NDC 0517-6103 Zinc Sulfate

Zinc Sulfate

NDC Product Code 0517-6103

NDC 0517-6103-25

Package Description: 25 VIAL in 1 TRAY > 10 mL in 1 VIAL (0517-6103-01)

NDC Product Information

Zinc Sulfate with NDC 0517-6103 is a a human prescription drug product labeled by American Regent, Inc.. The generic name of Zinc Sulfate is zinc sulfate. The product's dosage form is injection, solution and is administered via intravenous form.

Labeler Name: American Regent, Inc.

Dosage Form: Injection, Solution - A liquid preparation containing one or more drug substances dissolved in a suitable solvent or mixture of mutually miscible solvents that is suitable for injection.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Zinc Sulfate Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • ZINC SULFATE 3 mg/mL

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Copper Absorption Inhibitor - [EPC] (Established Pharmacologic Class)
  • Decreased Copper Ion Absorption - [PE] (Physiologic Effect)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: American Regent, Inc.
Labeler Code: 0517
FDA Application Number: NDA209377 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 10-01-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Zinc Sulfate Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Zinc Sulfate Injection is indicated in adult and pediatric patients as a source of zinc for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated.

2.1  Important Administration Information

Zinc Sulfate Injection is supplied as a pharmacy bulk package for admixing use only. It is not for direct intravenous infusion. Prior to administration, Zinc Sulfate Injection must be transferred to a separate parenteral nutrition container, diluted and used as an admixture in parenteral nutrition solutions.  The final parenteral nutrition solution is for intravenous infusion into a central or peripheral vein. The choice of a central or peripheral venous route should depend on the osmolarity of the final infusate. Solutions with osmolarity of 900 mOsm/L or greater must be infused through a central catheter [see Warnings and Precautions (5.2)].

2.2  Preparation And Administration Instructions

  • Zinc Sulfate Injection is not for direct intravenous infusion. Prior to administration, Zinc Sulfate Injection must be prepared and used as an admixture in parenteral nutrition solutions. Zinc Sulfate Injection is to be prepared only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). The key factor in the preparation is careful aseptic technique to avoid inadvertent touch contamination during mixing of solutions and addition of other nutrients.Visually inspect the diluted parenteral nutrition solution containing Zinc Sulfate Injection for particulate matter before admixing, after admixing, and prior to administration. The solution should be clear and there should be no precipitates. A slight yellow color does not alter the quality and efficacy of this product.

2.3  Preparation Instructions For Admixing Using A Parenteral Nutrition Container

  • Inspect Zinc Sulfate Injection Bulk Pharmacy Package for particulate matter.Transfer Zinc Sulfate Injection to the parenteral nutrition container following the admixture of amino acids, dextrose, lipid emulsion (if added), and electrolytes solutions.Because additives may be incompatible, evaluate all additions to the parenteral nutrition container for compatibility and stability of the resulting preparation. Consult with pharmacist, if available. Questions about compatibility may be directed to American Regent. If it is deemed advisable to introduce additives to the parenteral nutrition container, use aseptic technique. Inspect the final parenteral nutrition solution containing Zinc Sulfate Injection to ensure that:Precipitates have not formed during mixing or addition on additives.The emulsion has not separated, if lipid emulsion has been added.  Separation of the emulsion can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion.Discard if any precipitates are observed.Stability and StoragePenetrate vial closure only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents.Use Zinc Sulfate Injection for admixing promptly once the sterile transfer set has been inserted into the Pharmacy Bulk Package container or not more than 4 hours at room temperature 20°C to 25°C (68°F to 77°F) (25ºC/77ºF) after the container closure has been penetrated. Discard any remaining drug.Use parenteral nutrition solutions containing Zinc Sulfate Injection promptly after mixing. Any storage of the admixture should be under refrigeration from 2ºC to 8ºC (36ºF to 46ºF) and limited to a brief period of time, no longer than 24 hours. After removal from refrigeration, use promptly and complete the infusion within 24 hours. Discard any remaining admixture.Protect the parenteral nutrition solution from light during storage.

