Ibsrela
Tenapanor hydrochloride · Tablet · Oral
Uses
1 INDICATIONS AND USAGE 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. ( 1 )
Dosage and administration
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.
Dosage forms and strengths
Tablets: 50 mg tenapanor supplied as an oval, white to off-white tablet debossed with " 50" on one side and "5791" on the other side. Tablets: 50 mg tenapanor. ( 3 ) Image
Contraindications
4 CONTRAINDICATIONS 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 . Pediatric patients less than 6 years of age. ( 4 , 5.1 , 8.4 ) Patients with known or suspected mechanical gastrointestinal obstruction. ( 4 )
Warnings and precautions
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.
Side effects
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. Table 1: Most Common Adverse Reactions Reported in at least 2% of patients in IBSRELA-treated patients and at an incidence greater than placebo in Patients with IBS-C in Trial 1 (26 Weeks) Adverse Reactions IBSRELA N=293 % Placebo N=300 % Diarrhea 16 4 Abdominal Distension 3 <1 Flatulence 3 1 Dizziness 2 <1 The adverse reaction profile was similar during the 12-week double-blind placebo-controlled treatment period of Trial 2 (610 patients: 309 IBSRELA-treated and 301 placebo-treated) with diarrhea (15% with IBSRELA vs 2% with placebo) and abdominal distension (2% with IBSRELA vs 0% with placebo) as the most common adverse reactions. Adverse Reaction of Special Interest – Severe Diarrhea Severe diarrhea was reported in 2.5% of IBSRELA-treated patients compared to 0.2% of placebo-treated patients during the 26 weeks of Trial 1 and the 12 weeks of Trial 2 [see Warnings and Precautions (5.2) ] . Patients with Renal Impairment In Trials 1 and 2, there were 368 patients (31%) with baseline renal impairment (defined as eGFR less than 90 mL/min/1.73m 2 ). In patients with renal impairment, diarrhea, including severe diarrhea, was reported in 20% (39/194) of IBSRELA-treated patients and 0.6% (1/174) of placebo-treated patients. In patients with normal renal function at baseline, diarrhea, including severe diarrhea, was reported in 13% (53/407) of IBSRELA-treated patients and 3.5% (15/426) of placebo-treated patients. No other differences in the safety profile were reported in the renally impaired subgroup. The incidence of diarrhea and severe diarrhea in IBSRELA-treated patients did not correspond to the severity of renal impairment. Adverse Reactions Leading to Discontinuation Discontinuations due to adverse reactions occurred in 7.6% of IBSRELA-treated patients and 0.8% of placebo-treated patients during the 26 weeks of Trial 1 and the 12 weeks of Trial 2. The most common adverse reaction leading to discontinuation was diarrhea: 6.5% of IBSRELA-treated patients compared to 0.7% of placebo-treated patients. Less Common Adverse Reactions Adverse reactions reported in less than 2% of IBSRELA-treated patients and at an incidence greater than placebo during the 26 weeks of Trial 1 and the 12 weeks of Trial 2 were: rectal bleeding and abnormal gastrointestinal sounds. Hyperkalemia In a trial of another patient population with chronic kidney disease (defined by eGFR from 25 to 70 mL/min/1.73m 2 ) and Type 2 diabetes mellitus, three serious adverse reactions of hyperkalemia resulting in hospitalization were reported in 3 patients (2 IBSRELA-treated patients and 1 placebo-treated patient). 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of IBSRELA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity reactions : pruritis, rash, and urticaria
Drug interactions
7 DRUG INTERACTIONS OATP2B1 Substrates: Potential for reduced exposure of the concomitant drug (e.g., enalapril). Monitor for signs related to loss of efficacy and adjust the dosage of the concomitantly administered drug as needed. ( 7.1 ) 7.1 OATP2B1 Substrates Tenapanor is an inhibitor of intestinal uptake transporter, OATP2B1 [see Clinical Pharmacology (12.3) ] . Drugs which are substrates of OATP2B1 may have reduced exposures when concomitantly taken with IBSRELA. Monitor for signs related to loss of efficacy and adjust the dosage of concomitantly administered drug as needed. Enalapril is a substrate of OATP2B1. When enalapril was coadministered with tenapanor (30 mg twice daily for five days, a dosage 0.6 times the recommended dosage), the peak exposure (C max ) of enalapril and its active metabolite, enalaprilat, decreased by approximately 70% and total systemic exposures (AUC) decreased by approximately 50% to 65% compared to when enalapril was administered alone [see Clinical Pharmacology (12.3) ] . Monitor blood pressure and increase the dosage of enalapril, if needed, when IBSRELA is coadministered with enalapril.
