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 under-dosing. Doses are expressed as mg of elemental iron.
Anemia of prematurity: Limited data available; dosing regimens variable: IV: 1 mg/kg/day infused over 2 hours or 6 mg/kg/dose once weekly infused over 1 hour; daily dosing based on results of a small comparative trial of 29 premature neonates (GA <31 weeks) who received oral iron (n=9), oral iron plus epoetin (n=10), or 2 mg/kg/day for 3 weeks of iron sucrose plus epoetin (n=10, mean age: 23.3 ± 2.9 days; mean weight: 1,266 ± 81 g); higher reticulocyte counts and fewer transfusions were observed in infants who received iron sucrose compared oral treatment; due to potential oxidative injury risk in smaller, less stable premature neonates, the authors suggest that lower doses of 1 mg/kg/day should be considered (Ref). Weekly dosing based on a small comparative trial of 42 neonates (GA <33 weeks, birthweight <1,500 g) who received both epoetin and oral iron (n=21) or 6 mg/kg/dose once weekly of iron sucrose (n=21, mean age: 26.4 ± 8.4 days and mean weight of 1,292 ± 173.3 g); hematologic response was similar in both groups; however, iron sucrose was not associated with a decline in ferritin suggesting improved iron storage compared to oral (Ref).
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.
Iron deficiency anemia in chronic kidney disease (CKD):
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.
Repletion treatment: Limited data available: Children ≥2 years and Adolescents ≤15 years: IV: 1 mg/kg/dialysis; repeat dose with each dialysis session until patient specific lab goals are met, then follow with maintenance dosing. Dosing based on a dose-finding trial in 14 pediatric patients (ages 2 to 15 years) receiving iron sucrose in combination with epoetin for absolute or functional iron deficiency. Due to a rapid increase in ferritin levels (from 59 mcg/L to 496 mcg/L) observed in the first 6 weeks of the trial, the dosing protocol for iron sucrose was changed from 3 mg/kg/dialysis session to 1 mg/kg/dialysis session; the dose of 1 mg/kg/dialysis session was continued until a patient was considered replete based on study criteria, at which point the patient was transitioned to the maintenance group within the study (Ref).
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 (Ref): 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.
Nondialyzable. There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Iron sucrose: Drug information")
Note: Route of administration: IV iron replacement is preferred over oral replacement in several clinical situations (eg, poor GI absorption, lack of response to or poor tolerability of oral iron, need for rapid repletion, chronic kidney disease, active inflammatory bowel disease, cancer, chronic or extensive blood loss) (Ref). Dosage expression: Dose is expressed in mg of elemental iron. Test dose: A test dose typically is not required.
Chemotherapy-associated anemia (off-label use): IV: 200 mg once every 3 weeks for 5 doses (Ref) or 100 mg once weekly during weeks 0 to 6, followed by 100 mg every other week from weeks 8 to 14 (Ref) or 200 mg once a week after each platinum-based chemotherapy cycle for up to 6 doses (Ref) or 200 mg after each platinum-based chemotherapy cycle for 6 cycles (Ref).
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).
Iron-deficiency anemia, treatment, patients without chronic kidney disease (off-label use): IV: 100 to 300 mg per dose; repeat doses may be given until total iron requirements are met (Ref). Dosing schedule depends on iron deficit and ease of scheduling. Cumulative doses >1 g generally are not required during a single treatment course unless there is ongoing blood loss (Ref).
Chronic kidney disease, non-dialysis-dependent: No dosage adjustment necessary (indicated for use in non-dialysis-dependent chronic kidney disease [CKD] patients).
Hemodialysis: No dosage adjustment necessary (indicated for use in CKD patients on hemodialysis); not dialyzable.
Peritoneal dialysis: No dosage adjustment necessary (indicated for use in CKD patients on peritoneal dialysis).
There are no dosage adjustments provided in the manufacturer's labeling.
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)
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Venofer: 20 mg/mL (5 mL)
Generic: 20 mg/mL (5 mL)
Strength of iron sucrose is expressed as elemental iron.
Parenteral: May administer IV; not for IM use.
