Ferric Citrate

Tetraferric tricitrate decahydrate is an iron containing phosphate binder used to treat hyperphosphatemia and iron deficiency anemia in adults with chronic kidney disease.

Tetraferric tricitrate decahydrate was granted FDA approval on 5 September 2014.

Ferric citrate is a phosphate binder used to control serum phosphorus levels or as an iron supplement.

Tetraferric tricitrate decahydrate is indicated to control serum phosphorous in adults with chronic kidney disease who require dialysis. Tetraferric tricitrate decahydrate is also indicated to treat iron deficiency anemia in adults with chronic kidney disease who are not on dialysis.

• Hyperphosphataemia
• Iron Deficiency Anemia (IDA)

Tetraferric tricitrate decahydrate is an iron containing product indicated to treat iron deficiency anemia and hyperphosphatemia. It has a wide therapeutic index, as doses can be varied significantly between patients. Tetraferric tricitrate decahydrate has a long duration of action in the treatment of iron deficiency anemia, due to the slow loss of iron from the body, and a moderate duration of action in the treatment of hyperphosphatemia, due to its action being dependant on residence time in the gastrointestinal tract. Patients should be counselled regarding the risk of iron overload.

Ferric (Fe³⁺) iron is absorbed from the gastrointestinal tract by divalent metal transporter-1, and reduced to ferrous (Fe²⁺) iron by ferrireductase and cytochrome b reductase 1. Ferrous iron is stored intracellularly in ferritin and transported into the blood by ferroportin 1. Transport by ferroportin 1 is coupled with oxidation to ferric iron by hephaestin or ceruloplasmin. Ferric iron in plasma is bound to transferrin, which carries iron to other cells. Iron is transported to mitochondria for the synthesis of heme or iron-sulfur clusters, which are integral parts of several metalloproteins like hemoglobin.

Ferric iron can also bind to phosphate in the gastrointestinal tract, which precipitates as the insoluble ferric phosphate. Ferric phosphate remains unabsorbed and is eliminated in the feces. Decreased phosphate absorption gradually lowers phosphate levels in the blood.

Ferric iron has been shown to have inferior bioavailability to ferrous iron preparations. Tetraferric tricitrate decahydrate has 19% the bioavailability of ferrous ascorbate.

Ferric iron is reduced to ferrous iron, which is carried by transferrin in serum.

Unabsorbed oral Tetraferric tricitrate decahydrate is eliminated in the feces. The absorbed iron from Tetraferric tricitrate decahydrate is generally not eliminated from the body by any route other than blood loss and exfoliation of epithelial cells.

Data regarding the clearance of iron is not readily available. However, iron loss due to exfoliation of epithelial cells is approximately 1mg/day.

Patients experiencing an overdose of iron may present with nausea, vomiting, abdominal pain, diarrhea, fluid and blood loss, hypovolemia, hematemesis, perforation, and peritonitis. Mild overdoses can be treated with symptomatic and supportive measures. More severe overdoses may require more intense treatment including chelating agents, and intravenous fluids. Activated charcoal is not expected to be beneficial in the case of iron overdose.

The acute oral LD₅₀ in rats is 1487mg/kg and in mice is 1520mg/kg. The acute dermal LD₅₀ in rabbits is 2000mg/kg.

• Take with food.

• Starting dose is 2 tablets orally 3 times per day with meals
• Adjust dose by 1 to 2 tablets as needed to maintain serum phosphorus at target levels, up to a maximum of 12 tablets daily. Dose can be titrated at 1-week or longer intervals.

• Starting dose is 1 tablet orally 3 times per day with meals
• Adjust dose as needed to achieve and maintain hemoglobin goal, up to a maximum of 12 tablets daily or as directed by the physician.