`
`
`
`or more must be infused through a central catheter. (2.1, 5.2)
`
`
`
`
`
`
` • Increased blood urea nitrogen (BUN): Monitor laboratory parameters and
`
`
`
`discontinue if exceeds normal postprandial limits and continues to increase.
`
`(5.3)
`
` • Acid-Base Imbalance: Monitor laboratory parameters and supplement with
`
`
`electrolytes as needed. (5.4)
`
`
` • Hepatobiliary Disorders: Monitor liver function parameters and ammonia
`
`
`
`levels. (5.5)
` • Hyperammonemia: Neurocognitive delay possible in infants; monitor blood
`
`
`ammonia levels. (5.6, 8.4)
`
`
`
` • Aluminium Toxicity: Increased risk in patients with renal impairment,
`
`
`including preterm infants. (5.7, 8.4)
`
`
` • Monitoring and Laboratory Tests: Monitor fluid and electrolytes, serum
`
`
`osmolarity, blood glucose, kidney and liver function, blood count and
`coagulation parameters throughout treatment. (5.8)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`------------------------------ ADVERSE REACTIONS ----------------------------
`
`
`
`
`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 at 1-888-451-4321 or FDA at 1-800-FDA-1088 or
`
`
`www.fda.gov/medwatch.
`
`
`See 17 for PATIENT COUNSELING INFORMATION.
`
`
`
`
`Revised: 04/2019
`
`
`
`
`
`
`
`5.8 Monitoring and Laboratory Tests
`
`
`6 ADVERSE REACTIONS
`
`
`8 USE IN SPECIFIC POPULATIONS
`
`8.1 Pregnancy
`8.2 Lactation
`
`8.4 Pediatric Use
`
`8.5 Geriatric Use
`
`
`8.6 Renal Impairment
`8.7 Hepatic Impairment
`
`
`10 OVERDOSAGE
`
`11 DESCRIPTION
`
`12 CLINICAL PHARMACOLOGY
`
`12.1 Mechanism of Action
`
`15 REFERENCES
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`17 PATIENT COUNSELING INFORMATION
`
`*Sections or subsections omitted from the full prescribing information are not listed.
`
`
`
` HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`
` These highlights do not include all the information needed to use ELCYS
` safely and effectively. See full prescribing information for ELCYS.
`
`
`
` ELCYS (cysteine hydrochloride injection), for intravenous use
`
`
`
` Initial U.S. Approval: 1971
`
`
`
`
`
`
`
`
` --------------------------- INDICATIONS AND USAGE -------------------------
` 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)
`
`
`
`
`
`
`
` ---------------------- DOSAGE AND ADMINISTRATION ---------------------
` • ELCYS is for admixing use only. Not for direct intravenous infusion. (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)
`
`
`
`
`--------------------- DOSAGE FORMS AND STRENGTHS -------------------
`
`
`
`
`Injection: 500 mg/10 mL (50 mg/mL) cysteine hydrochloride, USP in a 10 mL
`
`
`
`
`
`single-dose vial. (3)
`
`
`
`------------------------------ CONTRAINDICATIONS ----------------------------
`
`
`
`
` • Hypersensitivity to one or more amino acids (4)
`
`
`
`• Inborn errors of amino acid metabolism (4)
`
`
` • Pulmonary edema or acidosis due to low cardiac output (4)
`
`
`
`
`
`
`
`
`
`
`
` ----------------------- WARNINGS AND PRECAUTIONS ---------------------
` • Pulmonary Embolism due to Pulmonary Vascular Precipitates: If signs of
`
`
`
`pulmonary distress occur, stop the infusion and initiate a medical
`
`evaluation. (5.1)
`
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
`1 INDICATIONS AND USAGE
`2 DOSAGE AND ADMINISTRATION
`
`
`2.1 Important Administration Information
`
`
`
`2.2 Preparation and Administration Instructions
`
`
`
`
`2.3 Preparation Instructions for Admixing Using a Parenteral Nutrition
`
`
`
`
`(PN) Container
`
`2.4 Dosing Considerations
`
`
`
`
`2.5 Recommended Dosage in Pediatric and Adults
`
`
`3 DOSAGE FORMS AND STRENGTHS
`
`
`4 CONTRAINDICATIONS
`
`5 WARNINGS AND PRECAUTIONS
`5.1 Pulmonary Embolism due to Pulmonary Vascular Precipitates
`
`
`
`
`5.2 Vein Damage and Thrombosis
`
`
`
`
`5.3 Increased Blood Urea Nitrogen (BUN)
`
`
`
`5.4 Acid-Base Imbalance
`
`
`5.5 Hepatobiliary Disorders
`
`5.6 Hyperammonemia
`
`5.7 Aluminum Toxicity
`
`
`
`
`
`
`
`Reference ID: 4420190
`
`1
`
`EXELA 2004
`Eton Pharmaceuticals v. Exela Pharma Sciences
`PGR2020-00064
`
`
`
`
`FULL PRESCRIBING INFORMATION
`
`
`
` 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.