2.4  Dosing Considerations

  • The dosage of the final parenteral nutrition solution containing Zinc Sulfate Injection must be based on the concentrations of all components in the solution and the recommended daily nutritional requirements [see Dosage and Administration (2.5)]. Consult the prescribing information of all added components to determine the recommended nutritional requirements for dextrose and lipid emulsion, as applicable.Prior to administration of parenteral nutrition solution containing Zinc Sulfate Injection, correct severe fluid, electrolyte and acid-base disorders.
  • Zinc Sulfate Injection provides 3 mg/mL or 5 mg/mL of zinc.The dosage of Zinc Sulfate Injection should be individualized based on the patient’s clinical condition, nutritional requirements, and the contribution of oral or enteral zinc intake. AdultsThe recommended adult dosage is 3 mg/day for metabolically stable patients, with potential need for a higher daily dosage in monitored patients with small bowel fluid loss or excess stool or ileostomy output.Pediatric PatientsThe recommended pediatric dosage is shown in Table 1 by age and estimated weight. The dosages in Table 1 are general recommendations intended for most pediatric patients.  However, based on clinical requirements, some patients may require a higher dosage.Table 1:  Recommended Dosage of Zinc Sulfate Injection for Pediatric Patients by Age and Estimated Weight PopulationEstimated Weight for AgeRecommended Daily Dosage Pediatric patients10 kg and above50 mcg/kg (up to 3 mg/day) 5 kg to less than 10 kg100 mcg/kgTerm neonates3 kg to less than 5 kg250 mcg/kg* Preterm neonatesLess than 3 kg400 mcg/kg*Term neonates have higher requirements in the first 3 months of lifeMonitoring Monitor zinc concentrations during treatment.  Also monitor patients clinically for signs and symptoms of zinc deficiency, especially in pediatrics.  Zinc concentrations may vary depending on the assay used and the laboratory reference range.  The collection, processing, and storage of the blood samples for zinc analysis should be performed according to the laboratory’s sample requirements.  Zinc concentrations in hemolyzed samples are falsely elevated due to release of zinc from erythrocytes.  The lower end of the reported range in healthy adults in serum is 60 mcg/dL

3 Dosage Forms And Strengths

  • Zinc Sulfate Injection, USP: 30 mg/10 mL (3 mg/mL) of zinc as a clear, colorless solution in a 10 mL Pharmacy Bulk Package vial.25 mg/5 mL (5 mg/mL) of zinc as a clear, colorless solution in a 5 mL Pharmacy Bulk Package vial.

4 Contraindications

Zinc Sulfate Injection is contraindicated in patients with known hypersensitivity to zinc [see Warnings and Precautions (5.6)]

5.1  Pulmonary Embolism Due To Pulmonary Vascular Precipitates

Pulmonary vascular precipitates causing pulmonary vascular emboli and pulmonary distress have been reported in patients receiving parenteral nutrition. The cause of precipitate formation has not been determined in all cases; however, in some fatal cases, pulmonary emboli occurred as a result of calcium phosphate precipitates.  Precipitation has occurred following passage through an in-line filter; in vivo precipitate formation may also have occurred. If signs of pulmonary distress occur, stop the parenteral nutrition infusion and initiate a medical evaluation. In addition to inspection of the solution [see Dosage and Administration (2.2, 2.3)], the infusion set and catheter should also periodically be checked for precipitates.

5.2  Vein Damage And Thrombosis

Zinc Sulfate Injection has a low pH and must be prepared and used as an admixture in parenteral nutrition solutions. It is not for direct intravenous infusion. In addition, consider the osmolarity of the final parenteral nutrition solution in determining peripheral versus central administration.  Solutions with an osmolarity of 900 mOsm/L or greater must be infused through a central catheter [see Dosage and Administration (2.1)]. The infusion of hypertonic nutrient solutions into a peripheral vein may result in vein irritation, vein damage, and/or thrombosis. The primary complication of peripheral access is venous thrombophlebitis, which manifests as pain, erythema, tenderness or a palpable cord. Remove the catheter as soon as possible, if thrombophlebitis develops.

5.3  Aluminum Toxicity

Zinc Sulfate Injection contains aluminum that may be toxic.  Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Preterm infants are particularly at risk for aluminum toxicity because the kidneys are immature, and they require large amounts of calcium and phosphate solutions, which also contain aluminum. Patients with impaired kidney function, including preterm infants, who receive greater than 4 to 5 mcg/kg/day of parenteral aluminum can accumulate aluminum at levels associated with central nervous system and bone toxicity.  Tissue loading may occur at even lower rates of administration.Exposure to aluminum from Zinc Sulfate Injection is not more than 0.6 mcg/kg/day. When prescribing Zinc Sulfate Injection for use in parenteral nutrition containing other small volume parenteral products, the total daily patient exposure to aluminum from the admixture should be considered and maintained at no more than 5 mcg/kg/day [see Use in Specific Populations (8.4)].

