IBSRELA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IBSRELA (IBSRELA).
IBSRELA (tenapanor) is a small-molecule inhibitor of the sodium-hydrogen exchanger 3 (NHE3). By inhibiting NHE3 in the gastrointestinal tract, it reduces sodium and phosphate absorption, leading to increased intestinal water secretion and accelerated transit, thereby improving stool consistency and frequency.
| Metabolism | Tenapanor is minimally metabolized, primarily via CYP3A4/5, with the majority of the drug excreted unchanged in feces. |
| Excretion | Primarily fecal as unchanged drug (approximately 95%); renal excretion is negligible (<1%). |
| Half-life | Terminal elimination half-life is approximately 4.8 hours; clinically, this supports once-daily dosing in adults. |
| Protein binding | Approximately 90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 50–60 L (0.7 L/kg for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 70% based on absorption from the gastrointestinal tract. |
| Onset of Action | Oral: Onset within 6–12 hours, with initial bowel movement typically occurring within 24 hours of first dose. |
| Duration of Action | Duration of laxative effect persists for approximately 24 hours after a single oral dose, allowing once-daily dosing for chronic constipation. |
IBRELA (tenapanor) 50 mg orally twice daily, immediately before breakfast and dinner.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. Not recommended for patients with GFR <30 mL/min or end-stage renal disease on dialysis due to lack of data. |
| Liver impairment | No dose adjustment required for mild or moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established; no recommended dosing. |
| Geriatric use | No specific dose adjustment in elderly patients; however, monitor for electrolyte abnormalities due to age-related renal function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IBSRELA (IBSRELA).
| Breastfeeding | No data are available on the presence of tenapanor in human milk, effects on the breastfed infant, or effects on milk production. Tenapanor has low systemic absorption (approximately 2%) following oral administration, so maternal levels are likely low. However, due to the potential for adverse effects in the breastfed infant (e.g., gastrointestinal effects), 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 the drug or underlying maternal condition. |
| Teratogenic Risk | Tenapanor (IBSRELA) has no adequate and well-controlled studies in pregnant women. In animal reproduction studies, no evidence of fetal harm was observed at exposures up to 27 times the human AUC at the recommended dose. However, animal studies are not always predictive of human response. The drug is minimally absorbed systemically, reducing the likelihood of fetal exposure. Risk cannot be completely excluded; therefore, use during pregnancy only if clearly needed. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known or suspected mechanical gastrointestinal obstruction."]
| Precautions | ["Risk of serious dehydration: Use with caution in patients at risk for volume depletion; monitor for signs of dehydration.","Not recommended in patients with known or suspected mechanical gastrointestinal obstruction."] |
| Food/Dietary | No known food interactions. May be taken with or without food. Avoid excessive consumption of high-sugar or high-fat foods that may exacerbate IBS symptoms. |
| Clinical Pearls |
Loading safety data…
| Fetal Monitoring | No specific maternal or fetal monitoring is required beyond standard prenatal care. Because systemic absorption is minimal, tenapanor is not expected to require additional monitoring for fetal effects. However, as with any medication during pregnancy, monitor for maternal adverse effects such as diarrhea or electrolyte disturbances, which could indirectly affect pregnancy. |
| Fertility Effects | In animal fertility studies, tenapanor had no adverse effects on fertility or reproductive performance in male or female rats at exposures up to 12 times the human AUC at the recommended dose. There are no data on human fertility. The low systemic absorption suggests minimal impact on fertility; however, caution is warranted in women attempting conception. |
| IBSRELA (tenapanor) is a sodium-hydrogen exchanger 3 (NHE3) inhibitor that reduces sodium absorption, increasing water in the gut. It is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Monitor for severe diarrhea, which may cause dehydration and electrolyte abnormalities. May be taken with or without food, but should be taken consistently. Discontinue if diarrhea persists or worsens. |
| Patient Advice | Take IBSRELA exactly as prescribed, usually 50 mg twice daily. · Do not take IBSRELA if you have a bowel blockage (intestinal obstruction). · Common side effects include diarrhea, which can be severe. Contact your doctor if you have severe or persistent diarrhea. · Do not take IBSRELA with other laxatives or stool softeners unless directed by your doctor. · Store at room temperature, away from moisture and heat. · If you miss a dose, skip it and take your next dose at the regular time. Do not take two doses at once. |