Intravenous iron sucrose is approved for the treatment of iron deficiency anemia in patients with chronic kidney disease. Oral sucroferric oxyhydroxide, which is a synonym for iron sucrose and is the same therapeutic ingredient per the National Library of Medicine, is approved as a phosphate binder for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis. Intravenous iron sucrose is one of the oldest parenteral iron preparations available; it has been used clinically for more than 50 years. Intravenous iron is preferred over oral iron therapy when rapid repletion of iron-depleted patients is desired. Intravenous iron has been used to treat the anemia associated with dialysis and may reduce the need for erythropoietin dosage by about 40%. Intravenous iron sucrose appears less likely to cause hypersensitivity reactions than iron dextran and has been used in patients with a hypersensitivity to iron dextran. However, hypersensitivity may also occur with intravenous iron sucrose; serious and fatal anaphylactic reactions have been reported. Intravenous iron sucrose rapidly increases serum iron concentrations, which can be reliably measured 48 hours after administration. Oral sucroferric oxyhydroxide is a calcium-free phosphate binder. In clinical trials, oral sucroferric oxyhydroxide effectively lowered serum phosphorus concentrations at doses of 1,000 to 3,000 mg/day PO with treatment effect seen as early as 1 to 2 weeks. This effect was consistently maintained through 12 months of treatment in a 28-week extension study.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
Chewable tablets
-Chew or crush before swallowing; do not swallow whole.
-Take with meals. No additional fluid above the amount usually taken by the patient is required.
-If 1 or more doses are missed, resume the medication with the next meal. Do not attempt to replace a missed dose.
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-The dosage of iron sucrose is expressed in mg of elemental iron.
-Each mL contains 20 mg of elemental iron.
-Do not mix iron sucrose with other medications or TPN solution.
-Prior to and at regular intervals during parenteral iron therapy, evaluate serum iron, hemoglobin, and hematocrit. Ferritin and transferrin are also recommended monitoring parameters.
-Administer early during a hemodialysis session (generally within the first hour).
-Storage: Discard any unused portions; contains no preservatives.
Intravenous Administration
Slow Intravenous Injection
-No dilution necessary.
-In adults, a 100 to 200 mg dose may be given undiluted (into the dialysis line for hemodialysis patients) over 2 to 5 minutes.
-In pediatric patients, the maintenance dose may be given undiluted over 5 minutes.
-Storage: When stored undiluted in a plastic syringe, solution is stable for 7 days at controlled room temperature (25 +/- 2 degrees C) and under refrigeration (4 +/- 2 degrees C).
Intravenous Infusion
-May be administered by IV infusion (into the dialysis line for hemodialysis patients). This may reduce the risk of hypotensive episodes.
-For doses of 100 or 200 mg (adults): Dilute in a maximum of 100 mL of 0.9% Sodium Chloride Injection and infuse over a period of at least 15 minutes.
-For doses of 300 to 500 mg (adults): Dilute in a maximum of 250 mL of 0.9% Sodium Chloride Injection. Per FDA-approved labeling, infuse doses of 300 mg over a period of 1.5 hours; infuse doses of 400 mg over 2.5 hours. During clinical experiences, doses of 500 mg have been administered over 3.5 to 4 hours.
-In pediatric patients, maintenance dose may be diluted in 0.9% Sodium Chloride Injection at a concentration of 1 to 2 mg/mL and administered over 5 to 60 minutes. Do not dilute to concentrations less than 1 mg/mL.
-Storage: When diluted at a concentration of 2 to 10 mg/mL elemental iron and stored in a plastic syringe, solution is stable for 7 days at controlled room temperature (25 +/- 2 degrees C) and under refrigeration (4 +/- 2 degrees C). When added to IV infusion bags (PVC or non-PVC) containing 0.9% Sodium Chloride Injection at a concentration of 1 to 2 mg/mL elemental iron, solution is stable for 7 days at controlled room temperature (25 +/- 2 degrees C).
