Auryxia (Ferric citrate)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved September 2014

Specific Treatments:

hyperphosphatemia in patients with chronic kidney disease

Therapeutic Areas

Find Related Trials for The Following Conditions

General Information

Auryxia (Ferric citrate) is an iron-based compound that has the capacity to bind to phosphate and form non-absorbable complexes. It lowers phosphate levels without raising calcium or aluminum levels.

Ferric citrate is specifically indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis. 

Ferric citrate is supplied as a tablet for oral administration. The recommended starting dose is 2 tablets orally 3 times per day with meals. Serum phosphorus levels should be monitored and the dose of Ferric Citrate titrated in decrements or increments of 1 to 2 tablets per day as needed to maintain serum phosphorus at target levels, up to a maximum dose of 12 tablets daily. Dose can be titrated at 1-week or longer intervals. 

Clinical Results

FDA Approval

The FDA approval of Ferric citrate was based on one 56-week, safety and efficacy trial, consisting of a 52-week active-controlled phase and a 4-week, placebo-controlled, randomized withdrawal period, and one 4-week open-label trial of different fixed doses of Ferric Citrate. Both trials excluded subjects who had an absolute requirement for aluminum containing drugs with meals. 

Long-term, Randomized, Controlled, Safety and Efficacy Trial 

After the 2-week washout period during which phosphate binders were held, patients with a mean serum phosphorus of 7.5 mg/dL during washout were randomized 2:1 to Ferric Citrate (N=292) or active control (calcium acetate and/or sevelamer carbonate; N=149). The majority of subjects were on hemodialysis. The starting dose of Ferric Citrate was 6 tablets/day, divided with meals. The starting dose of active control was the patient’s dose prior to the washout period. The dose of phosphate binder was increased or decreased as needed to maintain serum phosphorus levels between 3.5 and 5.5 mg/dL, to a maximum of 12 tablets/day. Following completion of the 52-week active-controlled phase, Ferric Citrate-treated patients were eligible to enter a 4-week placebo-controlled randomized withdrawal phase, in which patients were re-randomized in a 1:1 ratio to receive Ferric Citrate (N=96) or placebo (N=96). The study met the primary endpoint by demonstrating a highly statistically significant change in serum phosphorus versus placebo over the four-week Placebo Control Period. During the placebo-controlled period, the serum phosphorus concentration rose by 2.2 mg/dL in the placebo arm relative to the Ferric Citrate arm. Ferric citrate also demonstrated statistically significant increases in serum ferritin and transferrin saturation (TSAT), and significant reductions in the use of IV iron and ESAs, versus an active control of sevelamer carbonate and/or calcium acetate over the 52-week Active Control Period of the study. In addition, mean hemoglobin levels were higher in subjects treated with Zerenex as compared to subjects treated with active control.

Fixed-Dose Trial

Following a 1- to 2-week washout from all phosphate-binding agents, 154 patients with hyperphosphatemia (mean serum phosphorus of 7.5 mg/dL) and CKD on dialysis were randomized in a 1:1:1 ratio to 1, 6, or 8 tablets/day of Ferric Citrate for 4 weeks. Ferric Citrate was administered with meals; subjects receiving 1 tablet/day were instructed to take it with their largest meal of the day, and subjects on 6 or 8 tablets/day took divided doses in any distribution with meals. Dose-dependent decreases in serum phosphorus were observed by Day 7 and remained relatively stable for the duration of treatment. The demonstrated reductions from baseline to Week 4 in mean serum phosphorus were significantly greater with 6 and 8 tablets/day than with 1 tablet/day (p<0.0001). Mean reduction in serum phosphorus at Week 4 was 0.1 mg/dL with 1 tablet/day, 1.9 mg/dL with 6 tablets/day, and 2.1 mg/dL with 8 tablets/day. 

 

Side Effects

Adverse effects associated with the use of Ferric citrate may include, but are not limited to, the following:

  • diarrhea
  • discolored feces
  • constipation
  • nausea
  • vomiting

Mechanism of Action

Ferric iron binds dietary phosphate in the GI tract and precipitates as ferric phosphate. This compound is insoluble and is excreted in the stool. By binding phosphate in the GI tract and decreasing absorption, ferric citrate lowers the phosphate concentration in the serum.

Additional Information

For additional information regarding Ferric citrate or hyperphosphatemia in patients with chronic kidney disease, please visit www.keryx.com