A Comprehensive Monograph on Ferric Pyrophosphate Citrate (Triferic®, Triferic AVNU®): A Novel Parenteral Iron for Hemodialysis-Dependent Chronic Kidney Disease

1.0 Executive Summary

Ferric Pyrophosphate Citrate (FPC) is a novel, small-molecule iron replacement product specifically engineered for the management of anemia in adult patients with hemodialysis-dependent chronic kidney disease (HDD-CKD). Marketed under the brand names Triferic® and Triferic AVNU®, FPC represents a significant departure from traditional carbohydrate-based intravenous (IV) iron therapies. Its fundamental distinction lies in its chemical structure—a water-soluble, non-colloidal complex iron salt that contains no carbohydrate shell. This unique composition enables a novel mechanism of action: the direct and immediate donation of iron to circulating transferrin, thereby bypassing the reticuloendothelial system (RES) where conventional IV irons are processed.

This physiological pathway offers several key therapeutic advantages. By circumventing the RES, FPC avoids the inflammatory-mediated sequestration of iron by macrophages, a process governed by the hormone hepcidin, which is typically elevated in the chronic inflammatory state of CKD. This allows for more efficient iron utilization for erythropoiesis. Furthermore, the slow, continuous administration during each hemodialysis session is designed to replace the precise amount of iron lost during the procedure (approximately 5-7 mg), mimicking natural iron absorption and maintaining hemoglobin levels without causing a significant increase in ferritin, a marker of stored iron and inflammation.