Patients who receive parenteral iron, rarely, if ever, develop hemochromatosis unless a genetic predisposition to the disorder is also present. Hemochromatosis results in aberrations of iron absorption, metabolism and storage; iron accumulates in the body and excess iron deposition occurs in the parenchymal tissues. With hemochromatosis, the liver becomes enlarged, and skin discoloration, specifically a bronze hue, occurs. Pancreatic dysfunction, diabetes mellitus, cardiac failure, liver failure and other tissue disorders may occur secondary to hemochromatosis.
Fatal immediate hypersensitivity or anaphylactoid reactions have been reported in patients receiving therapy with many iron carbohydrate complexes, including IV iron sucrose. Fetal adverse reactions, including fetal bradycardia, have been associated with maternal hypersensitivity reactions, especially during the second and third trimester of pregnancy. Intravenous iron sucrose is less likely to cause hypersensitivity reactions than iron dextran and may be used as an alternative therapy in patients with a prior hypersensitivity reaction to iron dextran. Of 1,151 patients evaluated in 4 U.S. trials in HDD-CKD patients, 130 (11%) were reported to be intolerant of other intravenous iron products (defined as precluding further use of that iron product). When these patients were treated with IV iron sucrose, there were no occurrences of adverse events that precluded further use of iron sucrose. Potentially fatal hypersensitivity reactions characterized by anaphylactic shock, loss of consciousness, collapse, and clinically significant low blood pressure have been reported in patients receiving IV iron sucrose. Most reactions occur within 30 minutes of the completion of the infusion. Angioedema was noted in postmarketing reports. If hypersensitivity reactions occur during administration of IV iron sucrose, immediately discontinue the infusion. Facilities for cardiopulmonary resuscitation must be available during intravenous administration. Serious anaphylactoid reactions require appropriate resuscitation measures. Monitor patients for at least 30 minutes and until clinically stable following completion of the iron sucrose infusion. Unlike iron dextran, iron sucrose is approved for use by undiluted slow IV injection, without the need for a test dose. Close clinical monitoring is advised when administering any IV iron product.
In premarketing clinical trials of patients receiving IV iron sucrose, 2.2% to 3.9% experienced pruritus. An injection site reaction including pain or burning (5.8%) or extravasation (2.2%) has also been reported. Rash has been reported with oral sucroferric oxyhydroxide in postmarketing surveillance.
General adverse events reported during IV iron sucrose clinical trials include asthenia (0.7% to 2.7%), chest pain (unspecified) (1.4% to 6.1%), feeling abnormal (3%), graft complication (1.4% to 9.5%), and fluid overload/hypervolemia (1.3% to 3%). Fever occurred in 0.7% to 3% and 4% of adult and pediatric patients, respectively. Arteriovenous fistula thrombosis (2%) and renal transplant (4%) were reported during pediatric clinical trials. Hyperhidrosis and chromaturia have been noted in postmarketing reports. Edema may be associated with total IV iron sucrose dosage or with rapid infusion. Slowing the infusion rate may alleviate this. Peripheral edema has been noted in 2.6% to 7.2% of patients.
Dosages of IV iron sucrose in excess of iron needs may lead to accumulation of iron in storage sites leading to iron overload which may cause iatrogenic hemosiderosis. Hemosiderosis is the result of deposition of hemosiderin, an iron-containing pigment, in the tissues of the liver and spleen. Hemosiderosis has primarily been reported in dialysis patients who receive long-term parenteral iron treatment. Patients receiving IV iron sucrose should receive periodic monitoring of hematologic and iron parameters, including hemoglobin, hematocrit, serum ferritin, and transferrin saturation. Do not administer IV iron sucrose to patients with evidence of iron overload.
Intravenous iron sucrose may cause clinically significant hypotension. This may be a result of hypersensitivity or may be related to the rate of administration or total dose administered. Symptoms may respond to IV fluids or slowing the infusion rate. Hypotension has been reported in 2.2% to 39.4% of adult patients and 2% of pediatric patients. Hypertension (6.5% to 8% in adult patients, 2.1% in pediatric patients) and congestive heart failure (more than 1%) have also been noted in clinical trials. Bradycardia was noted in postmarketing reports.
