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
Venofer® injection may cause serious hypersensitivity reactions and hypotension.  Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.   See Important Safety Information below.

Drug Interactions
Drug interactions involving Venofer® have not been studied.  However, Venofer® may reduce the absorption of concomitantly administered oral iron preparations.8
American Regent. Enriching the lives of anemia patients. ™

IMPORTANT SAFETY INFORMATION:

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Venofer® (iron sucrose injection, USP). Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop Venofer® immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Venofer® administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Venofer® when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions.

Venofer® may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Venofer®. Hypotension following administration of Venofer® may be related to rate of administration and total dose delivered.

Venofer® is contraindicated in patients with known hypersensitivity to Venofer®. Do not administer to patients with evidence of iron overload.

In efficacy studies in non-dialysis dependent-CKD patients (N=139), the most frequent adverse events (≥5%) whether or not related to Venofer® administration, were nausea (8.6%), taste disturbance

(7.9%), peripheral edema (7.2%), diarrhea (7.2%), dizziness (6.5%), hypertension (6.5%), infusion site pain or burning (5.8%), dyspnea (5.8%), and vomiting (5.0%).

In multi-dose efficacy studies in HDD-CKD patients (N=231), the most frequent adverse events (> 5%) whether or not related to Venofer® 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 the study of PDD-CKD patients (N=75), the most frequent adverse events, whether or not related to Venofer®, reported by ≥5% of these patients were infections and infestations (nasopharyngitis, sinusitis, upper respiratory tract, pharyngitis) (16.0%), diarrhea (8.0%), vomiting (8.0%), hypertension (8.0%), peripheral edema (5.3%), and nausea (5.3%).


Please see Full Prescribing Information.


References