025). In the NORMALIZE study authors’ words, most people with kidney failure and high phosphate have difficulty controlling it despite dialysis, diet and binders (Silva 2023).

The Phosphate Trials

All of the trials below measured blood phosphate. Their main end point was a change in a laboratory number, not death, heart events or fractures. Phosphate is given in mg/dL; the usual adult range is about 2.5 to 4.5 mg/dL.

• Dose-finding trial (4 weeks, 162 patients). After binders were stopped, six tenapanor doses were compared with placebo. Phosphate fell by 0.47 to 1.98 mg/dL depending on dose, against 0.54 mg/dL on placebo. Diarrhea affected 18% to 68% on tenapanor (most at the highest doses) and 12% on placebo. Only 71% completed the trial (Block 2017).
• First phase 3 trial (219 patients). Over 8 weeks on 3, 10 or 30 mg twice a day, phosphate fell by 1.00, 1.02 and 1.19 mg/dL. In a following 4-week withdrawal, phosphate rose by 0.85 mg/dL in patients switched to placebo and by 0.02 mg/dL in those kept on tenapanor (Block 2019). The label reports this difference as 0.7 mg/dL.
• PHREEDOM (52 weeks, 564 patients). Patients were randomised 3:1 to tenapanor 30 mg twice a day or to the binder sevelamer carbonate as a safety comparison. Of the 423 on tenapanor, 255 (60%) completed 26 weeks and were re-randomised to stay on tenapanor or switch to placebo for 12 weeks. Among patients whose phosphate had dropped by at least 1.2 mg/dL, the difference between tenapanor and placebo over the withdrawal was −1.4 mg/dL; across everyone re-randomised (intention-to-treat), it was −0.7 mg/dL. Loose stools affected 53% in the first 26 weeks. Serious adverse events were reported in 16% to 23% on sevelamer and 11% to 17% on tenapanor across the study periods (Block 2021). A correction notice to this paper was published in 2026.
• AMPLIFY (4 weeks, 236 patients). Patients whose phosphate stayed between 5.5 and 10 mg/dL despite binders added tenapanor 30 mg twice a day or placebo. Phosphate fell by 0.84 mg/dL with tenapanor plus binder versus 0.19 mg/dL with placebo plus binder. Diarrhea led 3.4% on tenapanor and 1.7% on placebo to stop (Pergola 2021). This is the add-on situation the U.S. approval covers; the label gives the difference as 0.7 mg/dL.
• NORMALIZE (up to 18 months, 172 patients). An open-label extension of PHREEDOM, aiming for the normal range of 2.5 to 4.5 mg/dL with tenapanor alone or with sevelamer. At the end, 57 of 171 (33%) were in that range, and 8 of the 23 (35%) who were on tenapanor alone. Mean phosphate was 2.0 mg/dL lower than at the PHREEDOM start. Diarrhea affected 22% and led 2% to stop (Silva 2023).
• OPTIMIZE (10 weeks plus extension, 333 patients). An open-label U.S. study of ways to start tenapanor. A phosphate of 5.5 mg/dL or less was reached by 34.4% who switched straight from binders, 38.2% who halved their binders and added tenapanor, and 63.3% of a small group who had never used binders (30 patients). Mean falls were 0.87 to 0.99 mg/dL. 84.4% of those who answered questionnaires reported a better phosphate routine. Diarrhea affected 39.9% (Sprague 2024). A correction notice was published in 2026.
• Japan, added to binders (8 weeks, 169 patients). In patients whose phosphate stayed between 6.1 and 10.0 mg/dL on binders, adding tenapanor lowered phosphate by 2.00 mg/dL versus 0.24 mg/dL with placebo, a difference of 1.76 mg/dL. Diarrhea affected 63.1% versus 14.1%, all mild or moderate (Nitta 2023).
• China (4 weeks, 150 patients). Tenapanor 30 mg twice a day lowered phosphate by 1.17 mg/dL more than placebo; 44.6% versus 10.1% reached below 5.5 mg/dL. Treatment-related diarrhea affected 28.6% versus 2.7% (Gan 2024).
• Peritoneal dialysis, Japan (16 weeks, 54 patients). In a single-group, open-label trial with no placebo, phosphate fell from 7.65 mg/dL to 6.14 at week 8 and 5.44 at week 16. Only 34 of 54 completed the study. Diarrhea affected 74.1%, and 5.6% stopped because of it (Nakayama 2024).

