INFeD is indicated for treatment of adult and pediatric patients of age 4 months and older with documented iron deficiency who have intolerance to oral iron or have had an unsatisfactory response to oral iron.

{ "type": "p", "children": [], "text": "INFeD is indicated for treatment of adult and pediatric patients of age 4 months and older with documented iron deficiency who have intolerance to oral iron or have had an unsatisfactory response to oral iron." }

Discontinue administration of any iron-containing products prior to administration of INFeD.

Assess baseline hematologic (hemoglobin and hematocrit) and iron storage parameters (serum iron, total iron binding capacity, and percent saturation of transferrin) to monitor response to therapy.

Administer a test dose of INFeD prior to administration of therapeutic dose [see Dosage and Administration (2.4)].

Calculate the INFeD dose based upon Table 1 and formulas below. Continue INFeD until hemoglobin is within the normal range and iron stores are replete.

Administer daily doses of no more than 2 mL of INFeD until the total required dose is administered. Monitor response to therapy by evaluating hematologic parameters (hemoglobin and hematocrit) and iron storage parameters (serum iron, total iron binding capacity, and percent saturation of transferrin). Iron storage parameters may improve prior to hematologic parameters. Serum ferritin may not be an accurate measure of body iron stores in patients on chronic dialysis.

<div class="scrollingtable"><table> <caption> <span>Table 1: Total INFeD Requirement for Hemoglobin Restoration and Iron Stores Replacement in Patients with Iron Deficiency Anemia*</span> </caption> <col width="55"/> <col width="55"/> <col width="60"/> <col width="61"/> <col width="61"/> <col width="60"/> <col width="61"/> <col width="60"/> <col width="60"/> <col width="61"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold">P</span><span class="Bold">A</span><span class="Bold">T</span><span class="Bold">I</span><span class="Bold">E</span><span class="Bold">N</span><span class="Bold">T</span> <br/> <span class="Bold">LE</span><span class="Bold">A</span><span class="Bold">N</span><span class="Bold"> </span><span class="Bold">BODY WE</span><span class="Bold">I</span><span class="Bold">GHT</span></td><td align="center" class="Lrule Rrule Toprule" colspan="8"><span class="Bold">Recommended Volume (mL)</span><span class="Bold"> </span><span class="Bold">o</span><span class="Bold">f</span><span class="Bold"> </span><span class="Bold">I</span><span class="Bold">N</span><span class="Bold">FeD</span><span class="Bold"> </span><span class="Bold">B</span><span class="Bold">a</span><span class="Bold">s</span><span class="Bold">ed</span><span class="Bold"> </span><span class="Bold">o</span><span class="Bold">n</span><span class="Bold"> </span><span class="Bold">O</span><span class="Bold">b</span><span class="Bold">s</span><span class="Bold">e</span><span class="Bold">r</span><span class="Bold">v</span><span class="Bold">ed</span><span class="Bold"> </span><span class="Bold">H</span><span class="Bold">e</span><span class="Bold">m</span><span class="Bold">o</span><span class="Bold">g</span><span class="Bold">lobi</span><span class="Bold">n</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">kg</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">lb</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">3</span> <br/> <span class="Bold">(g/d</span><span class="Bold">L</span><span class="Bold">)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">4</span> <br/> <span class="Bold">(g/d</span><span class="Bold">L</span><span class="Bold">)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">5</span> <br/> <span class="Bold">(g/d</span><span class="Bold">L</span><span class="Bold">)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">6</span> <br/> <span class="Bold">(g/d</span><span class="Bold">L</span><span class="Bold">)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">7</span> <br/> <span class="Bold">(g/d</span><span class="Bold">L</span><span class="Bold">)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">8</span> <br/> <span class="Bold">(g/d</span><span class="Bold">L</span><span class="Bold">)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">9</span> <br/> <span class="Bold">(g/d</span><span class="Bold">L</span><span class="Bold">)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">10</span> <br/> <span class="Bold">(g/d</span><span class="Bold">L</span><span class="Bold">)</span> <br/> </td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">5<br/>10<br/>15<br/>20<br/>25<br/>30<br/>35<br/>40<br/>45<br/>50<br/>55<br/>60<br/>65<br/>70<br/>75<br/>80<br/>85<br/>90<br/>95<br/>100<br/>105<br/>110<br/>115<br/>120</td><td align="center" class="Lrule Rrule Toprule">11<br/>22<br/>33<br/>44<br/>55<br/>66<br/>77<br/>88<br/>99<br/>110<br/>121<br/>132<br/>143<br/>154<br/>165<br/>176<br/>187<br/>198<br/>209<br/>220<br/>231<br/>242<br/>253<br/>264</td><td align="center" class="Lrule Rrule Toprule">3<br/>7<br/>10<br/>16<br/>20<br/>23<br/>27<br/>31<br/>35<br/>39<br/>43<br/>47<br/>51<br/>55<br/>59<br/>63<br/>66<br/>70<br/>74<br/>78<br/>82<br/>86<br/>90<br/>94</td><td align="center" class="Lrule Rrule Toprule">3<br/>6<br/>9<br/>15<br/>18<br/>22<br/>26<br/>29<br/>33<br/>37<br/>41<br/>44<br/>48<br/>52<br/>55<br/>59<br/>63<br/>66<br/>70<br/>74<br/>77<br/>81<br/>85<br/>88</td><td align="center" class="Lrule Rrule Toprule">3<br/>6<br/>9<br/>14<br/>17<br/>21<br/>24<br/>28<br/>31<br/>35<br/>38<br/>42<br/>45<br/>49<br/>52<br/>55<br/>59<br/>62<br/>66<br/>69<br/>73<br/>76<br/>80<br/>83</td><td align="center" class="Lrule Rrule Toprule">3<br/>5<br/>8<br/>13<br/>16<br/>19<br/>23<br/>26<br/>29<br/>32<br/>36<br/>39<br/>42<br/>45<br/>49<br/>52<br/>55<br/>58<br/>62<br/>65<br/>68<br/>71<br/>75<br/>78</td><td align="center" class="Lrule Rrule Toprule">2<br/>5<br/>7<br/>12<br/>15<br/>18<br/>21<br/>24<br/>27<br/>30<br/>33<br/>36<br/>39<br/>42<br/>45<br/>48<br/>51<br/>54<br/>57<br/>60<br/>63<br/>67<br/>70<br/>73</td><td align="center" class="Lrule Rrule Toprule">2<br/>4<br/>7<br/>11<br/>14<br/>17<br/>20<br/>22<br/>25<br/>28<br/>31<br/>34<br/>36<br/>39<br/>42<br/>45<br/>48<br/>50<br/>53<br/>56<br/>59<br/>62<br/>64<br/>67</td><td align="center" class="Lrule Rrule Toprule">2<br/>4<br/>6<br/>10<br/>13<br/>15<br/>18<br/>21<br/>23<br/>26<br/>28<br/>31<br/>34<br/>36<br/>39<br/>41<br/>44<br/>46<br/>49<br/>52<br/>54<br/>57<br/>59<br/>62</td><td align="center" class="Lrule Rrule Toprule">2<br/>3<br/>5<br/>9<br/>12<br/>14<br/>17<br/>19<br/>21<br/>24<br/>26<br/>28<br/>31<br/>33<br/>35<br/>38<br/>40<br/>42<br/>45<br/>47<br/>50<br/>52<br/>54<br/>57</td> </tr> <tr class="Last"> <td class="Toprule" colspan="10">*Table values were calculated based on a normal adult hemoglobin of 14.8 g/dL for patients with body weights greater than 15 kg (33 lbs) and a hemoglobin of 12 g/dL for patients with body weights less than or equal to 15 kg (33 lbs).<br/> </td> </tr> </tbody> </table></div>

Alternatively, the total dose may be calculated using the formulas below:

Adults and Children over 15 kg (33 lbs)

      Dose (mL) = 0.0442 (Desired Hb - Observed Hb) x LBW + (0.26 x LBW)

      Based on:

           • Desired Hb = the target hemoglobin in g/dL [Normal hemoglobin (males and females) for body weight over 15 kg (33 lbs) is 14.8 g/dL.]