`
`
`
`
`
` 2 DOSAGE AND ADMINISTRATION
`
`
`
` 2.1
`
`
`
` Important Administration Information
`
`
`ELCYS is for admixing use only. It is not for direct intravenous infusion. Prior to administration, ELCYS must be diluted
`
`
`
`
`and used as an admixture in parenteral nutrition (PN) solutions.
`
`
`
`
`
`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)].
`
`
`
`
`
` 2.2
`
`
`
` Preparation and Administration Instructions
`
`
`
`
`
` • ELCYS is not for direct intravenous infusion. Prior to administration, ELCYS must be diluted and used as an
`
`
`
`
` admixture in PN solutions.
`
`
`
`
`
`
`• 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.
`
`
`
`
`
`
`•
`
`
`•
`
`Reference ID: 4420190
`
`2
`
`
`
`
`
` 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:
`
`
`
`
`
` 1. Transfer dextrose injection to the parental nutrition pooling container
`
`
`
`
`
`
`
` 2. Transfer phosphate salt
`
`
`
`
`
`
`
`
`
` 3. Transfer ELCYS-containing amino acid solution
`
`
`
`
`
`
`
` 4. Transfer electrolytes
`
`
`
`
`
` 5. 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
`
`
`
`
`• For single use only. Discard used container of ELCYS.
`
`
`
`
`
`• 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.
`
`Reference ID: 4420190
`
`3
`
`
`
`
`
` • 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
`
`
`
`
` Recommended
`
` Recommended
`
` Proteina
`
` Dosage
` Requirement
`
` (mg ELCYS/g AA)
`
`
` (g AA/kg/day)1
`
`
` 3 to 4
`
` 2 to 3
`
`
` 1 to 2
`
`
` 0.8 to 1.5
` 0.8 to 1
`
`
` 1.5 to 2
`
` Recommended
`
` Volume
` (mL ELCYS/g AA)
`
`
`
` Age
`
`
`
`
`
`
`
` Preterm and term infants less than 1 month of age
` Pediatric patients 1 month to less than 1 year of age
`
`
`
`
`
` Pediatric patients 1 year to 11 years of age
`
`
`
`
`
`
`
`
` Pediatric patients 12 years to 17 years of age
`
`
`
`
`
`
`
` Adults: Stable Patients
`
`
`
` Adults: Critically Ill Patientsb
`
`
`
`
`
` 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)]
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 22
`
` 22
`
` 22
` 7
`
`
` 7
`
` 7
`
`
`
`
`
`
` 0.44
`
` 0.44
`
` 0.44
`
` 0.14
`
` 0.14
`
` 0.14
`
`
`
` 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
`
`
`
`
`
` 3 DOSAGE FORMS AND STRENGTHS
`
`
`
` Injection: 500 mg/10 mL (50 mg/mL) cysteine hydrochloride, USP as a clear, colorless, sterile solution in a 10 mL single-
`
` dose vial.
