Acetylcysteine, the N -acetyl derivative of the naturally occurring amino acid, l-cysteine, is an antidote for acetaminophen overdosage as well as a mucolytic agent and sulfhydryl donor.102, 108, 120
Antidote for Acetaminophen Overdosage
Acetylcysteine is used orally or by IV infusion as an antidote to prevent or lessen hepatic injury, which may occur following the ingestion of a potentially hepatotoxic quantity of acetaminophen.102, 103, 108 Acetylcysteine injection is designated an orphan drug by FDA for the treatment of moderate to severe acetaminophen overdosage.121
When administered within 8 hours of acetaminophen ingestion, oral or IV acetylcysteine can effectively prevent or minimize hepatotoxicity associated with acute overdosage of acetaminophen.102, 108, 109 The effectiveness of oral acetylcysteine depends on early administration, with benefits seen principally in patients treated within 16 hours of overdose.102 The manufacturer of oral acetylcysteine states that it is essential to initiate treatment as soon as possible after the overdose, with treatment beginning within 24 hours of ingestion.102 According to the manufacturer of acetylcysteine injection , the critical ingestion-treatment interval for maximal protection against severe hepatic injury is between 0 and 8 hours.108 Efficacy diminishes progressively after 8 hours and treatment initiation between 15 and 24 hours after ingestion of acetaminophen yields limited efficacy.108 However, acetylcysteine does not appear to worsen the patient's condition and should not be withheld, particularly since the reported time of ingestion may be incorrect.108
Clinical studies have clearly demonstrated efficacy of orally administered acetylcysteine, and oral administration may result in higher intrahepatic concentrations of the drug than IV administration.109 However, oral administration often produces nausea and vomiting, and administration of antiemetic agents may be needed to complete therapy; IV administration obviates potential difficulties associated with administration of an antiemetic.109 Intravenous administration achieves higher plasma concentrations compared with oral administration; it has been suggested that higher plasma concentrations may exert useful extrahepatic effects.109 However, anaphylactoid reactions have been reported following IV administration.108, 109
In all cases of suspected acetaminophen overdosage, a regional poison control center (800-222-1222) may be contacted immediately for assistance in diagnosis and for directions in the use of acetylcysteine as an antidote.108 Consult the manufacturer's labeling for information on appropriate acetaminophen assay methodology and supportive treatment for acetaminophen overdosage.102
Acetylcysteine is used by oral inhalation or intratracheal instillation as a mucolytic agent in the adjunctive treatment of patients with abnormal, viscid, or inspissated mucous secretions in such conditions as acute and chronic bronchopulmonary disorders (e.g., pneumonia, bronchitis, emphysema, tracheobronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis, primary amyloidosis of the lung); atelectasis caused by mucus obstruction; pulmonary complications of cystic fibrosis; pulmonary complications of surgery; and post-traumatic chest conditions.102 Acetylcysteine is also used during anesthesia and in the preparation of patients for bronchograms, bronchospirometry, bronchial wedge catheterization, and other diagnostic bronchial studies.102 The drug also is used in tracheostomy care to prevent endotracheal crusting and to reduce or eliminate the need for bronchoscopy.102
Prevention of Nephropathy Associated with Radiographic Contrast Media
Acetylcysteine has been used to prevent radiographic contrast media-induced nephropathy†.100, 101, 110, 111, 112, 113, 114, 116, 117, 122, 123, 124, 125, 126, 127 The most important risk factor for contrast-induced acute kidney injury (CI-AKI) is preexisting severe renal insufficiency.125, 126, 129, 130, 131 Other risk factors may include diabetes mellitus, older age, low hematocrit, hemodynamic instability, or conditions resulting in low effective circulating blood volume (e.g., heart failure, left ventricular systolic dysfunction).110, 113, 114, 123, 124, 126, 127, 129, 130, 131 In addition, the risk of contrast media-induced decreases in renal function depends on contrast media properties (high osmolality, ionic compound, increased viscosity) and administration of a larger volume of contrast media.110, 116, 123, 124, 130
