Zinc Sulfate Injection,

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. Zinc Sulfate Injection is a trace element 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. (1)

2 DOSAGE AND ADMINISTRATION Pharmacy Bulk Package. Not for direct intravenous infusion. (2.1) See full prescribing information for information on preparation, administration, and general dosing considerations. ( 2.1 , 2.2 , 2.3 , 2.4 ) Recommended Dosage and Monitoring ( 2.5 ) Zinc Sulfate Injection provides 1 mg/mL, 3 mg/mL, or 5 mg/mL of zinc. Zinc Sulfate Injection in a concentration of 1 mg/mL is recommended for use in pediatric patients, particularly those weighing less than 12 kg. Individualize the dosage based upon the patient's clinical condition, nutritional requirements, and the contribution of oral or enteral zinc intake. Adults : The 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. Pediatrics : The recommended dosage in pediatric patients is shown by age and estimated weight. The dosages in the table are general recommendations intended for most pediatric patients. However, based on clinical requirements, some patients may require a higher dosage. Population Estimated Weight for Age Recommended Daily Dosage Pediatric Patients 10 kg and above 50 mcg/kg (up to 3 mg/day) 5 kg to less than 10 kg 100 mcg/kg Term Neonates 3 kg to less than 5 kg 250 mcg/kg* Preterm Neonates Less than 3 kg 400 mcg/kg * Term neonates have higher requirements in the first 3 months of life Monitor zinc concentrations and signs and symptoms of zinc deficiency, especially in pediatric patients, during treatment. 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. 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 mOsmol/L or greater must be infused through a central catheter [see Warnings and Precautions (5.2) ] . 2.2 Preparation and Administration Instruction 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 solution. 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. 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 Zydus Pharmaceuticals (USA) Inc. 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: o Precipitates have not formed during mixing or addition on additives. o 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. o Discard if any precipitates are observed. Stability and Storage Penetrate 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 period of time no longer than 9 days. After removal from refrigeration, use promptly and complete the infusion within 24 hours. Discard any remaining admixture. Protect the admixed parenteral nutrition solution from light. 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. 2.5 Recommended Dosage and Monitoring in Adult and Pediatric Patients Zinc Sulfate Injection provides 1 mg/mL, 3 mg/mL, or 5 mg/mL of zinc. Zinc Sulfate Injection in a concentration of 1 mg/mL is recommended for use in pediatric patients, particularly those weighing less than 12 kg. 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. Adults The 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 Patients The 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 Population Estimated Weight for Age Recommended Daily Dosage Pediatric Patients 10 kg and above 50 mcg/kg (up to 3 mg/day) 5 kg to less than 10 kg 100 mcg/kg Term Neonates 3 kg to less than 5 kg 250 mcg/kg* Preterm Neonates Less than 3 kg 400 mcg/kg *Term neonates have higher requirements in the first 3 months of life. Monitoring 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.

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 )] No zinc-related adverse reactions in patients receiving intravenously administered parenteral nutrition solutions containing zinc within the recommended dosage range. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

12.3 Pharmacokinetics Distribution Over 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. Elimination In 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.