HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`
` These highlights do not include all the information needed to use
`
` NOURESS ™ safely and effectively. See full prescribing information for
`
`
`
`
`NOURESS.
`
`
`NOURESS (cysteine hydrochloride injection), for intravenous use
`
`
`
`Initial U.S. Approval: 1971
`
`
`
`__________________INDICATIONS AND USAGE _________________
`
`
`
`NOURESS is a sulfur-containing amino acid indicated for use as an additive
`
`
`
`to amino acids solutions to meet nutritional requirements of neonates (preterm
`
`
`
`
`
`and term infants less than one month of age) requiring total parenteral
`
`
`nutrition. (1)
`
`
`_______________DOSAGE AND ADMINISTRATION ______________
`
`
`
`NOURESS is for intravenous infusion after dilution and admixing only.
`
`
`
`
`
`•
`(2.1)
`
`See full prescribing information for information on preparation,
`
`
`
`administration, and instructions for use. (2.1, 2.2, 2.3, 2.4)
`
`
`
`The recommended dosage in neonates is based upon the recommended
`
`
`
`daily protein (amino acid) requirements: 22 mg NOURESS/g amino
`
`acids. The corresponding volume is 0.44 mL NOURESS/g amino acids.
`
`
`(2.5)
`
` ______________
` _____________
`DOSAGE FORMS AND STRENGTHS
`Injection: 500 mg/10 mL (50 mg/mL) cysteine hydrochloride, USP in a
`
`
`
`
`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)
`
`Vein Damage and Thrombosis: Solutions with osmolarity of 900
`
`
`mOsm/L or more must be infused through a central catheter (2.1, 5.2)
`
`
`
`Increased Blood Urea Nitrogen (BUN): Monitor laboratory parameters
`
`and discontinue if BUN 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: Neurocognitive delay possible in infants;
`
`
`monitor liver function parameters and ammonia levels. (5.5, 8.4)
`
`
`Aluminum Toxicity: Increased risk in patients with renal impairment,
`
`
`
`
`including preterm infants. (5.6, 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. (5.7)
`
`
`
`___________________ ADVERSE REACTIONS ___________________
`
`
`
`Most common adverse reactions are local reactions (warm sensation,
`
`
`erythema, phlebitis, and thrombosis at the infusion site), generalized flushing,
`
`
`fever, nausea, and metabolic acidosis. (6)
`
`
`To report SUSPECTED ADVERSE REACTIONS, contact Avadel at 1­
`
`
`877-638-4579 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
`
`
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION.
`
`
`
`
`
`•
`
`
`•
`
`
`•
`
`
`Revised: 12/2019
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
`
`
`1
`INDICATIONS AND USAGE
`
`
`2
`DOSAGE AND ADMINISTRATION
`
`
`Important Administration Information
`2.1
`
`
`Preparation and Administration Information
`2.2
`
`
`2.3
`Preparation Instructions for Admixing Using a Parenteral
`
`
`
`Nutrition Container
`
`
`2.4 Dosing Considerations
`
`
`2.5 Recommended Dosage for Neonates
`
`
`DOSAGE FORMS AND STRENGTHS
`3
`
`
`CONTRAINDICATIONS
`4
`
`
`5 WARNINGS AND PRECAUTIONS
`
`
`Pulmonary Embolism due to Pulmonary Vascular Precipitates
`5.1
`
`
`
`
`5.2 Vein Damage and Thrombosis
`
`
`5.3
`Increased Blood Urea Nitrogen (BUN)
`
`
`5.4 Acid-Base Imbalance
`
`
`5.5 Hepatobiliary Disorders
`
`
`5.6 Aluminum Toxicity
`
`
`
`
`6
`
`8
`
`
`
`5.7 Monitoring and Laboratory Tests
`
`ADVERSE REACTIONS
`
`USE IN SPECIFIC POPULATIONS
`
`
`8.1
`Pregnancy
`
`
`8.2 Lactation
`
`
`8.4
`Pediatric Use
`
`
`10 OVERDOSAGE
`
`
`11 DESCRIPTION
`
`
`12 CLINICAL PHARMACOLOGY
`
`
`12.1 Mechanism of Action
`
`15 REFERENCES
`
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`
`PATIENT COUNSELING INFORMATION
`17
`
`
`*Sections or subsections omitted from the full prescribing information
`
`are not listed.
`
`
`Reference ID: 4533723
`
`
`
` 1
`
`