Premature neonates: Infusion: Infuse over at least 1 to 2 hours (Ref)
Infants, Children, and Adolescents: Dependent upon indication:
CKD treatment of iron deficiency anemia:
Slow IV injection: Administer undiluted over 5 minutes
Infusion: Dilute and infuse over 5 to 60 minutes
Nonrenal treatment of iron deficiency anemia: One trial reported infusion of a diluted 1 mg/mL solution at 1 to 1.3 mL/minute (Ref).
Others suggest the following recommendations (Ref):
For doses ≤100 mg, infuse over at least 30 minutes
For doses >100 mg and ≤200 mg, infuse over at least 60 minutes
For doses >200 mg and ≤300 mg, infuse over at least 90 minutes
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.
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).
Treatment of iron deficiency anemia in hemodialysis-dependent chronic kidney disease (HDD-CKD) (FDA approved in ages ≥2 years and adults); treatment of iron deficiency anemia with concurrent erythropoietin therapy in peritoneal dialysis-dependent (PDD) CKD and nondialysis-dependent (NDD) CKD (FDA approved in ages ≥2 years); treatment of iron deficiency anemia in PDD-CKD and NDD-CKD (FDA approved in adults); has also been used for treatment of nonrenal iron deficiency anemia and supplementation of iron in patients for which oral therapy is neither effective nor tolerated (eg, long-term TPN).
Iron sucrose may be confused with ferric carboxymaltose, ferric gluconate, ferumoxytol, iron dextran complex
Venofer may be confused with Vfend, Vimpat
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults with hemodialysis dependent (HD), non-dialysis dependent (NDD), or peritoneal dialysis dependent (PDD) chronic kidney disease, unless otherwise noted.
>10%:
Cardiovascular: Hypotension (adults: HD: 39%, NDD/PDD: 2% to 3%; children: 2%)
Gastrointestinal: Nausea (adults: 5% to 15%; children: 3%)
Nervous system: Headache (adults: HD: 13%, NDD/PDD: 3% to 4%; children: 6%)
Neuromuscular & skeletal: Muscle cramps (HD: 29%, NDD/PDD: ≤3%)
Respiratory: Nasopharyngitis (≤16%) pharyngitis (≤16%), sinusitis (≤16%), upper respiratory tract infection (≤16%)
1% to 10%:
Cardiovascular: Arteriovenous fistula site complication (thrombosis: children: 2%), chest pain (1% to 6%), heart failure (>1%), hypertension (adults: 7% to 8%; children: 2%), peripheral edema (3% to 7%)
Dermatologic: Pruritus (2% to 4%)
Endocrine & metabolic: Hyperglycemia (3%), hypervolemia (1% to 3%), hypoglycemia (HD/NDD: <1%, PDD: 4%)
Gastrointestinal: Abdominal pain (1% to 4%), diarrhea (5% to 8%), dysgeusia (≤8%), peritonitis (children: 4%), vomiting (adults: 5% to 9%; children: 4%)
Infection: Sepsis (>1%)
Local: Infusion-site reaction (≤6%; including burning and infusion-site pain)
Nervous system: Asthenia (≤3%), dizziness (adults: HD/NDD: 7%, PDD: 1%; children: 4%), feeling abnormal (3%)
Neuromuscular & skeletal: Arthralgia (1% to 4%), back pain (1% to 2%), gout (3%), limb pain (3% to 6%), myalgia (1% to 4%)
Ophthalmic: Conjunctivitis (≤3%)
Otic: Otalgia (2%)
Respiratory: Cough (adults: 1% to 3%; children: 4%), dyspnea (1% to 6%), nasal congestion (1%), viral respiratory tract infection (children: 4%)
Miscellaneous: Fever (adults: ≤3%; children: 4%)
Postmarketing (any population):
Cardiovascular: Bradycardia, collapse, ischemic heart disease, shock
Dermatologic: Hyperhidrosis
Genitourinary: Urine discoloration
Hypersensitivity: Angioedema, hypersensitivity reaction (including anaphylaxis)
Nervous system: Confusion, loss of consciousness, paresthesia, seizure
Neuromuscular & skeletal: Joint swelling
Respiratory: Bronchospasm
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
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.