5.4  Monitoring And Laboratory Tests

Monitor zinc concentrations, fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count and coagulation parameters throughout treatment [see Dosage and Administration (2.4)].

5.5  Copper Deficiency

Several post-marketing cases have reported that high doses of supplemental zinc (approximately 10 times the recommended dosage of 3 mg/day Zinc Sulfate Injection in adults) taken over extended periods of time (i.e., months to years) may result in decreased enteral copper absorption and copper deficiency. The cases reported the following complications of copper deficiency: anemia, leukopenia, thrombocytopenia, myeloneuropathy, and nephrotic-range proteinuria [see Adverse Reactions (6)].  If a patient develops signs and symptoms of copper deficiency during treatment with Zinc Sulfate Injection, interrupt zinc treatment and check zinc, copper, and ceruloplasmin levels. Copper deficiency should be treated with supplemental copper administration and discontinuation of zinc supplementation.

5.6  Hypersensitivity Reactions

Hypersensitivity reactions to subcutaneously administered zinc-containing insulin products were identified in postmarketing case reports. Reported reactions included injection site induration, erythema, pruritus, papular rash, generalized urticaria, facial swelling, and dyspnea. Patients did not manifest symptoms after changing to zinc-free insulin or another insulin product with a reduced amount of zinc.  In some cases, allergy testing confirmed the allergy to the zinc component of the insulin product.  If hypersensitivity reactions occur, discontinue Zinc Sulfate Injection and initiate appropriate medical treatment [see Contraindications (4)].

6 Adverse Reactions

  • No zinc-related adverse reactions have been reported in clinical studies or post-marketing reports in patients receiving intravenously administered parenteral nutrition solutions containing zinc sulfate within the recommended dosage range.  The following were identified in clinical studies or post-marketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Adverse reactions with other components of parenteral nutrition solutions:Pulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions (5.1)]Vein damage and thrombosis [see Warnings and Precautions (5.2)]Aluminum toxicity [see Warnings and Precautions (5.3)]Adverse reactions with the use of zinc-containing products administered by other routes of administration:Copper deficiency [see Warnings and Precautions (5.5)]Hypersensitivity reactions [see Warnings and Precautions (5.6)]

8.1  Pregnancy

Risk SummaryAdministration of the approved recommended dose of Zinc Sulfate Injection in parenteral nutrition is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with intravenous zinc sulfate.  The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.  All pregnancies have a background risk of birth defect, 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 to 4% and 15 to 20%, respectively.Clinical ConsiderationsDisease-associated Maternal and/or Embryo-Fetal Risk Deficiency of trace elements, including zinc, is associated with adverse pregnancy and fetal outcomes. Pregnant women have an increased metabolic demand for trace elements, including zinc.  Parenteral nutrition with zinc should be considered if a pregnant woman’s nutritional requirements cannot be fulfilled by oral or enteral intake.

8.2  Lactation

Risk SummaryZinc is present in human milk. Administration of the approved recommended dose of Zinc Sulfate Injection in parenteral nutrition is not expected to cause harm to a breastfed infant. There is no information on the effects of zinc sulfate on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Zinc Sulfate Injection and any potential adverse effects on the breastfed infant from Zinc Sulfate Injection or from the underlying maternal condition.

8.4  Pediatric Use

Zinc Sulfate Injection is approved for use in the pediatric population, including neonates, as a source of zinc for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. Safety and dosing recommendations in pediatric patients are based on published literature describing controlled studies of zinc-containing products in pediatric patients [see Dosage and Administration (2.2)].Because of immature renal function, preterm infants receiving prolonged parenteral nutrition treatment with Zinc Sulfate Injection may be at higher risk of aluminum toxicity [see Warnings and Precautions (5.3)].

8.5  Geriatric Use

Reported clinical experience with intravenous zinc sulfate has not identified a difference in zinc requirements between elderly and younger patients.  In general, dose selection should be individualized based on the patient’s clinical condition, nutritional requirements, and additional nutritional intake provided orally or enterally to the patient.