Gastrointestinal (GI) adverse events have been reported with both IV iron sucrose and oral sucroferric oxyhydroxide during clinical trials in adult patients. Stool discoloration (12% to 16%) was a commonly reported adverse event in oral sucroferric oxyhydroxide clinical trials. Diarrhea and nausea were reported with both dosage forms. Diarrhea occurred at an incidence of 5.2% to 8% in adult IV iron sucrose trials and an incidence of 6% to 24% in oral sucroferric oxyhydroxide trials. Nausea was reported at an incidence of 5.3% to 14.7% in adult IV iron sucrose trials and an incidence of 10% in oral sucroferric oxyhydroxide trials. Other GI-related adverse reactions reported with IV iron sucrose in adults include abdominal pain (1.4% to 4%), dysgeusia (0.9% to 7.9%), and vomiting (5% to 9.1%). Nausea and vomiting were reported in 3% and 4% of pediatric patients, respectively. Nausea, vomiting, and abdominal pain occurring with IV therapy may be associated with total iron sucrose dosage administered or with a rapid rate of infusion; slowing the infusion rate may alleviate symptoms. Peritonitis occurred in 4% of pediatric patients during clinical trials. In a small retrospective review of chronic kidney disease patients (not on dialysis) receiving high dose IV iron sucrose (n = 73), constipation was reported in 2 patients. The authors concluded constipation was possibly related to iron sucrose therapy as this reaction could not be attributed to other causes. Mild constipation was also reported in 1 patient in 4 prospective studies evaluating the safety of IV iron sucrose in dialysis patients intolerant to other parenteral iron products (n = 130).
Infectious adverse events were reported in 2.2% to 16% of patients during IV iron sucrose clinical trials and included nasopharyngitis, sinusitis, upper respiratory tract infection, and pharyngitis. Respiratory tract viral infections occurred in 4% of pediatric patients. Sepsis was reported in more than 1% of patients.
Adverse events of the special senses that were reported during clinical trials with IV iron sucrose include ear pain (2.2%) and conjunctivitis (0.4% to 2.7%).
Metabolism and nutrition disorders reported during IV iron sucrose clinical trials include gout (2.9%), hyperglycemia (2.9%), and hypoglycemia (0.4% to 4%).
Musculoskeletal adverse events reported during IV iron sucrose clinical trials include arthralgia (1.4% to 4%), back pain (1.3% to 2.2%), muscle cramps (0.7% to 29.4%), myalgia (1.3% to 3.6%), and pain in the extremity (2.7% to 5.6%). Swelling of the joints was noted in postmarketing reports. Joint aches and muscle pain (musculoskeletal pain) may be associated with the total IV iron sucrose dosage administered or with a rapid rate of infusion; slowing the infusion rate may alleviate symptoms.
Nervous system adverse events that were reported during IV iron sucrose clinical trials included dizziness (1.3% to 6.5%) and headache (2.9% to 12.6%). In trials involving pediatric patients, headache occurred in 6% of patients, and dizziness in 4%. Convulsions (seizures), light-headedness, and confusion were noted in postmarketing reports. Headache, dizziness, and paresthesias may be associated with the total IV iron sucrose dosage administered or with a rapid rate of infusion; slowing the infusion rate may alleviate symptoms.
Respiratory adverse events reported during IV iron sucrose clinical trials in adult patients included cough (1.3% to 3%), dyspnea (1.3% to 5.8%), and nasal congestion (1.3% to 1.4%). Cough occurred in 4% of pediatric patients. Bronchospasm was also noted in postmarketing reports. Dyspnea may be associated with the total IV iron sucrose dosage administered or with a rapid rate of infusion; slowing the infusion rate may alleviate symptoms.
Tooth discoloration has been reported with oral sucroferric oxyhydroxide in postmarketing surveillance.