Read together, the size of the effect varies with the design and the patients. In AMPLIFY, the U.S. add-on trial that matches the approved use, phosphate fell by 0.84 versus 0.19 mg/dL; in the Japanese add-on trial, where starting phosphate was higher and the dose was stepped up, it fell by 2.00 versus 0.24 mg/dL. In PHREEDOM the difference halved, from 1.4 to 0.7 mg/dL, when everyone re-randomised was counted instead of only those who had already responded. Diarrhea rates ranged from about one in five to three in four patients.

What the Pooled Phosphate Evidence Shows

A 2025 meta-analysis pooled 8 short placebo-controlled trials (4 to 8 weeks) with 1,001 hemodialysis patients (Khan 2025). Compared with placebo, tenapanor lowered phosphate by a mean of 1.39 mg/dL more, and patients on tenapanor were 2.80 times as likely to reach the common target of 5.5 mg/dL or less. On the other side of the ledger, drug-related side effects, stomach and bowel side effects and diarrhea were all more common with tenapanor. The authors conclude that the drug lowers phosphate and helps patients reach target, “although drug-related side effects were common”, and that because every included trial was short, longer studies are needed to confirm that the effect and the safety last. The same meta-analysis is summarised on the Hyperphosphatemia page.

A 2026 narrative review of 12 studies in hemodialysis and peritoneal dialysis reached a similar reading: phosphate fell more and targets were reached more often on tenapanor, but drug-induced diarrhea may lead people to stop it (Waldman 2026).

The Irritable Bowel Syndrome Trials

Irritable bowel syndrome with constipation combines belly pain with hard or infrequent stools; the condition and its subtypes are described on the Irritable Bowel Syndrome page. The tenapanor trials counted a patient as a “responder” in a given week if worst abdominal pain fell by at least 30% and complete spontaneous bowel movements (bowel movements without a laxative that feel complete) rose by at least one per week, both in the same week. A patient who met that test in at least 6 of the first 12 weeks counted as a responder overall.

• Phase 2 trial (12 weeks, 356 patients). At 50 mg twice a day, 60.7% versus 33.7% on placebo had more complete bowel movements, and 50.0% versus 23.6% met the combined pain-and-bowel test. Diarrhea affected 11.2% at this dose (Chey 2017).
• T3MPO-1 (12 weeks plus 4-week withdrawal, 606 patients). 27.0% on tenapanor 50 mg twice a day versus 18.7% on placebo were combined responders — about 8 more responders per 100 people treated. Abdominal and overall symptoms also improved. Diarrhea led 6.5% on tenapanor and 0.7% on placebo to stop (Chey 2020). On the label, the separate parts were 34% versus 29% for bowel movements and 44% versus 33% for pain.
• T3MPO-2 (26 weeks, 593 patients). 36.5% versus 23.7% were combined responders, about 13 more per 100. Diarrhea was usually short-lived and mild to moderate, and led 6.5% versus 0.7% to stop (Chey 2021). On the label, the parts were 47% versus 33% for bowel movements and 50% versus 38% for pain. A correction notice to this paper was published in 2026.
• T3MPO-3 (open-label extension, 312 patients). Patients from the first two trials took tenapanor for up to 39 more weeks; 90 reached 52 weeks or more. Diarrhea affected 10.6%, with two severe cases and no deaths. There was no placebo group (Lembo 2023).

A 2026 meta-analysis of 3 randomised trials with 1,378 patients found tenapanor 1.54 times as likely as placebo to produce a bowel-movement response and about 1.3 to 1.4 times as likely to improve each abdominal symptom (pain, bloating, cramping, discomfort, fullness). It also found treatment-related side effects 2.3 times as common and side effects leading to stopping about 9 times as common. The authors call for more long-term safety data (Aref 2026).

Put plainly, most people in these trials did not meet the combined responder test on either tenapanor or placebo, and the placebo response was large. The gap between drug and placebo was 8 to 13 responders per 100 people. How the U.S. and other guidelines rank tenapanor against linaclotide, plecanatide, lubiprostone and polyethylene glycol is set out on the Irritable Bowel Syndrome Medications Guide.