`
`
`
`
`
`
`
`
`
`
`
` 4 CONTRAINDICATIONS
`
`
`
` ELCYS is contraindicated in:
`
`
`
` • Patients with known hypersensitivity to one or more amino acids.
`
`
`
`
`
` • Patients with inborn errors of amino acid metabolism due to risk of severe metabolic or neurologic complications.
`
`
` • Patients with pulmonary edema or acidosis due to low cardiac output.
`
`
`
`
`
`
`
`
`
`Reference ID: 4420190
`
`4
`
`
`
`
`
` 5 WARNINGS AND PRECAUTIONS
`
`
`
` Pulmonary Embolism due to Pulmonary Vascular Precipitates
`5.1
`
`
` Pulmonary vascular precipitates causing pulmonary vascular emboli and pulmonary distress have been reported in
`
`
` patients receiving PN. In some fatal cases, pulmonary embolism occurred as a result of calcium phosphate precipitates.
`Precipitation following passage through an in-line filter and suspected in vivo precipitate formation has also been
`
`
`
`reported. If signs of pulmonary distress occur, stop the PN infusion and initiate a medical evaluation. In addition to
`
`
`inspection of the solution [see Dosage and Administration (2.1, 2.2)], the infusion set and catheter should also
`
`
`periodically be checked for precipitates.
`
`
`
` Vein Damage and Thrombosis
` 5.2
`
`
`
`
`
`
` ELCYS must be diluted and used as an admixture in PN solutions. It is not for direct intravenous infusion. 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 injections 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.
`
`
`
` Increased Blood Urea Nitrogen (BUN)
` 5.3
`
`
`
` Intravenous infusion of amino acids may induce a rise in blood urea nitrogen (BUN), especially in patients with impaired
`
` hepatic or renal function. Appropriate laboratory tests should be performed periodically and infusion discontinued if BUN
`
`
` levels exceed normal postprandial limits and continue to rise. It should be noted that a modest rise in BUN normally
`
` occurs as a result of increased protein intake.
`
`Administration of amino acid solutions in the presence of impaired renal function may augment an increasing BUN, as
`
` does any protein dietary component.
`
` Acid-Base Imbalance
` 5.4
`
`
`
`
` Administration of ELCYS may result in metabolic acidosis in preterm infants.
`
`
`
`
`
`
`
` Administration of amino acid solutions to a patient with hepatic impairment may result in serum amino acid imbalances,
`
` metabolic alkalosis, prerenal azotemia, hyperammonemia, stupor and coma.
`
`
`
`
`
`
`
` Frequent clinical evaluation and laboratory determinations are necessary for proper monitoring of acid-base balance
`
` during parenteral nutrition therapy. Significant deviations from normal concentrations may require the use of additional
`
` electrolyte supplements.
`
` 5.5 Hepatobiliary Disorders
`
`
` Hepatobiliary disorders are known to develop in some patients without preexisting liver disease who receive PN,
`
`
`
` including cholecystitis, cholelithiasis, cholestasis, hepatic steatosis, fibrosis and cirrhosis, possibly leading to hepatic
`
`
`
` failure. The etiology of these disorders is thought to be multifactorial and may differ between patients.
`
`
`
` Monitor liver function parameters and ammonia levels. Patients developing signs of hepatobiliary disorders should be
`
` assessed early by a clinician knowledgeable in liver diseases in order to identify possible causative and contributory
`
` factors, and possible therapeutic and prophylactic interventions.
`
` 5.6 Hyperammonemia
`
`
` Hyperammonemia is of special significance in infants, as it can result in neurocognitive delays. Therefore, it is essential
`
`
` that blood ammonia levels be measured frequently in infants.
`
`
`
`
`
`
`
`Reference ID: 4420190
`
`5
`
`
`
`
`
` Instances of asymptomatic hyperammonemia have been reported in patients without overt liver dysfunction. The
`
`
` mechanisms of this reaction are not clearly defined but may involve genetic defects and immature or subclinically
`
`
` impaired liver function [see Contraindications (4), Use in Specific Populations (8.4)].