The use of IV iron sucrose requires a specialized care setting in which facilities for cardiopulmonary resuscitation must be available during dosing and where the patient can be observed during administration. Serious hypersensitivity reactions, including life-threatening and fatal anaphylactic-type reactions, have been reported in patients receiving IV iron sucrose. Patients may present with shock, loss of consciousness, collapse and/or significantly low blood pressure, wheezing, dyspnea, rashes, or pruritus. IV iron sucrose is contraindicated in patients with known hypersensitivity to iron sucrose or any of its inactive components. Close patient monitoring is advised during IV iron administration. Observe for signs and symptoms of hypersensitivity during and for at least 30 minutes after administration. If hypersensitivity reactions occur, stop iron sucrose administration. Serious anaphylactoid reactions require appropriate resuscitation measures.
Hypotension has been reported frequently in patients receiving intravenous iron products and may be unrelated to hypersensitivity. Use caution in administering IV iron sucrose in patients with pre-existing hypotension. Hypotension (36% incidence in pre-marketing hemodialysis trials) following administration of IV iron sucrose may be related to rate of infusion, the total dose administered, and patient risk factors. Patients with preexisting cardiac disease may have exacerbation of cardiovascular symptoms if adverse effects such as hypotension occur following IV iron sucrose administration. Iron sucrose injection is strongly alkaline and should not be administered by intramuscular administration or subcutaneous administration.
Do not administer IV iron sucrose to patients with evidence of iron overload (e.g., patients with hemochromatosis). Oral sucroferric oxyhydroxide has not been studied in patients with hemochromatosis or other diseases with iron accumulation. Unnecessary or prolonged administration of iron may lead to iron overload and consequently the possibility of exogenous hemosiderosis. Patients with hemoglobinopathy and other refractory anemias that might be erroneously diagnosed as iron deficiency anemias are at particular risk for such iron overload. The type of anemia and the underlying cause or causes should be determined before starting therapy with IV iron sucrose. Since the anemia may be a result of a systemic disturbance, such as recurrent blood loss, the underlying cause(s) should be corrected, if possible. Patients receiving exogenous iron therapy require periodic monitoring of hematologic and hematinic parameters (i.e., hemoglobin, hematocrit, serum ferritin, and transferrin saturation) to avoid iron overload.
Some patients with chronic hepatic disease may also have hemochromatosis or moderate iron overload in hepatic tissues. Use IV iron sucrose with caution in patients with hepatic disease. The liver is one of the main storage sites for iron, and advanced chronic liver disease may result in excess storage of iron in the liver.
Fetal adverse reactions, including fetal bradycardia, have been associated with maternal hypersensitivity reactions, especially during the second and third trimester of pregnancy. Data with intravenous iron sucrose use during human pregnancy have not shown adverse maternal or fetal outcomes; however, reports of intravenous iron sucrose use in pregnant women during the first trimester are insufficient to assess the risk of major birth defects or miscarriage. Treat iron deficiency anemia during pregnancy because there are risks to the mother and fetus associated with untreated iron deficiency anemia during pregnancy. There are no adequate and well-controlled studies of oral sucroferric oxyhydroxide use in pregnant women; however, animal studies have not shown any evidence of impaired fertility or fetal harm at doses up to 16 and 4 times, respectively, the human maximum recommended clinical dose. Sucroferric oxyhydroxide is not absorbed systemically following oral administration, and maternal use is not expected to result in fetal exposure to the drug.
Iron sucrose is present in human milk, and available data after exposure to 100 to 300 mg of intravenous iron sucrose have not reported adverse reactions in breast-fed infants. Limited data indicate iron found in breast milk is not increased after intravenous administration of iron sucrose. There are no data on the effects of iron sucrose on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for intravenous iron sucrose and any potential adverse effects on the breast-fed infant from intravenous iron sucrose or the underlying maternal condition. Monitor breastfed infants exposed to intravenous iron sucrose for gastrointestinal toxicity (i.e., constipation, diarrhea). Sucroferric oxyhydroxide is not absorbed systemically following oral administration and breast-feeding is not expected to result in exposure of the child to sucroferric oxyhydroxide.