Use in specific populations
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. Tenapanor doses of 10 and 30 mg/kg/day were not tolerated by the pregnant rats and was associated with mortality and moribundity with body weight loss. The 10 and 30 mg/kg dose group animals were sacrificed early, and the fetuses were not examined for intrauterine parameters and fetal morphology. No adverse fetal effects were observed in rats at 1 mg/kg/day (approximately 0.1 times the maximum recommended human dose) and in rabbits at doses up to 45 mg/kg/day (approximately 8.8 times the maximum recommended human dose, based on body surface area). In a pre- and post-natal developmental study in mice, tenapanor at doses up to 200 mg/kg/day (approximately 9.7 times the maximum recommended human dose, based on body surface area) had no effect on pre- and post-natal development. 8.2 Lactation Risk Summary Tenapanor and its major metabolite, M1, were not detected in the breast milk of lactating women (see Data ) . In adults, concentrations of tenapanor were below the limit of quantitation in plasma following multiple doses of IBSRELA [see Clinical Pharmacology (12.3) ] . Maternal use of IBSRELA is not expected to result in exposure to tenapanor or its major metabolite in breastfed infants. There is no information on the effects of tenapanor or its major metabolite on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for IBSRELA and any potential adverse effects on the breastfed infant from IBSRELA or from the underlying maternal condition. Data A clinical lactation study was conducted in seven healthy adult women who were 22 to 37 years of age. Following oral administration of IBSRELA 50 mg twice daily for 3 days, the concentrations of tenapanor and its major metabolite were below the limit of quantitation (<1 ng/mL and <1 ng/mL) in all breast milk samples collected over 24 hours post-dosing. 8.4 Pediatric Use IBSRELA is contraindicated in patients less than 6 years of age. Avoid IBSRELA in patients 6 years to less than 12 years of age [see Contraindications (4) , Warnings and Precautions (5.1) ]. The safety and effectiveness of IBSRELA in patients less than 18 years of age have not been established. In nonclinical studies, deaths occurred in young juvenile rats (less than 1 week-old-rats approximate human age equivalent of less than 2 years of age) following oral administration of tenapanor, as described below in Juvenile Animal Toxicity Data. Juvenile Animal Toxicity Data In a 21-day oral dose range finding toxicity study in juvenile rats, tenapanor was administered to neonatal rats (post-natal day (PND) 5) at doses of 5 and 10 mg/kg/day. Tenapanor was not tolerated in male and female pups and the study was terminated on PND 16 due to mortalities and decreased body weight (24% to 29% reduction in females at the respective dose groups and 33% reduction in males in the 10 mg/kg/day group, compared to control). In a second dose range finding study, tenapanor doses of 0.1, 0.5, 2.5, or 5 mg/kg/day were administered to neonatal rats from PND 5 through PND 24. Treatment-related mortalities were observed at 0.5, 2.5, and 5 mg/kg/day doses. These premature deaths were observed as early as PND 8, with majority of deaths occurring between PND 15 and 25. In the 5 mg/kg/day group, mean body weights were 47% lower for males on PND 23 and 35% lower for females on PND 22 when compared to the controls. Slightly lower mean tibial lengths (5% to 11%) were noted in males and females in the 0.5, 2.5, and 5 mg/kg/day dose groups on PND 25 and correlated with the decrements in body weight noted in these groups. Lower spleen, thymus, and/or ovarian weights were noted at the 0.5, 2.5 and 5 mg/kg/day doses. Tenapanor-related gastrointestinal distension and microscopic bone findings of increased osteoclasts, eroded bone, and/or decreased bone in sternum and/or femorotibial joint were noted in males and females in the 0.5, 2.5 and 5 mg/kg/day dose groups [see Contraindications (4) , Warnings and Precautions (5.1) ]. 8.5 Geriatric Use Of the 1203 patients in placebo-controlled clinical trials of IBSRELA, 100 (8%) were 65 years of age and older. No overall differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Pregnancy
