Tenapanor

Tenapanor is a locally acting inhibitor of the sodium/hydrogen exchanger 3 (NHE3), an antiporter expressed on the apical surface of the small intestine and colon primarily responsible for the absorption of dietary sodium. In vitro and animal studies indicate its major metabolite, M1, is not active against NHE3.

• IBSRELA is indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults. IBSRELA is a sodium/hydrogen exchanger 3 (NHE3) inhibitor indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults.ICD-10: K58.9, K59.00

• IBSRELA is contraindicated in: Patients less than 6 years of age due to the risk of serious dehydration [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ]. Patients with known or suspected mechanical gastrointestinal obstruction .contraindicated

The recommended dosage of IBSRELA in adults is 50 mg orally twice daily. The recommended dosage in adults is 50 mg, orally twice daily. ( 2 ) Take immediately prior to breakfast or the first meal of the day and immediately prior to dinner. ( 2 ) Administration Instructions Take IBSRELA immediately prior to breakfast or the first meal of the day and immediately prior to dinner [see Clinical Pharmacology (12.2) ] . If a dose is missed, skip the missed dose and take the next dose at the regular time. Do not take 2 doses at the same time.

Diarrhea: Patients may experience severe diarrhea. If severe diarrhea occurs, suspend dosing and rehydrate patient. ( 5.2 ) 5.1 Risk of Serious Dehydration in Pediatric Patients IBSRELA is contraindicated in patients below 6 years of age. The safety and effectiveness of IBSRELA in patients less than 18 years of age have not been established. In young juvenile rats (less than 1 week old; approximate human age equivalent of less than 2 years of age), decreased body weight and deaths occurred, presumed to be due to dehydration, following oral administration of tenapanor. There are no data available in older juvenile rats (human age equivalent 2 years to less than 12 years). Avoid the use of IBSRELA in patients 6 years to less than 12 years of age. Although there are no data in older juvenile rats, given the deaths in younger rats and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of IBSRELA in patients 6 years to less than 12 years of age [see Contraindications (4) , Warnings and Precautions (5.2) , Use in Specific Populations (8.4) ] . 5.2 Diarrhea Diarrhea was the most common adverse reaction in two randomized, double-blind, placebo-controlled trials of IBS-C. Severe diarrhea was reported in 2.5% of IBSRELA-treated patients [see Adverse Reactions (6.1) ] . If severe diarrhea occurs, suspend dosing and rehydrate patient.

Most common adverse reactions (≥2%) are diarrhea, abdominal distension, flatulence and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ardelyx at 1-844-427-7352 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described below reflect data from 1203 adult patients with IBS-C in two randomized, double-blind, placebo-controlled clinical trials (Trial 1 and Trial 2). Patients were randomized to receive placebo or IBSRELA 50 mg twice daily for up to 52 weeks. Demographic characteristics were comparable between treatment groups in the two trials [see Clinical Studies (14) ] . Most Common Adverse Reactions The most common adverse reactions reported in at least 2% of patients in IBSRELA-treated patients and at an incidence greater than placebo during the 26-week double-blind placebo-controlled treatment period of Trial 1 are shown in Table 1.

8.1 Pregnancy Risk Summary Tenapanor is minimally absorbed systemically, with plasma concentrations below the limit of quantification (less than 0.5 ng/mL) following oral administration [see Clinical Pharmacology (12.3) ]. Therefore, maternal use is not expected to result in fetal exposure to the drug. The available data on IBSRELA exposure from a small number of pregnant women have not identified any drug associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In reproduction studies with tenapanor in pregnant rats and rabbits, no adverse fetal effects were observed in rats at 0.1 times the maximum recommended human dose and in rabbits at doses up to 8.8 times the maximum recommended human dose (based on body surface area). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study in rats, tenapanor was administered orally to pregnant rats during the period of organogenesis at dose levels of 1, 10 and 30 mg/kg/day.

Metabolism

Absorption Tenapanor is minimally absorbed following repeated twice daily oral administration. Plasma concentrations of tenapanor were below the limit of quantitation (less than 0.5 ng/mL) in the majority of samples from healthy subjects following single and repeated oral administration of IBSRELA 50 mg twice daily.

Based on nonclinical data, overdose of IBSRELA may result in gastrointestinal adverse effects such as diarrhea as a result of exaggerated pharmacology with a risk for dehydration if diarrhea is severe or prolonged [see Warnings and Precautions (5.1) ].