`
`
`
` Aluminum Toxicity
` 5.7
`
`
`
`
` ELCYS contains aluminum that may be toxic.
`
`
`
` Aluminum may reach toxic levels with prolonged parenteral administration in patients with renal impairment. Preterm
`
`
`
`
`
`
`
` infants are particularly at risk for aluminum toxicity because their kidneys are immature, and they require large amounts
` of calcium and phosphate solutions, which also contain aluminum.
`
`
` Patients with renal impairment, including preterm infants, who receive greater than 4 to 5 mcg/kg/day of parenteral
`
`
`
`
`
`
` aluminum can accumulate aluminum to levels associated with central nervous system and bone toxicity. Tissue loading
` may occur at even lower rates of administration.
`
`
`
`
`
`
`
`
` Exposure to aluminum from ELCYS is not more than 0.21 mcg/kg/day when preterm and term infants less than 1 month
`
` of age are administered the recommended maximum dosage of ELCYS (15 mg cysteine/g of amino acids and 4 g of
`
`
`
`
`
`
`
` amino acids/kg/day) [see Table 1, Dosage and Administration (2.5)]. When prescribing ELCYS for use in PN 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)].
`
`
`
`
`
`
`
`
`
`
`
` 5.8 Monitoring and Laboratory Tests
`
`
`
` Monitor 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)].
`
`
`
`
`
` 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
`
`
`
`
`
`
`
`
` 8 USE IN SPECIFIC POPULATIONS
`
`
`
` Pregnancy
`8.1
`
`
` Risk Summary
`
`
`
`
`
`Appropriate administration of ELCYS is not expected to cause major birth defects, miscarriage or adverse maternal or
`
`
`
`fetal outcomes. Animal reproduction studies have not been conducted with cysteine hydrochloride.
`
`Reference ID: 4420190
`
`6
`
`
`
` The estimated background risk for 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 defect and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15
`
`
`
`
`
`
`
` to 20%, respectively.
`
`
`
`
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` Lactation
`8.2
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` Risk Summary
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`Data available on the effects of cysteine hydrochloride on infants, either directly or through breastmilk, do not suggest a
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`significant risk of adverse events from exposure. Although there are no data on the presence of cysteine hydrochloride in
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`human or animal milk or the effects on milk production, appropriate administration of ELCYS is not expected to cause
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`harm to a breastfed infant. The development and health benefits of breastfeeding should be considered along with the
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`mother’s clinical need for ELCYS and any potential adverse effects on the breastfed infant from ELCYS or from the
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`underlying maternal condition.
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`Pediatric Use
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`8.4
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`ELCYS is approved for use in pediatric patients, from birth to 17 years of age, for use as an additive to amino acid
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`solutions to meet the nutritional requirements of newborn infants, including preterm infants, requiring total parenteral
`nutrition (TPN) and pediatric patients with severe liver disease who may have impaired enzymatic processes and require
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`TPN. The safety profile for ELCYS use in pediatric patients includes risks of acid-base imbalance and hyperammonemia.
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`Acid-base imbalance, including metabolic acidosis, may occur with ELCYS administration in preterm infants. Frequent
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`clinical and laboratory assessments are necessary to monitor and manage fluid balance, electrolyte concentrations, and
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`acid-base balance during parenteral nutrition therapy [see Warnings and Precautions (5.4)].
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`Hyperammonemia is of special significance in infants (birth to two years of age). This reaction appears to be related to a
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`deficiency of the urea cycle amino acids of genetic or product origin. It is essential that blood ammonia be measured
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`frequently in infants [see Warnings and Precautions (5.6)].
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`Because of immature renal function, preterm infants receiving prolonged PN treatment with ELCYS may be at higher risk
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`of aluminum toxicity [see Warnings and Precautions (5.7)].
