Venofer

  Mode of Administration

Administer Venofer only intravenously by slow injection or by infusion. The dosage of Venofer is expressed in mg of elemental iron. Each mL contains 20 mg of elemental iron.

Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)

Administer Venofer 100 mg undiluted as a slow intravenous injection over 2 to 5 minutes, or as an infusion of 100 mg diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes, per consecutive hemodialysis session [see How Supplied/Storage and Handling .]  Administer Venofer early during the dialysis session (generally within the first hour).  The usual total treatment course of Venofer is 1000 mg. Venofer treatment may be repeated if iron deficiency reoccurs.

Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD)

Administer Venofer 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of Venofer, diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14 [see How Supplied/Storage and Handling .]Venofer treatment may be repeated if iron deficiency reoccurs.

Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD)

Administer Venofer in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute Venofer in a maximum of 250 mL of 0.9% NaCl [see How Supplied/Storage and Handling .]   Venofer treatment may be repeated if iron deficiency reoccurs.

Pediatric Patients (2 Years of Age and Older) with HDD-CKD for Iron Maintenance Treatment

For iron maintenance treatment: Administer Venofer at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 0.9% NaCl at a concentration of 1 to 2 mg/mL and administered over 5 to 60 minutes. Do not dilute to concentrations below 1 mg/mL [see How Supplied/Storage and Handling [ 16.2].)   Venofer treatment may be repeated if necessary.

The dosing for iron replacement treatment in pediatric patients with HDD-CKD has not been established.

Pediatric Patients (2 Years of Age and Older) with NDD-CKD or PDD-CKD who are on Erythropoietin Therapy for Iron Maintenance Treatment

For iron maintenance treatment: Administer Venofer at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every four weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 0.9% NaCl at a concentration of 1 to 2 mg/mL and administered over 5 to 60 minutes. Do not dilute to concentrations below 1 mg/mL [see How Supplied/Storage and Handling .]   Venofer treatment may be repeated if necessary.

The dosing for iron replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

Pregnancy

Risk Summary

Published studies on intravenous iron sucrose treatment after the first trimester of pregnancy have not shown adverse maternal or fetal outcomes (see Data). Available reports of intravenous iron sucrose use in pregnant women during the first trimester are insufficient to assess the risk of major birth defects and miscarriage. There are risks to the mother and fetus associated with untreated IDA in pregnancy as well as risks to the fetus associated with maternal severe hypersensitivity reactions (see Clinical Considerations). Animal reproduction studies of iron sucrose administered to rats and rabbits during the period of organogenesis at elemental iron doses equivalent to the maximum recommended human dose based on body surface area revealed no evidence of harm to the fetus (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.  Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications.  In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Iron deficiency anemia during pregnancy should be treated. Untreated IDA in pregnancy is associated with adverse maternal outcomes such as post-partum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.

Fetal/Neonatal adverse reactions

Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Venofer) which may cause fetal bradycardia, especially during the second and third trimester.

Data

Human Data

Published data from randomized controlled studies and prospective observational studies on the use of Venofer in pregnant women have not reported an association of Venofer and adverse developmental outcomes. However, these studies did not include women exposed during the first trimester of pregnancy and were not designed to assess the risk of major birth defects. Maternal adverse events reported in these studies are similar to those reported during clinical trials in adult males and non-pregnant females [seeAdverse Reactions (6.1)].

Animal Data

Iron sucrose was administered intravenously to rats and rabbits during the period of organogenesis at elemental iron doses up to 13 mg/kg/day (0.25 times or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus.

Lactation

Risk Summary

Iron sucrose is present in human milk, and available published reports following exposure to 100-300 mg intravenous iron sucrose have not reported adverse reactions in breastfed infants (see Data).  There are no data on the effects on milk production. The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for Venofer and any potential adverse effects on the breastfed child from Venofer or from the underlying maternal condition.

Data

A published study showed no difference in iron concentration in the colostrum of 10 iron deficient breastfeeding women who were 2 to 3 days postpartum and received a single dose of 100 mg of intravenous iron sucrose compared to 5 breastfeeding women who received no iron. These results may underestimate the amount of iron in breastmilk following the standard dose of Venofer.

A published report of 78 breastfeeding women who received 300 mg of intravenous iron sucrose over 3 days (infant age not reported) did not report on the safety of iron sucrose in breastfed infants; however adverse reactions in breastfed infants were not reported.

Clinical Considerations

Monitor breastfed infants for gastrointestinal toxicity (constipation, diarrhea).

Pediatric Use

Safety and effectiveness of Venofer for iron replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

Safety and effectiveness of Venofer for iron maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Venofer at doses of 0.5 mg/kg, 1 mg/kg, and 2 mg/kg was administered. All three doses maintained hemoglobin between 10.5 g/dL and 14.0 g/dL in about 50% of subjects over the 12-week treatment period with stable EPO dosing [see Clinical Studies ( 14.7)].

Venofer has not been studied in patients younger than 2 years of age.

In a country where Venofer is available for use in children, at a single site, five premature infants (weight less than 1,250 g) developed necrotizing enterocolitis and two of the five died during or following a period when they received Venofer, several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Venofer or any other drugs could be established.

Geriatric Use

Of the 1,051 patients in two post-marketing safety studies of Venofer, 40% were 65 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Venofer. 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. Most reactions associated with intravenous iron preparations occur within 30 minutes of the completion of the infusion [see Adverse Reactions ].

Hypotension

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 the rate of administration and/or total dose administered [see Dosage and Administration , Warnings and Precautions , and Adverse Reactions ].

Iron Overload

Excessive therapy with parenteral iron can lead to excess storage of iron with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Venofer require periodic monitoring of hematologic and iron parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Venofer to patients with evidence of iron overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of iron sucrose; do not perform serum iron measurements for at least 48 hours after intravenous dosing [see Dosage and Administration and Overdosage ].