Intravenous iron sucrose has not been studied in neonates, infants, and children younger than 2 years. In a country where it is available for use in children, fatal necrotizing enterocolitis was reported in premature neonates (weight less than 1,250 g) who received IV iron sucrose, several other medications, and erythropoietin; causality was not established. The dosing of IV iron sucrose for iron replacement treatment in pediatric patients with hemodialysis-dependent chronic kidney disease has not been established. The safety and efficacy of oral sucroferric oxyhydroxide have also not been established in pediatric patients.
Patients with peritonitis during peritoneal dialysis, significant gastric disorders, or those following major gastrointestinal surgery were not included in clinical trials evaluating oral sucroferric oxyhydroxide therapy. When administering oral sucroferric oxyhydroxide, monitor effect and iron homeostasis in these patients.
For the treatment of iron-deficiency anemia in patients with chronic kidney disease:
NOTE: The dosage of iron sucrose is expressed in mg of elemental iron. Each mL contains 20 mg of elemental iron.
-for the treatment of iron-deficiency anemia in patients with non-dialysis-dependent chronic kidney disease:
Intravenous dosage:
Adults: 200 mg IV on 5 different days within a 14-day period for a cumulative dose of 1,000 mg. There is limited experience with 500 mg IV on days 1 and 14. Treatment may be repeated if iron deficiency recurs.
Children and Adolescents 2 to 17 years: Dosing for iron replacement treatment in pediatric patients is not established. For iron maintenance treatment, 0.5 mg/kg/dose (Max: 100 mg/dose) IV every 4 weeks for 12 weeks. Treatment may be repeated if necessary.
-for the treatment of iron-deficiency anemia in patients with hemodialysis-dependent chronic kidney disease:
Intravenous dosage:
Adults: 100 mg IV per consecutive hemodialysis session. The usual total treatment course is 1,000 mg. Treatment may be repeated if iron deficiency recurs.
Children and Adolescents 2 to 17 years: Dosing for iron replacement treatment in pediatric patients is not established. For iron maintenance treatment, 0.5 mg/kg/dose (Max: 100 mg/dose) IV every 2 weeks for 12 weeks. Treatment may be repeated if necessary.
-for the treatment of iron-deficiency anemia in patients with peritoneal dialysis-dependent chronic kidney disease:
Intravenous dosage:
Adults: 300 mg IV on days 1 and 14 and 400 mg IV on day 28 for a cumulative dose of 1,000 mg. Treatment may be repeated if iron deficiency recurs.
Children and Adolescents 2 to 17 years: Dosing for iron replacement treatment in pediatric patients is not established. For iron maintenance treatment, 0.5 mg/kg/dose (Max: 100 mg/dose) IV every 4 weeks for 12 weeks. Treatment may be repeated if necessary.
For the management of hyperphosphatemia in patients with chronic kidney disease on dialysis:
Oral dosage:
Adults: Initially, 500 mg PO 3 times daily with meals. To maximize the dietary phosphate binding, the total daily dose should be divided across the meals of the day. Monitor serum phosphorus concentration, and at weekly intervals, titrate the dose by 500 mg per day as needed until an acceptable serum phosphorus concentration (5.5 mg/dL or less) is reached; continue monitoring regularly. Patients enrolled in clinical studies generally required an average of 1,500 to 2,000 mg/day PO to control serum phosphorus concentration. The maximum daily dosage evaluated in a phase 3 trial in end stage renal disease patients was 3,000 mg/day PO.
For the treatment of restless legs syndrome (RLS)*:
Intravenous dosage:
Children and Adolescents: 3 to 6 mg/kg/dose (Max: 120 mg/dose) IV may be considered if at least 3 months of oral iron treatment has not provided adequate benefit or an appreciable rise in serum ferritin concentrations (target serum ferritin = 50 mcg/L or more), has been discontinued due to intolerance, or a significant comorbidity exists that will impair oral iron absorption. Administer in an infusion center with pediatric experience. Reassess iron and clinical status after 8 to 12 weeks.