`

`FULL PRESCRIBING INFORMATION
`
`
` 1
`
`
` INDICATIONS AND USAGE
` NOURESS is indicated for use as an additive to amino acids solutions to meet nutritional
`
`
`
`
`
`
` requirements of neonates (preterm and term infants less than one month of age) requiring total
`
` parenteral nutrition.
`
`
`
`
`
`
`
`
`
`
`
`
`
` 2
`
` DOSAGE AND ADMINISTRATION
`
` Important Administration Information
`
`
`
` 2.1
`
`
` NOURESS is for intravenous infusion after dilution and admixing use only. Prior to
` administration, NOURESS must be diluted and used as an admixture in parenteral nutrition
`
`
`
`
` 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)].
`
`
`
` Preparation and Administration Information
` 2.2
` • Prior to administration, NOURESS must be diluted and used as an admixture in
`
`
`
`
` parenteral nutrition solutions.
`
`
`
` • NOURESS 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.
` • NOURESS is for addition to amino acid solutions prior to further admixing with dextrose
`
`
`
` injection using a parenteral nutrition container.
` • Calcium and phosphate ratios must be considered. Excess addition of calcium and
` phosphate, especially in the form of mineral salts, may result in the formation of calcium
`
`
`
`
` phosphate precipitates [see Warnings and Precautions (5.1)].
` • Use a dedicated line for parenteral nutrition solutions.
`
`
`
`
`Intravenous lipid emulsions can be infused concurrently into the same vein as
`
`•
`
`
` NOURESS-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, 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
`
`
`
`
`
`
`
`Reference ID: 4533723
`
`
`
` 2
`
`
`

`

`
`
`
`
` 2.3
`
`
`
`
`
`
`
`
` container to increase flow rates, and if administration is controlled by a pumping device,
` turn off pump before the container runs dry.
`
`
` • Visually inspect the diluted parenteral nutrition solution containing NOURESS for
`
`
`
`
` particulate matter and discoloration before admixing, after admixing, after removal from
` refrigeration, 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.
`
` Preparation Instructions for Admixing Using a Parenteral Nutrition
`
` Container
` • Remove NOURESS vial from the carton and inspect for particulate matter.
`
`
`
` • Transfer the required amount of NOURESS to an amino acid solution using strict aseptic
`
`
`
` techniques to avoid microbial contamination.
`
`
`
` • The amino acid solution containing NOURESS can then be used to prepare admixtures in
`
` the parenteral nutrition container using strict aseptic techniques.
`
`
` • Amino acids solution containing NOURESS 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 NOURESS-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 parenteral nutrition
`
`
`
`
`
` container for compatibility and stability of the resulting preparation. Consult with
`
`
` pharmacist, if available. Questions about compatibility may be directed to Avadel
`
`
`
` Pharmaceuticals. If it is deemed advisable to introduce additives to the parenteral
`
`
`
` nutrition container, use aseptic technique.
` Inspect the final parenteral nutrition solution containing NOURESS to ensure that
`
`
`
`
`
` precipitates have not formed during mixing or on addition of additives. Discard if any
`
`
` precipitates are observed.
`
` Stability and Storage
` • For single use only. Discard unused portion of the vial of NOURESS.
`
`
`
`
`• Use parenteral nutrition solution containing NOURESS promptly after mixing. Any
`
`
`
`
`
`
` storage of the admixture should be under refrigeration at 2ºC to 8ºC (36ºF to 46ºF) and
`
`
` limited to a brief period of time, no longer than 24 hours. After removal from
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`•
`
`Reference ID: 4533723
`
`
`
` 3
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Dosage
`
` (mg NOURESS/g Amino Acids)
`
` 22
`
` Volume
`
`
` (mL NOURESS/g Amino Acids)
`
` 0.44
`
`
`
`
`
`
`
`
` refrigeration, inspect for precipitates, use promptly, and complete the infusion within 24
` hours. Discard if any precipitates are observed.
`
`
` • Discard any remaining admixture.
`
`
`
` • Protect parenteral nutrition solution from light.
`
`
`
`
`
` 2.4
` Dosing Considerations
` The dosage of the final parenteral nutrition solution containing NOURESS 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.
`
`
`The dosage of NOURESS 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, and complete blood count.
`
`Prior to administration of parenteral nutrition solution containing NOURESS, correct severe
`
`
`
`fluid, electrolyte and acid-base disorders.
`
`
`
`
`
` Recommended Dosage for Neonates
` 2.5
` The recommended dosage and volume of NOURESS is based upon the recommended daily
`
`
` protein (amino acid) requirements.
`
`
`
` Table 1. Recommended Daily Dosage of NOURESS in Neonates (Preterm and Term Infants Less
` Than One Month of Age)
`
`
`
`
`
` Proteina Requirement
`
` (g Amino Acids/kg/day)1
` Neonates
` 3 to 4
`
`
`
`
` a Protein is provided as amino acids.
`
` NOURESS contains 50 mg/mL of cysteine hydrochloride (equivalent to 34.5 mg/mL of
`
` cysteine). Therefore, the recommended dosage of NOURESS provides 15 mg cysteine/gram of
`
`
`
`
`
` amino acids for neonates.
`
`
`
`
`
` Dosage
`
`
`
`
`
`
`
`
`
` DOSAGE FORMS AND STRENGTHS
` 3
`
`
`
` Injection: 500 mg/10 mL (50 mg/mL) cysteine hydrochloride, USP as a clear, colorless, sterile
`
` solution in a single-dose vial.
`
`
`
` CONTRAINDICATIONS
` 4
`
`
`
` NOURESS is contraindicated in:
`
`Reference ID: 4533723
`
`
`4
`
`
`

