New Treatment Option for HYPERKALEMIA: patiromer
This First Report Managed Care Treatment Innovations highlights 2 studies. Weir et al looks at the efficacy and safety of Veltassa (patiromer) in patients with chronic kidney disease (CKD) receiving renin-angiotensin-aldosterone system (RAAS) inhibitors, while Bakris et al evaluates patiromer over 52 weeks in hyperkalemic patients with CKD and type 2 diabetes taking RAAS inhibitors.
TWO STUDIES SHOW PATIROMER EFFECTIVE IN POTASSIUM LOWERING
Among patients with CKD and hyperkalemia who were taking at least 1 RAAS inhibitor, OPAL-HK (A Two-Part, Single-Blind, Phase 3 Study Evaluating the Safety and Efficacy of Patiromer for the Treatment of Hyperkalemia) found that treatment with patiromer was associated with a reduction in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia.
The study had 2 phases—a 4-week, single-group, single-blind treatment phase and an 8-week, placebo-controlled, single-blind, randomized, withdrawal phase. In the initial treatment phase, 243 patients were assigned to 1 of 2 patiromer starting doses (at an initial dose of 4.2 g or 8.4 g twice daily) according to hyperkalemia severity. Patiromer significantly decreased potassium levels from baseline to week 4 (-1.01 ± 0.03 mEq/L; P<.001). At 4 weeks, 76% of patients had potassium levels in the target range (3.5-<5.1 mmol/L). Subsequently, 107 patients were randomly assigned to patiromer or placebo for the second phase of the study. During this phase, patients taking patiromer had no change in median potassium from baseline (0.00 mEq/L), whereas potassium levels significantly increased in the placebo group (0.72 mEq/L). Hyperkalemia recurred in more patients who were switched to placebo versus the patiromer treatment arm through week 8 (60% vs 15%, respectively). Mild-to-moderate constipation was the most common adverse event (AE) reported in 11% of patients.
The effect of treatment with patiromer for up to 52 weeks was evaluated in AMETHYST-DN (RLY5016 in the Treatment of Hyperkalemia in Patients With Hypertension and Diabetic Nephropathy). The phase 2, open-label, dose-ranging, randomized trial included 304 hyperkalemic patients with CKD and type 2 diabetes mellitus on RAAS inhibitor therapy. Patients were stratified by baseline serum potassium level into mild or moderate hyperkalemia groups and randomly assigned in a 1:1:1 ratio to 1 of 3 patiromer doses (mild hyperkalemia: 4.2 g, 8.4 g, or 12.6 g twice daily; moderate hyperkalemia: 8.4 g, 12.6 g, or 16.8 g twice daily).
Patiromer starting doses of 4.2 g to 16.8 g twice daily resulted in statistically significant mean decreases in serum potassium levels after 4 weeks of treatment, lasting through 52 weeks. Over the 52 weeks, hypomagnesemia (7.2%) was the most common treatment-related AE, mild-to-moderate constipation (6.3%) was the most common gastrointestinal AE, and hypokalemia occurred in 5.6% of patients.
Safety Notes
Patiromer has a Boxed Warning because it binds to many other orally administered medications, which could decrease their absorption and reduce their effectiveness. The warning recommends taking it and any other orally administered medication at least 6 hours apart. In clinical trials, the most commonly reported AEs (incidence ≥2%) were constipation, hypomagnesemia, diarrhea, nausea, abdominal discomfort, and flatulence.
Patiromer Facts
•In clinical trials, patiromer significantly reduced blood potassium and kept levels in the target range for up to 1 year in patients with hyper kalemia, allowing for chronic, daily treatment of hyperkalemia.
• Patiromer is manufactured by Relypsa Inc.
Additional Resource
Prescribing Information for patiromer: https://www.relypsa.com/veltassa/prescribing-information/
References
1. Weir MR,Bakris GL,Bushinsky DA,et al.Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Eng J Med. 2015;372(3):211-221.
2. Bakris GL, Pitt B, Weir MR, et al. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: The AMETHYST-DN Randomized Clinical Trial. JAMA. 2015;314(2):151-161.
3. Relypsa announces FDA approval of Veltassa (patiromer) for oral suspension for the treatment of hyperkalemia [news release]. Redwood City, CA. Relypsa Inc. Accessed December 2, 2015.
4. Veltassa [package insert]. Redwood City, CA: Relypsa Inc; October 2015.
