Tenapanor hydrochloride as a strategy for laxative reduction in hemodialysis patients: a clinical study and review

Abstract Background Constipation is more frequently observed in patients undergoing hemodialysis than in the general population, and the use of laxatives is commonly required. Factors contributing to constipation include use of phosphate and potassium binders, fluid restrictions, reduced intake of dietary fiber reflecting potassium restrictions and limited consumption of plant-based foods, and decreased physical activity. Tenapanor hydrochloride (tenapanor) was approved in Japan in September 2023 as a treatment for hyperphosphatemia in patients on hemodialysis. However, its use has been limited owing to the high frequency of diarrhea as an adverse event. Participants and methods The study population consisted of 15 patients undergoing maintenance hemodialysis who were receiving oral laxatives. One patient developed constipation immediately after the initiation of tenapanor and was excluded from the trial. The remaining 14 patients were included in the analysis. The primary endpoint was the reduction or discontinuation of laxative therapy, while the secondary endpoint was the control of serum phosphorus levels. Tenapanor was initiated at a dose of 2.86–10 mg/day (2.86 mg/day corresponds to 5 mg administered four times per week) without reducing the existing laxative regimen, and the dosage was adjusted as necessary on the basis of the concomitant laxative dosage. Results During the 6-month observation period, stimulant laxatives were discontinued in 10 of 14 patients, while a reduction in nonstimulant laxatives was achieved in only 1 patient. Two adverse events were observed: As previously described, one patient discontinued after a single dose of tenapanor owing to constipation, and another discontinued owing to myocardial infarction. No discontinuations were attributable to diarrhea. Phosphate binders were reduced or discontinued in seven patients. Following tenapanor administration, both the mean serum phosphorus levels and the area under the curve (AUC) tended to decrease, although no significant difference was observed in phosphorus variability, as assessed by standard deviation. Conclusions The administration of tenapanor may allow for the reduction or discontinuation of conventional laxatives in hemodialysis patients who had been receiving them. No significant changes in serum phosphorus levels were observed before and after tenapanor treatment.