FDA approves Patiromer (Veltassa), new drug to treat hyperkalemia.

October 21, 2015

The U.S. Food and Drug Administration approved Veltassa (patiromer for oral suspension) to treat hyperkalemia.

DESCRIPTION

Veltassa is a powder for suspension in water for oral administration. The active ingredient is patiromer sorbitex calcium which consists of the active moiety, patiromer, a non-absorbed potassium-binding polymer, and a calcium-sorbitol counterion.

Each gram of patiromer is equivalent to a nominal amount of 2 grams of patiromer sorbitex calcium. The chemical name for patiromer sorbitex calcium is cross-linked polymer of calcium 2-fluoroprop-2-enoate with diethenylbenzene and octa-1,7-diene, combination with D-glucitol.

patiromer

Each packet of Veltassa contains 8.4 grams, 16.8 grams or 25.2 grams of patiromer, the active moiety. The inactive ingredient is xanthan gum.

CLINICAL PHARMACOLOGY

Mechanism of Action

Veltassa is a non-absorbed, cation exchange polymer that contains a calcium-sorbitol counterion. Veltassa increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract. Binding of potassium reduces the concentration of free potassium in the gastrointestinal lumen, resulting in a reduction of serum potassium levels.

patiromer1

INDICATIONS AND USAGE

Veltassa is a potassium binder indicated for the treatment of hyperkalemia.

Veltassa should not be used as an emergency treatment for lifethreatening hyperkalemia because of its delayed onset of action.

DOSAGE AND ADMINISTRATION

• The recommended starting dose of Veltassa is 8.4 grams administered orally once daily with food.

• Adjust dose by 8.4 grams daily as needed at one week intervals to obtain desired serum potassium target range.

Veltassa Clinical Trial Data

The FDA approval of Veltassa was based on a clinical development program that studied patients who are representative of people who typically experience high blood potassium levels, including people who had CKD, heart failure, diabetes and hypertension.

  • The pivotal Phase 3 OPAL-HK study showed Veltassa significantly decreased potassium levels in hyperkalemic CKD patients taking RAAS inhibitors (mean decrease of -1.01 ± 0.03 mEq/L from baseline; p<0.001). At four weeks, 76 percent of patients had potassium levels in the target range (3.8 to <5.1 mEq/L). During the second part of the trial, patients taking Veltassa 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; p<0.001).
  • The Phase 2 AMETHYST-DN trial evaluated use of Veltassa over 52 weeks in hyperkalemic patients with CKD and type 2 diabetes who were taking RAAS inhibitors. Throughout the year-long study, the majority of patients had potassium levels in the target range (3.8-5.0 mEq/L).
  • An open-label, uncontrolled, Phase 1 study evaluated Veltassa’s onset-of-action in 25 hyperkalemic CKD patients. The mean baseline blood potassium level was 5.9 mEq/L. A statistically significant reduction in blood potassium levels was first observed at 7 hours after the first dose. Potassium levels continued to decline during the 48-hour treatment period of the study (-0.8 mEq/L at 48 hours after the first dose).

In the clinical trials, most adverse reactions were mild to moderate.  The most common adverse reactions in all trials included constipation (7.2 percent: 5.4 percent mild and 1.8 percent moderate), hypomagnesemia (low magnesium levels; 5.3 percent), diarrhea (4.8 percent), nausea (2.3 percent), abdominal discomfort (2.0 percent) and flatulence (2.0 percent).

BOXED WARNING: BINDING TO OTHER ORAL MEDICATIONS

Veltassa has a boxed warning because it binds to many orally administered medications, which could decrease their absorption and reduce their effectiveness. Administer other oral medications at least 6 hours before or 6 hours after Veltassa.

ADVERSE REACTIONS

Most common adverse reactions (incidence ≥ 2%) are constipation, hypomagnesemia, diarrhea, nausea, abdominal discomfort and flatulence.

Contraindications

Veltassa is contraindicated in patients with a history of a hypersensitivity reaction to Veltassa or any of its components.

Worsening of Gastrointestinal Motility  
Use of Veltassa should be avoided in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders, because Veltassa may be ineffective and may worsen gastrointestinal conditions. Patients with a history of bowel obstruction or major gastrointestinal surgery, severe gastrointestinal disorders, or swallowing disorders were not included in clinical studies.

Hypomagnesemia
Veltassa binds to magnesium in the colon, which can lead to hypomagnesemia.  In clinical studies, hypomagnesemia was reported as an adverse reaction in 5.3 percent of patients treated with Veltassa. Approximately 9 percent of patients in clinical trials developed hypomagnesemia with a serum magnesium value <1.4 mg/dL. Doctors should monitor serum magnesium and consider magnesium supplementation in patients who develop low serum magnesium levels.

Veltassa is manufactured by Relypsa Inc. of Redwood City, California.

Source:

FDA News

Prescribing Information