Tenapanor
Sources réglementaires consultées
Indications approuvées
- Traitement du syndrome de l'intestin irritable avec constipation chez l'adulte.
Contre-indications
Absolues
- Patients âgés de moins de 6 ans en raison du risque de déshydratation grave.
- Obstruction gastro-intestinale mécanique connue ou suspectée.
Mises en garde cliniques
- Mise en garde encadrée · Avertissement encadré concernant la déshydratation grave chez les patients pédiatriques : contre-indiqué avant 6 ans et à éviter de 6 à 11 ans. La sécurité et l'efficacité ne sont pas établies avant 18 ans. — FDA NDA 211801, IBSRELA; DailyMed setid 2102da5f-a1a0-4ac7-a1f6-38698cf7273a
- Mise en garde majeure · Peut provoquer une diarrhée sévère. Si elle survient, suspendre l'administration et réhydrater. — FDA NDA 211801, IBSRELA; DailyMed setid 2102da5f-a1a0-4ac7-a1f6-38698cf7273a
Interactions médicamenteuses
- ModéréeÉnalapril et autres substrats d'OATP2B1C09AA02
Mécanisme: Le ténapanor inhibe le transporteur intestinal OATP2B1 et peut réduire l'exposition au médicament concomitant ; il a nettement réduit l'exposition à l'énalapril et à l'énalaprilate.
Recommandation: Surveiller les signes de perte d'efficacité et ajuster le médicament concomitant si nécessaire. Avec l'énalapril, surveiller la pression artérielle et n'augmenter sa dose que si cela est cliniquement indiqué.
FDA NDA 211801DailyMed setid 2102da5f-a1a0-4ac7-a1f6-38698cf7273a
Effets indésirables
Communs (≥1%)
Diarrhée · Distension abdominale · Flatulences · Étourdissements
Rares mais graves
Diarrhée sévère avec déshydratation
Grossesse et allaitement
Le ténapanor présente une absorption systémique minimale ; une exposition fœtale n'est donc pas attendue. Les données humaines disponibles sont limitées et n'ont pas mis en évidence de risque lié au médicament. Le ténapanor et son métabolite M1 n'ont pas été détectés dans le lait humain, et aucune exposition du nourrisson allaité n'est attendue.
Bibliographie récente (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).