Tenapanor Hydrochloride

FDA Drug Information • Also known as: Ibsrela

Brand Names: Ibsrela
Dosage Form: POWDER
Product Type: BULK INGREDIENT

⚠ Boxed Warning (Black Box)

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS IBSRELA is contraindicated in patients less than 6 years of age; in nonclinical studies in young juvenile rats administration of tenapanor caused deaths presumed to be due to dehydration [see Contraindications (4) , Use in Specific Populations (8.4) ]. Avoid use of IBSRELA in patients 6 years to less than 12 years of age [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ]. The safety and effectiveness of IBSRELA have not been established in patients less than 18 years of age [see Use in Specific Populations (8.4) ] . WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS See full prescribing information for complete boxed warning. IBSRELA is contraindicated in patients less than 6 years of age; in young juvenile rats, tenapanor caused death presumed to be due to dehydration. ( 4 , 8.4 ) Avoid use of IBSRELA in patients 6 years to less than 12 years of age. ( 5.1 , 8.4 ) The safety and effectiveness of IBSRELA have not been established in pediatric patients less than 18 years of age. ( 8.4 )

Description

11 DESCRIPTION IBSRELA (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

What Is Tenapanor Hydrochloride 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 )

Dosage and Administration

2 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.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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...

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.

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 )

Pregnancy and Breastfeeding

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...

Overdosage

10 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) ].

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

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.