Therapeutic Drug Monitoring:
IV Iron sucrose:
-Total dosage with iron sucrose should be individualized to achieve patient target goals for serum iron, hemoglobin, hematocrit, and other iron storage parameters (e.g., serum ferritin, total iron binding capacity, and transferrin saturation). Serum iron levels greater than 300 mcg/dL, elevated ferritin levels, and transferrin over saturation may indicate iron poisoning. Iron therapy should be withheld in patients with evidence of iron overload.
-Transferrin saturation values increase rapidly after IV administration of iron sucrose. Thus, serum iron values may be reliably obtained 48 hours after IV dosing.
Oral Sucroferric oxyhydroxide:
-Serum phosphorus levels should be monitored prior to and regularly throughout therapy.
-In patients with a history of hemochromatosis or other disease with iron accumulation, monitor iron homeostasis.
Maximum Dosage Limits:
-Adults
500 mg/dose IV has been administered on 2 consecutive days in patients with chronic kidney disease. Up to 3,000 mg/day PO has been studied in patients with end stage renal disease.
-Geriatric
500 mg/dose IV has been administered on 2 consecutive days in patients with chronic kidney disease. Up to 3,000 mg/day PO has been studied in patients with end stage renal disease.
-Adolescents
0.5 mg/kg/dose (Max: 100 mg/dose) IV for iron maintenance; 6 mg/kg/dose (Max: 120 mg/dose) IV has been recommended for off-label treatment of restless leg syndrome. Safety and efficacy of iron sucrose chewable tablets have not been established.
-Children
2 to 12 years: 0.5 mg/kg/dose (Max: 100 mg/dose) IV for iron maintenance; 6 mg/kg/dose (Max: 120 mg/dose) IV has been recommended for off-label treatment of restless leg syndrome. Safety and efficacy of iron sucrose chewable tablets have not been established.
1 year : Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Patients with hepatic disease should receive IV iron sucrose with caution. The liver is one of the main storage sites for iron, and some patients with chronic liver disease may have excessive iron storage. Specific guidelines for dosage adjustments are not available.
Patients with Renal Impairment Dosing
Dosage adjustments are not necessary.
Intermittent hemodialysis
Before supplementing hemodialysis patients with iron, a diagnosis of absolute or functional iron deficiency should be made. Follow recommended dosage for IV iron sucrose in hemodialysis patients. IV iron sucrose is not dialyzable.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Acetaminophen; Aspirin: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Alendronate: (Moderate) Separate administration of alendronate and iron supplements by at least 30 minutes. Iron will interfere with the absorption of alendronate.
Alendronate; Cholecalciferol: (Moderate) Separate administration of alendronate and iron supplements by at least 30 minutes. Iron will interfere with the absorption of alendronate.
Aspirin, ASA: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Aspirin, ASA; Caffeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Aspirin, ASA; Dipyridamole: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Aspirin, ASA; Omeprazole: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Aspirin, ASA; Oxycodone: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Baloxavir Marboxil: (Major) Do not administer baloxavir with products that contain oral iron sucrose, sucroferric oxyhydroxide. Polyvalent cations, such as iron, can chelate with baloxavir, reducing its absorption.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
Cephalexin: (Moderate) Administer cephalexin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of cephalexin, leading to decreased absorption.
Demeclocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Dimercaprol: (Major) Avoid concomitant use of dimercaprol and products containing iron. Dimercaprol forms toxic-chelates with iron which increases the risk for nephrotoxicity and other adverse effects.
Doxycycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Enteral Feedings: (Minor) Ferrous sulfate elixir has an acidic pH and has been reported to form precipitates with enteral feedings and may clog feeding tubes.
