Physical Description and Chemical Formula1
Venofer® (iron sucrose injection, USP) is a brown, sterile, aqueous complex of polynuclear iron (III)-hydroxide in sucrose containing 20 mg elemental iron per mL. The sterile solution has an osmolarity of 1250 mOsmol/L.

Molecular Formula:   [Na2Fe5O8(OH) · 3(H2O)]n · m(C12H22O11)
Molecular Weight:   Approximately 34,000–60,000 daltons
Description:   Iron sucrose is a brown, aqueous solution with a pH of 10.5–11.1



The product does not contain preservatives.

Mechanism of Action2
Iron is essential to the formation of hemoglobin and to the function and formation of other heme and nonheme compounds. Untreated depletion of iron stores leads to iron-deficient erythropoiesis and, in turn, to iron deficiency anemia. Administration of Venofer® replenishes tissue iron stores, reverses iron depletion and iron-deficient erythropoiesis, and corrects or prevents iron deficiency anemia.

Following intravenous administration, Venofer® is dissociated into iron and sucrose by the reticuloendothelial system, and iron is transferred from the blood to a pool of iron in the liver and bone marrow. Ferritin, an iron storage protein, binds and sequesters iron in anontoxic form, from which iron is easily available. Iron binds to plasma transferrin, which carries iron within the plasma and the extracellular fluid to supply the tissues. The transferrin receptor, located in the cell membrane, binds the transferrin iron complex, which is then internalized in vesicles. Iron is released within the cell, and the transferrin-receptor complex is returned to the cell membrane. Transferrin without iron (apotransferrin) is then released to the plasma. The intracellular iron becomes (mostly) hemoglobin in circulating red blood cells (RBCs). Transferrin synthesis is increased and ferritin production reduced in iron deficiency. The converse is true when iron is plentiful.

The stability of Venofer® allows a competitive exchange of iron between iron sucrose and selective iron-binding proteins such as transferrin and ferritin. Pharmacokinetic parameters show that the administered iron disappears very rapidly from the serum, insuring a rapid correction of iron deficiency anemia.2

Pharmacokinetics3-7
In healthy adults treated with intravenous doses of Venofer® (iron sucrose injection, USP), its iron component exhibits first-order kinetics:

  • Elimination T1/2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 hours
  • Total clearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Liters per hour
  • Non-steady-state apparent volume of distribution . . . . 10.0 Liters
  • Steady-state apparent volume of distribution . . . . . . . . 7.9 Liters


Since iron disappearance from the serum depends on the need for iron in the iron stores and iron-utilizing tissues of the body, serum clearance of iron is expected to be more rapid in iron-deficient patients treated with Venofer® (iron sucrose injection, USP) as compared with healthy individuals.

  Distribution
In healthy adults, the Venofer® iron component appears to distribute mainly in the blood and to some extent in extravascular fluid.
   
  Metabolism
Iron sucrose is dissociated into iron and sucrose by the reticuloendothelial system.
   
  Elimination
The sucrose component is eliminated mainly by urinary excretion. Some iron is also eliminated in the urine (approximately 5%).


Ferrokinetics4
Following a single dose of 100 mg iron, iron uptake in bone marrow, liver, and spleen is rapid, followed by emergence of injected iron in circulating RBCs. Total RBC uptake accounts for 68% to 97% of injected iron within 2 to 4 weeks.

Adverse Reactions5,6
Serious hypersensitivity reactions have been reported in patients receiving Venofer®.  No life-threatening hypersensitivity reactions were observed in the clinical studies.  Several cases of mild or moderate hypersensitivity reactions were observed in these studies.  There are post-marketing spontaneous reports of life-threatening hypersensitivity reactions in patients receiving Venofer®.   See Important Safety Information below.
 

Drug Interactions
As with all parenteral iron preparations, Venofer® (iron sucrose injection, USP) should not be administered concomitantly with oral iron preparations since the absorption of oral iron may be reduced. In patients previously receiving oral iron therapy, administration of Venofer® should prompt discontinuation of oral iron agents.8
American Regent. Enriching the lives of anemia patients. ™

IMPORTANT SAFETY INFORMATION: Venofer® (iron sucrose injection, USP) is contraindicated in patients with evidence of iron overload, in patients with known hypersensitivity to VenoferŪ or any of its inactive components, and in patients with anemia not caused by iron deficiency. Serious hypersensitivity reactions have been reported in patients receiving VenoferŪ. In clinical studies, several patients experienced hypersensitivity reactions presenting with wheezing, dyspnea, hypotension, rashes, or pruritus. The post-marketing spontaneous reporting system includes reports of patients who experienced serious or life-threatening reactions (anaphylactic shock, loss of consciousness or collapse, bronchospasm with dyspnea, or convulsion) associated with VenoferŪ administration.

Hypotension has been reported frequently in non-dialysis dependent-CKD patients receiving IV iron. Hypotension following administration of VenoferŪ may be related to rate of administration and total dose delivered.

In a multi-dose efficacy study in non-dialysis dependent-CKD patients (N=91), the most frequent adverse events (≥5%) whether or not related to VenoferŪ administration, were taste disturbance (7.7%), peripheral edema (7.7%), diarrhea (5.5%), constipation (5.5%), nausea (5.5%), dizziness (5.5%), and hypertension (5.5%). In an additional study of VenoferŪ with varying erythropoietin doses in 96 treated NDD-CKD patients, adverse events, whether or not related to VenoferŪ reported by ≥5% of VenoferŪ exposed patients are as follows: diarrhea (16.5%), edema (16.5%), nausea (13.2%), vomiting (12.1%), arthralgia (7.7%), back pain (7.7%), headache (7.7%), hypertension (7.7%), taste disturbance (7.7%), dizziness (6.6%), extremity pain (5.5%), and injection site burning (5.5%).

In multi-dose efficacy studies in HDD-CKD patients (N=231), the most frequent adverse events (> 5%) whether or not related to VenoferŪ administration, were hypotension (39.4%), muscle cramps (29.4%), nausea (14.7%), headache (12.6%), graft complications (9.5%), vomiting (9.1%), dizziness (6.5%) hypertension (6.5%), chest pain (6.1%), and diarrhea (5.2%). In post-marketing safety studies in HDD-CKD patients (N=1051), the most frequent adverse events reported (>1%), whether or not related to VenoferŪ administration, were congestive heart failure, sepsis, and taste disturbance. In the study of PDD-CKD patients (N=75), the most frequent adverse events, whether or not related to VenoferŪ, reported by ≥5% of these patients were diarrhea (8.0%), peritoneal infection (8.0%) vomiting (8.0%), hypertension (8.0%), pharyngitis (6.7%), peripheral edema (5.3%), and nausea (5.3%).


Please see Full Prescribing Information.


References