What Is Not Known

• Hard outcomes in dialysis. None of the phosphate trials above measured death, heart attacks, strokes, fractures, blood-vessel calcification or hospital stays as their end point. They measured blood phosphate. Whether lowering phosphate with tenapanor leads to fewer of those events has not been tested, and the one trial that tried to test phosphate targets themselves (HiLo) could not answer the question.
• Long-term use. The pooled phosphate trials lasted 4 to 8 weeks. The longer studies (PHREEDOM, NORMALIZE, the 52-week Japanese study, T3MPO-3) were largely open-label or used a withdrawal design, and the label counts only 75 dialysis patients exposed for a year or more.
• The exact mechanism. Whether tenapanor reduces phosphate uptake by changing the tight junctions between gut cells (King 2018) or by changing the chemistry of the gut contents (Nakanishi 2025) is unsettled.
• Head-to-head comparisons. In PHREEDOM, sevelamer served as a safety comparison, not as a test of which drug lowers phosphate better. No trial on this page tested tenapanor against other irritable bowel syndrome drugs.
• Children. There are no safety or effectiveness data in anyone under 18, and the labels rule out use under 6 because of the deaths in young rats.
• Who tolerates it. Diarrhea is common in dialysis patients (43% to 53% on the label), and reviews name it as a reason people stop the drug (Waldman 2026). Which patients can stay on it long term is not well described.

Decisions about phosphate medicines for people on dialysis are made with the kidney care team, which follows blood phosphate on regular tests; more on dialysis care is on the Dialysis and Kidney Transplant page.

Key Research Papers

1. Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. Journal of the American Society of Nephrology. 2004;15(8):2208-18. PubMed PMID: 15284307
2. Chiu YW, Teitelbaum I, Misra M, et al. Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. Clinical Journal of the American Society of Nephrology. 2009;4(6):1089-96. PubMed PMID: 19423571
3. King AJ, Siegel M, He Y, et al. Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Science Translational Medicine. 2018;10(456):eaam6474. PubMed PMID: 30158152
4. Nakanishi T, Drueke TB, Kuragano T. Mechanism of reduced intestinal phosphate absorption by tenapanor: a hypothesis. Clinical Kidney Journal. 2026;19(1):sfaf375. PubMed PMID: 41498065
5. Lacy BE, Rosenbaum D, Edelstein S, et al. Intestinal Permeability, Irritable Bowel Syndrome with Constipation, and the Role of Sodium-Hydrogen Exchanger Isoform 3 (NHE3). Clinical and Experimental Gastroenterology. 2024;17:173-183. PubMed PMID: 38860153
6. Markham A. Tenapanor: First Approval. Drugs. 2019;79(17):1897-1903. PubMed PMID: 31677150
7. Block GA, Rosenbaum DP, Leonsson-Zachrisson M, et al. Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis. Journal of the American Society of Nephrology. 2017;28(6):1933-1942. PubMed PMID: 28159782
8. Block GA, Rosenbaum DP, Yan A, et al. Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial. Journal of the American Society of Nephrology. 2019;30(4):641-652. PubMed PMID: 30846557
9. Block GA, Bleyer AJ, Silva AL, 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(10):1600-1610. PubMed PMID: 35372979 (A correction notice was published in 2026: PubMed PMID 42096282.)
10. Pergola PE, Rosenbaum DP, Yang Y, et al. A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY). Journal of the American Society of Nephrology. 2021;32(6):1465-1473. PubMed PMID: 33766811
11. Silva AL, Chertow GM, Hernandez GT, et al. Tenapanor Improves Long-Term Control of Hyperphosphatemia in Patients Receiving Maintenance Dialysis: the NORMALIZE Study. Kidney360. 2023;4(11):1580-1589. PubMed PMID: 37853560
12. Sprague SM, Weiner DE, Tietjen DP, et al. Tenapanor as Therapy for Hyperphosphatemia in Maintenance Dialysis Patients: Results from the OPTIMIZE Study. Kidney360. 2024;5(5):732-742. PubMed PMID: 38323855 (A correction notice was published in 2026: PubMed PMID 41996191.)
13. Nitta K, Itoyama S, Ikejiri K, et al. Randomized Study of Tenapanor Added to Phosphate Binders for Patients With Refractory Hyperphosphatemia. Kidney International Reports. 2023;8(11):2243-2253. PubMed PMID: 38025211
14. Gan L, Xing L, Xu Y, et al. Tenapanor in Chinese ESRD patients with hyperphosphatemia on haemodialysis: a randomised, phase 3 trial. Clinical Kidney Journal. 2024;17(1):sfad216. PubMed PMID: 38186905
15. Nakayama M, Kobayashi S, Kusakabe M, et al. Tenapanor for peritoneal dialysis patients with hyperphosphatemia: a phase 3 trial. Clinical and Experimental Nephrology. 2024;28(2):153-164. PubMed PMID: 37910313
16. Akizawa T, Sato Y, Ikejiri K, et al. Effect of Tenapanor on Phosphate Binder Pill Burden in Hemodialysis Patients. Kidney International Reports. 2021;6(9):2371-2380. PubMed PMID: 34514198
17. Koiwa F, Sato Y, Ohara M, et al. Long-term safety and decrease of pill burden by tenapanor therapy: a phase 3 open-label study in hemodialysis patients with hyperphosphatemia. Scientific Reports. 2023;13(1):19100. PubMed PMID: 37925471
18. Khan LA, Alam B, Ladhwani NK, et al. Efficacy and Safety of Tenapanor in Hemodialysis Patients with Hyperphosphatemia: A Systematic Review and Meta-Analysis of Short-Term Randomized Controlled Trials. American Journal of Nephrology. 2026;57(3):316-327. PubMed PMID: 40633530
19. Waldman M, Johnson S, Newkirk M, et al. The Impact of Tenapanor on Serum Phosphate in Adult Dialysis Patients: A Narrative Review. Kidney Medicine. 2026;8(3):101237. PubMed PMID: 41993686
20. Edmonston D, Isakova T, Dember LM, et al. Higher versus Lower Phosphate Targets for Patients Undergoing In-Center Hemodialysis: A Randomized Controlled Trial. Journal of the American Society of Nephrology. 2025;36(12):2445-2455. PubMed PMID: 40638247
21. 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. American Journal of Gastroenterology. 2017;112(5):763-774. PubMed PMID: 28244495
22. Chey WD, Lembo AJ, Rosenbaum DP. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1). American Journal of Gastroenterology. 2020;115(2):281-293. PubMed PMID: 31934897
23. Chey WD, Lembo AJ, Yang Y, et al. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2). American Journal of Gastroenterology. 2021;116(6):1294-1303. PubMed PMID: 33337659 (A correction notice was published in 2026: PubMed PMID 42447341.)
24. Lembo AJ, Friedenberg KA, Fogel RP, et al. Long-term safety of tenapanor in patients with irritable bowel syndrome with constipation in the T3MPO-3 study. Neurogastroenterology and Motility. 2023;35(11):e14658. PubMed PMID: 37668173 (A correction notice was published in 2026: PubMed PMID 42252906.)
25. Aref A, Aldemerdash MA, Mohamed I, et al. Efficacy and safety of tenapanor in the management of irritable bowel syndrome with constipation: a systematic review and meta-analysis. European Journal of Gastroenterology & Hepatology. 2026;38(5):554-560. PubMed PMID: 41342330

