Sodium Ferric Gluconate Complex In Sucrose

Description

11 DESCRIPTION Sodium ferric gluconate complex in sucrose injection, an iron replacement product, is a stable macromolecular complex with an apparent molecular weight on gel chromatography of 289,000 – 440,000 daltons. The macromolecular complex is negatively charged at alkaline pH and is present in solution with sodium cations. The product has a deep red color indicative of ferric oxide linkages. The chemical name is D-Gluconic acid, iron (3+) sodium salt. The structural formula is considered to be [NaFe 2 O 3 (C 6 H 11 O 7 )(C 12 H 22 O 11 )5] n≈200 . Each sterile, single dose vial of 5 mL of sodium ferric gluconate complex in sucrose injection for intravenous injection contains 62.5 mg (12.5 mg/mL) of elemental iron as the sodium salt of a ferric ion carbohydrate complex in an alkaline aqueous solution with approximately 20% sucrose w/v (195 mg/mL) in water for injection, pH 7.7 - 9.7. Each mL contains 9 mg of benzyl alcohol as an inactive ingredient.

What Is Sodium Ferric Gluconate Complex In Sucrose Used For?

1 INDICATIONS AND USAGE Sodium ferric gluconate complex in sucrose injection is indicated for the treatment of iron deficiency anemia in adult patients and in pediatric patients age 6 years and older with chronic kidney disease receiving hemodialysis who are receiving supplemental epoetin therapy. Sodium ferric gluconate complex in sucrose injection is an iron replacement product for treatment of iron deficiency anemia in adult patients and in pediatric patients age 6 years and older with chronic kidney disease receiving hemodialysis who are receiving supplemental epoetin therapy. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Adult Patients - The recommended adult dosage is 10 mL (125 mg of elemental iron) diluted in 100 mL of 0.9% sodium chloride administered by intravenous infusion over 1 hour per dialysis session or undiluted as a slow intravenous injection (at a rate of up to 12.5 mg/min) per dialysis session. ( 2.2 ) Pediatric Patients - The recommended pediatric dosage is 0.12 mL/kg (1.5 mg/kg of elemental iron) diluted in 25 mL 0.9% sodium chloride and administered by intravenous infusion over 1 hour per dialysis session. ( 2.3 ) Do not mix sodium ferric gluconate complex in sucrose injection with other medications or add to parenteral nutrition solutions for intravenous infusion. Administer in 0.9% saline. ( 2 ) 2.1 Important Administration Instructions The dosage of sodium ferric gluconate complex in sucrose injection is expressed in terms of mg of elemental iron. Each 5 mL sterile, single dose vial contains 62.5 mg of elemental iron (12.5 mg/mL). Do not mix sodium ferric gluconate complex in sucrose injection with other medications or add to parenteral nutrition solutions for intravenous infusion. The compatibility of sodium ferric gluconate complex in sucrose injection with intravenous infusion vehicles other than 0.9% sodium chloride has not been evaluated. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever the solution and container permit. If diluted, use immediately. Sodium ferric gluconate complex in sucrose injection treatment may be repeated if iron deficiency reoccurs. 2.2 Adult Dosage and Administration The recommended dosage of sodium ferric gluconate complex in sucrose injection for the repletion treatment of iron deficiency in hemodialysis patients is 10 mL of sodium ferric gluconate complex in sucrose injection (125 mg of elemental iron). Sodium ferric gluconate complex in sucrose injection may be diluted in 100 mL of 0.9% sodium chloride administered by intravenous infusion over 1 hour per dialysis session. Sodium ferric gluconate complex in sucrose injection may also be administered undiluted as a slow intravenous injection (at a rate of up to 12.5 mg/min) per dialysis session. For repletion treatment most patients may require a cumulative dose of 1000 mg of elemental iron administered over 8 dialysis sessions. Sodium ferric gluconate complex in sucrose injection has been administered at sequential dialysis sessions by infusion or by slow intravenous injection during the dialysis session itself. Data from sodium ferric gluconate complex in sucrose injection postmarketing spontaneous reports indicate that individual doses exceeding 125 mg may be associated with a higher incidence and/or severity of adverse events [see Adverse Reactions ( 6.2 ) ]. 