General Information

Venofer (iron sucrose injection) is a complex of polynuclear iron (3)-hydroxide in sucrose. It is approved for use in replenishing iron in patients receiving erythropoietin (a hormone that stimulates red blood cell production) and undergoing chronic hemodialysis, which involves filtering the blood in order to remove waste products. In these patients, an iron deficiency is caused by blood loss during the dialysis procedure, increased erythropoiesis (red blood cell production) and insufficient absorption of iron from the gastrointestinal tract. Iron is essential for the synthesis of hemoglobin, which is responsible for the transport of oxygen throughout the body.

Mechanism of Action

Following intravenous administration of Venofer, iron sucrose is dissociated by the reticuloendothelial system into iron and sucrose. Venofer's iron component appears to distribute mainly in the blood and to some extent in the extravascular fluid. A study evaluating Venofer containing 100 mg of iron labeled with 52Fe/59Fe in patients with iron deficiency showed that a significant amount of the administered iron distributes in the liver, spleen and bone marrow, and that the bone marrow is an iron trapping compartment and not a reversible volume of distribution (from FDA label).

Side Effects

Hypotension (low blood pressure) has been frequently reported in patients receiving intravenous iron, and may be related to the rate of administration of Venofer and to the total dose received. As a result, caution should be taken to ensure that Venofer is administered as directed.

Adverse reactions noted in the three Venofer trials include the following (reported by more than 5 percent of the treated patients):

• hypotension (36 percent)
• cramps/leg cramps (23 percent)
• nausea
• headache
• vomiting
• diarrhea

Additionally, serious hypersensitivity reactions have been reported in patients receiving therapy with iron carbohydrate complexes. While fatal hypersensitivity reactions have not been observed in Venofer clinical trials, physician vigilance is advised while any patient is receiving an intravenous iron product.

Clinical Trial Results

Three trials were conducted to assess the safety and effectiveness of Venofer. Two trials were conducted in the United States and one was conducted in South Africa.

Study A was a multicenter, open-label, historically-controlled trial involving 101 hemodialysis patients (77 patients receiving Venofer and 24 patients in the historical control) with iron deficiency anemia. Venofer 5 mL (one vial) containing 100 mg of elemental iron was administered through the dialysis line at a total of 10 dialysis sessions with a cumulative dose of 1000 mg elemental iron. The mean change in hemoglobin from baseline to day 24 (end of treatment), day 36 and day 57 was assessed. Patients in the Venofer-treated population showed a statistically significant increase in hemoglobin and hematocrit compared to patients in the historical control population. Serum ferritin and transferrin saturation also increased significantly compared to the historical control.

Study B was a multicenter, open-label trial of Venofer involving 23 iron deficient hemodialysis patients who had been discontinued from iron dextran due to intolerance. All 23 patients were evaluated for drug effectiveness and statistically significant increases in mean hemoglobin, hematocrit, serum ferritin and transferrin saturation were observed.

Study C was a multicenter, open-label, two-period (treatment followed by observation period) trial in iron deficient hemodialysis patients. Venofer was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined, calculated total dose of iron was administered. Twenty-seven patients (20 percent) were receiving erythropoietin treatment at trial entry and they continued to receive the same erythropoietin dose for the duration of the trial. Significant increases from baseline in mean hemoglobin, hematocrit, serum ferritin and serum transferrin saturation were observed at week 2 of the observation period and these values remained significantly increased at week 4 (from FDA label).