`

` • 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.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` WARNINGS AND PRECAUTIONS
` 5
`
`
` 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 parenteral nutrition. 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 parenteral nutrition 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.
`
`
`
`
` 5.2
` Vein Damage and Thrombosis
` NOURESS must be diluted and used as an admixture in parenteral nutrition solutions. 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.
`
`
` 5.4
` Acid-Base Imbalance
` Administration of NOURESS may result in metabolic acidosis in neonates.
`
`
`
`
`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.
`
`
`
`
`
`
`Reference ID: 4533723
`
`5
`
`
`
`

`

`
`
` 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, including neonates, without
`
`
`
`
` preexisting liver disease who receive parenteral nutrition, 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.
`
`
`
`
` Instances of asymptomatic hyperammonemia have been reported in patients receiving parenteral
` nutrition 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)]
`
` Hyperammonemia is of special significance in infants, as it can result in neurocognitive delays.
`
`
`
`
` Monitor liver function parameters and ammonia levels during treatment with NOURESS.
` 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
` Aluminum Toxicity
` NOURESS contains aluminum that may be toxic.
`
`
`Aluminum may reach toxic levels with prolonged parenteral administration in patients with renal
`
`
`
`
`
`
`impairment. Neonates and 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 neonates and 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 NOURESS is not more than 0.25 mcg/kg/day when preterm and
`
`
`
`
`
`term neonates are administered the recommended maximum dosage of NOURESS (22 mg
`
`
`
`
`cysteine hydrochloride/g of amino acids and 4 g of amino acids/kg/day) [see Dosage and
`
`
`
`
`Administration (2.5)]. When prescribing NOURESS 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)].
`
`
` 5.7
` Monitoring and Laboratory Tests
`
` Monitor fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function,
` ammonia levels, blood count and coagulation parameters throughout treatment [see Dosage and
`
`
` Administration (2.4)].
`
`
`Reference ID: 4533723
`
`6
`
`
`
`

`

` ADVERSE REACTIONS
` 6
`
`
`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 Warning and Precautions (5.5)]
`
`
`
` • Aluminum toxicity [see Warnings and Precautions (5.6)]
`
`
`
`
` Adverse reactions with the use of cysteine hydrochloride injection were identified in clinical
`
`
` studies or postmarketing reports. Because these reactions are reported voluntarily from a
`
`population of uncertain size, it is not always possible to estimate their frequency reliably or to
`
`
`establish a causal relationship to drug exposure.
`
`
`• Metabolic acidosis
`
`• Local infusion site reactions, including a warm sensation, erythema, phlebitis, and
`
`thrombosis at the infusion site
`
`
`• Generalized flushing, fever, and nausea
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` USE IN SPECIFIC POPULATIONS
` 8
`
`
` Pregnancy
`
` 8.1
`
` Risk Summary
`
`
`
`
`NOURESS for use as an additive to amino acid solutions to meet nutritional requirements is not
`
`
`
`
`
`indicated for use in adults. Appropriate administration of NOURESS 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.
`
`
` 8.2
` Lactation
`
` Risk Summary
`
`
`
` NOURESS is used as an additive to amino acid solutions to meet nutritional requirements of
`
`
`
` neonates requiring total parenteral nutrition and is not indicated for use in adults. There are no
`
`
`
` data on the presence of cysteine hydrochloride in human or animal milk or the effects on milk
`
`
`
`
` production. Data available on the effects of cysteine hydrochloride on infants, either directly or
`
`
`
` through breastmilk, do not suggest a significant risk of adverse reactions from exposure.
`
`
`
`
`
`
`Reference ID: 4533723
`
`7
`
`
`
`