2.3 Pediatric Dosage and Administration The recommended pediatric dosage of sodium ferric gluconate complex in sucrose injection for the repletion treatment of iron deficiency in hemodialysis...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Hypersensitivity [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 ) ] Hypotension [see Warnings and Precautions ( 5.2 ) ] The most commonly reported adverse reactions (≥10%) in adult patients were nausea, vomiting and/or diarrhea, injection site reaction, hypotension, cramps, hypertension, dizziness, dyspnea, chest pain, leg cramps, and pain. In patients 6 to 15 years of age the most common adverse reactions (≥10%) were hypotension, headache, hypertension, tachycardia and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The most commonly reported adverse reactions (≥10%) in adult patients were nausea, vomiting and/or diarrhea, injection site reaction, hypotension, cramps, hypertension, dizziness, abnormal erythrocytes (e.g., changes in morphology, color, or number of red blood cells), dyspnea, chest pain, leg cramps and pain. In patients 6 to 15 years of age the most common adverse reactions (≥10%) were hypotension, headache, hypertension, tachycardia and vomiting. Studies A and B In multiple dose Studies A and B (total 126 adult patients), the most frequent treatment emergent adverse reactions following sodium ferric gluconate complex in sucrose injection were: Body as a Whole: injection site reaction (33%), chest pain (10%), pain (10%), asthenia (7%), headache (7%), fatigue (6%), fever (5%), malaise, infection, abscess, chills, rigors, carcinoma, flu-like syndrome, sepsis, lightheadedness, weakness. Nervous System: cramps (25%), dizziness (13%), paresthesias (6%), agitation, somnolence, decreased level of consciousness. Respiratory System: dyspnea (11%), coughing (6%), upper respiratory infections (6%), rhinitis, pneumonia. Cardiovascular System: hypotension (29%), hypertension (13%), syncope (6%), tachycardia (5%), bradycardia, vasodilatation, angina pectoris, myocardial infarction, pulmonary edema. Gastrointestinal System: nausea, vomiting and/or diarrhea (35%), anorexia, abdominal pain (6%), rectal disorder, dyspepsia, eructation, flatulence, gastrointestinal disorder, melena. Musculoskeletal System: leg cramps (10%), myalgia, arthralgia, back pain, arm pain. Skin and Appendages: pruritus (6%), rash, increased sweating. Genitourinary System: urinary tract infection, and menorrhagia. Special Senses: conjunctivitis, rolling of the eyes, watery eyes, puffy eye lids, arcus senilis, redness of the eye, diplopia, and deafness. Metabolic and Nutritional Disorders: hyperkalemia (6%), generalized edema (5%), leg edema, peripheral edema, hypoglycemia, edema, hypervolemia, hypokalemia. Hematologic System: abnormal erythrocytes (11%) (changes in morphology, color, or number of red blood cells), anemia, leukocytosis, lymphadenopathy. Study C – Pediatric Pediatric Patients: In a clinical trial of 66 iron-deficient pediatric hemodialysis patients, 6 to 15 years of age, inclusive, who were receiving a stable erythropoietin dosing regimen, the most common adverse reactions, occurring in ≥5%, regardless of treatment dosage, were: hypotension (35%), headache (24%), hypertension (23%), tachycardia (17%), vomiting (11%), fever (9%), nausea (9%), abdominal pain (9%), pharyngitis (9%), diarrhea (8%), infection (8%), rhinitis (6%), and thrombosis (6%). More patients in the higher dose group (3.0 mg/kg) than in the lower dose group (1.5 mg/kg) experienced the following adverse events: hypotension (41% vs. 28%), tachycardia (21% vs. 13%), fever (15% vs. 3%), headache (29% vs. 19%),...