           • Observed Hb = the patient’s current hemoglobin in g/dL

           • LBW = Lean body weight in kg [A patient’s lean body weight (or actual body weight if less than lean body weight) should be utilized when determining dosage.]             •       For males: LBW = 50 kg + 2.3 kg for each inch of patient’s height over 5 feet             •       For females: LBW = 45.5 kg + 2.3 kg for each inch of patient’s height over 5 feet             •       To calculate a patient's weight in kg when lbs are known:

Children 5 to 15 kg (11 to 33 lbs)

Otherwise, the total dose may be calculated using the formula below:

      Dose (mL) = 0.0442 (Desired Hb - Observed Hb) x W + (0.26 x W)

      Based on:

           • Desired Hb = the target hemoglobin in g/dL [Normal hemoglobin for children with body weight of 15 kg (33 lbs) or less is 12 g/dL.]

           • W = body weight in kg              •       To calculate a patient's weight in kg when lbs are known:

Calculate the INFeD dose based upon the formula below which is based upon the approximate amount of blood loss and pretreatment hematocrit.

The formula is based on the approximation that 1 mL of normocytic, normochromic red cells contains 1 mg of elemental iron.

      INFeD Dose (in mL) = [Blood loss (in mL) x hematocrit] ÷ 50 mg/mL

             Example: Blood loss of 500 mL with 20% hematocrit

             Replacement Iron = 500 x 0.20 = 100 mg

              INFeD dose volume = 

The total volume of INFeD required for the treatment of iron deficiency anemia is determined from Table 1 or the appropriate formula listed [see Dosage and Administration (2.2)].

The total volume of INFeD required for the treatment of iron replacement for blood loss is determined from an appropriate formula listed [see Dosage and Administration (2.3)].

NOTE: Do not mix INFeD with other medications or add to parenteral nutrition solutions for intravenous infusion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.

Discard unused portion.

Intravenous Injection

Test Dose

Prior to the first intravenous INFeD therapeutic dose, administer an intravenous test dose of 0.5 mL [see Boxed Warning and Warnings and Precautions (5.1)]. Administer the test dose at a gradual rate over at least 30 seconds. Delay administration of the initial therapeutic INFeD dose until 1 hour or more after the test dose. If a hypersensitivity reaction occurs with the test dose, manage medically and do not administer further doses of INFeD.

INFeD is given undiluted at a slow gradual rate not to exceed 50 mg (1 mL) per minute.

The maximum daily dose of INFeD should not exceed 2 mL.

Intramuscular Injection

Test Dose

Prior to the first intramuscular INFeD therapeutic dose, administer an intramuscular test dose of 0.5 mL [see Boxed Warning and Warnings and Precautions (5.1)]. Administer the test dose at a gradual rate over at least 30 seconds into the buttock. Delay administration of the initial therapeutic INFeD dose until 1 hour or more after the test dose. If a hypersensitivity reaction occurs with the test dose, manage medically and do not administer further doses of INFeD.

If no adverse reactions are observed, INFeD can be given according to the following schedule until the calculated total required dose has been reached. Each day’s dose should not exceed 0.5 mL (25 mg of iron) for infants with body weight under 5 kg (11 lbs); 1 mL (50 mg of iron) for children with body weight under 10 kg (22 lbs); and 2 mL (100 mg of iron) for other patients.

The maximum daily dose of INFeD should not exceed 2 mL.

INFeD should be injected only into the muscle mass of the upper outer quadrant of the buttock - never into the arm or other exposed areas - and should be injected deeply, with a 2-inch or 3-inch 19 or 20 gauge needle. If the patient is standing, he/she should be bearing his/her weight on the leg opposite the injection site, or if in bed, he/she should be in the lateral position with injection site uppermost. To avoid injection or leakage into the subcutaneous tissue, a Z-track technique (displacement of the skin laterally prior to injection) is recommended.

Injection: 100 mg/2 mL (50 mg/1 mL), dark brown, slightly viscous, sterile solution in single-dose vials

{ "type": "p", "children": [], "text": "Injection: 100 mg/2 mL (50 mg/1 mL), dark brown, slightly viscous, sterile solution in single-dose vials" }

INFeD is contraindicated in patients who have demonstrated a previous hypersensitivity to iron dextran [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "INFeD is contraindicated in patients who have demonstrated a previous hypersensitivity to iron dextran [see Warnings and Precautions (5.1)]. " }

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported following the parenteral administration of iron dextran products, including INFeD. Such reactions have been generally characterized by sudden onset of respiratory difficulty and/or cardiovascular collapse. Fatal reactions have been reported following the test dose of iron dextran and have also occurred in situations where the test dose was tolerated.

Administer only in a setting where resuscitation equipment and medications are available. Administer a test dose of INFeD prior to the first therapeutic dose [see Dosage and Administration (2.4)]. Observe patients for at least one hour after the test dose before administering the remainder of the initial therapeutic dose. During all INFeD administrations, observe patients for signs or symptoms of anaphylactic-type reactions. Use INFeD only in patients in whom clinical and laboratory investigations have established an iron deficient state not amenable to oral iron therapy.

The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Additionally, concomitant use of angiotensin-converting enzyme inhibitor drugs may increase the risk for reactions to an iron dextran product. The extent of risk for anaphylactic-type reactions following exposure to any specific iron dextran product is unknown and may vary among the products.

If hypersensitivity reactions occur during administration, stop INFeD immediately and manage reaction medically.

Large intravenous doses, such as used with total dose infusions (TDI), have been associated with an increased incidence of adverse reactions. The adverse reactions are frequently delayed (1 to 2 days) reactions typified by one or more of the following symptoms: arthralgia, backache, chills, dizziness, moderate to high fever, headache, malaise, myalgia, nausea, and vomiting. The onset is usually 24 to 48 hours after administration and symptoms generally subside within 3 to 4 days. The etiology of these reactions is not known. Do not exceed a total daily dose of 2 mL undiluted INFeD.

Monitor for iron toxicity when INFeD is used in patients with serious impairment of liver function. It should not be used during the acute phase of infectious kidney disease.

Adverse reactions experienced following administration of INFeD may exacerbate cardiovascular complications in patients with pre-existing cardiovascular disease.

Patients with rheumatoid arthritis may have an acute exacerbation of joint pain and swelling following the administration of INFeD.

Patients with a history of significant allergies and/or asthma may have an increased risk of hypersensitivity reactions [see Dosage and Administration (5.1)].

Excessive therapy with parenteral iron can lead to excess storage of iron with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving INFeD require periodic monitoring of hematologic and iron parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer INFeD to patients with evidence of iron overload.

The following clinically significant adverse reactions are described elsewhere in the labeling:

{ "type": "p", "children": [], "text": "The following clinically significant adverse reactions are described elsewhere in the labeling:" }

{ "type": "ul", "children": [ "Hypersensitivity Reactions [see Warnings and Precautions (5.1)]\n\n", "Delayed Reactions [see Warnings and Precautions (5.2)]\n\n", "Increased Risk of Toxicity in Patients with Underlying Conditions [see Warnings and Precautions (5.3)]\n\n", "Iron Overload [see Warnings and Precautions (5.4)]\n\n", "Fetal bradycardia [see Use in Specific Populations (8.1)]\n" ], "text": "" }

The following adverse reactions associated with the use of INFeD were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

{ "type": "p", "children": [], "text": "The following adverse reactions associated with the use of INFeD were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure." }

Blood and lymphatic system disorders: Leukocytosis, lymphadenopathy.

{ "type": "p", "children": [], "text": "\nBlood and lymphatic system disorders: Leukocytosis, lymphadenopathy." }

Gastrointestinal disorders: Abdominal pain, nausea, vomiting, diarrhea.

{ "type": "p", "children": [], "text": "\nGastrointestinal disorders: Abdominal pain, nausea, vomiting, diarrhea. " }

General disorders and administration site conditions: chest pain, chest tightness, weakness, malaise, febrile episodes, chills, shivering, sterile abscess, atrophy/fibrosis (intramuscular injection site), brown skin and/or underlying tissue discoloration (staining), soreness or pain at or near intramuscular injection sites, swelling, inflammation.

{ "type": "p", "children": [], "text": "\nGeneral disorders and administration site conditions: chest pain, chest tightness, weakness, malaise, febrile episodes, chills, shivering, sterile abscess, atrophy/fibrosis (intramuscular injection site), brown skin and/or underlying tissue discoloration (staining), soreness or pain at or near intramuscular injection sites, swelling, inflammation." }

Musculoskeletal and connective tissue disorders: Arthralgia, arthritis (may represent reactivation in patients with quiescent rheumatoid arthritis – [see Warnings and Precautions (5.3)], myalgia, backache. 

{ "type": "p", "children": [], "text": "\nMusculoskeletal and connective tissue disorders: Arthralgia, arthritis (may represent reactivation in patients with quiescent rheumatoid arthritis – [see Warnings and Precautions (5.3)], myalgia, backache. " }

Nervous system disorders: Convulsions, seizures, syncope, headache, unresponsiveness, paresthesia, dizziness, numbness, unconsciousness, altered taste.

