Tenapanor Hydrochloride (Monograph)

Brand name: Ibsrela
Drug class: GI Drugs, Miscellaneous

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

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Introduction

Locally acting inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), a protein that facilitates absorption of intestinal sodium through proton exchange.

Uses for Tenapanor Hydrochloride

Irritable Bowel Syndrome (IBS) with Constipation

Symptomatic treatment of IBS with constipation in adults.

AGA guideline conditionally recommends use of tenapanor (moderate certainty of evidence) in patients with IBS with constipation.

Tenapanor Hydrochloride Dosage and Administration

Administration

Oral Administration

Administer orally twice daily, immediately prior to breakfast or the first meal of the day and immediately prior to dinner. Administration 5–10 minutes before a meal increases 24-hour stool sodium excretion compared with administration under fed or fasting conditions.

If a dose is missed, omit the missed dose and administer the next dose at the regularly scheduled time. Do not administer 2 doses at the same time to make up for a missed dose.

Dosage

Available as tenapanor hydrochloride; dosage expressed in terms of tenapanor.

Adults

IBS with Constipation

Oral

50 mg twice daily.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations.

Geriatric Patients

Manufacturer makes no specific dosage recommendations.

Cautions for Tenapanor Hydrochloride

Contraindications

• Pediatric patients <6 years of age due to the risk of serious dehydration.

• Known or suspected mechanical GI obstruction.

Warnings/Precautions

Warnings

Risk of Serious Dehydration in Pediatric Patients

Lethality reported in young juvenile rats, presumably due to dehydration (see Boxed Warning). Contraindicated in pediatric patients <6 years of age; avoid use in children 6 to <12 years of age.

Other Warnings and Precautions

Diarrhea

In clinical trials in patients with IBS with constipation, diarrhea or severe diarrhea reported in 15–16 or 2.5%, respectively, of patients receiving tenapanor and 2–4 or 0.2%, respectively, of those receiving placebo.

Suspend tenapanor therapy and rehydrate patient if severe diarrhea develops.

Specific Populations

Pregnancy

Minimally absorbed following oral administration; not expected to result in fetal exposure if administered to pregnant women. Limited data regarding tenapanor exposure during pregnancy have not identified any drug-associated risk for major birth defects, spontaneous abortion, or adverse maternal or fetal outcomes.

No adverse fetal or prenatal/postnatal developmental effects observed in animal studies.

Lactation

Not known whether tenapanor distributes into milk, affects milk production, or affects breast-fed infants.

Manufacturer states that the minimal systemic absorption following oral administration will not result in clinically important exposure to breast-fed infants.

Consider benefits of breast-feeding along with the woman's clinical need for tenapanor and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Contraindicated in pediatric patients <6 years of age; avoid use in children 6 to <12 years of age. Safety and efficacy in patients <18 years of age not established.

Deaths reported in juvenile rats (age approximately equivalent to human age of <2 years). Data lacking in older juvenile rats (age approximately equivalent to human age of 2 to <12 years).

One toxicology study in neonatal rats terminated early because of deaths and decreased body weight at dosages of 5–10 mg/kg daily.

In second study in neonatal rats receiving tenapanor (0.1–5 mg/kg daily on postnatal days 5–24), deaths observed at dosages of 0.5–5 mg/kg daily as early as postnatal day 8; most deaths occurred between postnatal days 15 and 25. At 5-mg/kg dosage, mean body weight decreased by 35–47% compared with controls. At dosages of 0.5–5 mg/kg daily, slight (5–11%) reductions in mean tibial length (correlated with decrements in body weight); decreased spleen, thymus, and/or ovary weight; GI distension; and microscopic findings of increased osteoclasts, eroded bone, and/or decreased bone in sternum and/or femorotibial joint observed.

Geriatric Use

No overall differences in efficacy or safety observed between geriatric patients and younger adults; however, possibility of increased sensitivity to the drug cannot be ruled out.

Hepatic Impairment

After single 100 mg dose of tenapanor in patients with moderate hepatic impairment (Child-Pugh class B), plasma concentrations were below limit of quantitation and pharmacokinetic parameters of the drug were indeterminable. Exposure and maximum serum concentration of the major metabolite of tenapanor were reduced in patients with moderate hepatic impairment as compared to healthy subjects; however, reduction in exposure not clinically relevant.

