Tenapanor
Regulatory sources consulted
Approved indications
- Treatment of irritable bowel syndrome with constipation in adults.
Contraindications
Absolute
- Patients younger than 6 years because of the risk of serious dehydration.
- Known or suspected mechanical gastrointestinal obstruction.
Clinical warnings
- Boxed warning · Boxed warning for serious dehydration in paediatric patients: contraindicated below 6 years and should be avoided from 6 through 11 years. Safety and effectiveness have not been established below 18 years. — FDA NDA 211801, IBSRELA; DailyMed setid 2102da5f-a1a0-4ac7-a1f6-38698cf7273a
- Major warning · May cause severe diarrhoea. If it occurs, suspend dosing and rehydrate. — FDA NDA 211801, IBSRELA; DailyMed setid 2102da5f-a1a0-4ac7-a1f6-38698cf7273a
Drug interactions
- ModerateEnalapril and other OATP2B1 substratesC09AA02
Mechanism: Tenapanor inhibits the intestinal OATP2B1 transporter and may reduce exposure to the concomitant medicine; it substantially reduced exposure to enalapril and enalaprilat.
Recommendation: Monitor for signs of reduced efficacy and adjust the concomitant medicine when needed. With enalapril, monitor blood pressure and increase its dose only when clinically indicated.
FDA NDA 211801DailyMed setid 2102da5f-a1a0-4ac7-a1f6-38698cf7273a
Adverse events
Common (≥1%)
Diarrhoea · Abdominal distension · Flatulence · Dizziness
Rare but serious
Severe diarrhoea with dehydration
Pregnancy and lactation
Tenapanor has minimal systemic absorption, so fetal exposure is not expected; available human data are limited and have not identified a drug-associated risk. Tenapanor and its M1 metabolite were not detected in human milk, and exposure of the breastfed infant is not expected.
Recent literature (PubMed)
Phosphorus is one of the most abundant minerals in the body and plays a critical role in numerous cellular and metabolic processes. Most of the phosphate is deposited in bones, 14% is present in soft tissues as various organic phosphates, and only 1% is found in extracellular space, mainly as inorganic phosphate. The plasma inorganic phosphate concentration is closely maintained between 2.5 and 4.5 mg/dL by intertwined interactions between fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), and vitamin D, which tightly regulate the phosphate trafficking across the gastrointestinal tract, kidneys, and bones. Disruption of the strict hemostatic control of phosphate balance can lead to altered cellular and organ functions that are associated with high morbidity and mortality. In the past three decades, there has been a steady increase in the prevalence of kidney failure (KF) among populations. Individuals with KF have unacceptably high mortality, and well over half of deaths are related to cardiovascular disease. Abnormal phosphate metabolism is one of the major factors that is independently associated with vascular calcification and cardiovascular mortality in KF. In early stages of CKD, adaptive processes involving FGF-23, PTH, and vitamin D occur in response to dietary phosphate load to maintain plasma phosphate level in the normal range. However, as the CKD progresses, these adaptive events are unable to overcome phosphate retention from continued dietary phosphate intake and overt hyperphosphatemia ensues. As these hormonal imbalances and the associated adverse consequences are driven by the underlying hyperphosphatemic state in KF, it appears logical to strictly control serum phosphate. Conventional dialysis is inadequate in removing phosphate and most patients require dietary restrictions and pharmacologic interventions to manage hyperphosphatemia. However, diet control comes with many challenges with adherence and may place patients at risk for ina
Tenapanor, a first-in-class local inhibitor of sodium/hydrogen exchanger isoform 3, acts as a phosphate absorption inhibitor by decreasing paracellular phosphate absorption. Tenapanor alone or with phosphate binders achieved P ≤ 5.5 mg/dl over 10 weeks in 34%–38% of patients taking phosphate binders at baseline. Tenapanor can help adults with CKD on maintenance dialysis achieve normal serum phosphate concentrations. OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dl. Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline P > 5.5 mg/dl and ≤ 10.0 mg/dl, or were PB-naive with baseline P > 4.5 mg/dl and ≤ 10.0 mg/dl, were included in OPTIMIZE. Participants taking PBs at baseline were randomized to switch from PBs to tenapanor (Straight Switch; n=151) or reduce PB dosage by ≥50% and add tenapanor (Binder Reduction; n=152); PB-naive patients started tenapanor alone (Binder-Naive; n=30). Participants received tenapanor 30 mg twice a day for 10 weeks (part A), followed by an elective, 16-week open-label extension (part B). Outcomes included changes from baseline in P, intact fibroblast growth factor 23, parathyroid hormone, serum calcium, and medication burden; patient-reported outcomes; and safety. By part A end point, 34.4% (Straight Switch), 38.2% (Binder Reduction), and 63.3% (Binder-Naive) of patients achieved P ≤ 5.5 mg/dl. Mean P reduction and median pill burden reduction from baseline to part A end point were 0.91±1.7 mg/dl and 4 pills/d for the Straight Switch and 0.99±1.8 mg/dl and 1 pill/d for the Binder Reduction group. The mean P reduction for Binder-Naive patients was 0.87±1.5 mg/dl. Among Straight Switch and Binder Reduction patients who completed patient experience questionnaires, 205 of 243 (84.4%) reported an imp
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction associated with significant disease burden. This American Gastroenterological Association guideline is intended to support practitioners in decisions about the use of medications for the pharmacological management of IBS-C and is an update of a prior technical review and guideline. The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The technical review panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of the following agents: tenapanor, plecanatide, linaclotide, tegaserod, lubiprostone, polyethylene glycol laxatives, tricyclic antidepressants, selective serotonin reuptake inhibitors, and antispasmodics. The Guideline Panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. The panel agreed on 9 recommendations for the management of patients with IBS-C. The panel made a strong recommendation for linaclotide (high certainty) and conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty), polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).