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` 8.5 Geriatric Use
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` Clinical studies with ELCYS have not been performed to determine whether patients aged 65 and over respond differently
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` 8.6 Renal Impairment
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` Monitor patients with impaired renal function receiving PN solutions containing the recommended dosage of ELCYS with
` frequent clinical evaluation and laboratory tests to assess renal function, including serum electrolytes and fluid balance
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` [see Dosage and Administration (2.4), Warnings and Precautions (5.8)].
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` 8.7 Hepatic Impairment
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` Monitor patients with impaired liver function receiving PN solutions containing the recommended dosage of ELCYS with
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` frequent clinical evaluation and laboratory tests to assess liver function, such as bilirubin and liver function parameters
` [see Dosage and Administration (2.4), Warnings and Precautions (5.8)].
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` 10 OVERDOSAGE
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`In the event of over hydration or solute overload, re-evaluate the patient and institute appropriate corrective measures [see
`Warnings and Precautions (5.3, 5.4, 5.5, 5.7, 5.8)].
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`Reference ID: 4420190
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`7
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` 11 DESCRIPTION
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` ELCYS (cysteine hydrochloride injection) is a sterile, nonpyrogenic solution for intravenous use. Each 10 mL of ELCYS
` contains 500 mg of cysteine hydrochloride, USP (equivalent to 345 mg of cysteine) in water for injection. Sodium
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` hydroxide and/or hydrochloric acid are used as needed to adjust the pH. The pH range is 1.0 to 2.5.
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` The active ingredient is cysteine hydrochloride. Cysteine is a sulfur-containing amino acid. The chemical name of
` cysteine hydrochloride is L-cysteine hydrochloride monohydrate and is chemically designated as C3H7NO2S • HCI • H2O
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`having a molecular weight of 175.63. Cysteine hydrochloride is a white crystalline powder soluble in water. Cysteine
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`aqueous solution is prone to oxidation when exposed to air, and when mixed with amino acids solutions, cysteine may
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`convert to insoluble cystine which leads to precipitation over time. It has the following structural formula:
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`ELCYS contains no more than 120 mcg/L of aluminum.
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` 12 CLINICAL PHARMACOLOGY
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` 12.1 Mechanism of Action
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` Endogenous cysteine is synthesized from methionine by the enzyme, cystathionase, via the trans-sulfuration pathway, and
` serves as a precursor substrate for both glutathione and taurine. ELCYS provides cysteine to the systemic circulation of
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` patients who require PN and cannot synthesize adequate quantities of cysteine due to insufficient or deficient
` cystathionase activity.
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` 15 REFERENCES
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` 1. Ayers P. et al. A.S.P.E.N. Parenteral Nutrition Handbook, 2nd ed. 2014 pg. 123 and 124.
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` 16 HOW SUPPLIED/STORAGE AND HANDLING
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` ELCYS is supplied as follows:
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` 500 mg/10 mL (50 mg/mL) of cysteine hydrochloride, USP is a clear, colorless, sterile and nonpyrogenic solution in 10
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`mL single-dose vials (51754-1007-1), packaged as 10 per carton (NDC 51754-1007-3)
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`Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature]. Avoid excessive heat. Protect from
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`freezing. If accidentally frozen, discard the vial.
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`For storage of admixed solution see Dosage and Administration (2.3).
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` 17 PATIENT COUNSELING INFORMATION
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` Inform patients, caregivers, or home healthcare providers of the following risks of ELCYS:
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` • Pulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions (5.1)]
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`Reference ID: 4420190
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`8
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`• Vein damage and thrombosis [see Warnings and Precautions (5.2)]
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`Increased BUN [see Warnings and Precautions (5.3)]
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`• Acid base imbalance [see Warnings and Precautions (5.4)]
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`• Hepatobiliary disorders [see Warnings and Precautions (5.5)]
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`• Hyperammonemia [see Warnings and Precautions (5.6)]
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`• Aluminum toxicity [see Warnings and Precautions (5.7)]
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`• Monitoring and laboratory tests [see Warnings and Precautions (5.8)]
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`Manufactured and Distributed by:
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`Exela Pharma Sciences, LLC
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`Lenoir, NC 28645
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`Reference ID: 4420190
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