Erdafitinib: (Major) Avoid coadministration of iron sucrose; sucroferric oxyhydroxide with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Iron sucrose; sucroferric oxyhydroxide decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by iron sucrose; sucroferric oxyhydroxide may interfere with the determination of this initial dose increase.
Ferric Maltol: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
Food: (Major) For better iron absorption, administer iron salts 1 hour before or 2 hours after meals. If GI irritation occurs, the iron supplement may be administered with meals. However, where possible, avoid administering coffee, tea, or dairy products within 1 hour before or 2 hours after giving iron.
Iron Salts: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
Iron Salts: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
Iron: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
Levothyroxine: (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral iron supplements.
Levothyroxine; Liothyronine (Porcine): (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral iron supplements.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral iron supplements.
Liothyronine: (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral iron supplements.
Minocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
Omadacycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Paricalcitol: (Moderate) According to the manufacturer of oral iron sucrose, sucroferric oxyhydroxide an interaction was seen with paricalcitol in in vitro studies. Consider separating the administration of the two drugs and monitor for clinical response to paricalcitol.
Sarecycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Tetracyclines: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Thyroid hormones: (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral iron supplements.
Trientine: (Major) In general, oral mineral supplements should not be given since they may block the oral absorption of trientine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and trientine each inhibit oral absorption of the other, 2 hours should elapse between administration of trientine and iron doses.
IV Iron Sucrose
Normal erythropoiesis depends on the concentration of iron and erythropoietin available in the plasma, both being decreased in renal failure. Exogenous administration of erythropoietin increases red blood cell production and iron utilization, contributing to iron deficiency in hemodialysis patients. Intravenous iron has been used to treat the anemia associated with hemodialysis and may reduce the need for erythropoietin dosage by about 40%. Following IV administration of iron sucrose, the complex of polynuclear iron (III)-hydroxide in sucrose is dissociated into iron and sucrose by the reticuloendothelial system. In addition, a competitive exchange of iron takes place from the iron sucrose complex to the iron-binding protein transferrin. A therapeutic response to treatment with iron therapy is dependent upon the patient's iron stores and the ability to use the iron. Use of iron is influenced by the cause of the deficiency as well as other illnesses that can affect normal erythropoiesis. Protein-energy malnutrition can prevent the incorporation of iron into the erythrocyte regardless of the quantity of iron stored. Only when lean body mass expands will iron be used. Iron therapy alone does not increase red blood cell production. Administration of iron only improves anemia which is associated with iron deficiency.
Iron-containing proteins and enzymes are important in oxidation-reduction reactions, especially those of the mitochondria. Iron is a component of myoglobin and several heme-enzymes, including the cytochromes, catalase, and peroxidase. Iron is an essential component of the metalloflavoprotein enzymes and the mitochondrial enzyme alpha-glycerophosphate oxidase. Iron-containing proteins and enzymes are important in oxidation-reduction reactions, especially those of the mitochondria. Furthermore, iron is a cofactor for enzymes such as aconitase and tryptophan pyrrolase. Iron deficiency not only causes anemia and decreased oxygen delivery, but it also reduces the metabolism of muscle and decreases mitochondrial activity. Iron deficiency can also lead to defects in learning or thermoregulation. Thus iron is important to several metabolic functions which are independent of its importance to erythropoiesis.
Oral Sucroferric Oxyhydroxide
In the management of serum phosphorus concentrations in patients with chronic kidney disease, oral sucroferric oxyhydroxide is a phosphate binder. Oral sucroferric oxyhydroxide binds dietary phosphate within the gastrointestinal tract via ligand exchange between hydroxyl groups and water in sucroferric oxyhydroxide and the phosphate in the diet. Bound phosphate is eliminated in the feces. As a result of reduced absorption of dietary phosphate, both serum phosphorus and calcium-phosphorus product concentrations are reduced.
