Patiromer approved for the management of hyperkalemia

In October, FDA approved patiromer (Veltassa; Relypsa) to treat hyperkalemia. Patiromer is an oral potassium binder that is not absorbed systemically. It functions as a cation exchange polymer with calcium as a counterion, leading to fecal excretion of potassium.

Efficacy

A phase III trial (OPAL-HK) studied patiromer in patients with stage 3 or 4 chronic kidney disease (CKD) who took a stable dose of at least one inhibitor of the renin-angiotensin-aldosterone system (RAAS) and had a serum potassium of 5.1 to <6.5 mmol/L at screening. A four-week, single-arm, single-blinded treatment phase allowed patiromer treatment dosed at 4.2 g or 8.4 g twice daily, depending on potassium levels. Those with a potassium of 5.5 mmol/L or higher at baseline and between 3.8 to <5.1 mmol/L at the end of the acute phase were randomized to continue their dose or to placebo, in a double-blind eight-week withdrawal study.

In the acute phase, 243 patients were treated, most (62.1%) having moderate-to-severe hyperkalemia. The mean change in potassium from baseline to week four was -1.01 mmol/L (95% CI, -1.07 to -0.95), with a greater change observed for those with a higher baseline potassium level. Seventy-six percent of patients achieved a target potassium of 3.8 to <5.1 mmol/L at the end of the acute phase, with an average daily dose of 12.8g and 21.4g in those with mild and moderate-to-severe hyperkalemia, respectively.

A total of 107 patients were randomized to the withdrawal phase, where a difference in change of potassium between those randomized to patiromer vs. placebo was found to be 0.72 mmol/L (0.46 to 0.99). The time to first hyperkalemic recurrence was prolonged in those continuing on patiromer. At the end of the withdrawal phase, most patients in the patiromer group (94%) were able to continue their RAAS therapy, as opposed to 44% in the placebo group. 

Long-term efficacy of patiromer was demonstrated in an open-label, 52-week study (AMETHYST-DN) in patients with CKD and type 2 diabetes mellitus, in whom optimization of antihypertensive therapy was indicated. Patients were managed with combinations of losartan and spironolactone, and those developing hyperkalemia during this run-in phase were randomized into one of six patiromer treatment groups, stratified by baseline potassium levels. Doses were titrated to a target potassium of 5.0 mEq/L or less. Potassium levels decreased in all patiromer groups at week 4 and were maintained over 52 weeks. In PEARL-HF, patiromer use led to significant decreases in potassium, lower incidence of hyperkalemia, and more frequent achievement of daily dose of 50 mg spironolactone compared to placebo, in normokalemic patients with heart failure who were started on spironolactone.

Safety

Long-term data from the AMETHYST-DN trial indicate that the most common treatment-related adverse events include hypomagnesemia, mild or moderate constipation, diarrhea, hypomagnesemia, nausea, abdominal discomfort, or flatulence. The drug label suggests magnesium monitoring in patients taking patiromer and magnesium supplementation if necessary.

Patiromer is contraindicated in patients with hypersensitivity to the drug. The binding of patiromer with other orally administered medications may decrease their absorption and efficacy, so administration of other oral drugs should occur six hours before or after the patiromer dose. In addition, patiromer should be avoided in patients with severe constipation, bowel obstruction, or impaction, since the gastrointestinal condition may worsen with patiromer treatment. Patiromer is not indicated for acute, life-threatening hyperkalemia due to its slower onset of action.

Dosing

Patiromer is available in single-use packets of 8.4 g, 16.8 g, or 25.5 g. The recommended dose is 8.4 g daily, titrated weekly by 8.4 g to achieve the desired potassium level, to a maximum of 25.2 g per day. Patiromer should be taken with food in its reconstituted form and not taken dry, heated, or mixed with any heated foods or liquids. Patients should follow manufacturer’s recommended preparation instructions. No dose adjustments are required in renal impairment. Patiromer should be refrigerated; if stored at room temperature, it should be used within three months.