{ "type": "p", "children": [], "text": "\nNervous system disorders: Convulsions, seizures, syncope, headache, unresponsiveness, paresthesia, dizziness, numbness, unconsciousness, altered taste." }

Psychiatric disorders: Disorientation

{ "type": "p", "children": [], "text": "\nPsychiatric disorders: Disorientation" }

Respiratory, thoracic and mediastinal disorders: Respiratory arrest, dyspnea, bronchospasm, wheezing.

{ "type": "p", "children": [], "text": "\nRespiratory, thoracic and mediastinal disorders: Respiratory arrest, dyspnea, bronchospasm, wheezing." }

Renal and urinary disorders: Hematuria.

{ "type": "p", "children": [], "text": "\nRenal and urinary disorders: Hematuria." }

Skin and subcutaneous disorders: Urticaria, pruritus, purpura, rash, sweating.

{ "type": "p", "children": [], "text": "\nSkin and subcutaneous disorders: Urticaria, pruritus, purpura, rash, sweating. " }

Cardiovascular disorders: Cardiac arrest, tachycardia, bradycardia, arrhythmias, acute myocardial ischemia with or without myocardial infarction or with in-stent thrombosis in the context of a hypersensitivity reaction, cyanosis, shock, hypertension, hypotension, flushing (flushing and hypotension may occur from too rapid injections by the intravenous route), local phlebitis at or near intravenous injection site.

{ "type": "p", "children": [], "text": "\nCardiovascular disorders: Cardiac arrest, tachycardia, bradycardia, arrhythmias, acute myocardial ischemia with or without myocardial infarction or with in-stent thrombosis in the context of a hypersensitivity reaction, cyanosis, shock, hypertension, hypotension, flushing (flushing and hypotension may occur from too rapid injections by the intravenous route), local phlebitis at or near intravenous injection site." }

Drug interactions involving INFeD have not been studied.

Concomitant use of angiotensin-converting enzyme inhibitor drugs may increase the risk for anaphylactic-type reactions to an iron dextran product.

Large doses of iron dextran (5 mL or more) have been reported to give a brown color to serum from a blood sample drawn 4 hours after administration.

INFeD may cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium. 

Serum iron determinations (especially by colorimetric assays) may not be meaningful for 3 weeks following the administration of INFeD.

Examination of the bone marrow for iron stores may not be meaningful for prolonged periods following iron dextran therapy because residual iron dextran may remain in the reticuloendothelial cells.

Bone scans involving 99m Tc-diphosphonate have been reported to show a dense, crescentic area of activity in the buttocks, following the contour of the iliac crest, 1 to 6 days after intramuscular injections of INFeD.

Bone scans with 99m Tc-labeled bone seeking agents, in the presence of high serum ferritin levels or following INFeD infusions, have been reported to show reduction of bony uptake, marked renal activity, and excessive blood pool and soft tissue accumulation.

Risk Summary Parenteral iron administration may be associated with hypersensitivity reactions [see Warnings and Precautions (5.1)], which may have serious consequences, such as fetal bradycardia (see Clinical Considerations). Advise pregnant persons of the potential risk to the fetus. Available data from postmarketing reports with iron dextran use in pregnancy are insufficient to assess the risk of major birth defects or miscarriage. There are risks to the pregnant person and fetus associated with untreated iron deficiency anemia in pregnancy (see Clinical Considerations). Iron dextran has been shown to be teratogenic and embryocidal in mice, rats, rabbits, dogs, and monkeys when given in doses of about 3 times the maximum human dose.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. 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  Untreated iron deficiency anemia (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 persons with intravenous iron administration (such as INFeD) which may have serious consequences on the fetus such as fetal bradycardia, especially during the second and third trimester.

Data Animal Data No consistent adverse fetal effects were observed in mice, rats, rabbits, dogs, and monkeys at doses of 50 mg iron/kg or less. Fetal and maternal toxicity has been reported in monkeys at a total intravenous dose of 90 mg iron/kg over a 14 day period. Similar effects were observed in mice and rats on administration of a single dose of 125 mg iron/kg. Fetal abnormalities in rats and dogs were observed at doses of 250 mg iron/kg and higher. The animals used in these tests were not iron deficient.

Risk Summary Trace amounts of unmetabolized iron dextran are present in human milk. There are no data on the effects of iron dextran in breastfed infants or effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for INFeD in addition to any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

INFeD is not recommended for use in infants under 4 months of age [see Dosage and Administration (2.2)].

Reports in the literature from countries outside the United States (in particular, New Zealand) have suggested that the use of intramuscular iron dextran in neonates has been associated with an increased incidence of gram-negative sepsis, primarily due to E. Coli.

Excessive dosages of INFeD may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. Do not administer INFeD to patients with iron overload [see Warnings and Precautions (5.4)]. INFeD is not removed by hemodialysis [see Clinical Pharmacology (12.3)]. 

{ "type": "p", "children": [], "text": "Excessive dosages of INFeD may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. Do not administer INFeD to patients with iron overload [see Warnings and Precautions (5.4)]. INFeD is not removed by hemodialysis [see Clinical Pharmacology (12.3)]. " }

INFeD (iron dextran injection USP) is an iron replacement product provided as a dark brown, slightly viscous sterile liquid complex of ferric hydroxide and dextran for intravenous or intramuscular use.

{ "type": "p", "children": [], "text": "INFeD (iron dextran injection USP) is an iron replacement product provided as a dark brown, slightly viscous sterile liquid complex of ferric hydroxide and dextran for intravenous or intramuscular use." }

Each mL contains the equivalent of 50 mg of elemental iron (as an iron dextran complex), approximately 0.9% sodium chloride, in water for injection. Sodium hydroxide and/or hydrochloric acid may have been used to adjust pH. The pH of the solution is between 4.5 to 7.0.

{ "type": "p", "children": [], "text": "Each mL contains the equivalent of 50 mg of elemental iron (as an iron dextran complex), approximately 0.9% sodium chloride, in water for injection. Sodium hydroxide and/or hydrochloric acid may have been used to adjust pH. The pH of the solution is between 4.5 to 7.0." }

The circulating iron released from iron dextran, which is subject to physiological control, replenishes hemoglobin and depleted iron stores. 

Changes in serum ferritin levels represent the changes in calculated cellular non-heme iron levels. After administration of iron dextran, evidence of a therapeutic response can be seen as an increase in the reticulocyte count.  

Following intramuscular injection, INFeD is absorbed within 72 hours with any remaining iron absorbed over the ensuing 3 to 4 weeks. Various studies involving intravenously administered 59Fe iron dextran to iron deficient subjects, some of whom had coexisting disease, have yielded half-life values ranging from 5 hours to more than 20 hours. The 5 hour value was determined for 59Fe iron dextran from a study that used laboratory methods to separate the circulating 59Fe iron dextran from the transferrin bound 59Fe. The 20 hour value reflects a half-life determined by measuring total 59Fe, both circulating and bound. It should be understood that these half-life values do not represent clearance of iron from the body. Serum ferritin peaks approximately 7 to 9 days after an intravenous dose of INFeD and returns to baseline after about 3 weeks.

Absorption Following intramuscular administration, INFeD is absorbed from the injection site into the capillaries and the lymphatic system. 

Distribution The circulating iron is bound to the available protein moieties to form hemosiderin or ferritin, or to a lesser extent to transferrin.

Elimination The half-life of free iron in the plasma circulation is approximately 5 hours. The half-life of total iron, including both circulating and bound, is approximately 20 hours. These half-life values do not represent clearance of iron from the body. 

Metabolism Following administration of INFeD, circulating iron dextran is split by the cells of the reticuloendothelial system into its components of iron and dextran.

Excretion Negligible amounts of iron are lost via the urinary or alimentary pathways after administration of iron dextran. Dextran, a polyglucose, is either metabolized or excreted.

Specific Populations  Patients with Renal Impairment  In vitro studies have shown that removal of iron dextran by dialysis is negligible. Six different dialyzer membranes were investigated (polysulfone, cuprophane, cellulose acetate, cellulose triacetate, polymethylmethacrylate and polyacrylonitrile), including those considered high efficiency and high flux.

Carcinogenesis The intramuscular injection of iron-carbohydrate complexes may be associated with an increased risk of carcinogenesis. In mice, rats, rabbits, and possibly hamsters, it has been demonstrated that these complexes may produce sarcoma following repeated administration of large or small doses of iron-carbohydrate complexes at a single injection site. There have been several reports in the literature describing tumors at the injection site in humans who had previously received intramuscular injections of iron-carbohydrate complexes.

