Ferric Pyrophosphate Citrate

• Approved Indications:
• Treatment and maintenance of iron deficiency in adult patients with chronic kidney disease (CKD) on hemodialysis.
• Management of anemia associated with iron deficiency in patients receiving chronic hemodialysis who are concurrently treated with erythropoiesis-stimulating agents (ESAs).
• Off-label/Clinically Accepted Uses:
• Use as an adjunct iron source during hemodialysis in patients with functional iron deficiency.
• Potential use in preventing iron depletion in other dialysis populations, though not officially approved.

• Route: Intravenous administration via dialysate during hemodialysis.
• Adults (hemodialysis patients):
• Administered intravenously via dialysate at a dose of 2 μg of iron per liter of dialysate.
• Dose per session is typically 6 to 9 μg of iron per hemodialysis session, depending on dialysate volume.
• Frequency: Administered with each hemodialysis session, generally three times per week.
• Duration: Chronic administration as long as patient remains on hemodialysis and requires iron supplementation.
• Pediatrics and Elderly: Safety and efficacy not established; use according to clinical judgment.
• Renal/Hepatic Impairment: Specifically designed for use in hemodialysis patients with renal impairment; no dose adjustment needed beyond standard dialysis parameters.

Ferric pyrophosphate citrate is a water-soluble iron complex designed for delivery directly into the bloodstream via dialysate during hemodialysis. Upon administration, iron dissociates from the citrate and pyrophosphate ligands and rapidly binds to transferrin, the primary iron transport protein in plasma. This facilitates efficient delivery of bioavailable iron to the bone marrow for erythropoiesis, supporting hemoglobin synthesis and reducing the need for additional intravenous iron infusions. The direct dialysate delivery bypasses gastrointestinal absorption issues, providing steady iron supplementation during dialysis.

• Absorption: Delivered intravenously through dialysate; 100% bioavailability.
• Distribution: Rapidly binds plasma transferrin; distributed primarily to erythroid marrow and iron storage sites.
• Metabolism: Iron is incorporated into hemoglobin or stored in ferritin; pyrophosphate and citrate are metabolized or excreted.
• Excretion: Excess iron is minimally excreted; tightly regulated by the body. Citrate and pyrophosphate metabolites are renally excreted.
• Half-life: Iron released from ferric pyrophosphate citrate has a plasma half-life consistent with transferrin-bound iron (~1 to 2 hours).
• Onset: Immediate iron availability during hemodialysis session.

• Pregnancy: Limited human data; animal studies do not indicate teratogenic effects. Use only if potential benefits justify potential risks.
• Lactation: Unknown if excreted in human milk. Caution advised; benefits should outweigh potential risks.

• Primary therapeutic class: Iron supplement
• Subclass: Intravenous iron delivered via dialysate

• Known hypersensitivity to ferric pyrophosphate citrate or any formulation excipients.
• Iron overload conditions such as hemochromatosis or hemosiderosis.
• Non-iron deficiency anemia.
• Active systemic infections (due to potential risk of exacerbating infection).

• Iron overload: Monitor iron indices (serum ferritin, transferrin saturation) to avoid iron overload.
• Hypersensitivity reactions: Although rare, serious allergic reactions including anaphylaxis may occur.
• High-risk patients: Use caution in patients with active infections or liver disease.
• Monitoring: Regular assessment of iron status and hematologic response is essential.
• Use during dialysis: Ensure proper delivery via dialysate circuit to avoid dosing errors.

Common:

• Mild gastrointestinal symptoms (rare due to dialysate delivery).
• Headache.
• Dizziness.
• Hypotension during dialysis.

Serious but rare:

• Hypersensitivity reactions including rash, urticaria, anaphylaxis.
• Iron overload with long-term excessive dosing.

• No known significant drug-drug interactions due to administration route.
• Iron may reduce absorption of oral tetracyclines and quinolones if administered orally.
• No significant CYP450 enzyme involvement.
• Caution with erythropoiesis-stimulating agents (ESAs); iron therapy is complementary.

• Recent nephrology guidelines emphasize the use of ferric pyrophosphate citrate as an effective maintenance iron therapy during hemodialysis, reducing the need for intravenous iron infusions.
• No major changes in approved dosing; focus on safety and monitoring iron overload.
• FDA and EMA continue to monitor post-marketing safety; no new black box warnings have been added.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Protect from freezing and direct light.
• Keep in original container until use.
• No refrigeration required.
• Handle with care to maintain sterility of solution.