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. Tenapanor doses of 10 and 30 mg/kg/day were not tolerated by the pregnant rats and was associated with mortality and moribundity with body weight loss. The 10 and 30 mg/kg dose group animals were sacrificed early, and the fetuses were not examined for intrauterine parameters and fetal morphology. No adverse fetal effects were observed in rats at 1 mg/kg/day (approximately 0.1 times the maximum recommended human dose) and in rabbits at doses up to 45 mg/kg/day (approximately 8.8 times the maximum recommended human dose, based on body surface area). In a pre- and post-natal developmental study in mice, tenapanor at doses up to 200 mg/kg/day (approximately 9.7 times the maximum recommended human dose, based on body surface area) had no effect on pre- and post-natal development.
Pediatric use
8.4 Pediatric Use IBSRELA is contraindicated in patients less than 6 years of age. Avoid IBSRELA in patients 6 years to less than 12 years of age [see Contraindications (4) , Warnings and Precautions (5.1) ]. The safety and effectiveness of IBSRELA in patients less than 18 years of age have not been established. In nonclinical studies, deaths occurred in young juvenile rats (less than 1 week-old-rats approximate human age equivalent of less than 2 years of age) following oral administration of tenapanor, as described below in Juvenile Animal Toxicity Data. Juvenile Animal Toxicity Data In a 21-day oral dose range finding toxicity study in juvenile rats, tenapanor was administered to neonatal rats (post-natal day (PND) 5) at doses of 5 and 10 mg/kg/day. Tenapanor was not tolerated in male and female pups and the study was terminated on PND 16 due to mortalities and decreased body weight (24% to 29% reduction in females at the respective dose groups and 33% reduction in males in the 10 mg/kg/day group, compared to control). In a second dose range finding study, tenapanor doses of 0.1, 0.5, 2.5, or 5 mg/kg/day were administered to neonatal rats from PND 5 through PND 24. Treatment-related mortalities were observed at 0.5, 2.5, and 5 mg/kg/day doses. These premature deaths were observed as early as PND 8, with majority of deaths occurring between PND 15 and 25. In the 5 mg/kg/day group, mean body weights were 47% lower for males on PND 23 and 35% lower for females on PND 22 when compared to the controls. Slightly lower mean tibial lengths (5% to 11%) were noted in males and females in the 0.5, 2.5, and 5 mg/kg/day dose groups on PND 25 and correlated with the decrements in body weight noted in these groups. Lower spleen, thymus, and/or ovarian weights were noted at the 0.5, 2.5 and 5 mg/kg/day doses. Tenapanor-related gastrointestinal distension and microscopic bone findings of increased osteoclasts, eroded bone, and/or decreased bone in sternum and/or femorotibial joint were noted in males and females in the 0.5, 2.5 and 5 mg/kg/day dose groups [see Contraindications (4) , Warnings and Precautions (5.1) ].
Geriatric use
8.5 Geriatric Use Of the 1203 patients in placebo-controlled clinical trials of IBSRELA, 100 (8%) were 65 years of age and older. No overall differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Overdosage
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) ].
