Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Venofer: 20 mg/mL (2.5 mL, 5 mL, 10 mL)
Pharmacology
Mechanism of Action
Iron sucrose is dissociated by the reticuloendothelial system into iron and sucrose. The released iron increases serum iron concentrations and is incorporated into hemoglobin.
Pharmacokinetics/Pharmacodynamics
Distribution
Vdss: Healthy adults: 7.9 L
Metabolism
Dissociated into iron and sucrose by the reticuloendothelial system
Excretion
Healthy adults: Urine (5%) within 24 hours
Onset of Action
Onset of action: Hematologic response to either oral or parenteral iron salts is essentially the same; red blood cell form and color changes within 3 to 10 days
Maximum effect: Peak reticulocytosis occurs in 5 to 10 days, and hemoglobin values increase within 2 to 4 weeks
Half-Life Elimination
Healthy adults: 6 hours; Non-dialysis-dependent adolescents: 8 hours
Use: Labeled Indications
Iron-deficiency anemia: Treatment of iron-deficiency anemia in chronic kidney disease (CKD)
KDIGO guideline recommendations: For CKD patients with anemia and receiving dialysis, IV iron may be indicated if an increase in the hemoglobin concentration (without initiating or increasing the dose of an erythropoiesis stimulating agent) is desired and the transferrin saturation (TSAT) is ≤30% and ferritin is ≤500 ng/mL; for CKD patients not on dialysis, a trial of oral iron is suggested, although the route of administration is selected based on the severity of iron deficiency, venous access, response to prior oral iron therapy, patient adherence, and cost. There is insufficient evidence to recommend IV iron if ferritin level is >500 ng/mL or TSAT is >30% (KDIGO 2012).
Use: Off Label
Chemotherapy-associated anemiaayes
Data from 2 multicenter, randomized clinical trials support the use of iron sucrose in the management of patients with chemotherapy-associated anemia Bastit 2008, Hedenus 2007. Data from 3 small studies also support the use of iron sucrose to prevent anemia and reduce the need for blood transfusions in patients with gynecologic malignancies receiving platinum-based chemotherapy Athibovonsuk 2013, Dangsuwan 2010, Kim 2007. Three systematic reviews (which included various IV iron products) also support the addition of iron sucrose to erythropoiesis-stimulating agents in the management of chemotherapy-associated anemia Gafter-Gvili 2013, Mhaskar 2016, Petrelli 2012.
Based on guidelines from the American Society of Clinical Oncology and the American Society of Hematology for Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents, the use of iron supplementation (either oral or IV) reduces the risk for red blood cell transfusions and should be considered (independent of iron status) in all patients receiving erythropoiesis-stimulating agents.
Contraindications
Known hypersensitivity to iron sucrose or any component of the formulation
Documentation of allergenic cross-reactivity for iron is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in the US labeling): Iron overload; anemia not caused by iron deficiency
Dosage and Administration
Dosing: Adult
Doses expressed in mg of elemental iron. Note: Test dose: Product labeling does not indicate need for a test dose in product-naive patients.
Iron-deficiency anemia in chronic kidney disease: IV:
Hemodialysis-dependent chronic kidney disease: 100 mg administered during consecutive dialysis sessions; the usual cumulative total dose is 1,000 mg (10 doses); may repeat treatment if clinically indicated.
Peritoneal dialysis-dependent chronic kidney disease: Two infusions of 300 mg administered 14 days apart, followed by a single 400 mg infusion 14 days later (total cumulative dose of 1,000 mg in 3 divided doses); may repeat treatment if clinically indicated.
Non-dialysis-dependent chronic kidney disease: 200 mg administered on 5 different occasions within a 14-day period (total cumulative dose: 1,000 mg in 14-day period); may repeat treatment if clinically indicated. Note: Dosage has also been administered as 2 infusions of 500 mg on day 1 and day 14 (limited experience).
Chemotherapy-associated anemia (off-label use): IV: 200 mg once every 3 weeks for 5 doses (Bastit 2008) or 100 mg once weekly during weeks 0 to 6, followed by 100 mg every other week from weeks 8 to 14 (Hedenus 2007) or 200 mg once a week after each platinum-based chemotherapy cycle for up to 6 doses (Kim 2007) or 200 mg after each platinum-based chemotherapy cycle for 6 cycles (Athibovonsuk 2013).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Multiple forms for parenteral iron exist; close attention must be paid to the specific product when ordering and administering; incorrect selection or substitution of one form for another without proper dosage adjustment may result in serious over- or underdosing. Doses are expressed as mg of elemental iron. Note: Per National Kidney Foundation DOQI Guidelines, initiation of iron therapy, determination of dose, and duration of therapy should be guided by results of iron status tests combined with the Hb level and the dose of the erythropoietin stimulating agent. See Reference Range for target levels. There is insufficient evidence to recommend IV iron if ferritin level >500 ng/mL.
