Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate)

Ganz, Tomas; Bino, Avi; Salusky, Isidro B.

doi:10.1007/s40265-019-01125-w

Cited by 28 publications

(32 citation statements)

References 95 publications

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“…In addition, ferric citrate treatment did not affect serum iFGF23 or serum phosphorus, suggesting that this iron supplementation with 0.3% ferric citrate treatment may not affect phosphorus metabolism. Ferric citrate is an iron-based compound, and has been approved in the USA as a phosphate binder for the control of serum phosphorus levels in adult patients with CKD on dialysis and also as an iron replacement product indicated for the treatment of iron deficiency anemia in adult patients with CKD not on dialysis [7]. It is approved in Japan for the improvement of hyperphosphatemia in patients with CKD.…”

Section: Discussionmentioning

confidence: 99%

“…It has been also reported that ferric citrate hydrate led to few serious adverse events in organ systems usually affected by iron overload, and improved iron parameters in patients with CKD and iron deficiency anemia without negatively perturbing serum phosphate [7]. Ferric citrate could be a safe and efficacious treatment for IDA due to the clinical results in patients with nondialysis-dependent CKD [6,7]. From these clinical results mentioned above, there is a possibility that ferric citrate could exert not only phosphate reducing effect but also hematopoietic effect in advanced CKD patients.…”

mentioning

confidence: 95%

“…in adult CKD patients treated with dialysis and as an iron replacement product for the treatment of IDA in adult CKD patients not treated with dialysis [7]. In fact, it has been reported that ferric citrate improved hyperphosphatemia, and would induce increases in hemoglobin, transferrin saturation (TSAT) and ferritin [6,16].…”

mentioning

confidence: 99%

“…In fact, it has been reported that ferric citrate improved hyperphosphatemia, and would induce increases in hemoglobin, transferrin saturation (TSAT) and ferritin [6,16]. It has been also reported that ferric citrate hydrate led to few serious adverse events in organ systems usually affected by iron overload, and improved iron parameters in patients with CKD and iron deficiency anemia without negatively perturbing serum phosphate [7]. Ferric citrate could be a safe and efficacious treatment for IDA due to the clinical results in patients with nondialysis-dependent CKD [6,7].…”

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confidence: 99%

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Conventional and novel impacts of ferric citrate on iron deficiency anemia and phosphorus metabolism in rats

Iida

Matsushita

Ohta

et al. 2020

The Journal of Veterinary Medical Science

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Ferric citrate is an oral iron-based phosphate binder, being known to affect iron status and improve iron deficiency anemia (IDA) in chronic kidney disease (CKD) patients. We examined whether oral administration of ferric citrate could change iron status and improve anemia without affecting phosphorus metabolism in iron deficiency anemia rats. In Normal rat study, normal rats were fed a diet containing 0.3 or 3% ferric citrate for 11 days for setting the dose and administration period of ferric citrate. The effects of ferric citrate on iron status-and phosphorus metabolism-related parameters were evaluated using blood and urine samples. Next, an iron deficiency anemia was induced by feeding iron-depleted diet in rats. After 7 days of starting the iron-depleted diet, 0.3% ferric citrate was administered for 7 days by dietary admixture. Iron status-and phosphorus metabolism-related parameters were evaluated with blood and urine samples. In Normal rat study, 3% ferric citrate treatment increased serum iron level and transferrin saturation (TSAT), and decreased serum phosphorus level, intact fibroblast growth factor 23 (iFGF23) level, and urinary phosphorus excretion, but 0.3% ferric citrate treatment showed no effects. On the other hand, in Iron deficiency anemia rat study, 0.3% ferric citrate treatment increased iron status-related parameters and improved anemia, but did not show any apparent changes in phosphorus metabolism-related parameters. In conclusion, ferric citrate could have hematopoietic effects without affecting phosphorus metabolism, and could be a potential option for the treatment of IDA in patients without CKD.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Conventional and novel impacts of ferric citrate on iron deficiency anemia and phosphorus metabolism in rats

