Cysteine is a sulfur-containing amino acid indicated to meet the nutritional needs of neonates requiring parenteral nutrition (PN) and of adults and pediatric patients with severe liver disease who may have impaired enzymatic processes and require PN. Cysteine can also be added to amino acid solutions to provide a more complete profile of amino acids for protein synthesis. Cysteine is considered to be a conditionally essential amino acid in neonates due to the biochemical immaturity of the enzyme necessary to convert methionine to cysteine in these patients. Cysteine injection should only be used for admixing in PN; it should not be given by direct IV administration. Cysteine injection is FDA-approved for patients as young as neonates, including premature neonates.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Cysteine injection must be diluted and used as an admixture in parenteral nutrition solutions; do not administer by direct IV infusion.
-Follow proper admixing sequence as related to parenteral nutrition to minimize pH-related issues.
-Use a dedicated line for peripheral nutrition solutions. Intravenous lipid emulsions can be infused concurrently into the same vein by a Y connector located near the infusion site; flow rates of each solution should be controlled separately by infusion pumps.
-For administration without lipids, use a 0.22-micron filter.
-For administration with lipids, do not use administration sets and lines that contain DHEP; administration sets that contain PVC components have DEHP as a plasticizer.
-Storage: Use of cysteine injection for admixing should be limited to up to 4 hours at room temperature after container has been penetrated; discard any remaining drug. After mixing in parenteral nutrition solutions, admixtures are stable for 24 hours under refrigeration; after removal from refrigeration, use solution promptly and complete the infusion within 24 hours. Discard any remaining admixture.
The most common adverse reactions associated with use of cysteine injection include a local injection site reaction, such as warm sensation, erythema, phlebitis, and thrombosis, generalized flushing, fever, and nausea.
Administration of cysteine may result in metabolic acidosis in premature neonates. Administration of amino acid solutions to patients with renal or hepatic impairment may induce an increase in BUN; a modest increase in BUN normally occurs because of increased protein intake. Administration of amino acid solutions to patients with hepatic impairment may result in metabolic alkalosis, prerenal azotemia, hyperammonemia, stupor, and coma.
Hepatobiliary adverse reactions reported with parenteral nutrition include cholecystitis, cholelithiasis, cholestasis, hepatic steatosis, fibrosis, and cirrhosis (intestinal failure-associated liver disease [IFALD] or parenteral nutrition-associated liver disease [PNALD]), potentially leading to hepatic failure. Monitor liver function parameters closely in patients receiving parenteral nutrition, particularly premature infants.
Cysteine injection contains no more than 150 mcg/L of aluminum (content varies with specific product). However, aluminum toxicity may occur with prolonged administration in high-risk patients, including those with renal impairment and premature neonates. Premature neonates are at particular risk for aluminum toxicity because of immature renal function, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with renal impairment, who receive parenteral aluminum at rates more than 4 to 5 mcg/kg/day, may develop aluminum toxicity (central nervous system and bone toxicity). Tissue loading may occur at lower administration rates.
Cysteine injection is contraindicated in patients with known hypersensitivity to 1 or more amino acids, patients with inborn errors of amino acid metabolism (i.e., galactosemia, hereditary fructose intolerance, phenylketonuria) due to risk of severe metabolic or neurologic complications, and patients with pulmonary edema or metabolic acidosis due to low cardiac output.
Cysteine injection must be diluted and used as an admixture in parenteral nutrition solutions; do not administer by direct IV infusion. Hypertonic solutions (osmolarity of 900 mOsm/L or greater) should be infused through a central catheter. Infusion of hypertonic nutrient solutions through a peripheral vein may result in vein irritation/damage, thrombophlebitis, and/or thrombosis. Remove the IV catheter as soon as possible if thrombophlebitis occurs.
Intravenous infusion of amino acids may cause an increase in BUN, especially in patients with renal disease or renal impairment. Monitor renal function parameters periodically through treatment and discontinue infusion if BUN concentrations exceed normal postprandial limits and continue to increase. A modest rise in BUN normally occurs because of increased protein intake. Cysteine injection contains aluminum (approximately 120 to 150 mcg/L; content varies with specific product chosen) and aluminum toxicity may occur with prolonged administration in high-risk patients, including those with renal impairment and premature neonates. Premature neonates are at particular risk for aluminum toxicity because of immature renal function, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with renal impairment, who receive parenteral aluminum at rates more than 4 to 5 mcg/kg/day, may develop aluminum toxicity (central nervous system and bone toxicity). Tissue loading may occur at lower administration rates.