Iron deficiency anemia in CKD:
Repletion treatment: Limited data available: Children ≥2 years and Adolescents <15 years: IV: 1 mg/kg/dialysis; dosing based on a dose-finding trial in 14 pediatric patients and successfully increased ferritin therapeutic levels; iron overload (serum ferritin >400 ng/mL) was reported with the higher dose used in the study (3 mg/kg/dialysis) (Leijn 2004)
Maintenance therapy: Children ≥2 years and Adolescents:
Hemodialysis-dependent CKD: IV: 0.5 mg/kg/dose (maximum dose: 100 mg) every 2 weeks for 12 weeks (6 doses); may repeat if clinically indicated
Peritoneal dialysis-dependent CKD; concurrent erythropoietin therapy: IV: 0.5 mg/kg/dose (maximum dose: 100 mg) every 4 weeks for 12 weeks (3 doses); may repeat if clinically indicated
Nondialysis-dependent CKD; concurrent erythropoietin therapy: IV: 0.5 mg/kg/dose (maximum dose: 100 mg) every 4 weeks for 12 weeks (3 doses); may repeat if clinically indicated
Iron deficiency anemia, nonrenal causes; treatment in patients refractory to oral therapy (eg, long-term TPN, GI malabsorption): Limited data available (Norman 2011; Pinsk 2008): Infants, Children, and Adolescents:
Calculate Iron Deficit: Total replacement dose (mg of iron) = 0.6 x weight (kg) x [100 - (actual Hgb /12 x 100)]; Note: In this equation, 12 is the desired target Hgb concentration; in some patients, a different target may be required.
Initial dose: IV: 5 to 7 mg/kg/dose; maximum initial dose: 100 mg/dose
Maintenance dose: IV: 5 to 7 mg/kg/dose every 1 to 7 days until total replacement dose achieved; maximum single dose: 300 mg/dose
Reconstitution
Doses ≤200 mg may be administered undiluted or diluted in a maximum of 100 mL NS. Doses >200 mg should be diluted in a maximum of 250 mL NS. Do not dilute to concentrations <1 mg/mL.
Administration
IV: Administer intravenously as a slow IV injection (not for rapid IV injection) or as an IV infusion. Can be administered through dialysis line.
Slow IV injection: May administer doses ≤200 mg undiluted by slow IV injection over 2 to 5 minutes. When administering to hemodialysis-dependent patients, give iron sucrose early during the dialysis session (generally within the first hour).
Infusion: Infuse diluted doses ≤200 mg over at least 15 minutes; infuse diluted 300 mg dose over 1.5 hours; infuse diluted 400 mg dose over 2.5 hours; infuse diluted 500 mg dose over 3.5 to 4 hours (limited experience). When administering to hemodialysis-dependent patients, give iron sucrose early during the dialysis session.
Storage
Store intact vials in original carton at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze. Iron sucrose is stable for 7 days at room temperature (23°C to 27°C [73°F to 81°F]) or under refrigeration (2°C to 6°C [36°F to 43°F]) when undiluted in a plastic syringe or following dilution in normal saline in a plastic syringe (concentration 2 to 10 mg/mL) or for 7 days at room temperature (23°C to 27°C [73°F to 81°F]) following dilution in normal saline in an IV bag (concentration 1 to 2 mg/mL).
Drug Interactions
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dimercaprol: May enhance the nephrotoxic effect of Iron Preparations. Avoid combination
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Adverse Reactions
Events and incidences are associated with use in adults unless otherwise specified.
>10%:
Cardiovascular: Hypotension (2% to 3%; children: 2%; hemodialysis patients: 39%; may be related to total dose or rate of administration)
Central nervous system: Headache (3% to 13%; children: 6%)
Gastrointestinal: Nausea (5% to 15%; children: 3%)
Neuromuscular & skeletal: Muscle cramps (1% to 3%; hemodialysis patients: 29%)
Respiratory: Nasopharyngitis (2% to 16%), pharyngitis (2% to 16%), sinusitis (2% to 16%), upper respiratory tract infection (2% to 16%; children: 4%)
1% to 10%:
Cardiovascular: Hypertension (7% to 8%; children: 2%), peripheral edema (3% to 7%), chest pain (1% to 6%), thrombosis (children: 2%; arteriovenous fistula), cardiac failure (>1%)
Central nervous system: Dizziness (1% to 7%; children: 4%)
Dermatologic: Pruritus (2% to 4%)
Endocrine & metabolic: Hypoglycemia (≤4%), hypervolemia (1% to 3%), gout (≤3%), hyperglycemia (≤3%)
Gastrointestinal: Vomiting (5% to 9%; children: 4%), diarrhea (5% to 8%), dysgeusia (≤8%), peritonitis (children: 4%), abdominal pain (1% to 4%)
Immunologic: Graft complications (≤10%)
Infection: Sepsis (>1%)
Local: Injection site reaction (≤6%)
Neuromuscular & skeletal: Limb pain (3% to 6%), arthralgia (1% to 4%), myalgia (≤4%), weakness (1% to 3%), back pain (1% to 2%)
Ophthalmic: Conjunctivitis (≤3%)
Otic: Otalgia (≤2%)
Respiratory: Dyspnea (1% to 6%), cough (1% to 3%; children: 4%), nasal congestion (≤1%)
Miscellaneous: Fever (1% to 3%; children: 4%)
<1%, postmarketing, and/or case reports: Anaphylactic shock, anaphylactoid reaction, angioedema, bradycardia, bronchospasm, circulatory shock, confusion, facial rash, hyperhidrosis, hypersensitivity reaction (including wheezing), hypoesthesia, joint swelling, local discoloration (at injection site following extravasation), loss of consciousness, necrotizing enterocolitis (reported in premature infants; no causal relationship established), paresthesia, seizure, shock, urine discoloration, urticaria
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Cases of hypersensitivity reactions, including anaphylactic and anaphylactoid reactions (some fatal), have been reported. Monitor patients during administration and for at least 30 minutes after the infusion is complete; discontinue immediately for signs/symptoms of a hypersensitivity reaction (eg, shock, hypotension, loss of consciousness, collapse) or if signs of intolerance occur. Equipment for resuscitation and trained personnel experienced in handling medical emergencies should always be immediately available. Most reactions occur within 30 minutes after completion of infusion.