U.S. Prescribing Information and Approval Records

1. U.S. National Library of Medicine, DailyMed. Tenapanor 50 mg tablets for irritable bowel syndrome with constipation: prescribing information (boxed warning, indication, dosage, contraindications, adverse reactions, mechanism, clinical studies). DailyMed setid 2102da5f-a1a0-4ac7-a1f6-38698cf7273a
2. U.S. National Library of Medicine, DailyMed. Tenapanor 10, 20 and 30 mg tablets for serum phosphorus in chronic kidney disease on dialysis: prescribing information (indication, dosage, contraindications, adverse reactions, mechanism, clinical studies). DailyMed setid c57e279c-0f1b-4238-81b7-4e0dc0cc60c5
3. U.S. Food and Drug Administration, Drugs@FDA. New Drug Application 211801 (original approval 12 September 2019). Drugs@FDA NDA 211801
4. U.S. Food and Drug Administration, Drugs@FDA. New Drug Application 213931 (original approval 17 October 2023). Drugs@FDA NDA 213931

PubMed Topic Searches

1. tenapanor hyperphosphatemia dialysis
2. tenapanor irritable bowel syndrome constipation
3. NHE3 inhibition paracellular phosphate absorption
4. phosphate binder pill burden dialysis
5. serum phosphate target hemodialysis randomized trial

Connections

• Drugs — every drug page on the site
• Hyperphosphatemia (High Phosphate) — why high phosphate matters and how it is treated
• Kidney Disease — chronic kidney disease, its stages and causes
• Dialysis and Kidney Transplant — the setting of the phosphate trials
• High Phosphate and Itching — the itch many people on dialysis describe
• Irritable Bowel Syndrome — the condition and its subtypes
• Irritable Bowel Syndrome Medications Guide — tenapanor beside the other drugs and the guidelines
• Constipation — causes and treatments of constipation

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