Tetraferric tricitrate decahydrate

Uses and Indications

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

Dosage and Administration

The recommended dosage for Ferric Citrate, also known as Auryxia, varies based on the indication and patient condition.

For the management of hyperphosphatemia in patients with chronic kidney disease on dialysis, the starting dose is 2 tablets taken 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 adjustments can be made at intervals of one week or longer.

In the case of iron deficiency anemia in patients with chronic kidney disease who are not on dialysis, the initial dosage is 1 tablet taken orally three times per day with meals. Similar to the previous indication, the dose may be adjusted as needed to achieve and maintain the hemoglobin target, with a maximum of 12 tablets per day.

It is essential for healthcare professionals to monitor patients closely and adjust dosages accordingly to ensure optimal therapeutic outcomes.

Contraindications

Iron overload syndromes, such as hemochromatosis, are contraindications for the use of Ferric Citrate and Auryxia. Due to the risk of exacerbating these conditions, the use of these medications is not recommended in affected patients.

Warnings and Precautions

Iron overload is a significant concern when using Ferric Citrate or Auryxia. It is essential to monitor ferritin and transferrin saturation (TSAT) levels regularly, as patients may require a reduction in dose or discontinuation of intravenous iron based on these results.

Serious Warnings

Accidental overdose of iron-containing products poses a serious risk, particularly in children under 6 years of age, where it is a leading cause of fatal poisoning. Therefore, it is crucial to keep this product out of reach of children. In the event of an accidental overdose, immediate medical attention should be sought by calling a doctor or poison control center.

Monitoring Requirements

Regular laboratory tests are recommended to monitor ferritin and TSAT levels to prevent iron overload.

Emergency Medical Help

In case of accidental overdose, it is imperative to call a doctor or poison control center immediately for assistance.

No additional general precautions or specific instructions to stop taking the medication and contact a doctor were specified in the provided data.

Side Effects

Patients may experience a range of adverse reactions while using Ferric Citrate (Auryxia). The most common adverse reactions reported include:

• Discolored feces

• Diarrhea

• Constipation

• Nausea

• Vomiting

• Cough

• Abdominal pain

• 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 therapy.

There is a significant risk associated with accidental overdose of iron-containing products, which is a leading cause of fatal poisoning in children under 6 years of age. It is crucial to keep this product out of reach of children. In the event of an accidental overdose, patients should seek immediate medical attention or contact a poison control center.

Furthermore, iron overload syndromes, such as hemochromatosis, may occur. 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 Ferric Citrate tablets (Auryxia).

Drug Interactions

When using Ferric Citrate, it is important to consider potential drug interactions that may arise during treatment. Clinically significant interactions may necessitate the separation of the timing of administration to mitigate adverse effects. Additionally, monitoring clinical responses or blood levels of concomitant medications is advised to ensure patient safety and therapeutic efficacy.

In contrast, Auryxia does not provide specific information regarding drug interactions or interactions with laboratory tests. Therefore, no additional precautions or monitoring strategies are outlined for this formulation.

Pediatric Use

The safety and efficacy of ferric citrate tablets, marketed as 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. Since ferric citrate is recommended to be taken with meals, infants 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 ferric citrate and Auryxia included a total of 292 subjects aged 65 years and older, with 104 subjects aged 75 years and older. The clinical study experience for both medications has not identified any significant differences in tolerability or efficacy between geriatric patients and younger patients. Therefore, no specific dosage adjustments are recommended based solely on age. However, healthcare providers should continue to monitor elderly patients for any potential adverse effects or changes in response to treatment, as individual patient factors may still necessitate careful consideration.

Pregnancy

There are no available data on the use of ferric citrate or Auryxia in pregnant patients to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies have not been conducted for either product. Notably, skeletal and encephalic malformations were 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 did not result in fetal malformations.

An overdose of iron in pregnant women may carry risks for spontaneous abortion, gestational diabetes, and fetal malformation. The estimated background risk of major birth defects and miscarriage for the indicated population remains unknown. Adverse outcomes in pregnancy can occur regardless of maternal health or medication use. 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.

The effects of ferric citrate and Auryxia on the absorption of vitamins and other nutrients have not been studied in pregnant women, and it is important to note that requirements for vitamins and other nutrients are increased during pregnancy. Therefore, healthcare providers should exercise caution and consider these factors when prescribing these medications to pregnant patients.

Lactation

There are no human data available regarding the effects of ferric citrate or Auryxia in human milk, nor their effects on breastfed infants or milk production. However, studies in rats indicate that iron can be transferred into milk via divalent metal transporter-1 (DMT-1) and ferroportin-1 (FPN-1). Consequently, there is a potential for infant exposure when these medications are administered to lactating mothers.

When considering the use of ferric citrate or Auryxia in nursing women, it is essential to weigh the benefits of breastfeeding against the mother's clinical need for these medications. Additionally, healthcare providers should assess any potential adverse effects on the breastfed child stemming from the medications or the underlying maternal condition.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available labeling for Ferric Citrate and Auryxia. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function in the provided information. Therefore, healthcare professionals should exercise caution and consider individual patient circumstances when prescribing these medications to patients with renal impairment.

Hepatic Impairment

Patients with hepatic impairment have no specific dosage adjustments, monitoring requirements, or precautions outlined for the use of Ferric Citrate or Auryxia. The available information does not indicate any need for special considerations in this population. Therefore, standard dosing may be applied in the absence of specific guidance regarding hepatic function.

Overdosage

In cases of overdose with ferric citrate, there is limited data available regarding the specific effects and management of such incidents. The maximum dose studied in patients with chronic kidney disease was 2,520 mg of ferric iron, equivalent to 12 tablets of ferric citrate per day. It is important to note that excessive iron absorption from ferric citrate tablets may lead to significantly elevated iron stores, particularly when used in conjunction with intravenous iron.

Symptoms of iron overload may include elevated ferritin levels and increased transferrin saturation (TSAT). In clinical observations, one case of elevated liver iron was confirmed by biopsy in a patient on dialysis who was administered both intravenous iron and ferric citrate tablets.

In the event of an accidental overdose, particularly in children under 6 years of age, which is a leading cause of fatal poisoning, immediate medical attention is crucial. It is recommended to contact a healthcare professional or poison control center without delay. Monitoring of ferritin and TSAT levels is advised, and patients may require a reduction in dosage or discontinuation of intravenous iron therapy to manage iron overload effectively.

Nonclinical Toxicology

Data from carcinogenesis studies indicate that ferric citrate is not carcinogenic in both mice and rats when administered via intramuscular or subcutaneous routes. Furthermore, ferric citrate has demonstrated a lack of mutagenic potential, as evidenced by negative results in the bacterial reverse mutation assay (Ames test) and the chromosomal aberration test conducted in Chinese hamster fibroblasts.

The potential for ferric citrate to impair reproductive performance or to induce fetal malformation has not been evaluated in the available studies.

Storage and Handling

Ferric Citrate is supplied in tablet form, specifically as film-coated tablets. The product 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. It is essential to protect the product from moisture to maintain its integrity and efficacy.