- Hypotension: Clinically significant hypotension has been reported; monitor for signs/symptoms of hypotension. Hypotension may be related to total dose or rate of administration (avoid rapid IV injection).
- Infection: Avoid administering IV iron to patients with active systemic infection (KDIGO 2012).
Other warnings/precautions:
- Iron overload: Excessive iron therapy may lead to excess storage of iron (with the possibility of iatrogenic hemosiderosis). Do not administer iron in the presence of iron overload; periodic monitoring of hemoglobin, hematocrit, serum ferritin, and transferrin saturation is recommended. Transferrin saturation values increase rapidly following IV iron administration; wait at least 48 hours after a dose to assess serum iron measurements.
Monitoring Parameters
CKD patients: Hematocrit, hemoglobin, serum ferritin, serum iron, transferrin, percent transferrin saturation (TSAT), total iron-binding capacity (TIBC) (takes ~4 weeks of treatment to see increased serum iron and ferritin, and decreased TIBC); iron status should be assessed ≥48 hours after last dose (due to rapid increase in values following administration); signs/symptoms of hypersensitivity reactions (during and ≥30 minutes following infusion); hypotension (during and following infusion).
Evaluate iron status (TSAT and ferritin) when deciding to start or continue iron therapy, and at least every 3 months in patients also receiving erythropoietin-stimulating agent (ESA) therapy. Monitor ferritin and TSAT more frequently when monitoring response to IV iron therapy, when initiating or increasing ESA dose, when there is blood loss, and in any other situations where iron stores may become depleted (KDIGO 2012).
Chemotherapy-associated anemia (off-label use): Iron, total iron-binding capacity, transferrin saturation, or ferritin levels at baseline and periodically (ASCO/ASH [Bohlius 2019])
Pregnancy
Pregnancy Considerations
Maternal iron requirements increase during pregnancy. Adequate iron concentrations to the fetus can be maintained regardless of maternal iron status, except in severe cases of anemia (IOM 2001). Untreated iron deficiency and iron deficiency anemia (IDA) in a pregnant female may be associated with adverse events, including low birth weight, preterm birth, or increased perinatal mortality (ACOG 95 2008; IOM 2001; Pavord 2012).
In general, treatment of iron deficiency or IDA in pregnancy is the same as in non-pregnant females. The majority of studies note iron therapy improves maternal hematologic parameters; however, information related to clinical outcomes in the mother and neonate is limited (Qassim 2018; Reveiz 2011; Siu 2015). Oral preparations are generally sufficient; however, parenteral iron therapy may be used in females who cannot tolerate or will not take oral iron, in cases of severe iron deficiency, or when malabsorption is present (ACOG 95 2008; Pavord 2012). Due to limited safety data in early pregnancy, use of intravenous iron is generally not started until the second or third trimester (Breymann 2017; Pavord 2012). Iron sucrose has been evaluated in multiple studies for the treatment of IDA during pregnancy (Bhavi 2017; Christoph 2012; Qassim 2018; Reveiz 2011; Shi 2015).
Patient Education
What is this drug used for?
- It is used to treat anemia.
Frequently reported side effects of this drug
- Diarrhea
- Muscle cramps
- Nausea
- Vomiting
- Back pain
- Joint pain
- Stuffy nose
- Sore throat
- Change in taste
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Chest pain
- Severe dizziness
- Passing out
- Vision changes
- Severe headache
- Cough
- Sweating
- Throat tightness
- Shortness of breath
- Swelling of arms or legs
- Injection site irritation
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