Various strategies have been investigated for prophylaxis of contrast media-induced nephropathy.110, 117, 124, 125, 130, 131 Available evidence supports use of hydration as a prophylactic measure.110, 117, 123, 130, 131 Several pharmacologic agents, including acetylcysteine, have been evaluated for prophylaxis of contrast media-induced nephropathy.110, 111, 112, 117, 122, 123, 124, 125, 126, 127, 130, 131
Some controlled studies and meta-analyses have suggested benefit of acetylcysteine for prevention of CI-AKI; however, a large amount of unexplained heterogeneity among the studies has been observed.110, 117, 122, 123, 124, 125 Two large randomized controlled trials including a total of >7000 patients undergoing angiography showed no effect of oral acetylcysteine for prevention of CI-AKI.126, 127 Homogeneous results indicating no benefit of acetylcysteine for prevention of CI-AKI were seen when only large studies (with ≥500 patients) were included.122 In an analysis of randomized clinical trials of any size in which mortality (41 trials) or need for kidney replacement (45 trials) was assessed, no benefit of acetylcysteine on these clinical outcomes was reported.122 The proposed mechanism of the drug's effects in preventing CI-AKI has been called into question, and the possibility that reductions in creatinine associated with acetylcysteine are due to analytical interference rather than an effect on kidney function has been suggested, highlighting the limitations of using creatinine measurements as a surrogate for clinical outcomes.122, 128, 129
Based on insufficient evidence of its effectiveness, use of acetylcysteine for prevention of CI-AKI is not recommended in the 2021 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography & Interventions (ACC/AHA/SCAI) Guideline for Coronary Artery Revascularization.130 In addition, the 2023 American College of Radiology (ACR) Manual on Contrast Media does not recommend acetylcysteine for prevention of CI-AKI in patients receiving IV contrast media.131
As an antidote for acetaminophen overdosage, acetylcysteine is administered as an oral solution or by IV infusion.102, 103, 108 As a mucolytic agent, acetylcysteine, usually in a 10-20% solution, may be administered by nebulization, direct instillation, or intratracheal instillation.102
Acetylcysteine has been administered orally100, 110, 117 or by IV infusion110, 117 for prevention ofradiographic contrast media-induced nephropathy†.
For the treatment of acetaminophen overdosage, acetylcysteine may be administered orally as a 5% solution prepared from the commercially available 20% solution.102 To prepare the solution, dilute the 20% solution 1:3 with a diet cola soft drink or other diet soft drink; if administered via a gastric tube or Miller-Abbott tube, water may be used as the diluent.102 Diluted solutions should be freshly prepared and used within 1 hour.102 Store the solution at 20-25°C (excursions permitted to 15-30°C).102 Store opened vials of undiluted solution in the refrigerator and use within 96 hours.102 Do not store admixtures.102
Alternatively, an oral solution may be prepared from commercially available packets containing 500 mg or 2.5 g of acetylcysteine (available as acetylcysteine lysine [Legubeti®]).103 To prepare the oral solution, dissolve the appropriate number of packets in the volume of caffeine-free diet cola or other diet soft drink, as indicated in dosing tables provided in the prescribing information.103 The Legubeti® preparation is for oral administration only and should not be used for nebulization or intratracheal instillation.103
Store the packets at 20-25°C (excursions permitted to 15-30°C).103 Use the prepared solution within 1 hour after preparation.103
If the patient is persistently unable to retain orally administered acetylcysteine, the drug may be administered via a duodenal or nasoduodenal tube; alternatively, an IV formulation may be considered.102, 103
Acetylcysteine injection concentrate must be diluted in 5% dextrose injection, 0.45% sodium chloride injection, or sterile water for injection prior to IV infusion.108 Acetylcysteine solution for inhalation or oral administration should not be administered by injection.102
