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Iron Sucrose


General


Pronunciation

(EYE ern SOO krose)


Brand Names: U.S.

  • Venofer

Indications


Use: Labeled Indications

Iron deficiency anemia: Treatment of iron-deficiency anemia in chronic kidney disease (CKD)


Contraindications


Known hypersensitivity to iron sucrose or any component of the formulation


Dosing 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 (CKD): IV:

Hemodialysis-dependent patient: 100 mg administered during consecutive dialysis sessions to a cumulative total dose of 1000 mg (10 doses); may repeat treatment if clinically indicated.

Peritoneal dialysis-dependent patient: Two infusions of 300 mg administered 14 days apart, followed by a single 400 mg infusion 14 days later (total cumulative dose of 1000 mg in 3 divided doses); may repeat treatment if clinically indicated.

Nondialysis-dependent patient: 200 mg administered on 5 different occasions within a 14-day period (total cumulative dose: 1000 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)


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

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 (CKD): Children ≥2 years and Adolescents: IV: Note: Not indicated for iron replacement treatment in children and adolescents.

Hemodialysis-dependent patient: Maintenance therapy: 0.5 mg/kg/dose (maximum: 100 mg) every 2 weeks for 6 doses; may repeat if clinically indicated.

Nondialysis-dependent patient: Maintenance therapy: 0.5 mg/kg/dose (maximum: 100 mg) every 4 weeks for 3 doses; may repeat if clinically indicated

Peritoneal dialysis-dependent patient: Maintenance therapy: 0.5 mg/kg/dose (maximum: 100 mg) every 4 weeks for 3 doses; may repeat if clinically indicated


Dosing: Renal Impairment

No dosage adjustment provided in manufacturer 's labeling.

Hemodialysis: Not dialyzable


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer 's labeling.


Reconstitution

Children: May administer undiluted or diluted in 25 mL of NS. Do not dilute to concentrations <1 mg/mL.

Adults: 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

Administer intravenously as a slow IV injection (not for rapid IV injection) or as an IV infusion. Can be administered through dialysis line.

Children and Adolescents:

Slow IV injection: Administer undiluted over 5 minutes

Infusion: Infuse diluted solution over 5-60 minutes

Adults:

Slow IV injection: May administer doses ≤200 mg undiluted by slow IV injection over 2-5 minutes. When administering to hemodialysis-dependent patients, give iron sucrose early during the dialysis session.

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 3.5-4 hours (limited experience). When administering to hemodialysis-dependent patients, give iron sucrose early during the dialysis session.


Storage

Store intact vials at controlled room temperature of 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 2-10 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 1-2 mg/mL).


Dosage Forms/Strengths


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)


Compatibility

Stable in NS; variable stability (consult detailed reference) in TPN. The manufacturer recommends not adding to parenteral nutrition solutions; however, iron sucrose at concentrations of 0.1 mg/dL and 0.25 mg/dL in 2-in-1 parenteral nutrition solutions with neonatal-range amino acid and cysteine were shown to be stable for 24 hours; precipitation occurred at higher concentrations (ie, 1-10 mg/dL) (MacKay, 2009).


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

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

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dimercaprol: May enhance the nephrotoxic effect of Iron Salts. 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: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. 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

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


Monitoring Parameters

CKD patients: Hematocrit, hemoglobin, serum ferritin, serum iron, transferrin, percent transferrin saturation, 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 (following infusion)

Chemotherapy-associated anemia (off-label use): Iron, total iron-binding capacity, transferrin saturation, or ferritin levels at baseline and periodically (Rizzo, 2011)


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%), arteriovenous fistula thrombosis (children: 2%), 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% (Limited to important or life-threatening): Anaphylactic shock, anaphylactoid reaction, angioedema, bradycardia, bronchospasm, circulatory shock, hypersensitivity reaction (including wheezing), loss of consciousness, necrotizing enterocolitis (reported in premature infants; no causal relationship established), seizure, shock, urine discoloration


Warnings/Precautions


Concerns related to adverse effects:

- Hypersensitivity reactions: Cases of hypersensitivity reactions, including rare postmarketing anaphylactic and anaphylactoid reactions (some fatal), have been reported. Monitor patients during and for ≥30 minutes postadministration; discontinue immediately for signs/symptoms of a hypersensitivity reaction (shock, hypotension, loss of consciousness). Equipment for resuscitation and trained personnel experienced in handling medical emergencies should always be immediately available.

- Hypotension: Significant hypotension has been reported frequently in hemodialysis-dependent patients. Has also been reported in peritoneal dialysis and nondialysis patients. Hypotension may be related to total dose or rate of administration (avoid rapid IV injection), follow recommended guidelines.

Other warnings/precautions:

- Appropriate use: Withhold iron in the presence of tissue iron overload; periodic monitoring of hemoglobin, hematocrit, serum ferritin, and transferrin saturation is recommended.


Pregnancy Risk Factor

B


Pregnancy Considerations

Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Based on limited data, iron sucrose may be effective for the treatment of iron-deficiency anemia in pregnancy. It is recommended that pregnant women meet the dietary requirements of iron with diet and/or supplements in order to prevent adverse events associated with iron deficiency anemia in pregnancy. Treatment of iron deficiency anemia in pregnant women is the same as in nonpregnant women and in most cases, oral iron preparations may be used. Except in severe cases of maternal anemia, the fetus achieves normal iron stores regardless of maternal concentrations.


Actions


Pharmacology

Iron sucrose is dissociated by the reticuloendothelial system into iron and sucrose. The released iron increases serum iron concentrations and is incorporated into hemoglobin.


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 3-10 days

Maximum effect: Peak reticulocytosis occurs in 5-10 days, and hemoglobin values increase within 2-4 weeks


Half-Life Elimination

Healthy adults: 6 hours; Nondialysis-dependent adolescents: 8 hours


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience diarrhea, cramps, nausea, vomiting, or change in taste. Have patient report immediately to prescriber angina, severe dizziness, passing out, burning or numbness feeling, joint pain, severe headache, shortness of breath, swelling of arms or legs, or injection site pain or irritation (HCAHPS).

- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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