Renal Impairment

Diarrhea reported in 20 or 0.6% of patients with renal impairment (eGFR <90 mL/minute per 1.73 m²) receiving tenapanor or placebo, respectively, compared with 13 or 3.5% of patients with normal renal function receiving these respective treatments. Incidence of diarrhea and severe diarrhea in tenapanor-treated patients did not correspond to severity of renal impairment. No other differences in safety observed in patients with renal impairment.

Common Adverse Effects

Most common adverse effects (≥2%) include: Diarrhea, abdominal distension, flatulence, dizziness.

Drug Interactions

Metabolized principally by CYP3A4/5.

Tenapanor and M1 (major metabolite) do not inhibit CYP isoenzyme 1A2, 2B6, 2C8, 2C9, 2C19, or 2D6 and do not induce CYP isoenzyme 1A2 or 2B6 in vitro.

Tenapanor does not appear to inhibit or induce CYP3A4 in vivo.

Tenapanor and M1 do not inhibit P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), or organic anion transport polypeptide (OATP) 1B1 or 1B3; however, tenapanor is an inhibitor of OATP2B1. M1 does not inhibit P-gp, BCRP, OATP1B1, OATP1B3, organic anion transporter (OAT) 1 or 3, organic cation transporter (OCT) 2, or multidrug and toxin extrusion transporter (MATE) 1 or 2-K.

Tenapanor is not a substrate of P-gp, BCRP, OATP1B1, or OATP1B3. M1 is a substrate of P-gp but is not a substrate of BCRP, OAT1, OAT3, OCT2, MATE-1, or MATE2-K.

Specific Drugs

Tenapanor Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Minimally absorbed following oral administration. Plasma tenapanor concentrations below limit of quantitation in most samples obtained following oral administration of single or repeated (50 mg twice daily) doses.

AUC and peak plasma concentration not determined because of minimal systemic absorption.

Distribution

Extent

Not known whether distributed into milk.

Plasma Protein Binding

Tenapanor: Approximately 99% (in vitro).

M1: Approximately 97% (in vitro).

Elimination

Metabolism

Metabolized principally by CYP3A4/5; major metabolite, M1 (not active against NHE3), is detected at low concentrations in plasma.

Elimination Route

Approximately 70 or 79% of dose eliminated in feces within 120 or 240 hours, respectively, mostly (65% within 144 hours) as unchanged drug. Approximately 9% of dose recovered in urine, mainly as metabolites; 1.5% recovered in urine as M1 within 144 hours.

Half-life

Half-life not determined because of minimal systemic absorption.

Special Populations

End-stage renal disease requiring hemodialysis (eGFR <15 mL/minute per 1.73 m²): Plasma concentrations of M1 not substantially different from those in healthy individuals.

Stability

Storage

Oral

Tablets

20–25°C in original container in a dry place, with lid tightly closed, to protect from moisture; do not remove desiccant from container; do not subdivide or repackage.

Actions

• Locally acting inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), which is expressed on apical surface of the small intestine and colon and is primarily responsible for absorption of dietary sodium from the intestinal lumen through proton exchange.

• Intestinal inhibition of NHE3 by tenapanor reduces sodium absorption from the small intestine and colon, resulting in increased water secretion into the intestinal lumen, which accelerates intestinal transit and softens stool.

• Reduced abdominal pain by decreasing visceral hypersensitivity and intestinal permeability in animal models. Reduced visceral hyperalgesia and normalized colonic sensory neuronal excitability in rat model of colonic hypersensitivity.

Advice to Patients

• Stress importance of reading the manufacturer's patient information (medication guide).

• Instruct patients to discontinue tenapanor and contact their clinician if severe diarrhea occurs.

• Advise patients that accidental ingestion of tenapanor by a child, especially a child <6 years of age, may result in severe diarrhea and dehydration; stress importance of storing tenapanor securely out of the reach of children.

• Instruct patients to take tenapanor twice daily, immediately prior to breakfast or the first meal of the day and immediately before dinner.

• Advise patients that if a dose is missed, the missed dose should be omitted and the next dose taken at the regularly scheduled time. Two doses should not be taken at the same time to make up for a missed dose.

• Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise patients to inform clinicians if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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