Patiromer: a clinical review.

IMPORTANCE

Patiromer FOS (for oral suspension), formerly known as RLY5016, is pending FDA approval for the treatment of hyperkalemia. Once approved, patiromer, as well as a second agent known as sodium zirconium cyclosilicate (ZS-9), will be among the new therapeutic options available to treat hyperkalemia in over 50 years.

OBJECTIVE

The primary objective of this review is to analyze the efficacy and safety of patiromer to treat hyperkalemia and compare its pharmacokinetics to currently available sodium polystyrene sulfonate (SPS) therapy. Patiromer was studied in patients with chronic kidney disease and/or heart failure for both acute and chronic therapy.

EVIDENCE REVIEW

Studies of patiromer were obtained via a literature search of PubMed database and Google Scholar (2000 to the present) using 'patiromer', 'RLY5016', and 'hyperkalemia management' as keywords. Additional references were identified from fda.gov, clinicaltrials.gov, and the pharmaceutical manufacturer, Relypsa Inc.

FINDINGS

Three published clinical trials, ten posters, one clinical trial commentary, three editorials and one oral presentation were obtained. The materials discussed three main clinical trials (PEARL-HF, OPAL-HK and AMETHYST-DN) and examined the safety and efficacy of patiromer in patients with hyperkalemia or at risk for hyperkalemia who have chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), hypertension and/or heart failure (HF) while receiving renin-angiotensin-aldosterone system inhibitors (RAASis). All three studies achieved their primary endpoints and reduced serum potassium. The PEARL-HF study increased the proportion of patients able to titrate their spironolactone dose from 25 mg/day to 50 mg/day in patients with normokalemia who had a history of hyperkalemia or an estimated glomerular filtration rate of <60 mL/min. The OPAL-HK study allowed patients receiving patiromer to remain on their RAASi therapy. The AMETHYST-DN study demonstrated that patiromer reduced and maintained mean serum potassium ≤5.0 mEq/L for up to 1 year, with a low rate of hypokalemia. Adverse events (AEs) were similar between studies. The most commonly reported adverse event was constipation.

CONCLUSIONS AND RELEVANCE

Patiromer is effective in decreasing serum potassium, preventing recurrence of hyperkalemia, and reducing RAASi discontinuation. Compared to current SPS therapy, patiromer may be the preferred option to treat hyperkalemia, once approved. Patiromer is well tolerated and is not associated with serious AEs.