INFeD (iron dextran injection USP) containing 50 mg of elemental iron per mL, is available as a dark brown, slightly viscous, sterile solution in 2 mL single-dose amber vials in cartons of 10 (NDC 0023-6082-10).

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature].

Hypersensitivity Reactions Question patients regarding any prior history of reactions to parenteral iron products. Advise patients to immediately report any symptoms of hypersensitivity that develop during and following INFeD administration such as arthralgia, backache, chills, dizziness, moderate to high fever, headache, malaise, myalgia, nausea, and vomiting [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions\nQuestion patients regarding any prior history of reactions to parenteral iron products. Advise patients to immediately report any symptoms of hypersensitivity that develop during and following INFeD administration such as arthralgia, backache, chills, dizziness, moderate to high fever, headache, malaise, myalgia, nausea, and vomiting [see Warnings and Precautions (5.1)].\n" }

Delayed Reactions Advise patients that delayed reactions can occur and that these must be reported to their healthcare provider immediately [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "\nDelayed Reactions\nAdvise patients that delayed reactions can occur and that these must be reported to their healthcare provider immediately [see Warnings and Precautions (5.2)].\n" }

Increased Risk of Toxicity in Patients with Underlying Conditions Advise patients to inform their healthcare provider if any liver impairment is identified as this may cause iron toxicity. Advise patients to consult their healthcare provider should they start to show symptoms of acute kidney infection as INFeD should not be used [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "\nIncreased Risk of Toxicity in Patients with Underlying Conditions\nAdvise patients to inform their healthcare provider if any liver impairment is identified as this may cause iron toxicity. Advise patients to consult their healthcare provider should they start to show symptoms of acute kidney infection as INFeD should not be used [see Warnings and Precautions (5.3)].\n" }

Advise patients with pre-existing cardiovascular disease and rheumatoid arthritis that INFeD administration may exacerbate symptoms and to contact their healthcare provider if any symptoms occur [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Advise patients with pre-existing cardiovascular disease and rheumatoid arthritis that INFeD administration may exacerbate symptoms and to contact their healthcare provider if any symptoms occur [see Warnings and Precautions (5.3)].\n" }

Advise patients with history of significant allergies and/or asthma to inform their healthcare provider as the risk of hypersensitivity reactions may be increased [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Advise patients with history of significant allergies and/or asthma to inform their healthcare provider as the risk of hypersensitivity reactions may be increased [see Warnings and Precautions (5.3)]." }

Iron Overload Advise the patient to consult a healthcare provider before taking any other iron containing products as this may cause serious side effects [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "\nIron Overload\nAdvise the patient to consult a healthcare provider before taking any other iron containing products as this may cause serious side effects [see Warnings and Precautions (5.4)]." }

Pregnancy Advise pregnant persons about the risk of hypersensitivity reactions which may have serious consequences for the fetus [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "\nPregnancy\nAdvise pregnant persons about the risk of hypersensitivity reactions which may have serious consequences for the fetus [see Use in Specific Populations (8.1)].\n" }

For all medical inquiries contact:AbbVieMedical Communications1-800-678-1605

{ "type": "p", "children": [], "text": "For all medical inquiries contact:AbbVieMedical Communications1-800-678-1605" }

Manufactured By: Patheon Italia S.p.A. Ferentino, Italy 03013

{ "type": "p", "children": [], "text": "Manufactured By: Patheon Italia S.p.A. Ferentino, Italy 03013" }

Distributed By: AbbVie Inc. North Chicago, IL 60064

{ "type": "p", "children": [], "text": "Distributed By: AbbVie Inc. North Chicago, IL 60064" }

© 2024 AbbVie. All rights reserved.INFED and its design are trademarks of Allergan Sales, LLC, an AbbVie company.

{ "type": "p", "children": [], "text": "© 2024 AbbVie. All rights reserved.INFED and its design are trademarks of Allergan Sales, LLC, an AbbVie company." }

NDC 0023-6082-1010 x 2 mL Single Dose VialsINFeD® (IRON DEXTRAN Injection USP) 100 mg elemental iron/ 2 mL (50 mg/mL)FOR INTRAMUSCULAR OR INTRAVENOUS USERx Only abbvie

{ "type": "p", "children": [], "text": "NDC 0023-6082-1010 x 2 mL Single Dose VialsINFeD®\n\n(IRON DEXTRAN Injection USP)\n100 mg elemental iron/ 2 mL (50 mg/mL)FOR INTRAMUSCULAR OR INTRAVENOUS USERx Only\nabbvie\n" }

Venofer is indicated for the treatment of iron deficiency anemia (IDA) in patients with chronic kidney disease (CKD).

{ "type": "p", "children": [], "text": "Venofer is indicated for the treatment of iron deficiency anemia (IDA) in patients with chronic kidney disease (CKD).\n" }

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.

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 (16.2)].  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.

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 (16.2)].  Venofer treatment may be repeated if iron deficiency reoccurs.

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 (16.2)].  Venofer treatment may be repeated if iron deficiency reoccurs.

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.

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 (16.2)].   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.

Injection: 50 mg/2.5 mL or 100 mg/5 mL (20 mg/mL) in single-dose vials.

{ "type": "p", "children": [], "text": "Injection: 50 mg/2.5 mL or 100 mg/5 mL (20 mg/mL) in single-dose vials." }

{ "type": "ul", "children": [ "Known hypersensitivity to Venofer\n" ], "text": "" }

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 (6.1 and 6.2)].

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 (2), Warnings and Precautions (5.1), and Adverse Reactions (6.2)].

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 (2) and Overdosage (10)].

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.

The frequency of adverse reactions associated with the use of Venofer has been documented in six clinical trials involving 231 patients with HDD-CKD, 139 patients with NDD-CKD and 75 patients with PDD-CKD. Adverse reactions reported by ≥ 2% of treated patients in the six clinical trials for which the rate for Venofer exceeds the rate for comparator are listed by indication in Table 1. Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks.