Iida

Matsushita

Ohta

et al. 2020

The Journal of Veterinary Medical Science

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“…X-ray crystallography reveals that pathway [54] and the mechanisms involving intestinal microflora [55]. Iron citrate complexes have been shown to capture and reduce phosphate and FGF23 levels in both dialyzed and non-dialyzed CKD patients [53]. As phosphates [56] and FGF23 [57] A significant reduction in the requirement for therapy with erythropoiesis stimulating agents was also reported [60].…”

Section: Sucrosomial Ironmentioning

confidence: 96%

Iron deficiency anemia – new possibilities of iron supplementation in various clinical conditions

Michalak

2020

Acta Haematologica Polonica

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Iron deficiency anemia (IDA) treatment is done to eliminate the causes of iron deficiency, iron supplementation, and rarely red blood cell transfusion. Divalent iron salts are the first line of oral treatment, but their use lead to frequent gastrointestinal adverse reactions. Iron is administered intravenously in the event of contraindications, intolerance, or inefficiency of oral therapy, but the parenteral route of drug delivery is not easily accepted by the patients. Intravenous preparations for single administration of a large dose of iron have a good therapy safety profile, but are more expensive than oral and are usually administered in a hospital setting. The availability of new iron compounds: sucrosomial iron, ferric citrate complexes, and ferric maltol widen the possibilities of IDA therapy and enable the better selection of iron preparations in various clinical situations. The innovative structure of sucrosomial iron leads to absorption in different ways (through endocytosis, the paracellular pathway, M cells of Peyer's patches), ensures high bioavailability, and good tolerance of therapy. Ferric citrate, in addition to iron supplementation, reduces phosphate levels, and is beneficial to chronic kidney disease. Ferric maltol is currently being studied for IDA treatment with various comorbidities. Some studies indicate that new iron formulas may be used where intravenous intake has been recommended so far. So, we can expect treatment with iron nanoparticles and drugs that affect the intestinal microflora in the future. The paper presents current knowledge about new iron preparations that are already available in everyday practice, but also those that are at various stages of pre-clinical and clinical studies.

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Effect of Phosphate Binders and a Dietary Iron Supplement on the Pharmacokinetics of a Single Dose of Vadadustat in Healthy Adults

Paulson

Martinez

Sawant

et al. 2022

Clinical Pharm in Drug Dev

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Vadadustat is a hypoxia-inducible factor prolyl-hydroxylase inhibitor being developed for the treatment of anemia in patients with chronic kidney disease. Sequelae of chronic kidney disease include hyperphosphatemia and anemia, which are frequently treated with phosphate binders and iron supplements, respectively. Two studies evaluating the pharmacokinetics, safety, and tolerability of a single oral dose of vadadustat coadministered with a phosphate binder or iron supplement were conducted in healthy adult participants. In study 1, 54 healthy women and men were administered vadadustat (300 mg) alone and 1 hour before, concurrently with, or 2 hours after a phosphate binder (sevelamer carbonate 1600 mg, calcium acetate 1334 mg, or ferric citrate 2000 mg). In study 2, 10 healthy men were administered vadadustat (450 mg) alone and concomitantly with the oral iron supplement ferrous sulfate (325 mg [equivalent to 65 mg of elemental iron]). Vadadustat exposure was reduced by coadministration with sevelamer carbonate, calcium acetate, ferric citrate, or ferrous sulfate. Geometric least squares mean ratios for area under the concentration-time curve from time 0 to infinity were reduced 37% to 55% by phosphate binders and 46% by ferrous sulfate. However, when vadadustat was administered 1 hour before phosphate binders, 90% confidence intervals for vadadustat exposure were within the no-effect boundaries of +50% to -33%, indicating that drug-drug interactions can be reduced by administering vadadustat 1 hour before phosphate binders. Vadadustat was well tolerated when administered in conjunction with phosphate binders or an iron supplement.

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Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate)

Cited by 28 publications

References 95 publications

Conventional and novel impacts of ferric citrate on iron deficiency anemia and phosphorus metabolism in rats

Conventional and novel impacts of ferric citrate on iron deficiency anemia and phosphorus metabolism in rats

Iron deficiency anemia – new possibilities of iron supplementation in various clinical conditions

Effect of Phosphate Binders and a Dietary Iron Supplement on the Pharmacokinetics of a Single Dose of Vadadustat in Healthy Adults

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