Auryxia

Description

Auryxia (ferric citrate), a phosphate binder and iron replacement product, is chemically defined as iron (+3), x (1, 2, 3-propanetricarboxylic acid, 2 hydroxy-), y (H2O). The product is available in the form of 210 mg ferric iron tablets for oral administration, which are equivalent to 1 g of ferric citrate. These tablets are film-coated, peach-colored, and oval-shaped, featuring the debossed imprint “KX52.” The inactive ingredients include pregelatinized starch and calcium stearate. The film-coating comprises hypromellose, titanium dioxide, triacetin, and color additives such as 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.

Uses and Indications

Auryxia is indicated for the control of serum phosphorus levels in adult patients with chronic kidney disease who are on dialysis. Additionally, Auryxia serves as an iron replacement product for the treatment of iron deficiency anemia in adult patients with chronic kidney disease who are not on dialysis.

Limitations of Use: Auryxia is not indicated for use in patients with chronic kidney disease who are not on dialysis for the control of serum phosphorus levels.

Dosage and Administration

For the management of hyperphosphatemia in patients with chronic kidney disease on dialysis, the recommended starting dose is 2 tablets administered orally three times per day with meals. The dosage may be adjusted by 1 to 2 tablets as necessary to maintain serum phosphorus levels within the target range, with a maximum allowable dose of 12 tablets per day. Dose titration should occur at intervals of one week or longer, based on clinical response and laboratory results.

In the treatment of iron deficiency anemia in patients with chronic kidney disease not on dialysis, the initial dose is 1 tablet taken orally three times per day with meals. The dosage may be modified as needed to achieve and sustain the hemoglobin target, with a maximum daily dose of 12 tablets. Regular monitoring of hemoglobin levels is recommended to guide dosage adjustments.

Contraindications

Use is contraindicated in patients with iron overload syndromes, such as hemochromatosis, due to the potential for exacerbating the condition.

Warnings and Precautions

Patients receiving intravenous iron therapy should be closely monitored for signs of iron overload. It is essential to regularly assess ferritin levels and transferrin saturation (TSAT) to ensure that iron levels remain within a safe range. In cases where iron overload is detected, a reduction in dosage or discontinuation of the iron product may be necessary to prevent adverse effects.

Iron-containing products pose a significant risk of accidental overdose, particularly in children under the age of six. Healthcare professionals must emphasize the importance of keeping these products out of reach of children. In the event of an accidental overdose, immediate medical attention is critical. Patients or caregivers should contact a healthcare provider or poison control center without delay.

Regular laboratory tests, specifically monitoring ferritin and TSAT, are recommended to manage and mitigate the risk of iron overload effectively.

Side Effects

Patients receiving treatment may experience a range of adverse reactions. The most common adverse reactions observed include discolored feces, diarrhea, constipation, nausea, vomiting, cough, abdominal pain, and hyperkalemia.

In addition to these common reactions, there are important considerations regarding iron overload. Patients should be monitored for ferritin and transferrin saturation (TSAT) levels, as they may require a reduction in dose or discontinuation of intravenous iron if iron overload occurs. Iron overload syndromes, such as hemochromatosis, have also been noted.

It is critical to highlight the risk of accidental overdose of iron-containing products, which is a leading cause of fatal poisoning in children under 6 years of age. Therefore, this product should be kept out of reach of children. In the event of an accidental overdose, it is imperative to contact a doctor or poison control center immediately.

In clinical trials, there was one reported case of elevated iron in the liver, confirmed by biopsy, in a patient on dialysis who was administered intravenous iron along with Auryxia. This underscores the importance of careful monitoring and management of iron levels in patients receiving this treatment.

Drug Interactions

There are currently no documented drug interactions associated with the use of this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are necessary at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Auryxia (ferric citrate), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and efficacy of Auryxia have not been established in pediatric patients. In animal studies, greater gastrointestinal toxicity was observed when ferric citrate was administered by gavage compared to administration with solid food. Given that Auryxia is recommended to be taken with meals, pediatric patients under 6 months of age, who are unlikely to be consuming solid food, may be at an increased risk of gastrointestinal toxicity.

Geriatric Use

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

While no specific dosage adjustments are recommended based solely on age, healthcare providers should remain vigilant in monitoring geriatric patients for any potential adverse effects, given the variability in pharmacokinetics and pharmacodynamics that may occur in this population. Caution is advised when prescribing Auryxia to elderly patients, and individualized treatment plans should be considered to ensure optimal safety and efficacy.