<div class="scrollingtable"><table> <caption> <span>Table 1. Adverse Reactions Reported in ≥ 2% of Study Populations and for which the Rate for Venofer Exceeds the Rate for Comparator </span> </caption> <col/> <col width="1px"/> <col width="1px"/> <col width="1px"/> <col/> <col/> <tfoot> <tr class="First Last"> <td colspan="6" valign="top">  <p class="First">* EPO=Erythropoietin </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="4"> <span class="Bold">Body System/Adverse Reactions</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"> <span class="Bold">HDD-CKD</span></td><td align="center" class="Botrule Rrule Toprule" colspan="2"> <span class="Bold">NDD-CKD</span></td><td align="center" class="Botrule Rrule Toprule" colspan="2"> <span class="Bold">PDD-CKD</span></td> </tr> <tr> <td align="center" class="Rrule"> <span class="Bold">Venofer</span></td><td align="center" class="Rrule"> <span class="Bold">Venofer</span></td><td align="center" class="Rrule"> <span class="Bold">Oral Iron</span></td><td align="center" class="Rrule"> <span class="Bold">Venofer</span></td><td align="center" class="Rrule"> <span class="Bold">EPO* Only</span></td> </tr> <tr> <td align="center" class="Rrule"> <span class="Bold">(N=231)</span></td><td align="center" class="Rrule"> <span class="Bold">(N=139)</span></td><td align="center" class="Rrule"> <span class="Bold">(N=139)</span></td><td align="center" class="Rrule"> <span class="Bold">(N=75)</span></td><td align="center" class="Rrule"> <span class="Bold">(N=46)</span></td> </tr> <tr> <td align="center" class="Botrule Rrule"> <span class="Bold">%</span></td><td align="center" class="Botrule Rrule"> <span class="Bold">%</span></td><td align="center" class="Botrule Rrule"> <span class="Bold">%</span></td><td align="center" class="Botrule Rrule"> <span class="Bold">%</span></td><td align="center" class="Botrule Rrule"> <span class="Bold">%</span></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <span class="Bold">Subjects with any adverse reaction</span></td><td align="center" class="Botrule Rrule"> 78.8 </td><td align="center" class="Botrule Rrule"> 76.3 </td><td align="center" class="Botrule Rrule"> 73.4 </td><td align="center" class="Botrule Rrule"> 72.0 </td><td align="center" class="Botrule Rrule"> 65.2 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Ear and Labyrinth Disorders</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Ear Pain </td><td align="center" class="Botrule Rrule"> 0 </td><td align="center" class="Botrule Rrule"> 2.2 </td><td align="center" class="Botrule Rrule"> 0.7 </td><td align="center" class="Botrule Rrule"> 0 </td><td align="center" class="Botrule Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Eye Disorders</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Conjunctivitis </td><td align="center" class="Botrule Rrule"> 0.4 </td><td align="center" class="Botrule Rrule"> 0 </td><td align="center" class="Botrule Rrule"> 0 </td><td align="center" class="Botrule Rrule"> 2.7 </td><td align="center" class="Botrule Rrule"> 0 </td> </tr> <tr> <td align="justify" class="Lrule Rrule" valign="top"> <span class="Bold">Gastrointestinal Disorders</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Abdominal pain </td><td align="center" class="Rrule"> 3.5 </td><td align="center" class="Rrule"> 1.4 </td><td align="center" class="Rrule"> 2.9 </td><td align="center" class="Rrule"> 4.0 </td><td align="center" class="Rrule"> 6.5 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Diarrhea </td><td align="center" class="Rrule"> 5.2 </td><td align="center" class="Rrule"> 7.2 </td><td align="center" class="Rrule"> 10.1 </td><td align="center" class="Rrule"> 8.0 </td><td align="center" class="Rrule"> 4.3 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Dysgeusia </td><td align="center" class="Rrule"> 0.9 </td><td align="center" class="Rrule"> 7.9 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Nausea </td><td align="center" class="Rrule"> 14.7 </td><td align="center" class="Rrule"> 8.6 </td><td align="center" class="Rrule"> 12.2 </td><td align="center" class="Rrule"> 5.3 </td><td align="center" class="Rrule"> 4.3 </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Vomiting </td><td align="center" class="Botrule Rrule"> 9.1 </td><td align="center" class="Botrule Rrule"> 5.0 </td><td align="center" class="Botrule Rrule"> 8.6 </td><td align="center" class="Botrule Rrule"> 8.0 </td><td align="center" class="Botrule Rrule"> 2.2 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">General Disorders and</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Administration Site Conditions</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Asthenia </td><td align="center" class="Rrule"> 2.2 </td><td align="center" class="Rrule"> 0.7 </td><td align="center" class="Rrule"> 2.2 </td><td align="center" class="Rrule"> 2.7 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Chest pain </td><td align="center" class="Rrule"> 6.1 </td><td align="center" class="Rrule"> 1.4 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 2.7 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Feeling abnormal </td><td align="center" class="Rrule"> 3.0 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Infusion site pain or burning </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 5.8 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Injection site extravasation </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 2.2 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Peripheral edema </td><td align="center" class="Rrule"> 2.6 </td><td align="center" class="Rrule"> 7.2 </td><td align="center" class="Rrule"> 5.0 </td><td align="center" class="Rrule"> 5.3 </td><td align="center" class="Rrule"> 10.9 </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Pyrexia </td><td align="center" class="Botrule Rrule"> 3.0 </td><td align="center" class="Botrule Rrule"> 0.7 </td><td align="center" class="Botrule Rrule"> 0.7 </td><td align="center" class="Botrule Rrule"> 1.3 </td><td align="center" class="Botrule Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Infections and Infestations</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Nasopharyngitis, Sinusitis, Upper <br/>     respiratory tract infections, Pharyngitis </td><td align="center" class="Botrule Rrule"> 2.6 </td><td align="center" class="Botrule Rrule"> 2.2 </td><td align="center" class="Botrule Rrule"> 4.3 </td><td align="center" class="Botrule Rrule"> 16.0 </td><td align="center" class="Botrule Rrule"> 4.3 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Injury, Poisoning and Procedural</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Complications</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Graft complication </td><td align="center" class="Botrule Rrule"> 9.5 </td><td align="center" class="Botrule Rrule"> 1.4 </td><td align="center" class="Botrule Rrule"> 0 </td><td align="center" class="Botrule Rrule"> 0 </td><td align="center" class="Botrule Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Metabolism and Nutrition Disorders</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Fluid overload </td><td align="center" class="Rrule"> 3.0 </td><td align="center" class="Rrule"> 1.4 </td><td align="center" class="Rrule"> 0.7 </td><td align="center" class="Rrule"> 1.3 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Gout </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 2.9 </td><td align="center" class="Rrule"> 1.4 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Hyperglycemia </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 2.9 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 2.2 </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Hypoglycemia </td><td align="center" class="Botrule Rrule"> 0.4 </td><td align="center" class="Botrule Rrule"> 0.7 </td><td align="center" class="Botrule Rrule"> 0.7 </td><td align="center" class="Botrule Rrule"> 4.0 </td><td align="center" class="Botrule Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Musculoskeletal and Connective</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Tissue Disorders</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Arthralgia </td><td align="center" class="Rrule"> 3.5 </td><td align="center" class="Rrule"> 1.4 </td><td align="center" class="Rrule"> 2.2 </td><td align="center" class="Rrule"> 4.0 </td><td align="center" class="Rrule"> 4.3 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Back pain </td><td align="center" class="Rrule"> 2.2 </td><td align="center" class="Rrule"> 2.2 </td><td align="center" class="Rrule"> 3.6 </td><td align="center" class="Rrule"> 1.3 </td><td align="center" class="Rrule"> 4.3 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Muscle cramp </td><td align="center" class="Rrule"> 29.4 </td><td align="center" class="Rrule"> 0.7 </td><td align="center" class="Rrule"> 0.7 </td><td align="center" class="Rrule"> 2.7 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Myalgia </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 3.6 </td><td align="center" class="Rrule"> 0 </td><td align="center" class="Rrule"> 1.3 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Pain in extremity </td><td align="center" class="Botrule Rrule"> 5.6 </td><td align="center" class="Botrule Rrule"> 4.3 </td><td align="center" class="Botrule Rrule"> 0 </td><td align="center" class="Botrule Rrule"> 2.7 </td><td align="center" class="Botrule Rrule"> 6.5 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Nervous System Disorders</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Dizziness </td><td align="center" class="Rrule"> 6.5 </td><td align="center" class="Rrule"> 6.5 </td><td align="center" class="Rrule"> 1.4 </td><td align="center" class="Rrule"> 1.3 </td><td align="center" class="Rrule"> 4.3 </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Headache </td><td align="center" class="Botrule Rrule"> 12.6 </td><td align="center" class="Botrule Rrule"> 2.9 </td><td align="center" class="Botrule Rrule"> 0.7 </td><td align="center" class="Botrule Rrule"> 4.0 </td><td align="center" class="Botrule Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Respiratory, Thoracic and</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Mediastinal Disorders</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Cough </td><td align="center" class="Rrule"> 3.0 </td><td align="center" class="Rrule"> 2.2 </td><td align="center" class="Rrule"> 0.7 </td><td align="center" class="Rrule"> 1.3 </td><td align="center" class="Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Dyspnea </td><td align="center" class="Rrule"> 3.5 </td><td align="center" class="Rrule"> 5.8 </td><td align="center" class="Rrule"> 1.4 </td><td align="center" class="Rrule"> 1.3 </td><td align="center" class="Rrule"> 2.2 </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Nasal congestion </td><td align="center" class="Botrule Rrule"> 0 </td><td align="center" class="Botrule Rrule"> 1.4 </td><td align="center" class="Botrule Rrule"> 2.2 </td><td align="center" class="Botrule Rrule"> 1.3 </td><td align="center" class="Botrule Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Skin and Subcutaneous</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Tissue Disorders</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">      Pruritus </td><td align="center" class="Botrule Rrule"> 3.9 </td><td align="center" class="Botrule Rrule"> 2.2 </td><td align="center" class="Botrule Rrule"> 4.3 </td><td align="center" class="Botrule Rrule"> 2.7 </td><td align="center" class="Botrule Rrule"> 0 </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <span class="Bold">Vascular Disorders</span></td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td><td align="center" class="Rrule"> </td> </tr> <tr> <td class="Lrule Rrule" valign="top">      Hypertension </td><td align="center" class="Rrule"> 6.5 </td><td align="center" class="Rrule"> 6.5 </td><td align="center" class="Rrule"> 4.3 </td><td align="center" class="Rrule"> 8.0 </td><td align="center" class="Rrule"> 6.5 </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top">      Hypotension </td><td align="center" class="Botrule Rrule"> 39.4 </td><td align="center" class="Botrule Rrule"> 2.2 </td><td align="center" class="Botrule Rrule"> 0.7 </td><td align="center" class="Botrule Rrule"> 2.7 </td><td align="center" class="Botrule Rrule"> 2.2 </td> </tr> </tbody> </table></div>

One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous iron therapy and were reported to be intolerant (defined as precluding further use of that iron product). When these patients were treated with Venofer there were no occurrences of adverse reactions that precluded further use of Venofer [see Warning and Precautions (5)].

