Tetraferric tricitrate decahydrate

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# Overview
Tetraferric tricitrate decahydrate is a phosphate binder that is FDA approved for the treatment of serum phosphorus levels in patients with chronic kidney disease on dialysis.   Common adverse reactions include diarrhea, discolored feces, constipation, nausea, and vomiting.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)

### Indications
- Auryxia (ferric citrate) is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis.

### Dosage
- The recommended starting dose is 2 tablets orally 3 times per day with meals. Serum phosphorus levels should be monitored and the dose of Auryxia 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.
- In a clinical trial conducted in the United States, patients required an average of 8 to 9 tablets a day to control serum phosphorus levels.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Tetraferric tricitrate decahydrate in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Tetraferric tricitrate decahydrate in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Tetraferric tricitrate decahydrate in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Tetraferric tricitrate decahydrate in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Tetraferric tricitrate decahydrate in pediatric patients.

# Contraindications
- Auryxia is contraindicated in patients with iron overload syndromes (e.g., hemochromatosis)

# Warnings
- 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 in which concomitant use of Auryxia and IV 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. Patients receiving IV iron may require a reduction in dose or discontinuation of IV iron therapy.
- Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6 years of age. Keep this product out of the reach of children. In case of accidental overdose, call a doctor or poison control center immediately.
- Patients with inflammatory bowel disease or active, symptomatic gastrointestinal bleeding were excluded from clinical trials. Safety has not been established in these populations.

# Adverse Reactions

## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to adverse reaction rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Adverse reactions to a drug are most readily ascertained by comparison with placebo, but there is little placebo-controlled experience with Auryxia, so this section describes adverse events with Auryxia, some of which may be disease-related, rather than treatment-related.
- A total of 289 patients were treated with Auryxia and 149 patients were treated with active control (sevelamer carbonate and/or calcium acetate) during the 52-week, randomized, open-label, active control phase of a trial in patients on dialysis. A total of 322 patients were treated with Auryxia for up to 28 days in three short-term trials. Across these trials, 557 unique patients were treated with Auryxia; dosage regimens in these trials ranged from 210 mg to 2,520 mg of ferric iron per day, equivalent to 1 to 12 tablets of Auryxia. In these trials, adverse events reported for Auryxia were similar to those reported for the active control group.
- Adverse events reported in more than 5% of patients treated with Auryxia in these trials included diarrhea (21%), nausea (11%), constipation (8%), vomiting (7%), and cough (6%).
- During the 52-week, active-control period, 60 patients (21%) on Auryxia discontinued study drug because of an adverse event, as compared to 21 patients (14%) in the active control arm. Patients who were previously intolerant to any of the active control treatments (calcium acetate and sevelamer carbonate) were not eligible to enroll in the study. Gastrointestinal adverse reactions were the most common reason for discontinuing Auryxia (14%).
- Auryxia is associated with discolored feces (dark stools) related to the iron content, but this staining is not clinically relevant and does not affect laboratory tests for occult bleeding, which detect heme rather than non-heme iron in the stool.

## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Tetraferric tricitrate decahydrate in the drug label.

# Drug Interactions
- There are no empirical data on avoiding drug interactions between Auryxia and most concomitant oral drugs. For oral medications where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, consider separation of the timing of the administration of the two drugs. The duration of separation depends upon the absorption characteristics of the medication concomitantly administered, such as the time to reach peak systemic levels and whether the drug is an immediate release or an extended release product. Consider monitoring clinical responses or blood levels of concomitant medications that have a narrow therapeutic range.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): B
- There are no adequate and well-controlled studies in pregnant women. It is not known whether Auryxia can cause fetal harm when administered to a pregnant woman. Animal reproduction studies have not been conducted.
- 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. An overdose of iron in pregnant women may carry a risk for spontaneous abortion, gestational diabetes and fetal malformation
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tetraferric tricitrate decahydrate in women who are pregnant.

### Labor and Delivery
- The effects of Auryxia on labor and delivery are unknown.

### Nursing Mothers
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.

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

### Geriatic Use
Clinical studies of Auryxia included 106 subjects aged 65 years and older (33 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.

### Gender
There is no FDA guidance on the use of Tetraferric tricitrate decahydrate with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Tetraferric tricitrate decahydrate with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Tetraferric tricitrate decahydrate in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Tetraferric tricitrate decahydrate in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Tetraferric tricitrate decahydrate in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Tetraferric tricitrate decahydrate in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Oral

### Monitoring
- Assess iron parameters (e.g., serum ferritin and TSAT) prior to initiating Auryxia and monitor iron parameters while on therapy

# IV Compatibility
There is limited information regarding IV Compatibility of Tetraferric tricitrate decahydrate in the drug label.

# Overdosage
There is limited information regarding Tetraferric tricitrate decahydrate overdosage.  If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

# Pharmacology
There is limited information regarding Tetraferric tricitrate decahydrate Pharmacology in the drug label.

## 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.

## Structure
- 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 embossed 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.

## Pharmacodynamics
In addition to effects on serum phosphorus levels, Auryxia has been shown to increase serum iron parameters, including ferritin, iron and TSAT. In dialysis patients treated with Auryxia in a 52-week study in which IV iron could also be administered, mean (SD) ferritin levels rose from 593 (293) ng/mL to 895 (482) ng/mL, mean (SD) TSAT levels rose from 31% (11) to 39% (17) and mean (SD) iron levels rose from 73 (29) mcg/dL to 88 (42) mcg/dL. In contrast, in patients treated with active control, these parameters remained relatively constant [

## Pharmacokinetics
Absorption and Distribution
- Formal pharmacokinetic studies have not been performed with Auryxia. Examination of serum iron parameters has shown that there is systemic absorption of iron from Auryxia.
Drug Interaction Studies
In vitro
- Of the drugs screened for an interaction with ferric citrate in vitro, only doxycycline showed the potential for interaction with at least 70% decrease in its concentration. This interaction can be avoided by spacing the administration of doxycycline and ferric citrate

## Nonclinical Toxicology
- Data from carcinogenesis studies have shown that ferric citrate is not carcinogenic in mice and rats when administered intramuscularly or subcutaneously. Ferric citrate was neither mutagenic in the bacterial reverse mutation assay (Ames test) nor clastogenic in the chromosomal aberration test in Chinese hamster fibroblasts.

# Clinical Studies
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.
- 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 patients 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.

# How Supplied
- Tablets: Auryxia 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. The 210 mg ferric iron tablets are film-coated, peach-colored, and oval-shaped tablets embossed with KX52.

## Storage
- Storage: Store at 20 to 25C (68 to 77F): excursions permitted to 15 to 30C (59F to 86F) . Protect from moisture.

# Images

## Drug Images

## Package and Label Display Panel

### PRINCIPAL DISPLAY PANEL

### Ingredients and Appearance

# Patient Counseling Information
Inform patients to take Auryxia as directed with meals and adhere to their prescribed diets. Instruct patients on concomitant medications that should be dosed apart from Auryxia.
- Advise patients that Auryxia may cause discolored (dark) stools, but this staining of the stool is considered normal with oral medications containing iron.
- Auryxia may cause diarrhea, nausea, constipation and vomiting. Advise patients to report severe or persistent gastrointestinal symptoms to their physician.

# Precautions with Alcohol
Alcohol-Tetraferric tricitrate decahydrate interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- AURYXIA

# Look-Alike Drug Names
There is limited information regarding Tetraferric tricitrate decahydrate Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price