Auryxia

 Hyperphosphatemia in Chronic Kidney Disease on Dialysis

Auryxia is indicated for the control of serum phosphorus levels in adult patients with chronic kidney disease on dialysis.

 Iron Deficiency Anemia in Chronic Kidney Disease Not on Dialysis

Auryxia is indicated for the treatment of iron deficiency anemia in adult patients with chronic kidney disease not on dialysis.

 Dosage for Hyperphosphatemia in Chronic Kidney Disease on Dialysis

The recommended starting dose is 2 tablets, swallowed whole, 3 times per day with meals. Auryxia tablets must not be chewed or crushed because it may cause discoloration of mouth and teeth. Monitor serum phosphorus levels and titrate the Auryxia dose 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.

In a clinical trial, patients required an average of 8 to 9 tablets a day to control serum phosphorus levels.

 Dosage for Iron Deficiency Anemia in Chronic Kidney Disease Not on Dialysis

The recommended starting dose is 1 tablet, swallowed whole, 3 times per day with meals. Auryxia tablets must not be chewed or crushed because it may cause discoloration of mouth and teeth. Titrate the dose of Auryxia as needed to achieve and maintain hemoglobin at target levels, up to a maximum dose of 12 tablets daily.

In a clinical trial in patients with chronic kidney disease not on dialysis (CKD-NDD), patients required an average of 5 tablets per day to increase hemoglobin levels.

Pregnancy

Risk Summary

There are no available data on Auryxia use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies have not been conducted using Auryxia. Skeletal and encephalic malformation was observed in neonatal mice when ferric gluconate was administered intraperitoneally to gravid dams on gestation days 7-9. However, oral administration of other ferric or ferrous compounds to gravid CD1-mice and Wistar-rats caused no fetal malformation.

An overdose of iron in pregnant women may carry a risk for spontaneous abortion, gestational diabetes and fetal malformation.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

The effect of Auryxia on the absorption of vitamins and other nutrients has not been studied in pregnant women. Requirements for vitamins and other nutrients are increased in pregnancy.

Lactation

Risk Summary

There are no human data regarding the effect of Auryxia in human milk, the effects on the breastfed child, or the effects on milk production. Data from rat studies have shown the transfer of iron into milk by divalent metal transporter-1 (DMT-1) and ferroportin-1 (FPN-1). Hence, there is a possibility of infant exposure when Auryxia is administered to a nursing woman. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Auryxia and any potential adverse effects on the breastfed child from Auryxia or from the underlying maternal condition.

Pediatric Use

The safety and efficacy of Auryxia have not been established in pediatric patients.

Juvenile Animal Toxicity Data

In animal studies, greater gastrointestinal toxicity was observed when ferric citrate was administered by gavage as compared to administration with solid food. Because Auryxia is recommended to be taken with meals and patients under 6 months of age are unlikely to be eating solid food, they may be at greater risk of gastrointestinal toxicity.

Geriatric Use

Clinical studies of Auryxia included 292 subjects aged 65 years and older (104 subjects aged 75 years and older). Overall, the clinical study experience has not identified any obvious differences in responses between the elderly and younger patients in the tolerability or efficacy of Auryxia.

 Iron Overload

Iron absorption from Auryxia may lead to excessive elevations in iron stores. Increases in serum ferritin and transferrin saturation (TSAT) levels were observed in clinical trials. In a 56-week safety and efficacy trial evaluating the control of serum phosphate levels in patients with chronic kidney disease on dialysis in which concomitant use of intravenous iron was permitted, 55 (19%) of patients treated with Auryxia had a ferritin level >1500 ng/mL as compared with 13 (9%) of patients treated with active control.

Assess iron parameters (e.g., serum ferritin and TSAT) prior to initiating Auryxia and monitor iron parameters while on therapy [see Contraindications , Overdosage and Clinical Pharmacology ]. Patients receiving intravenous iron may require a reduction in dose or discontinuation of intravenous iron therapy.

 Risk of Overdosage in Children Due to Accidental Ingestion

Accidental ingestion and resulting overdose of iron-containing products is a leading cause of fatal poisoning in children under 6 years of age [see Overdosage ]. Advise patients of the risks to children and to keep Auryxia out of the reach of children.