Administration of cysteine injection may result in acid/base imbalance, including metabolic acidosis and metabolic alkalosis. Preterm infants may be at particular risk. Monitor acid-base status frequently during parenteral nutrition therapy. Electrolyte supplements may be necessary.
Use amino acid solutions with caution in patients with hepatic disease. Administration to patients with hepatic impairment has resulted in serum amino acid imbalances, metabolic alkalosis, prerenal azotemia, hyperammonemia, stupor, and coma. Hyperammonemia is of particular concern in infants, as it can result in neurocognitive delays. Hepatobiliary disorders, including cholecystitis, cholelithiasis, cholestasis, hepatic steatosis, fibrosis, and cirrhosis (intestinal failure-associated liver disease [IFALD] or parenteral nutrition-associated liver disease [PNALD]), potentially leading to hepatic failure, may occur in patients without preexisting hepatic disease who receive parenteral nutrition. Monitor liver function parameters and ammonia concentrations frequently during treatment, particularly in infants and patients with hepatic impairment.
Appropriate administration of cysteine is not expected to cause major birth defects, miscarriage or adverse maternal or fetal outcomes during pregnancy. Animal reproduction studies have not been conducted with cysteine.
Data available on the effects of cysteine on infants, either directly or through breastmilk, do not suggest a significant risk of adverse events from exposure. Although there are no data on the presence of cysteine in human milk or the effects on human milk production, appropriate administration of cysteine is not expected to cause harm to an infant who is breast-feeding.
-Cysteine is added as a fixed ratio to amino acid solutions; the dosage will vary with the daily amino acid dosage.
-The dosage of cysteine 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 calories given orally/enterally to the patient.
For nutritional supplementation as an additive to amino acid solutions in infants requiring parenteral nutrition and for other patients with severe liver disease who may have impaired enzymatic processes and require parenteral nutrition:
Intravenous dosage:
Adults: 7 mg per g of Amino Acids/day IV; individualize dosage based on specific patient parameters.
Children and Adolescents 12 to 17 years: 7 mg per g of Amino Acids/day IV; individualize dosage based on specific patient parameters.
Children 1 to 11 years: 22 mg per g of Amino Acids/day IV; individualize dosage based on specific patient parameters.
Infants: 30 to 40 mg per g of Amino Acids/day IV is the usual dosage. However, doses as low as 20 mg per g of Amino Acids/day IV may be adequate and are recommended by ASPEN in times of cysteine shortage. FDA-approved dosage range: 22 to 40 mg per g of Amino Acids/day IV. Guidelines generally recommend that supplementation with cysteine be continued through the first year of life, although practice varies widely.
Neonates: 30 to 40 mg per g of Amino Acids/day IV is the usual dosage. However, doses as low as 20 mg per g of Amino Acids/day IV may be adequate and are recommended by ASPEN in times of cysteine shortage. FDA-approved dosage range: 22 to 40 mg per g of Amino Acids/day IV. Guidelines generally recommend that supplementation with cysteine be continued through the first year of life, although practice varies widely.
Maximum Dosage Limits:
-Adults
7 mg per g of Amino Acids/day IV.
-Geriatric
7 mg per g of Amino Acids/day IV.
-Adolescents
7 mg per g of Amino Acids/day IV.
-Children
12 years: 7 mg per g of Amino Acids/day IV.
1 to 11 years: 22 mg per g of Amino Acids/day IV.
-Infants
40 mg per g of Amino Acids/day IV is usual maximum dosage; however, for ELCYS, the manufacturer recommends a maximum dosage of 22 mg per g of Amino Acids/day IV.
-Neonates
40 mg per g of Amino Acids/day IV is usual maximum dosage; however, for ELCYS, the manufacturer recommends a maximum dosage of 22 mg per g of Amino Acids/day IV.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; the cysteine dose should be individualized based on clinical goals. Monitor liver function more closely in these patients.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; the cysteine dose should be individualized based on clinical goals. Monitor renal function more closely in these patients.
*non-FDA-approved indication
There are no drug interactions associated with Cysteine products.
Cysteine is a sulfur-containing amino acid. 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. Cysteine injection provides cysteine for patients who require parenteral nutrition and cannot synthesize adequate quantities of cysteine due to insufficient or inadequate cystathionase activity. Cysteine is considered a conditionally essential amino acid in neonates, particularly premature neonates, due to the biochemical immaturity of the enzyme necessary to convert methionine to cysteine in these patients. Cysteine lowers the pH of parenteral nutrition solutions, thereby increasing the solubility of supplemental calcium and phosphorus.
Cysteine is administered intravenously as part of amino acid solutions in patients requiring parenteral nutrition. There is 1 mmol HCl for each 160 mg of cysteine hydrochloride.