10 Overdosage

  • There are reported cases of overdosage with intravenous zinc in parenteral nutrition:Seven adult patients received an inadvertent overdosage of 50 mg to 75 mg elemental zinc per day in parenteral nutrition solution for 26 to 60 days; 6 of the 7 patients developed hyperamylasemia (peak amylase values of 557 to 1850 Klein units; normal: 130 to 310).  Amylase was not reported in one patient.  Serum zinc concentrations ranged from 310 to 670 mcg/dL.  None of the patients developed clinical signs of pancreatitis.  Five of the 7 patients died of septic complications.One adult patient died of infectious complications after receiving an inadvertent overdosage of 7.4 grams of zinc sulfate (equivalent to 1.2 grams of elemental zinc per day for 2.5 days) in parenteral nutrition solution over 60 hours.  The serum zinc concentration was 4184 mcg/dL.  Symptoms of zinc overdosage also included hyperamylasemia, thrombocytopenia, anemia, vomiting and diarrhea.One preterm infant born at 26 weeks gestation died of cardiac failure following a medication error in which the parenteral nutrition solution contained 330 mg/100 mL instead of 330 mcg/100 mL of zinc sulfate (overdosage of 1000-fold) Management There is no known antidote for acute zinc toxicity. Management of zinc overdosage is supportive care based on presenting signs and symptoms.

11 Description

Zinc Sulfate Injection, USP is a sterile, non-pyrogenic, clear, colorless, and odorless solution intended for use as a trace element and an additive to intravenous solutions for parenteral nutrition.30 mg/10 mL Pharmacy Bulk Package vial: Each mL contains 3 mg of zinc present as 7.41 mg of zinc sulfate and Water for Injection q.s.  25 mg/5 mL Pharmacy Bulk Package vial:  Each mL contains 5 mg of zinc present as 12.32 mg of zinc sulfate and Water for Injection q.s.  Both presentations do not contain preservatives free.  The pH range is 2 to 4; pH may be adjusted with sulfuric acid. Zinc Sulfate Injection contains no more than 2,500 mcg/L of aluminum and has a calculated osmolarity of 96.5 mOsmol/L for 3 mg/mL and 157.2 mOsmol/L for 5 mg/mL. Zinc sulfate heptahydrate has a molecular weight of 287.56 g/mol and a formula of ZnSO4·7H2O.

12.1  Mechanism Of Action

Zinc is an essential trace element.  Zinc functions as a cofactor of various enzymes including DNA polymerases, RNA polymerases, alcohol dehydrogenase, and alkaline phosphatases.  Zinc is a coordinator of protein structural folding, such as folding of “Zinc finger” motif that interacts with a variety of proteins, lipids, and nucleic acids.  In addition, zinc is a catalyst of essential biochemical reactions, including activation of substrates of carbonic anhydrase in erythrocyte.  Also, zinc is a signaling mediator modulating multiple signaling pathways.

12.2  Pharmacodynamics

Zinc sulfate exposure-response relationships and the time course of pharmacodynamic responses are unknown.

12.3  Pharmacokinetics

DistributionOver 85% of total body zinc is found in skeletal muscle and bone.  Other organs containing zinc are the liver, kidney, skin, brain, and heart.  In blood, zinc is mainly localized within erythrocytes.  Approximately 80% of serum zinc is bound to albumin and the remainder to alpha2-macroglobulin and amino acids.EliminationIn adults, zinc is primarily excreted via the gastrointestinal tract and eliminated in the feces. A smaller amount of zinc is excreted via the kidneys in the urine.  Urinary zinc excretion rates in very low birth weight preterm infants are relatively high in the neonatal period, and they decline to a level on a body weight basis that is similar to that of normal adults by two months of age.  Additionally, endogenous zinc loss occurs from hair, skin desquamation and sweat.

16  How Supplied/Storage And Handling

  • Zinc Sulfate Injection, USP is a clear, colorless solution supplied as:30 mg/10 mL (3 mg/mL) of zinc in a 10 mL Pharmacy Bulk Package vial.  Cartons of 25 vials (NDC 0517-6103-25)25 mg/5 mL (5 mg/mL) of zinc in a 5 mL Pharmacy Bulk Package vial. Cartons of 25 vials (NDC 0517-8005-25) Vial closure is not made with natural rubber latex.  Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].For storage of admixed solution see Dosage and Administration (2.3).

17 Patient Counseling Information

  • Inform patients, caregivers or home healthcare providers of the following risks of Zinc Sulfate Injection:Pulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions (5.1)]Vein damage and thrombosis [see Warnings and Precautions (5.2)]Aluminum toxicity [see Warnings and Precautions (5.3)]Copper deficiency [see Warnings and Precautions (5.5)]Hypersensitivity reactions [see Warnings and Precautions (5.6)]

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