Store the injection concentrate at 20-25°C.108 Do not use previously opened vials of acetylcysteine injection concentrate.108
The appropriate dose of acetylcysteine should be withdrawn from the required number of vials and added to an appropriate volume of 5% dextrose, 0.45% sodium chloride injection, or sterile water for injection (see Table 1).108 The total volume administered should be adjusted for patients weighing <40 kg or requiring fluid restriction.108 In patients weighing ≤20 kg, the recommended volume of diluent is 3, 7, and 14 mL/kg for the loading, second, and third doses, respectively.108
Volume of Diluent for Indicated Dose | - | - | |
|---|---|---|---|
Patient's Weight (kg) | Loading Dose | First Maintenance Dose | Second Maintenance Dose |
≥41 | 200 mL | 500 mL | 1 L |
21-40 | 100 mL | 250 mL | 500 mL |
20 | 60 mL | 140 mL | 280 mL |
15 | 45 mL | 105 mL | 210 mL |
10 | 30 mL | 70 mL | 140 mL |
5 | 15 mL | 35 mL | 70 mL |
Dilution in the 3 compatible diluents results in different osmolarity of the solution for IV administration (see Table 2).108 Adjust osmolarity to a physiologically safe level (generally ≥150 mOsmol/L in pediatric patients).108
Acetylcysteine Concentration | Osmolarity in Sterile Water for Injection | Osmolarity in 0.45% Sodium Chloride Injection | Osmolarity in 5% Dextrose Injection |
|---|---|---|---|
7 mg/mL | 91 mOsmol/L | 245 mOsm/L | 343 mOsm/L |
24 mg/mL | 312 mOsmol/L | 466 mOsmol/L | 564 mOsmol/L |
Following dilution with 5% dextrose, 0.45% sodium chloride injection, or sterile water for injection, solutions are stable at controlled room temperature for 24 hours.108 The presence of a light pink to purple color in the diluted solution does not affect the quality of the product.108
When acetylcysteine is used for the treatment of acetaminophen overdosage, the manufacturer recommends that diluted solutions of the drug be infused IV as a loading dose given over 1 hour, followed by a first maintenance dose given over 4 hours, and then a second maintenance dose given over 16 hours.108
Oral Inhalation and Intratracheal Instillation
When used as a mucolytic agent by oral inhalation or intratracheal instillation, the commercially available 20% solution of acetylcysteine may be administered undiluted or may be diluted with sodium chloride injection, sodium chloride inhalation solution, sterile water for injection, or sterile water for inhalation.102 The 10% solution of acetylcysteine may be used undiluted.102 Solutions of acetylcysteine do not contain a preservative and care should be taken to minimize contamination of the sterile solution.102
The presence of a light purple color in acetylcysteine sodium oral inhalation solutions does not appreciably affect potency of the drug; however, it is best to utilize equipment constructed with plastic or glass and with stainless steel or another nonreactive metal when administering acetylcysteine by nebulization.102 The manufacturer states that solutions of acetylcysteine sodium are physically and/or chemically incompatible with solutions containing amphotericin B, tetracyclines, erythromycin lactobionate, or ampicillin sodium.102 When one of these anti-infectives is to be administered by aerosol inhalation, it should be nebulized separately.102 Acetylcysteine solutions are also physically incompatible with iodized oil, trypsin, chymotrypsin, and hydrogen peroxide.102 Consult the manufacturer's prescribing information for additional information on the physical and chemical compatibility of acetylcysteine solutions with other drugs.102
