Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral [preservative free]:
Cystech: 500 mg [dye free]
Solution, Intravenous, as hydrochloride:
Generic: 50 mg/mL (10 mL [DSC], 50 mL [DSC])
Solution, Intravenous, as hydrochloride [preservative free]:
Elcys: 50 mg/mL (10 mL)
Pharmacology
Mechanism of Action
Endogenous cysteine is an amino acid synthesized from methionine via the transulfuration pathway, and serves as a precursor substrate for both glutathione and taurine. Exogenous cysteine provides cysteine to the systemic circulation of patients requiring parenteral nutrition who cannot synthesize adequate quantities due to deficient or insufficient cystathionase activity.
Use: Labeled Indications
Component of parenteral nutrition: Additive to amino acid solutions to meet the nutritional requirements of the following patients requiring parenteral nutrition: Infants (L-cysteine [generic] and Elcys) or adult and pediatric patients with severe liver disease who may have impaired enzymatic processes (Elcys only).
Contraindications
Known hypersensitivity to one or more amino acids or any component of the formulation
L-cysteine (generic): Additional contraindications: Hepatic coma; metabolic disorders involving impaired nitrogen utilization
Elcys: Additional contraindications: Inborn errors of amino acid metabolism; pulmonary edema or acidosis due to low cardiac output
Dosage and Administration
Dosing: Adult
Note: Correct severe fluid, electrolyte, and acid-base disorders prior to administration. Cysteine dose is based on recommended daily protein (as amino acid) requirement.
Component of parenteral nutrition: Elcys only: IV:
Maintenance (stable patients): 0.8 to 1 g amino acids/kg/day; 7 mg cysteine hydrochloride/g amino acids (equivalent to 5 mg cysteine/g amino acids).
Severe stress level (critically-ill patients): 1.5 to 2 g amino acids/kg/day; 7 mg cysteine hydrochloride/g amino acids (equivalent to 5 mg cysteine/g amino acids).
Dosing: Pediatric
Parenteral nutrition additive: Added as a fixed ratio to crystalline amino acid solution; dosage will vary with the daily amino acid dosage. Note: Correct severe fluid, electrolyte, and acid-base disorders prior to administration.
ASPEN Recommendations: Infants: IV: 30 to 40 mg of cysteine hydrochloride per gram of amino acids; a dose as low as 20 mg of cysteine hydrochloride per gram of amino acids may be adequate and should be used in times of cysteine shortage (ASPEN [Corkins 2015]; Plogsted 2015); current practice suggests supplementation should be continued through the first year of life; practice varies widely (ASPEN [Corkins 2015]; ASPEN [Mirtallo 2004]); consult institution-specific policies.
Product-specific dosing:
L-cysteine: Infants: IV: 40 mg cysteine hydrochloride per gram of amino acids.
Elcys:
Infants and Children ≤11 years: IV: 22 mg cysteine hydrochloride per gram of amino acids.
Children ≥12 years and Adolescents: IV: 7 mg cysteine per gram of amino acids.
Administration
IV: Administered as a component of peripheral parenteral or central parenteral nutrition; not for direct IV infusion. Central or peripheral administration of nutrition is dependent upon osmolality of the final solution; solutions with osmolarity ≥900 mOsm/L must be infused via central venous catheter. Ensure proper catheter/needle placement prior to and during infusion; avoid extravasation. May require use of inline filter (consult specific product labeling and/or individual institutional policies and procedures). Refer to manufacturer's labeling for additional information.
Storage
L-cysteine (generic): Store at 15°C to 30°C (59°F to 86°F). Do not freeze. Use admixture immediately or within 1 hour of admixing or may be refrigerated and used within 24 hours of the time of admixing.
Elcys: Store at 20°C to 25°C (68°F to 77°F); avoid excessive heat. Do not freeze. Once opened, limit use for admixing to ≤4 hours at 25°C (77°F). Use admixture immediately or may store refrigerated for up to 24 hours (must use admixture within 24 hours after removal from refrigeration). Protect from light. Discard any remaining admixture.
Test Interactions
May interfere with estimations of nitrogen containing substances; do not withdraw venous blood for blood chemistries through the peripheral infusion site.
Adverse Reactions
Frequency not defined.