`

` 8.4
` Pediatric Use
`
`
`
`
`
` NOURESS is indicated for use as an additive to amino acid solutions to meet the nutritional
` requirements of neonates, including preterm infants, requiring total parenteral nutrition. The
`
`
` safety profile for NOURESS use in neonates includes risks of acid-base imbalance and
`
`
`
`
`
` hepatobiliary dysfunction.
`
`
`
` Acid-base imbalance, including metabolic acidosis, and liver dysfunction may occur with
` NOURESS administration in preterm infants. Frequent clinical and laboratory assessments are
`
`
`
`
`
`
`
` necessary to monitor and manage fluid balance, electrolyte concentrations, liver tests, and acid-
`
` base balance during parenteral nutrition therapy [see Warnings and Precautions (5.4)].
`
`
` Hyperammonemia is of special significance in neonates. This reaction appears to be related to a
`
` deficiency of the urea cycle amino acids of genetic or product origin. It is essential that blood
`
` ammonia be measured during treatment [see Warnings and Precautions (5.5)].
`
`
`
` Because of immature renal function, neonates including preterm infants, receiving prolonged
`
`
`
`
` parenteral nutrition with NOURESS may be at higher risk of aluminum toxicity [see Warnings
`
`
`
`
`
` and Precautions (5.7)].
`
`
`
`
`
` OVERDOSAGE
` 10
`
`
`
` 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, 5.8)].
`
`
`
`
`
`
` 11
`
`
` DESCRIPTION
` NOURESS (cysteine hydrochloride injection) is a sterile, nonpyrogenic solution for intravenous
`
`
`
`
`
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`
` use supplied as 500 mg/10 mL cysteine hydrochloride, USP in a single-dose vial.
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` Each mL of NOURESS contains 50 mg of cysteine hydrochloride, (equivalent to 34.5 mg of
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` cysteine), and 0.006 mL of hydrochloric acid (6M) in water for injection. Sodium hydroxide
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` and/or hydrochloric acid are used as needed to adjust the pH. The pH range of NOURESS is 1.0
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` to 1.5.
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` The active ingredient is cysteine hydrochloride. The chemical name of cysteine hydrochloride is
` L-cysteine hydrochloride monohydrate. Its molecular formula is C3H7NO2S • HCI • H2O and
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`molecular weight is 175.63. The chemical structure of L-cysteine hydrochloride monohydrate is
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`depicted below:
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`Reference ID: 4533723
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`Cysteine hydrochloride is a white crystalline powder soluble in water. Cysteine is a sulfur-
`containing amino acid and is prone to oxidation when exposed to air in aqueous solution, which
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`may convert cysteine to insoluble cystine resulting in precipitation over time.
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`NOURESS contains no more than 145 mcg/L of aluminum.
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` 12
` CLINICAL PHARMACOLOGY
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` 12.1 Mechanism of Action
` Endogenous cysteine is synthesized from methionine by the enzyme, cystathionase, via the trans­
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` sulfuration pathway, and serves as a precursor substrate for both glutathione and taurine.
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` NOURESS provides cysteine to the systemic circulation of neonates who require parenteral
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` nutrition and cannot synthesize adequate quantities of cysteine due to deficient cystathionase
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` 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
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` HOW SUPPLIED/STORAGE AND HANDLING
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` NOURESS (cysteine hydrochloride injection) is a clear, colorless, sterile and nonpyrogenic
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` solution supplied as follows:
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` 500 mg/10 mL (50 mg/mL) of cysteine hydrochloride, USP in single-dose vials (NDC 76014­
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` 006-05), packaged as 5 vials per carton (NDC 76014-006-05)
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` Store NOURESS at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to
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`86°F) [see USP Controlled Room Temperature].
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` Protect from light. Avoid excessive heat. Protect from freezing. If accidentally frozen, discard
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` the vial.
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` Vial stoppers are not made with natural rubber latex.
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` For storage of admixed solution see Dosage and Administration (2.3)
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` 17
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` PATIENT COUNSELING INFORMATION
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` Inform caregivers or home healthcare providers of the following risks of NOURESS:
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` • Pulmonary embolism due to pulmonary vascular precipitates [see Warnings and
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` Precautions (5.1)]
` • 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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`Reference ID: 4533723
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`• Hepatobiliary disorders [see Warning and Precautions (5.5)]
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`• Aluminum toxicity [see Warnings and Precautions (5.6)]
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`• Monitoring and laboratory tests [see Warnings and Precautions (5.7)]
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`Manufactured for:
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`Avadel Legacy Pharmaceuticals, LLC
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`Chesterfield, MO 63005
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` Rev. 12/19
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`Reference ID: 4533723
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