• Sep 12, 2019NDANDA211801Ardelyx Inc
• Oct 17, 2023NDANDA213931Ardelyx Inc

1. 1Diarrhoea37931%
2. 2Off Label Use988.0%
3. 3Product Use Issue826.7%
4. 4Abdominal Distension715.8%
5. 5Hospitalisation705.7%
6. 6Inappropriate Schedule Of Product Administration665.4%
7. 7Therapy Interrupted625.0%
8. 8Nausea584.7%
9. 9Abdominal Pain524.2%
10. 10Product Use In Unapproved Indication483.9%
11. 11Drug Ineffective453.7%
12. 12Constipation443.6%
13. 13Death423.4%
14. 14Abdominal Pain Upper413.3%
15. 15Flatulence393.2%

The 10 most recently updated of 38 ClinicalTrials.gov registrations naming Tenapanor as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study to Assess Safety and Efficacy of Tenapanor for Treatment of IBS-C in Pediatric Patients 12 to Less Than 18 Years
  Active not recruiting · Phase 3 · Interventional · 180 enrolled · Ardelyx
  NCT05643534updated 2026-06-04
• 4-Week, Multi-center Dose-Ranging Study for the IBS-C in Pts. 6 to <12 Yrs
  Active not recruiting · Phase 2 · Interventional · 72 enrolled · Ardelyx
  NCT06553547updated 2026-06-04
• Safety Study of Tenapanor for the Treatment of Pediatric Patients (6 to Less Than 18 Years Old) With IBS-C
  Enrolling by invitation · Phase 3 · Interventional · 150 enrolled · Ardelyx
  NCT05905926updated 2026-06-04
• A 26-Wk Study to Assess Safety & Efficacy of Tenapanor for T/t of Chronic Idiopathic Constipation in Adults
  Recruiting · Phase 3 · Interventional · 692 enrolled · Ardelyx
  NCT07382167updated 2026-06-04
• Assessing Tenapanor as a Treatment of CF-related Constipation.
  Recruiting · Phase 3 · Interventional · 25 enrolled · Massachusetts General Hospital
  NCT06810167updated 2026-03-18
• Effect of Tenapanor on the Metagenomics and Metabolomics of Patients With Irritable Bowel Syndrome With Constipation
  Completed · Phase 4 · Interventional · 36 enrolled · Kyle Staller, MD, MPH
  NCT05995899updated 2026-03-12
• A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk.
  Completed · Phase 4 · Interventional · 18 enrolled · University of Texas Southwestern Medical Center
  NCT06481150updated 2026-02-06
• Tenapanor in Synucleinopathy-Related Constipation
  Recruiting · Phase 2 · Interventional · 30 enrolled · Cedar Valley Digestive Health Center
  NCT06460038updated 2025-02-10
• An Open-label Study to Evaluate the Pharmacokinetics of Oral Tenapanor in Breast Milk of Lactating Females
  Completed · Phase 1 · Interventional · 7 enrolled · Ardelyx
  NCT06203444updated 2024-07-11
• Dose-finding Study of KHK7791 in Hyperphosphatemia Patients
  Completed · Phase 2 · Interventional · 207 enrolled · Kyowa Kirin Co., Ltd.
  NCT03864458updated 2024-03-07

Frequently asked questions

How does Tenapanor work?

Tenapanor is a locally acting inhibitor of the sodium/hydrogen exchanger 3 (NHE3), an antiporter expressed on the apical surface of the small intestine and colon primarily responsible for the absorption of dietary sodium. In vitro and animal studies indicate its major metabolite, M1, is not active against NHE3.

What is Tenapanor used for?

According to FDA labeling, Tenapanor carries indications including: IBSRELA is indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults. IBSRELA is a sodium/hydrogen exchanger 3 (NHE3) inhibitor indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tenapanor?

Tenapanor is classified as Other drugs for constipation, Sodium-Hydrogen Exchanger 3 Inhibitor, Antiporter Interactions, Organic Anion Transporting Polypeptide 2B1 Inhibitors, Sodium-Hydrogen Exchanger 3 Inhibitors, Decreased Inorganic Ion Absorption, Digestive/GI System Activity Alteration.

What are the brand names for Tenapanor?

Tenapanor is marketed under brand names including Ibsrela, Xphozah.

What are the contraindications for Tenapanor?

Tenapanor labeling lists contraindications including: IBSRELA is contraindicated in: Patients less than 6 years of age due to the risk of serious dehydration [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ]. Patients with known or suspected mechanical gastrointestinal obstruction .. Always consult the full prescribing information and a clinician.