In a randomized, open-label, dose-ranging trial for iron maintenance treatment with Venofer in pediatric patients with CKD on stable erythropoietin therapy [see Clinical Studies (14.7)], at least one adverse reaction was experienced by 57% (27/47) of the patients receiving Venofer 0.5 mg/kg, 53% (25/47) of the patients receiving Venofer 1 mg/kg, and 55% (26/47) of the patients receiving Venofer 2 mg/kg.

A total of 5 (11%) subjects in the Venofer 0.5 mg/kg group, 10 (21%) patients in the Venofer 1 mg/kg group, and 10 (21%) patients in the Venofer 2 mg/kg group experienced at least 1 serious adverse reaction during the study. The most common adverse reactions (>2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%).

The following adverse reactions have been identified during post-approval use of Venofer.  Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In the post-marketing safety studies in 1,051 treated patients with HDD-CKD, the adverse reactions reported by >1% were cardiac failure congestive, sepsis and dysgeusia. 

Symptoms associated with Venofer total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. These adverse reactions have occurred up to 30 minutes after the administration of Venofer injection. Reactions have occurred following the first dose or subsequent doses of Venofer. Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.

Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.

Venofer may reduce the absorption of concomitantly administered oral iron preparations.

{ "type": "p", "children": [], "text": "Venofer may reduce the absorption of concomitantly administered oral iron preparations. " }

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.

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).

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.

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.

No data are available regarding overdosage of Venofer in humans. Excessive dosages of Venofer may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. Do not administer Venofer to patients with iron overload [see Warnings and Precautions (5.3)].  Venofer is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes.

{ "type": "p", "children": [], "text": "No data are available regarding overdosage of Venofer in humans. Excessive dosages of Venofer may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. Do not administer Venofer to patients with iron overload [see Warnings and Precautions (5.3)].  Venofer is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes." }

Toxicities in single-dose studies in mice and rats, at intravenous iron sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.

{ "type": "p", "children": [], "text": "Toxicities in single-dose studies in mice and rats, at intravenous iron sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.\n" }

Venofer (iron sucrose injection, USP), an iron replacement product, is a brown, sterile, aqueous, complex of polynuclear iron (III)-hydroxide in sucrose for intravenous use. Iron sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:

{ "type": "p", "children": [], "text": "Venofer (iron sucrose injection, USP), an iron replacement product, is a brown, sterile, aqueous, complex of polynuclear iron (III)-hydroxide in sucrose for intravenous use. Iron sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:\n" }

[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)

{ "type": "p", "children": [], "text": "[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)\n" }

where: n is the degree of iron polymerization and m is the number of sucrose molecules associated with the iron (III)-hydroxide.

{ "type": "p", "children": [], "text": "where: n is the degree of iron polymerization and m is the number of sucrose molecules associated with the iron (III)-hydroxide.\n" }

Each mL contains 20 mg elemental iron as iron sucrose in water for injection. Venofer is available in 5 mL single-dose vials (100 mg elemental iron per 5 mL), and 2.5 mL single-dose vials (50 mg elemental iron per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL).  Sodium hydroxide may be added to adjust pH to 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.

{ "type": "p", "children": [], "text": "Each mL contains 20 mg elemental iron as iron sucrose in water for injection. Venofer is available in 5 mL single-dose vials (100 mg elemental iron per 5 mL), and 2.5 mL single-dose vials (50 mg elemental iron per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL).  Sodium hydroxide may be added to adjust pH to 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.\n" }

Venofer is an aqueous complex of poly-nuclear iron (III)-hydroxide in sucrose. Following intravenous administration, Venofer is dissociated into iron and sucrose and the iron is transported as a complex with transferrin to target cells including erythroid precursor cells. The iron in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.

Following intravenous administration, Venofer is dissociated into iron and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with iron sucrose containing 100 mg of iron, three times weekly for three weeks, significant increases in serum iron and serum ferritin and significant decreases in total iron binding capacity occurred four weeks from the initiation of iron sucrose treatment.

In healthy adults administered intravenous doses of Venofer, its iron component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The iron component appeared to distribute mainly in blood and to some extent in 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 is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible iron trapping compartment.

Following intravenous administration of Venofer, iron sucrose is dissociated into iron and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Venofer containing 1,510 mg of sucrose and 100 mg of iron in 12 healthy adults (9 female, 3 male: age range 32 to 52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some iron was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In this study and another study evaluating a single intravenous dose of iron sucrose containing 500 to 700 mg of iron in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the iron was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Venofer have not been studied.

In a single-dose PK study of Venofer, patients with NDD-CKD ages 12 to 16 (N=11) received intravenous bolus doses of Venofer at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following a single dose of Venofer, the half-life of total serum iron was 8 hours. The mean Cmax and AUC values were 8545 μg/dl and 31305 hr•μg/dL, respectively, which were 1.42- and 1.67-fold higher than dose adjusted adult Cmax and AUC values.

Venofer is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of iron sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).

Carcinogenicity studies have not been performed with iron sucrose.

Iron sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Iron sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

Iron sucrose at intravenous doses up to 15 mg/kg/day of elemental iron (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.

Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Venofer.

Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with Venofer treatment and 24 in the historical control group) with IDA. Eligibility criteria for Venofer treatment included patients undergoing chronic hemodialysis, receiving erythropoietin, hemoglobin level between 8.0 and 11.0 g/dL, transferrin saturation <20%, and serum ferritin <300 ng/mL. The mean age of the patients was 65 years with the age range of 31 to 85 years. Of the 77 patients, 44 (57%) were male and 33 (43%) were female.

Venofer 100 mg was administered at 10 consecutive dialysis sessions either as slow injection or a slow infusion. The historical control population consisted of 24 patients with similar ferritin levels as patients treated with Venofer, who were off intravenous iron for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31 to 36 for at least two months prior to study entry. The mean age of patients in the historical control group was 56 years, with an age range of 29 to 80 years. Patient age and serum ferritin level were similar between treatment and historical control patients.

Patients in the Venofer treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.

<div class="scrollingtable"><table> <caption> <span>Table 2. Changes from Baseline in Hemoglobin and Hematocrit </span> </caption> <col/> <col width="1px"/> <col width="1px"/> <col width="1px"/> <col/> <col/> <col/> <tfoot> <tr class="First Last"> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First">**p &lt; 0.01 and *p &lt; 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates. </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="justify" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="top"> <br/> <span class="Bold">Efficacy</span> <br/> <span class="Bold">parameters</span></td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"> <span class="Bold">End of treatment</span></td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"> <span class="Bold">2 week follow-up</span></td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"> <span class="Bold">5 week follow-up</span></td> </tr> <tr> <td align="center" class="Botrule Rrule" valign="top"> <span class="Bold">Venofer (n=69)</span></td><td align="center" class="Botrule Rrule" valign="top"> <span class="Bold">Historical Control (n=18)</span></td><td align="center" class="Botrule Rrule" valign="top"> <span class="Bold">Venofer</span> <br/> <span class="Bold">(n=73)</span></td><td align="center" class="Botrule Rrule" valign="top"> <span class="Bold">Historical Control</span> <br/> <span class="Bold">(n=18)</span></td><td align="center" class="Botrule Rrule" valign="top"> <span class="Bold">Venofer</span> <br/> <span class="Bold">(n=71)</span></td><td align="center" class="Botrule Rrule" valign="top"> <span class="Bold">Historical</span> <br/> <span class="Bold">Control</span> <br/> <span class="Bold">(n=15)</span></td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule" valign="top"> Hemoglobin (g/dL) </td><td align="center" class="Botrule Rrule" valign="top"> 1.0 ± 0.12** </td><td align="center" class="Botrule Rrule" valign="top"> 0.0 ± 0.21 </td><td align="center" class="Botrule Rrule" valign="top"> 1.3 ± 0.14** </td><td align="center" class="Botrule Rrule" valign="top"> -0.6 ± 0.24 </td><td align="center" class="Botrule Rrule" valign="top"> 1.2 ± 0.17* </td><td align="center" class="Botrule Rrule" valign="top"> -0.1 ± 0.23 </td> </tr> <tr class="Last"> <td align="justify" class="Botrule Lrule Rrule" valign="top"> Hematocrit (%) </td><td align="center" class="Botrule Rrule" valign="top"> 3.1 ± 0.37** </td><td align="center" class="Botrule Rrule" valign="top"> -0.3 ± 0.65 </td><td align="center" class="Botrule Rrule" valign="top"> 3.6 ± 0.44** </td><td align="center" class="Botrule Rrule" valign="top"> -1.2 ± 0.76 </td><td align="center" class="Botrule Rrule" valign="top"> 3.3 ± 0.54 </td><td align="center" class="Botrule Rrule" valign="top"> 0.2 ± 0.86 </td> </tr> </tbody> </table></div>

Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9.5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%).