Pregnancy

There are no available data on the use of Auryxia in pregnant patients to inform a drug-associated risk of major birth defects or miscarriage. Animal reproduction studies have not been conducted with Auryxia. However, skeletal and encephalic malformations were observed in neonatal mice when ferric gluconate was administered intraperitoneally to gravid dams during gestation days 7-9. In contrast, oral administration of other ferric or ferrous compounds to gravid CD1-mice and Wistar-rats did not result in fetal malformations.

It is important to note that an overdose of iron in pregnant women may pose risks, including spontaneous abortion, gestational diabetes, and fetal malformation. The estimated background risk of major birth defects and miscarriage for the indicated population remains unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are approximately 2 to 4% and 15 to 20%, respectively. Adverse outcomes in pregnancy can occur regardless of maternal health or medication use.

Additionally, the effect of Auryxia on the absorption of vitamins and other nutrients has not been studied in pregnant women, and it is recognized that the requirements for vitamins and other nutrients are increased during pregnancy. Therefore, healthcare professionals should exercise caution when considering the use of Auryxia in pregnant patients and weigh the potential risks and benefits.

Lactation

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 lactating mother's clinical need for Auryxia and any potential adverse effects on the breastfed child from Auryxia or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

There is no information available regarding dosage adjustments, special monitoring, or precautions for patients with hepatic impairment. Therefore, no specific recommendations can be made for the use of this medication in individuals with compromised liver function. It is advised that healthcare professionals exercise caution and consider the overall clinical context when prescribing this medication to patients with hepatic impairment.

Overdosage

Accidental overdose of iron-containing products poses a significant risk, particularly as it is a leading cause of fatal poisoning in children under 6 years of age. Healthcare professionals should be vigilant in educating caregivers about the dangers associated with these products.

In the event of an accidental overdose, it is imperative to contact a healthcare provider or poison control center immediately. Prompt action is crucial to mitigate potential harm.

For patients experiencing iron overload, it is essential to monitor ferritin levels and transferrin saturation (TSAT). Based on the results of these assessments, patients may require a reduction in the dosage of iron or, in some cases, discontinuation of intravenous iron therapy. Proper management of iron overload is critical to prevent adverse outcomes and ensure patient safety.

Nonclinical Toxicology

Data from carcinogenesis studies indicate that ferric citrate does not exhibit carcinogenic properties in mice and rats when administered via intramuscular or subcutaneous routes. Furthermore, ferric citrate has been shown to be non-mutagenic in the bacterial reverse mutation assay, commonly referred to as the Ames test, and it does not induce clastogenic effects in the chromosomal aberration test conducted with Chinese hamster fibroblasts.

The potential of ferric citrate to impair reproductive performance or to induce fetal malformations has not been assessed in available studies.

Postmarketing Experience

Postmarketing experience has identified that Auryxia may lead to discolored (dark) stools, a phenomenon that is considered normal with oral medications containing iron. Additionally, reports indicate that Auryxia may cause gastrointestinal symptoms, including diarrhea, nausea, constipation, and vomiting, as well as hyperkalemia, abdominal pain, and cough. Patients are advised to report any severe or persistent gastrointestinal symptoms to their physician for further evaluation.

Patient Counseling

Patients should be instructed to take Auryxia as directed, specifically with meals, and to adhere to their prescribed diets. It is important for patients to understand the necessity of dosing any concomitant medications apart from Auryxia to avoid potential interactions.

Patients must be advised to swallow the tablets whole and not to chew or crush them, as doing so may lead to discoloration of the mouth and teeth. They should be informed that Auryxia may cause discolored (dark) stools, which is a normal occurrence associated with oral medications containing iron.

Additionally, patients should be made aware that Auryxia may lead to side effects such as diarrhea, nausea, constipation, vomiting, hyperkalemia, abdominal pain, and cough. They should be encouraged to report any severe or persistent gastrointestinal symptoms to their physician for further evaluation.

Finally, it is crucial to advise patients to keep Auryxia out of the reach of children and to seek immediate medical attention in the event of accidental ingestion by a child.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) in accordance with USP controlled room temperature guidelines.

Additionally, it is essential to protect the product from moisture to maintain its integrity and efficacy. Proper handling and storage conditions are crucial for ensuring the quality of the product throughout its shelf life.

Additional Clinical Information

Clinicians should assess iron parameters, including serum ferritin and transferrin saturation (TSAT), prior to initiating Auryxia and continue to monitor these parameters during therapy. It is important to counsel patients about the potential risks to children and to ensure that Auryxia is kept out of their reach.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Auryxia as submitted by Akebia Therapeutics, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)