Cysteine Hydrochloride

1 INDICATIONS AND USAGE ELCYS ® is indicated for use as an additive to amino acid solutions to meet the nutritional requirements of newborn infants requiring total parenteral nutrition (TPN); and of adult and pediatric patients with severe liver disease who may have impaired enzymatic processes and require TPN. It can also be added to amino acid solutions to provide a more complete profile of amino acids for protein synthesis. ELCYS ® is a sulfur-containing amino acid indicated to meet the nutritional requirements of newborn infants requiring total parenteral nutrition (TPN); and of adult and pediatric patients with severe liver disease who may have impaired enzymatic processes and require TPN. It can also be added to amino acid solutions to provide a more complete profile of amino acids for protein synthesis. ( 1 )

2 DOSAGE AND ADMINISTRATION • ELCYS ® is for admixing use only. Not for direct intravenous infusion . ( 2.1 ) • PHARMACY BULK PACKAGE: Dispense single-doses to many patients in a pharmacy admixture program. Use within 4 hours of puncture. ( 2.1 ) • See full prescribing information for information on preparation, administration, instructions for use, dosing considerations, including the recommended dosage in pediatric patients and adults. ( 2.1 , 2.2 , 2.3 , 2.4 , 2.5 ) 2.1 Important Administration Information Prior to administration, ELCYS® must be diluted and used as an admixture in PN solutions. ELCYS® is not for direct intravenous infusion. The resulting 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 )] . ELCYS ® is supplied as a pharmacy bulk package, and consists of one pharmacy bulk vial which must be diluted prior to intravenous administration [see Dosage andAdministration ( 2.3 )]. As a pharmacy bulk vial, ELCYS ® is intended for dispensing of single doses to many patients. Dispensing from a pharmacy bulk vial should be completed within 4 hours after the vial is penetrated. Do not administer ELCYS ® as a direct, undiluted intravenous injection. 2.2 Preparation and Administration Instructions Prior to administration, ELCYS® must be diluted and used as an admixture in PN solutions. ELCYS® is not for direct intravenous infusion. • ELCYS ® 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. • ELCYS ® is for addition to amino acid solutions prior to further admixing with dextrose injection using a PN container. • Use a dedicated line for PN solutions. • Intravenous lipid emulsions can be infused concurrently into the same vein as ELCYS ® containing amino acid and dextrose solutions by a Y-connector located near the infusion site; flow rates of each solution should be controlled separately by infusion pumps. • For administration without lipid emulsion, use a 0.22 micron in-line filter. • To prevent air embolism, use a non-vented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible containers in series, fully evacuate residual gas in the container prior to administration, do not pressurize the flexible container to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the container runs dry. • If infused with lipid emulsion, do not use administration sets and lines that contain di-2-ethylhexyl phthalate (DEHP). Administration sets that contain polyvinyl chloride (PVC) components have DEHP as a plasticizer. • Visually inspect the diluted PN solution containing ELCYS ® 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 (PN) Container • Remove ELCYS ® vial from the carton and inspect for particulate matter. • Transfer the required amount of ELCYS ® to an amino acid solution using strict aseptic techniques to avoid microbial contamination. • The amino acid solution containing ELCYS ® can then be used to prepare admixtures in the PN container using strict aseptic techniques. • Amino acids solution containing ELCYS ® may be mixed with dextrose injection. The following proper mixing sequence must be followed to minimize pH related problems: • Transfer dextrose injection to the parental nutrition pooling container • Transfer phosphate salt • Transfer ELCYS ® -containing amino acid solution • Transfer electrolytes • Transfer trace elements • Use gentle agitation during admixing to minimize localized concentration effects; shake containers gently after each addition. • For automated compounding, refer to Instructions for Use of the applicable compounder. • Because additives may be incompatible, evaluate all additions to the PN container for compatibility and stability of the resulting