Study B was a multicenter, open label study of Venofer in 23 patients with iron deficiency and HDD-CKD who had been discontinued from iron dextran due to intolerance. Eligibility criteria were otherwise identical to Study A. The mean age of the patients in this study was 53 years, with ages ranging from 21 to 79 years. Of the 23 patients enrolled in the study, 10 (44%) were male and 13 (56%) were female.

All 23 enrolled patients were evaluated for efficacy. Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment.

Study C was a multicenter, open-label study in patients with HDD-CKD. This study enrolled patients with a hemoglobin ≤ 10 g/dL, a serum transferrin saturation ≤ 20%, and a serum ferritin ≤ 200 ng/mL, who were undergoing maintenance hemodialysis 2 to 3 times weekly. The mean age of the patients enrolled in this study was 41 years, with ages ranging from 16 to 70 years. Of 130 patients evaluated for efficacy in this study, 68 (52%) were male and 62 (48%) were female. Forty-eight percent of the patients had previously been treated with oral iron. Exclusion criteria were similar to those in studies A and B. Venofer was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of iron was administered. A 50 mg dose (2.5 mL) was given to patients within two weeks of study entry as a test dose. Twenty-seven patients (20%) were receiving erythropoietin treatment at study entry and they continued to receive the same erythropoietin dose for the duration of the study.

The modified intention-to-treat (mITT) population consisted of 131 patients. Increases from baseline in mean hemoglobin (1.7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.

Study D (NCT00236977) was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral iron versus Venofer in patients with NDD-CKD with or without erythropoietin therapy. Erythropoietin therapy was stable for 8 weeks prior to randomization. In the study 188 patients with NDD-CKD, hemoglobin of ≤ 11.0 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL were randomized to receive oral iron (325 mg ferrous sulfate three times daily for 56 days); or Venofer (either 200 mg over 2 to 5 minutes 5 times within 14 days or two 500 mg infusions on Day 1 and Day 14, administered over 3.5 to 4 hours). The mean age of the 91 treated patients in the Venofer group was 61.6 years (range 25 to 86 years) and 64 years (range 21 to 86 years) for the 91 patients in the oral iron group.

A statistically significantly greater proportion of Venofer subjects (35/79; 44.3%) compared to oral iron subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).

Study E (NCT00236938) was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous iron to patients with PDD-CKD receiving an erythropoietin alone without iron supplementation. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11.5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no iron or Venofer (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29). The mean age of the 75 treated patients in the Venofer / erythropoietin group was 51.9 years (range 21 to 81 years) vs. 52.8 years (range 23 to 77 years) for 46 patients in the erythropoietin alone group.

Patients in the Venofer / erythropoietin group had statistically significantly greater mean change from baseline to the highest hemoglobin value (1.3 g/dL), compared to subjects who received erythropoietin alone (0.6 g/dL) (p < 0.01). A greater proportion of subjects treated with Venofer / erythropoietin (59.1 %) had an increase in hemoglobin of ≥ 1 g/dL at any time during the study compared to the subjects who received erythropoietin only (33.3%).

Study F (NCT00239642) was a randomized, open-label, dose-ranging study for iron maintenance treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD on stable erythropoietin therapy. The study randomized patients to one of three doses of Venofer (0.5 mg/kg, 1 mg/kg or 2 mg/kg). The mean age was 13 years (range 2 to 20 years). Over 70% of patients were 12 years or older in all three groups. There were 84 males and 61 females. About 60% of patients underwent hemodialysis and 25% underwent peritoneal dialysis in all three dose groups. At baseline, the mean hemoglobin was 12 g/dL, the mean TSAT was 33% and the mean ferritin was 300 ng/mL. Patients with HDD-CKD received Venofer once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Venofer once every 4 weeks for 3 doses. Among 131 evaluable patients with stable erythropoietin dosing, the proportion of patients who maintained hemoglobin between 10.5 g/dL and 14.0 g/dL during the 12-week treatment period was 58.7%, 46.7%, and 45.0% in the Venofer 0.5 mg/kg, 1 mg/kg, and 2 mg/kg groups, respectively. A dose-response relationship was not demonstrated.

Venofer is supplied sterile in 5 mL and 2.5 mL single-dose vials. Each 5 mL vial contains 100 mg elemental iron, and each 2.5 mL vial contains 50 mg elemental iron (20 mg/mL).

<div class="scrollingtable"><table> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="justify" valign="top">   </td><td align="justify" valign="top"> </td><td align="justify" valign="top"> </td> </tr> <tr> <td align="justify" valign="top"> NDC-49230-534-10 </td><td align="justify" valign="top"> 100 mg/5 mL Single-Dose Vial </td><td align="justify" valign="top"> Packages of 10</td> </tr> <tr> <td align="justify" valign="top"> NDC-49230-534-25 </td><td align="justify" valign="top"> 100 mg/5 mL Single-Dose Vial </td><td align="justify" valign="top"> Packages of 25 </td> </tr> <tr> <td align="justify" valign="top">  </td><td align="justify" valign="top"> </td><td align="justify" valign="top">  </td> </tr> <tr> <td align="justify" valign="top"> NDC-49230-530-10</td><td align="justify" valign="top"> 50 mg/2.5 mL Single-Dose Vial</td><td align="justify" valign="top"> Packages of 10</td> </tr> <tr class="Last"> <td align="justify" valign="top"> NDC-49230-530-25 </td><td align="justify" valign="top"> 50 mg/2.5 mL Single-Dose Vial</td><td align="justify" valign="top"> Packages of 25 </td> </tr> </tbody> </table></div>

Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Do not freeze.

Syringe Stability: Venofer, when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental iron per mL, or undiluted (20 mg elemental iron per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C).

Intravenous Admixture Stability: Venofer, when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental iron per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C).

Do not dilute to concentrations below 1 mg/mL.

Do not mix Venofer with other medications or add to parenteral nutrition solutions for intravenous infusion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to infusion.

Prior History of Reactions to Parenteral Iron Products

{ "type": "p", "children": [], "text": "\nPrior History of Reactions to Parenteral Iron Products\n" }

Question patients regarding any prior history of reactions to parenteral iron products [see Warnings and Precautions (5)].

{ "type": "p", "children": [], "text": "Question patients regarding any prior history of reactions to parenteral iron products [see Warnings and Precautions (5)].\n" }

Serious Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nSerious Hypersensitivity Reactions\n" }

Advise patients to report any symptoms of hypersensitivity that may develop during and following Venofer administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)].

{ "type": "p", "children": [], "text": "Advise patients to report any symptoms of hypersensitivity that may develop during and following Venofer administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)]. " }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Fresenius Medical Care, NA Waltham, MA  024511-800-323-5188

{ "type": "p", "children": [], "text": "\nFresenius Medical Care, NA\nWaltham, MA  024511-800-323-5188" }

IN534100801.KMG # 25536 

{ "type": "p", "children": [], "text": "IN534100801.KMG # 25536 " }

Venofer is manufactured under license from American Regent, Inc. (Shirley, NY) and Vifor (International) Inc., Switzerland.

