How Safe Is Venofer^® (iron sucrose injection, USP)?

(The following information is adapted from the Venofer^® full prescribing information.)
Venofer^® (iron sucrose injection, USP) is used to replenish body iron stores in patients with iron deficiency on regular hemodialysis and receiving epoetin. In these patients, iron deficiency is caused by blood loss during the dialysis procedure, increased formation of new red blood cells (erythropoiesis), and insufficient absorption of iron from the gastrointestinal tract.

Iron is essential to the creation of hemoglobin (Hb), the oxygen-carrying pigment in red blood cells, and to the function and formation of other important iron-containing compounds. Most hemodialysis patients require intravenous iron to maintain sufficient iron stores to achieve and maintain hemoglobin of 11 to 12 g/dL.

Hypersensitivity Reactions
Serious hypersensitivity (oversensitivity) reactions have been rarely reported in patients receiving Venofer^®. No life-threatening hypersensitivity reactions were observed in three preapproval studies (see the How Effective Is Venofer^®? page), and in two postapproval safety studies. Several cases of mild or moderate hypersensitivity reactions were seen in these studies. A total of 83 hypersensitivity reactions including serious or life-threatening reactions have been reported in postmarketing spontaneous reports worldwide between 1992 and 2002 based on estimated use in more than 2 million patients.

Hypotension
Hypotension (low blood pressure) has been reported frequently in hemodialysis patients who receive intravenous iron. Hypotension after Venofer^® is given to a patient might be related to how fast and how much Venofer^® was given.

Drug Interactions
Venofer^® (iron sucrose injection, USP) should not be taken with oral iron preparations since the absorption of oral iron is reduced.

Side Effects
Exposure to Venofer^® has been documented in 231 patients undergoing regular hemodialysis in preapproval studies and in 1051 patients undergoing hemodialysis in two postapproval safety studies. About 1600 hemodialysis patients treated with Venofer^® have been reported in medical literature.

Side Effects Seen in Preapproval Studies
Side effects, whether or not related to Venofer^® administration, reported by more than 5% of treated patients from a total of 231 patients in the three preapproval studies are as follows:

• Low blood pressure (36%)
• Cramps/leg cramps (23%)
• Nausea
• Headache
• Vomiting
• Diarrhea

Side effects, whether or not related to being given Venofer^® (iron sucrose injection, USP), reported by more than 1% of treated patients from a total of 231 patients in the three studies are categorized below by body system and ranked in order of decreasing frequency within each body system. Some of these symptoms may be seen in patients with chronic renal failure or on hemodialysis not receiving intravenous iron:

• Body as a Whole: headache, fever, pain, asthenia, unwell, malaise, accidental injury
• Cardiovascular Disorders, General: hypotension, chest pain, hypertension, hypervolemia
• Gastrointestinal System Disorders: nausea, vomiting, abdominal pain, elevated liver enzymes
• Central and Peripheral Nervous System: dizziness
• Musculoskeletal System: cramps/leg cramps, musculoskeletal pain
• Respiratory System: dyspnea, pneumonia, cough
• Skin and appendages: pruritus, application site reaction

In the first postapproval safety study, 665 regular hemodialysis patients were treated with Venofer^® doses of 100 mg at each dialysis session for up to 10 consecutive dialysis sessions for their iron deficiency or on a weekly basis for 10 weeks for maintenance of iron stores. Serious side-effect and drug-related nonserious side-effect data were collected. In the second postapproval safety study, 386 hemodialysis patients were exposed to a single dose of Venofer^® (100 mg IV by slow injection over two minutes or 200 mg IV by slow injection over five minutes).

Side Effects Observed in Two Postapproval Studies
In the two postapproval safety studies, 665 patients received multiple doses of Venofer^®, and 386 patients received a single dose of Venofer^®. In the multiple-dose study, 72% of the patients received up to 10 doses, 27% received between 11 and 30 doses and 1% received 40 to 50 doses of Venofer^®; data on only serious side effects and nonserious side effects considered by the investigators to be drug related were collected.

Side effects reported by more than 1% of 1051 treated patients are as follows: congestive heart failure, sepsis, and taste perversion.

Overdose
Doses of Venofer^® in excess of iron needs may lead to accumulation of iron in storage sites. This might lead to a condition called hemosiderosis. Periodic monitoring of iron parameters, such as serum ferritin and transferrin saturation, may assist in recognizing iron accumulation.

Venofer^® should not be given to people with iron overload and should be stopped when serum ferritin levels equal or exceed established guidelines. Particular caution should be used to avoid iron overload where anemia that does not respond to treatment has been incorrectly diagnosed as iron deficiency anemia. Symptoms associated with overdose or infusing Venofer^® too rapidly included hypotension, headache, vomiting, nausea, dizziness, joint aches, paresthesia (abnormal sensation, such as tingling or burning), abdominal and muscle pain, edema, and cardiovascular collapse.

Most symptoms have been successfully treated with IV fluids, hydrocortisone, and/or antihistamines. Infusing the solution as recommended or at a slower rate also may alleviate symptoms.

IMPORTANT SAFETY INFORMATION
Venofer^® (iron sucrose injection, USP) is contraindicated in patients with evidence of iron overload, in patients with known hypersensitivity to Venofer^® or any of its inactive components, and in patients with anemia not caused by iron deficiency. Hypersensitivity reactions have been reported with injectable iron products. Hypotension has been reported frequently in patients receiving intravenous iron. Hypotension following administration of Venofer^® may be related to rate of administration and total dose delivered. In multidose efficacy studies (N=231), the most frequent adverse events, whether or not related to Venofer^® administration, were hypotension, cramps/leg cramps, nausea, headache, vomiting, and diarrhea. In postmarketing safety studies (N=1051), the most frequent adverse events reported (>1%) were congestive heart failure, sepsis, and taste perversion.
Please see Full Prescribing Information.