Description
(tenapanor) tablets contain tenapanor hydrochloride as an active ingredient. Tenapanor hydrochloride is a sodium/hydrogen exchanger 3 (NHE3) inhibitor for oral use. The chemical name for tenapanor hydrochloride is 12,15-Dioxa-2,7,9-triazaheptadecanamide, 17-[[[3-[(4S)-6,8-dichloro-1,2,3,4-tetrahydro-2-methyl-4-isoquinolinyl]phenyl]sulphonyl]amino]-N-[2-[2-[2-[[[3-[(4S)-6,8-dichloro-1,2,3,4-tetrahydro-2-methyl-4-isoquinolinyl]phenyl]sulphonyl]amino]ethoxy]ethoxy]ethyl]-8-oxo-, hydrochloride (1:2). Tenapanor hydrochloride has the molecular formula of C 50 H 68 Cl 6 N 8 O 10 S 2 , the molecular weight of 1218 Daltons, and the chemical structure below: Tenapanor hydrochloride is a white to off-white to light brown hygroscopic amorphous solid. It is practically insoluble in water. IBSRELA tablets contain 50 mg of tenapanor (equivalent to 53.2 mg of tenapanor hydrochloride). Inactive ingredients in the tablet are colloidal silicon dioxide, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, propyl gallate, stearic acid, tartaric acid, and the coating agent OPADRY ® , which consists of hypromellose, titanium dioxide and triacetin. Chemical Structure
Mechanism of action
12.1 Mechanism of Action 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. By inhibiting NHE3 on the apical surface of the enterocytes, tenapanor reduces absorption of sodium from the small intestine and colon, resulting in an increase in water secretion into the intestinal lumen, which accelerates intestinal transit time and results in a softer stool consistency. Tenapanor has also been shown to reduce abdominal pain by decreasing visceral hypersensitivity and by decreasing intestinal permeability in animal models. In rat model of colonic hypersensitivity, tenapanor reduced visceral hyperalgesia and normalized colonic sensory neuronal excitability.
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING IBSRELA tablets contain 50 mg tenapanor and are oval, white to off-white, debossed with " 50" on one side and "5791" on the other side. IBSRELA is supplied in a white, opaque, high-density polyethylene bottle containing 60 tablets with a silica gel canister (as the desiccant) and screw-top polypropylene child-resistant cap lined and induction-activated aluminum foil liner (NDC 73154-050-60). Storage Store at room temperature, between 68°F to 77°F (20°C to 25°C). Keep in original container and protect from moisture. Keep the container of IBSRELA tightly closed and in a dry place. Do not remove desiccant from the bottle. Do not subdivide or repackage. Image
Storage
Storage Store at room temperature, between 68°F to 77°F (20°C to 25°C). Keep in original container and protect from moisture. Keep the container of IBSRELA tightly closed and in a dry place. Do not remove desiccant from the bottle. Do not subdivide or repackage. Image
Patient information
Advise the patients to read the FDA-approved patient labeling (Medication Guide). Diarrhea Instruct patients to stop IBSRELA and contact their healthcare provider if they experience severe diarrhea [see Warnings and Precautions (5.2) ] . Accidental Ingestion Accidental ingestion of IBSRELA in children, especially children less than 6 years of age, may result in severe diarrhea and dehydration. Instruct patients to store IBSRELA securely and out of reach of children [see Contraindications (4) , Warnings and Precautions (5.1) ]. Administration and Handling Instructions Instruct Patients: To take IBSRELA immediately prior to breakfast or the first meal of the day and immediately before dinner [see Dosage and Administration (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 [see Dosage and Administration (2) ] . To keep IBSRELA in a dry place. Protect from moisture. Keep in the original bottle. Do not remove desiccant from the bottle. Do not subdivide or repackage. Keep bottles tightly closed [see How Supplied/Storage and Handling (16) ].
Label text from the FDA structured product label by Ardelyx, Inc. (revised May 28, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Tenapanor Hydrochloride in 1 product
Ibsrela NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 73154-050 | Tenapanor Hydrochloride 53.2 mg/1 Tablet | Ardelyx, Inc. | NDA |
Frequently asked questions
What is Ibsrela used for?
1 INDICATIONS AND USAGE 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. ( 1 )
What are the side effects of Ibsrela?
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… See the full label for the complete list.
Who makes Ibsrela?
Ibsrela is listed by 1 labeler in the FDA NDC directory, including Ardelyx, Inc..