Cardiovascular: Flushing
Central nervous system: Localized warm feeling
Dermatologic: Localized erythema
Endocrine & metabolic: Hyperammonemia, metabolic acidosis
Gastrointestinal: Nausea
Local: Infusion site reaction, injection site phlebitis, venous thrombosis at injection site
Miscellaneous: Fever
Warnings/Precautions
Concerns related to adverse effects:
- Hepatobiliary effects: Hepatobiliary disorders (eg, cholecystitis, cholelithiasis, cholestasis, cirrhosis, hepatic steatosis, fibrosis) may occur in patients without liver disease and may lead to hepatic failure. Increase in blood ammonia levels and hyperammonemia may also occur. Monitor liver function.
- Hyperammonemia: Asymptomatic hyperammonemia without overt liver dysfunction has been reported. Infants (birth to 2 years of age) are especially at risk. Monitor blood ammonia levels frequently in infants.
Disease-related concerns:
- Cardiac disease: Use with caution in patients with cardiac insufficiency.
- Diabetes: Hypertonic glucose solutions should be used with caution in patients with diabetes or prediabetic patients.
- Hepatic impairment: Use with caution in patients with hepatic impairment. Use in this patient population may result in hyperammonemia, metabolic alkalosis, prerenal azotemia, serum amino acid imbalances, stupor, and coma. In addition, IV infusion of parenteral nutrition in patients with impaired hepatic function may result in an increase in BUN (a modest rise is expected during increased protein intake).
- Renal impairment: Use with caution in patients with renal impairment; may require more frequent monitoring. IV infusion of parenteral nutrition in patients with impaired renal function will induce or augment an increase in BUN (a modest rise in BUN is to be expected during increased protein intake). Discontinue infusion, when clinically indicated, if BUN levels exceed normal postprandial limits and continue to rise.
- Pulmonary disease: Use with caution in patients with pulmonary disease.
Special populations:
- Infants: Metabolic acidosis has occurred in infants related to the additional acid provided by the "hydrochloride" component of cysteine; each 160 mg of L-cysteine delivers 1 mmol of hydrochloride; patients receiving the typical dose of L-cysteine of 40 mg for every gram of protein receive an additional 0.5 to 1 mEq/kg/day of chloride. To balance the extra hydrochloride ions and prevent acidosis, the use of acetate salts of electrolytes may be necessary (Cochran 1988; Heird 1988; Laine 1991; Plogsted 2015).
Dosage form specific issues:
- Aluminum: Contains aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal impairment. Premature infants are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses. See manufacturer's labeling.
- Precipitates: Periodically inspect solution, infusion set and catheter for precipitates. Pulmonary vascular precipitates causing pulmonary vascular emboli and pulmonary distress has been reported (some fatal). If signs of pulmonary distress occur, stop the infusion.
Other warnings/precautions:
- Acetate: Use acetate-containing solutions with extreme caution in patients with respiratory or metabolic alkalosis and in conditions in which there is an increased level or an impaired utilization of acetate such as severe hepatic impairment.
- Administration: For central or peripheral IV administration; peripheral administration of nutrition is dependent upon osmolality of solution.
- Potassium: Use potassium-containing solutions with extreme caution, if at all, in patients with severe renal failure, hyperkalemia, and in conditions where potassium retention is present (eg, metabolic acidosis).
- Sodium: Use sodium-containing solutions with extreme caution, if at all, in patients with severe renal impairment, heart failure, and conditions in which edema exists with sodium retention.
Monitoring Parameters
Fluid and electrolyte status, blood glucose, kidney and liver function, CBC and coagulation parameters throughout treatment, blood ammonia levels (if hepatic impairment present), triglycerides (if adding lipid emulsion), acid-base balance, serum proteins, blood culture, urine osmolarity and glucose, nitrogen intake; Monitor solution, infusion set, inline filter, and catheter for precipitates.
Pregnancy
Pregnancy Considerations
Cysteine is generally considered to be a nonessential amino acid in adults because it can be synthesized from methionine (an essential amino acid). The RDA for methionine + cysteine is increased in pregnant females (IOM 2005).
Appropriate use as an additive to amino acid solutions in pregnant females requiring parenteral nutrition would not be expected to cause adverse maternal or fetal outcomes.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
