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Tenapanor (Monograph)

Brand name: Ibsrela
Drug class: GI Drugs, Miscellaneous
- NHE3 Inhibitor
- Sodium/Hydrogen Exchanger Inhibitor
Chemical name: 1,1′-(Butane-1,4-diyl)bis{3-[2-(2-{2-[({3-[(4S)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl]phenyl}sulfonyl)amino]ethoxy}ethoxy)ethyl]urea} dihydrochloride
Molecular formula: C50H68Cl6N8O10S2
CAS number: 1234365-97-9

Medically reviewed by on May 15, 2023. Written by ASHP.


  • Contraindicated in pediatric patients <6 years of age; avoid use in children 6 to <12 years of age. Tenapanor caused deaths, presumably due to dehydration, in young juvenile rats. (See Pediatric Use under Cautions.)

  • Safety and efficacy not established in patients <18 years of age.


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

Uses for Tenapanor

Irritable Bowel Syndrome (IBS) with Constipation

Symptomatic treatment of IBS with constipation in adults.

Tenapanor Dosage and 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.


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


IBS with Constipation

50 mg twice daily.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations. (See Elimination Route under Pharmacokinetics.)

Renal Impairment

Manufacturer makes no specific dosage recommendations. (See Renal Impairment under Cautions.)

Geriatric Patients

Manufacturer makes no specific dosage recommendations. (See Geriatric Use under Cautions.)

Cautions for Tenapanor




Pediatric Risk

Lethality reported in young juvenile rats. Contraindicated in pediatric patients <6 years of age; avoid use in children 6 to <12 years of age. (See Pediatric Use under Cautions.)

Other Warnings and Precautions


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


Minimally absorbed following oral administration (see Absorption under Pharmacokinetics); 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.


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 (see Absorption under Pharmacokinetics) 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. (See Pediatric Use under Cautions.)

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.

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. (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

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. M1 does not inhibit 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





No change in pharmacokinetics of cefadroxil (peptide transporter 1 substrate)


Decreased AUC and peak plasma concentration of M1 metabolite

Effect of itraconazole (CYP3A4 inhibitor) on M1 exposure not considered clinically important since M1 is pharmacologically inactive


No change in pharmacokinetics of midazolam (CYP3A4 substrate)

Tenapanor Pharmacokinetics



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.



Not known whether distributed into milk.

Plasma Protein Binding

Tenapanor: Approximately 99% (in vitro).

M1: Approximately 97% (in vitro).



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 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.





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.


Advice to Patients


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.

Tenapanor Hydrochloride


Dosage Forms


Brand Names




50 mg (of tenapanor)



AHFS DI Essentials™. © Copyright 2024, Selected Revisions May 25, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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