Use parenteral iron products with caution in premature neonates; necrotizing enterocolitis has been reported; however, no causal relationship established.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dimercaprol: May enhance the nephrotoxic effect of Iron Preparations. Risk X: Avoid combination
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: 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. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Iron transfer to the fetus is regulated by the placenta (BSH [Pavord 2020]; NAS 2020).
There is a risk of adverse maternal reactions (eg, anaphylaxis, hypotension, shock) following use of parenteral iron that may result in fetal bradycardia, especially during the second and third trimesters. Although the risk is rare, immediate treatment for anaphylactoid and/or hypersensitivity reactions should be available (BSH [Pavord 2020]).
Maternal iron requirements increase during pregnancy. Untreated iron deficiency and iron deficiency anemia (IDA) in pregnant patients are associated with adverse pregnancy outcomes, including low birth weight, preterm birth, and increased perinatal mortality (ACOG 2021; BSH [Pavord 2020]). Maternal iron deficiency is also associated with fatigue, increased risk of postpartum depression, and possibly postpartum hemorrhage (BSH [Pavord 2020]).
Oral and parenteral iron are effective at replacing iron stores in pregnant patients (ACOG 2021), Most studies note iron therapy improves maternal hematologic parameters; however, data related to clinical outcomes in the mother and neonate are limited (FIGO 2019; NAS 2020; USPSTF [Siu 2015]). Parenteral iron therapy may be used in pregnant patients who cannot tolerate or respond to oral iron, when iron deficiency occurs later in pregnancy, or when malabsorption is present (ACOG 2021; BSH [Pavord 2020]).
Iron sucrose has been evaluated in multiple studies for the treatment of IDA during pregnancy (Govindappagari 2019; Hamm 2021; Lewkowitz 2019; Qassim 2018; Qassim 2019; Radhika 2019; Rogozińska 2021; Shin 2021). However, due to limited safety data in early pregnancy, use of IV iron is generally not started until the second or third trimester (ACOG 2021; BSH [Pavord 2020]; FIGO 2019).
Hematocrit, hemoglobin, serum ferritin, transferrin, percent transferrin saturation, TIBC; takes about 4 weeks of treatment to see increased serum iron and ferritin, and decreased TIBC. Serum iron concentrations should be drawn ≥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 (following infusion).
Serum iron: All ages: 22 to 184 mcg/dL
Total iron binding capacity:
Infants: 100 to 400 mcg/dL
Children, Adolescents, and Adults: 250 to 400 mcg/dL
Ferritin:
0 to 6 weeks: 0 to 400 ng/mL
7 weeks to 1 year: 10 to 95 ng/mL
1 to 9 years: 10 to 60 ng/mL
10 to 18 years:
Male: 10 to 300 ng/mL
Female: 10 to 70 ng/mL
Chronic kidney disease (CKD): Targets for iron therapy (KDOQI Guidelines, 2007) to maintain Hgb 11 to 12 g/dL:
Children: Nondialysis CKD, hemodialysis, or peritoneal dialysis: Ferritin: >100 ng/mL and TSAT >20%
Adults: Nondialysis (CKD) or peritoneal dialysis: Ferritin: >100 ng/mL and TSAT >20%
Hemodialysis: Ferritin >200 ng/mL and TSAT >20% or CHr (content of hemoglobin in reticulocytes) >29 pg/cell
Iron sucrose is dissociated by the reticuloendothelial system into iron and sucrose. The released iron increases serum iron concentrations and is incorporated into hemoglobin.
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
Distribution: Vdss: Healthy adults: 7.9 L
Metabolism: Dissociated into iron and sucrose by the reticuloendothelial system
Half-life elimination: Healthy adults: 6 hours; Non-dialysis-dependent adolescents: 8 hours
Excretion: Healthy adults: Urine (5%) within 24 hours
Contains sucrose: 300 mg/mL
Solution (Venofer Intravenous)
20 mg/mL (per mL): $8.83
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