Drug Interactions

7 DRUG INTERACTIONS Drug-drug interactions involving sodium ferric gluconate complex in sucrose injection have not been studied. Sodium ferric gluconate complex in sucrose injection may reduce the absorption of concomitantly administered oral iron preparations.

Contraindications

4 CONTRAINDICATIONS Sodium ferric gluconate complex in sucrose injection is contraindicated in patients with known hypersensitivity to sodium ferric gluconate or any of its components. Reactions have included anaphylaxis [see Warnings and Precautions ( 5.1 ) ]. Known hypersensitivity to sodium ferric gluconate or any of its inactive components. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Parenteral iron administration may be associated with hypersensitivity reactions [see Warnings and Precautions ( 5.1 ) ], which may have serious consequences, such as fetal bradycardia (see Clinical Considerations ). Advise pregnant women of the potential risk to the fetus. Available data from postmarketing reports with sodium ferric gluconate complex in sucrose injection use in pregnancy are insufficient to assess the risk of major birth defects and miscarriage. Sodium ferric gluconate complex in sucrose injection contains benzyl alcohol as a preservative. Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely. However, adverse reactions have occurred in premature neonates and low-birth-weight infants who received intravenously administered benzyl alcohol-containing drugs [see Warnings and Precautions ( 5.4 ) and Use in Specific Populations ( 8.4 ) ]. Consider alternative iron replacement therapies without benzyl alcohol. There are risks to the mother and fetus associated with untreated iron deficiency anemia in pregnancy (see Clinical Considerations ). In the absence of maternal toxicity, sodium ferric gluconate complex in sucrose injection was not teratogenic to offspring of pregnant mice or rats at clinically relevant exposures (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Untreated iron deficiency anemia (IDA) in pregnancy is associated with adverse maternal outcomes such as postpartum anemia. Adverse pregnancy outcomes associated with IDA include increased risk...

8.2. Lactation Risk Summary Sodium ferric gluconate complex in sucrose injection contains benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a lactating woman, benzyl alcohol exposure in the breastfed infant is unlikely. However, adverse reactions have occurred in premature neonates and low-birth-weight infants who received intravenously administered benzyl alcohol-containing drugs [see Warnings and Precautions ( 5.4 ) and Use in Specific Populations ( 8.4 ) ].Consider alternative iron replacement therapies without benzyl alcohol for use during lactation. There are no available data on the presence of sodium ferric gluconate complex in sucrose injection in human or animal milk, the effects on milk production, or the effects on the breastfed child.

Overdosage

10 OVERDOSAGE The sodium ferric gluconate complex in sucrose injection iron complex is not dialyzable. No data is available regarding overdose of sodium ferric gluconate complex in sucrose injection in humans. Excessive dosages of sodium ferric gluconate complex in sucrose injection may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. Do not administer sodium ferric gluconate complex in sucrose injection to patients with iron overload [see Warnings and Precautions ( 5.3 ) ]. Individual doses exceeding 125 mg may be associated with a higher incidence and/or severity of adverse events [see Adverse Reactions ( 6.2 ) ] . Sodium ferric gluconate complex in sucrose injection at elemental iron doses of 125 mg/kg, 78.8 mg/kg, 62.5 mg/kg and 250 mg/kg caused deaths in mice, rats, rabbits, and dogs respectively. The major symptoms of acute toxicity were decreased activity, staggering, ataxia, increases in the respiratory rate, tremor, and convulsions.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied NDC 0143-9298-10 Sodium ferric gluconate complex in sucrose injection is supplied in colorless glass vials. Each sterile, single dose vial contains 62.5 mg of elemental iron in 5 mL for intravenous use, packaged in cartons of 10 vials. Discard unused portion. Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Do not freeze. Keep out of the reach of children.