{ "type": "p", "children": [], "text": "Venofer is manufactured under license from American Regent, Inc. (Shirley, NY) and Vifor (International) Inc., Switzerland. " }

NDC 49230-530-01

{ "type": "p", "children": [], "text": "\nNDC 49230-530-01\n" }

VENOFER®

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(Iron Sucrose) Injection, USP

{ "type": "p", "children": [], "text": "(Iron Sucrose) Injection, USP " }

50 mg Elemental Iron per 2.5 mL (20 mg/mL)

{ "type": "p", "children": [], "text": "\n50 mg Elemental Iron per 2.5 mL (20 mg/mL)" }

2.5 mL Single-Dose Vial

{ "type": "p", "children": [], "text": "\n2.5 mL Single-Dose Vial" }

Discard Unused Portion

{ "type": "p", "children": [], "text": "Discard Unused Portion" }

For Intravenous Use Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Use Only\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n\n\n" }

NDC 49230-530-10

{ "type": "p", "children": [], "text": "\nNDC 49230-530-10\n" }

10 x 2.5 mL Single-Dose Vials

{ "type": "p", "children": [], "text": "10 x 2.5 mL Single-Dose Vials" }

VENOFER®

{ "type": "p", "children": [], "text": "\nVENOFER®\n" }

(Iron Sucrose) Injection, USP

{ "type": "p", "children": [], "text": "(Iron Sucrose) Injection, USP " }

50 mg Elemental Iron per 2.5 mL (20 mg/mL)

{ "type": "p", "children": [], "text": "\n50 mg Elemental Iron per 2.5 mL (20 mg/mL)\n" }

2.5 mL Single-Dose Vial - Discard Unused Portion

{ "type": "p", "children": [], "text": "\n2.5 mL Single-Dose Vial - Discard Unused Portion" }

For Intravenous Use Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Use Only\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

Each 2.5 mL contains: 50 mg elemental iron (as iron sucrose) in water for injection. The drug product contains approximately 30% sucrose w/v (300 mg/mL).  Sodium hydroxide may be added to adjust pH to 10.5 to 11.1.  Osmolarity 1,250 mOsmol/L.  Contains no preservatives.  Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).  Sterile.

{ "type": "p", "children": [], "text": "Each 2.5 mL contains: 50 mg elemental iron (as iron sucrose) in water for injection. The drug product contains approximately 30% sucrose w/v (300 mg/mL).  Sodium hydroxide may be added to adjust pH to 10.5 to 11.1.  Osmolarity 1,250 mOsmol/L.  Contains no preservatives.  Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).  Sterile." }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Fresenius Medical Care NA Waltham, MA  02451

{ "type": "p", "children": [], "text": "\nFresenius Medical Care NA\nWaltham, MA  02451" }

101327.D  Rev. 7/2020

{ "type": "p", "children": [], "text": "101327.D  Rev. 7/2020\n\n\n\n" }

NDC 49230-530-25

{ "type": "p", "children": [], "text": "\nNDC 49230-530-25\n" }

25 x 2.5 mL Single-Dose Vials

{ "type": "p", "children": [], "text": "25 x 2.5 mL Single-Dose Vials" }

Discard Unused Portion

{ "type": "p", "children": [], "text": "Discard Unused Portion" }

VENOFER®

{ "type": "p", "children": [], "text": "\nVENOFER®\n" }

(Iron Sucrose) Injection, USP

{ "type": "p", "children": [], "text": "(Iron Sucrose) Injection, USP " }

50 mg Elemental Iron per 2.5 mL (20 mg/mL)

{ "type": "p", "children": [], "text": "\n50 mg Elemental Iron per 2.5 mL (20 mg/mL)" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

For Intravenous Use Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Use Only\n" }

Each 2.5 mL contains: 50 mg elemental iron (as iron sucrose) in water for injection. The drug product contains approximately 30% sucrose w/v (300 mg/mL).  Sodium hydroxide may be added to adjust pH to 10.5 to 11.1.  Osmolarity 1,250 mOsmol/L.  Contains no preservatives.  Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).  Sterile.  Venofer® is manufactured under license from American Regent, Inc. (Shirley, NY) and Vifor (International) Inc., Switzerland. 

{ "type": "p", "children": [], "text": "Each 2.5 mL contains: 50 mg elemental iron (as iron sucrose) in water for injection. The drug product contains approximately 30% sucrose w/v (300 mg/mL).  Sodium hydroxide may be added to adjust pH to 10.5 to 11.1.  Osmolarity 1,250 mOsmol/L.  Contains no preservatives.  Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).  Sterile.  Venofer® is manufactured under license from American Regent, Inc. (Shirley, NY) and Vifor (International) Inc., Switzerland.  " }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Fresenius Medical Care NA Waltham, MA  02451 101329.DRev. 7/2020

{ "type": "p", "children": [], "text": "\nFresenius Medical Care NA\nWaltham, MA  02451\n101329.DRev. 7/2020\n\n\n\n" }

NDC 49230-534-01

{ "type": "p", "children": [], "text": "\nNDC 49230-534-01\n" }

VENOFER®

{ "type": "p", "children": [], "text": "\nVENOFER®\n" }

(Iron Sucrose) Injection, USP

{ "type": "p", "children": [], "text": "(Iron Sucrose) Injection, USP " }

100 mg Elemental Iron per 5 mL (20 mg/mL)

{ "type": "p", "children": [], "text": "\n100 mg Elemental Iron per 5 mL (20 mg/mL)" }

5 mL Single-Dose Vial

{ "type": "p", "children": [], "text": "\n5 mL Single-Dose Vial" }

Discard Unused Portion 

{ "type": "p", "children": [], "text": "Discard Unused Portion " }

For Intravenous Use Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Use Only\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n\n\n" }

NDC 49230-534-10

{ "type": "p", "children": [], "text": "\nNDC 49230-534-10\n" }

10 x 5 mL Single-Dose Vials

{ "type": "p", "children": [], "text": "10 x 5 mL Single-Dose Vials" }

VENOFER®

{ "type": "p", "children": [], "text": "\nVENOFER®\n" }

(Iron Sucrose) Injection, USP

{ "type": "p", "children": [], "text": "(Iron Sucrose) Injection, USP " }

100 mg Elemental Iron per 5 mL (20 mg/mL)

{ "type": "p", "children": [], "text": "\n100 mg Elemental Iron per 5 mL (20 mg/mL)\n" }

5 mL Single-Dose Vial - Discard Unused Portion

{ "type": "p", "children": [], "text": "\n5 mL Single-Dose Vial - Discard Unused Portion" }

For Intravenous Use Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Use Only\n" }

Each 5 mL contains: 100 mg elemental iron (as iron sucrose) in water for injection. The drug product contains approximately 30% sucrose w/v (300 mg/mL).  Sodium hydroxide may be added to adjust pH to 10.5 to 11.1.  Osmolarity 1,250 mOsmol/L.  Contains no preservatives.  Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).  Sterile.

{ "type": "p", "children": [], "text": "Each 5 mL contains: 100 mg elemental iron (as iron sucrose) in water for injection. The drug product contains approximately 30% sucrose w/v (300 mg/mL).  Sodium hydroxide may be added to adjust pH to 10.5 to 11.1.  Osmolarity 1,250 mOsmol/L.  Contains no preservatives.  Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).  Sterile. " }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Fresenius Medical Care NA Waltham, MA  02451 101327.D   Rev. 7/2020

{ "type": "p", "children": [], "text": "\nFresenius Medical Care NA\nWaltham, MA  02451\n101327.D   Rev. 7/2020\n\n\n" }

NDC 49230-534-25

{ "type": "p", "children": [], "text": "\nNDC 49230-534-25\n" }

25 X 5 mL Single-Dose Vials

{ "type": "p", "children": [], "text": "25 X 5 mL Single-Dose Vials" }

Discard Unused Portion

{ "type": "p", "children": [], "text": "Discard Unused Portion" }

VENOFER®

{ "type": "p", "children": [], "text": "\nVENOFER®\n" }

(Iron Sucrose) Injection, USP

{ "type": "p", "children": [], "text": "(Iron Sucrose) Injection, USP " }

100 mg Elemental Iron per 5 mL (20 mg/mL)

{ "type": "p", "children": [], "text": "\n100 mg Elemental Iron per 5 mL (20 mg/mL)" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

For Intravenous Use Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Use Only\n" }

Each 5 mL contains: 100 mg elemental iron (as iron sucrose) in water for injection. The drug product contains approximately 30% sucrose w/v (300 mg/mL). Sodium hydroxide may be added to adjust pH to 10.5 to 11.1.  Osmolarity 1,250 mOsmol/L.  Contains no preservatives.  Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).  Sterile.  Venofer® is manufactured under license from American Regent, Inc. (Shirley, NY) and Vifor (International) Inc., Switzerland. 

{ "type": "p", "children": [], "text": "Each 5 mL contains: 100 mg elemental iron (as iron sucrose) in water for injection. The drug product contains approximately 30% sucrose w/v (300 mg/mL). Sodium hydroxide may be added to adjust pH to 10.5 to 11.1.  Osmolarity 1,250 mOsmol/L.  Contains no preservatives.  Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).  Sterile.  Venofer® is manufactured under license from American Regent, Inc. (Shirley, NY) and Vifor (International) Inc., Switzerland.  " }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Fresenius Medical Care NA Waltham, MA  02451 100787.DRev. 7/2020

{ "type": "p", "children": [], "text": "\nFresenius Medical Care NA\nWaltham, MA  02451\n100787.DRev. 7/2020\n\n\n\n" }