preparation. Consult with pharmacist, if available. Questions about compatibility may be directed to Exela Pharma Sciences, LLC. If it is deemed advisable to introduce additives to the PN container, use aseptic technique. • Inspect the final PN solution containing ELCYS ® to ensure that precipitates have not formed during mixing or addition on additives. Discard if any precipitates are observed. Stability and Storage • Use of ELCYS ® for admixing should be limited to up to 4 hours at room temperature (25ºC/77ºF) after the container closure has been penetrated. Discard any remaining drug. • Use PN solution containing ELCYS ® promptly after mixing. Any storage of the admixture should be under refrigeration 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 PN solution from light. 2.4 Dosing Considerations • The dosage of the final PN solution containing ELCYS ® must be based on the concentrations of all components in the solution and the recommended 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. • The dosage of ELCYS ® should be individualized based on the patient’s clinical condition (ability to adequately metabolize amino acids), body weight and nutritional/fluid requirements, as well as additional energy given orally/enterally to the patient. Prior to initiating parenteral nutrition, the following patient information should be reviewed: review of all medications, gastrointestinal function and laboratory data (such as electrolytes (including magnesium, calcium, and phosphorus), glucose, urea/creatinine, liver panel, complete blood count and triglyceride level (if adding lipid emulsion). • Prior to administration of PN solution containing ELCYS ® , correct severe fluid, electrolyte and acid-base disorders. 2.5 Recommended Dosage in Pediatric Patients and Adults The recommended dosage and volume of ELCYS ® is shown in Table 1 and is based upon the recommended daily protein (amino acids) requirement. For pediatric patients from birth to less than 12 years of age, the recommended dosage of ELCYS ® is 22 mg/gram of amino acids. For adults and pediatric patients 12 years of age and older, the recommended dosage of ELCYS ® is 7 mg/gram of amino acids. Table 1. Recommended Daily Dosage of ELCYS ® in Pediatric Patients and Adults Age Recommended Protein a Requirement (g AA/kg/day) 1 Recommended Dosage (mg ELCYS/g AA) Recommended Volume (mL ELCYS/g AA) Preterm and term infants less than 1 month of age 3 to 4 22 0.44 Pediatric patients 1 month to less than 1 year of age 2 to 3 22 0.44 Pediatric patients 1 year to 11 years of age 1 to 2 22 0.44 Pediatric patients 12 years to 17 years of age 0.8 to 1.5 7 0.14 Adults: Stable Patients 0.8 to 1 7 0.14 Adults: Critically Ill Patients b 1.5 to 2 7 0.14 AA = Amino Acid a Protein is provided as amino acids (AA) b Includes patients requiring more than 2 to 3 days in the intensive care unit with organ failure, sepsis or postoperative major surgery. Do not use in patients with conditions that are contraindicated [see Contraindications ( 4 )] ELCYS ® contains 50 mg/mL of cysteine hydrochloride (equivalent to 34.5 mg/mL of cysteine). Therefore, the ELCYS ® dosages in Table 1 provide: • 15 mg cysteine/gram of amino acids for pediatric patients less than 12 years of age • 5 mg cysteine/gram of amino acids for adults and pediatric patients 12 years of age and older

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the prescribing information: • Pulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions ( 5.1 )] • Vein damage and thrombosis [see Warnings and Precautions ( 5.2 )] • Increased BUN [see Warnings and Precautions ( 5.3 )] • Acid-base imbalance [see Warnings and Precautions ( 5.4 )] • Hepatobiliary disorders [see Warnings and Precautions ( 5.5 )] • Hyperammonemia [see Warnings and Precautions ( 5.6 )] • Aluminum toxicity [see Warnings and Precautions ( 5.7 )] Adverse reactions with the use of cysteine hydrochloride injection were identified in clinical studies or postmarketing 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. • Local infusion site reactions, including a warm sensation, erythema, phlebitis and thrombosis at the infusion site • Generalized flushing, fever and nausea Most common adverse reactions are local reactions (warm sensation, erythema, phlebitis and thrombosis at the infusion site), generalized flushing, fever and nausea ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Exela Pharma Sciences, LLC or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.