Patiromer Lowers Serum Potassium When Taken without Food: Comparison to Dosing with Food from an Open-Label, Randomized, Parallel Group Hyperkalemia Study

Abstract

Background: Patiromer is a sodium-free, nonabsorbed, potassium binder approved for treatment of hyperkalemia. This open-label study compares the efficacy and safety of patiromer administered without food versus with food. Methods: Adults with hyperkalemia (potassium ≥5.0 mEq/L) were randomized (1:1) to receive patiromer once daily without food or with food for 4 weeks. The dosage was adjusted (maximum: 25.2 g/day) using a prespecified titration schedule to achieve and maintain potassium within a target range (3.8-5.0 mEq/L). The primary efficacy endpoint was the proportion of patients with serum potassium in the target range at either week 3 or week 4. Safety was assessed by adverse events (AEs) and laboratory testing. Results: Efficacy was evaluated in 112 patients; 65.2% were ≥65 years of age, 75.9% had chronic kidney disease, and 82.1% had diabetes. Baseline mean serum potassium was similar in the without-food (5.44 mEq/L) and with-food (5.34 mEq/L) groups. The primary endpoint was achieved by 87.3% (95% CI 75.5-94.7) and 82.5% (95% CI 70.1-91.3) of patients in the with-food and without-food groups, respectively; least squares mean changes in serum potassium from baseline to week 4 were -0.65 and -0.62 mEq/L, respectively (p < 0.0001). The most common AEs were diarrhea and constipation. Serum K⁺ remained ≥3.5 mEq/L in all patients; 5 patients developed serum magnesium <1.4 mg/dL, including 4 whose baseline magnesium was below the lower limit of normal. Conclusion: Patiromer is equally effective and well tolerated when taken without food or with food, thereby offering the potential for dosing flexibility.

Evidence in support of hyperkalaemia management strategies: A systematic literature review

“…Among the 30 identified RCTs, 10 investigated the safety and efficacy of ZS and organic cation‐exchangers (SPS, CPS, patiromer) for the management of hyperkalaemia through the removal of K + from the body, whereas 6 focused on temporising agents, such as insulin/dextrose, salbutamol, sodium bicarbonate or combinations thereof, in emergency hyperkalaemia treatment . Of note are substantial differences between sample sizes of the identified RCTs, as shown in Figure .…”

“…Of note are substantial differences between sample sizes of the identified RCTs, as shown in Figure . RCTs of ZS (ZS‐002 n = 90, ZS‐003 n = 754, and ZS‐004 [HARMONIZE] n = 251) and patiromer (AMETHYST‐DN n = 306, OPAL‐HK n = 237, TOURMALINE n = 114, and PEARL‐HF n = 104) included the greatest number of patients (1095 and 767, respectively) . By contrast, RCTs of SPS (SKIP n = 33, Nasir 2014 n = 97, Gruy‐Kapral 1998 n = 6) and CPS (Nasir 2014 n = 97) included a total of only 136 patients .…”

“…There were 4 patiromer studies identified, 3 of which included a correction phase (AMETHYST‐DN [phase 2], OPAL‐HK [phase 3], TOURMALINE [phase 4]); data from those phases indicated that patiromer was effective at lowering S‐K + levels within 4 wk of treatment ( P <.001) . In the maintenance phase of both OPAL‐HK and in PEARL‐HF (a phase 2 study on maintenance of normokalaemia), significantly more patients on placebo than on patiromer experienced a recurrence of hyperkalaemia (OPAL‐HK: P <.001, PEARL‐HF: P = .015) …”

Pharmacodynamic effects of the K + binder patiromer in a novel chronic hyperkalemia model in spontaneously hypertensive rats

“…Patiromer is a sodium-free, nonabsorbed K + -binding polymer approved for the treatment of HK in adults (Veltassa, 2015). Patiromer has demonstrated efficacy and was shown to be generally well tolerated when administered chronically across multiple clinical trials in the treatment of HK in patients with CKD, DM, and/or HF (Bakris et al, 2015;Pergola et al, 2017;Weir et al, 2015). Patiromer was also evaluated in the treatment of HK in patients on hemodialysis (Bushinsky et al, 2016), as well as in the prevention of HK in patients with HF treated with spironolactone (Pitt et al, 2011(Pitt et al, , 2018 and resistant hypertension (HTN) and advanced CKD (Agarwal et al, 2019).…”

Safety and efficacy of patiromer use with tacrolimus in kidney transplant recipients

“…Patiromer is a cation-exchange nonabsorbed potassium binder licensed for the treatment of hyperkalemia in adults [2]. The nonabsorbed polymer binds potassium in exchange for calcium, mainly in the distal colon where potassium has the highest concentration in the gastrointestinal tract [3].…”