Auryxia

1. Auryxia

Auryxia is a prescription medication used to control serum phosphorous levels in patients with chronic kidney disease (CKD) on dialysis.

Auryxia belongs to a group of drugs called ferric iron-based phosphate binders. These work by binding to phosphate in the body to pass it through the digestive system and eliminate the phosphate through the stool.

This medication comes in tablet form and is taken typically 3 times a day, with meals.

Common side effects of Auryxia include diarrhea, discolored (dark) stools, nausea, constipation, and vomiting.

Mechanism of Action

Phosphate binder; ferric iron binds dietary phosphate in the GI tract and precipitates as ferric phosphate, which is insoluble and is excreted in the feces

By binding phosphate in the GI tract and decreasing absorption, ferric citrate lowers the phosphate concentration in the serum

Absorption

Shown to increase serum iron parameters, including ferritin, iron, and TSAT

In a 52-week clinical trial, mean ferritin levels rose from 593 ng/mL to 895 ng/mL, mean TSAT levels rose from 31% to 39%, and mean iron levels rose from 73 mcg/dL to 88 mcg/dL

Keep this medicine out of the reach of children. An accidental overdose of ferric citrate by a child can be fatal.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Cough
• diarrhea
• difficulty having a bowel movement (stool)
• nausea
• vomiting

• Dark-colored stools

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• It is used to lower high phosphate levels.

Auryxia is contraindicated in patients with iron overload syndromes (e.g., hemochromatosis) [see Warnings and Precautions (5.1)].

Auryxia (ferric citrate) is known chemically as iron (+3), x (1, 2, 3-propanetricarboxylic acid, 2 hydroxy-), y (H2O)

Auryxia 210 mg ferric iron tablets, equivalent to 1g ferric citrate, are film-coated, peach-colored, and oval-shaped tablets debossed with “KX52”. The inactive ingredients are pregelatinized starch and calcium stearate. In addition, the film-coating contains the following inactive ingredients; hypromellose, titanium dioxide, triacetin, and FD&C Yellow #6/Sunset Yellow FCF Aluminum Lake, FD&C Red #40/Allura Red AC Aluminum Lake, and FD&C Blue #2/Indigo Carmine Aluminum Lake.

The ability of Auryxia to lower serum phosphorus in patients with CKD on dialysis was demonstrated in randomized clinical trials: 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 Auryxia. 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 Auryxia (N=292) or active control (calcium acetate and/or sevelamer carbonate; N=149). The majority (>96%) of subjects were on hemodialysis. The starting dose of Auryxia 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.

As shown in the figure below, serum phosphorus levels declined following initiation of therapy. The phosphorus lowering effect was maintained over 52 weeks of treatment.

Figure 1: Serum Phosphorus Control over 52 Weeks

Following completion of the 52-week active-controlled phase, Auryxia-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 Auryxia (N=96) or placebo (N=96). During the placebo-controlled period, the serum phosphorus concentration rose by 2.2 mg/dL on placebo relative to patients who remained on Auryxia.

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 Auryxia for 4 weeks. Auryxia 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.