Iron sucrose is administered intravenously while sucroferric oxyhydroxide is administered orally. The dose of intravenous iron sucrose is individualized according to patient goals for serum iron levels, iron storage parameters (e.g., ferritin, transferrin saturation) and serum hemoglobin concentrations whereas the dose of oral sucroferric oxyhydroxide is guided by serum phosphorus. Iron toxicity may occur with excessive or unnecessary iron therapy. The absorption of iron from oral sucroferric oxyhydroxide is low, and the risk of systemic iron toxicity with the oral formulation is negligible. Systemic iron is stored in compounds called ferritin and hemosiderin, which are used for future production of hemoglobin. The absorption of iron depends upon the route of entry. The tissue that first clears parenterally administered iron from the bloodstream determines the bioavailability. If the reticuloendothelial system clears iron, only small amounts will be available over time to the bone marrow. Transferrin accepts iron from the intestinal tract or from sites of storage or hemoglobin destruction. Iron is then transported in plasma bound to transferrin and distributed to the bone marrow for hemoglobin synthesis, to the reticuloendothelial system for storage, to all cells for enzymes containing iron, and to placental cells if needed to meet fetal needs. Transferrin eventually becomes available for reuse. There is no destructive metabolism of iron because it takes place in a closed system. In normal adults, 90% of metabolized iron is conserved and reutilized repeatedly. Very little iron is eliminated. In normal, healthy adults, some daily loss of iron occurs through normal skin, hair, and nail loss, and GI losses. Menstruating women have an increased loss as do other persons with loss of blood.
-Route-Specific Pharmacokinetics
Oral Route
The active moiety of oral sucroferric oxyhydroxide, polynuclear iron (III)-oxyhydroxide (pn-FeOOH), is essentially insoluble and therefore not absorbed or metabolized. The mononuclear iron species, a degradation product, can be released from the surface of pn-FeOOH and absorbed. The median uptake of radiolabeled iron in the blood on day 21 after administration of 2,000 mg oral sucroferric oxyhydroxide in 1 day was 0.04% in patients with chronic kidney disease compared with 0.43% in healthy subjects with low iron stores (serum ferritin less than 100 mcg/L). The sucrose and starch components of oral sucroferric oxyhydroxide can be digested to glucose and fructose, and maltose and glucose, respectively. These compounds can be absorbed into the blood. One tablet is equivalent to 1.4 g of carbohydrates.
Intravenous Route
In healthy adults receiving IV doses of iron sucrose, the iron component appears to distribute mainly in blood and to some extent in extravascular fluid. A significant amount of the administered iron distributes in the liver, spleen and bone marrow. The bone marrow is considered an iron trapping compartment and not a reversible volume of distribution. Following IV administration, iron sucrose is dissociated into iron and sucrose by the reticuloendothelial system. The sucrose component is eliminated primarily by urinary excretion (75.4% in 24 hours). Approximately 5% of the iron is excreted in the urine over 24 hours. In healthy adults treated with IV iron sucrose, the iron component exhibits linear kinetics with an elimination half-life of about 6 hours and a systemic clearance of 1.2 L/hour.
-Special Populations
Renal Impairment
Since clearance of iron depends on the need for iron (e.g., iron stores and utilization by systemic tissues), the serum clearance of IV iron sucrose is expected to be more rapid in iron-deficient patients, including hemodialysis patients. In hemodialysis patients receiving IV iron sucrose (100 mg iron 3 times weekly for 3 weeks) and erythropoietin, significant increases in serum iron and serum ferritin, and significant decreases in total iron binding capacity occurred 4 weeks after initiating therapy.
Pediatrics
Following a single-dose of IV iron sucrose, 7 mg/kg/dose (Max: 200 mg/dose) in patients 12 to 16 years (n = 11) with non-dialysis dependent chronic kidney disease, mean AUC was 31,305 mcg x hour/dL and mean Cmax was 8,545 mcg/dL, which were 1.67- and 1.42-fold higher than reported values in adults. The half-life of total serum iron was 8 hours.
Geriatric
The effects of age on the pharmacokinetics of IV iron sucrose have not been studied.
Gender Differences
The effects of gender on the pharmacokinetics of IV iron sucrose have not been studied.