When acetylcysteine is used as a mucolytic agent, the method of administration depends on the condition being treated and the equipment available.102 When administered by nebulization, compressed air should be used to provide pressure.102 Oxygen may also be used but the usual precautions in patients with severe respiratory disease and CO2 retention should be observed.102 Ultrasonic nebulizers may also be used to administer acetylcysteine.102 Hand-bulb nebulizers are not recommended because the output is usually too small and the particle size is often too large.102 Acetylcysteine may be administered using conventional nebulizers made of plastic or glass; however, certain materials used in nebulization equipment react with acetylcysteine (e.g., iron, copper, rubber), and any part of the equipment that may come in contact with acetylcysteine should be made of glass, plastic, or a metal that does not react with the drug.102 The nebulized solution may be breathed directly or a plastic face mask, face tent, mouthpiece, oxygen tent, or head tent may be used.102 Nebulizers may also be fitted to intermittent positive pressure breathing (IPPB) machines.102 Acetylcysteine solutions should not be placed directly into the chamber of heated (hot-pot) nebulizers.102 A heated nebulizer may be part of the nebulizer assembly to provide a warm saturated atmosphere if acetylcysteine is introduced by means of a separate unheated nebulizer and the usual precautions for administration of warm saturated nebulae are observed.102 When acetylcysteine is nebulized continuously with a dry gas, the solution may become over-concentrated and nebulization may be impaired; after three-fourths of the initial volume has been nebulized, it is advisable to dilute the remaining solution with an approximately equal volume of sterile water for injection.102 Nebulizing equipment should be cleaned immediately after use since residues may occlude fine orifices or corrode metal parts.102
Store the solution at 15-30°C.102 Store opened vials of undiluted solution in the refrigerator and use within 96 hours.102 Do not store admixtures.102
The manufacturer's labeling should be consulted for detailed information on equipment requirements and recommendations for nebulization of acetylcysteine.102
Antidote for Acetaminophen Overdosage
When indicated, initiate acetylcysteine therapy as soon as possible with an IV or oral loading dose in adults and pediatric patients.102, 103, 108, 109
When acetylcysteine is administered orally for the treatment of acetaminophen overdose, a loading dose of 140 mg/kg is recommended in adults and pediatric patients.102, 103 To complete a full course of therapy, the loading dose is followed by oral maintenance doses of 70 mg/kg every 4 hours for 17 doses.102, 103 If a patient receiving oral acetylcysteine vomits within 1 hour of administration of a loading or maintenance dose, the dose should be repeated.102, 103
Alternatively, acetylcysteine can be administered by IV infusion.108 Acetylcysteine is administered as a loading dose of 150 mg/kg infused over 1 hour, followed by a first maintenance dose of 50 mg/kg infused over 4 hours, and then a second maintenance dose of 100 mg/kg infused over 16 hours (for a full course consisting of 300 mg/kg administered IV over 21 hours).105, 106, 108, 109 Dosage of IV acetylcysteine for patients weighing <5 kg or >100 kg has not been studied.108
An IV regimen that delivers a total dose of 980 mg/kg over 48 hours† also has been used.105, 106, 109 This regimen involves IV administration of a loading dose of 140 mg/kg over 1 hour, followed by IV maintenance doses of 70 mg/kg every 4 hours for 12 additional doses.105, 106 Each maintenance dose is infused over 1 hour.105
When nebulized into a face mask, mouthpiece, or tracheostomy, as in the treatment of bronchopulmonary disease or cystic fibrosis, the usual adult or pediatric dosage of acetylcysteine is 3-5 mL of the 20% solution or 6-10 mL of the 10% solution 3 or 4 times daily; however, 1-10 mL of the 20% solution or 2-20 mL of the 10% solution may be given every 2-6 hours.102 When a closed tent or croupette is used, maintenance of a heavy mist may require up to 300 mL of the 10 or 20% solution for a single, continuous treatment.102 The volume of acetylcysteine solution should be sufficient to maintain a very heavy mist in the tent or croupette for the desired period.102 Administration for intermittent or continuous prolonged periods, including overnight, may be desirable.102
When acetylcysteine is administered by direct instillation in adults or pediatric patients, 1-2 mL of a 10-20% solution may be given as often as every hour.102
When acetylcysteine is administered by instillation through a percutaneous intratracheal catheter in adults or pediatric patients, 1-2 mL of the 20% solution or 2-4 mL of the 10% solution may be given every 1-4 hours via a syringe attached to the catheter.102
When acetylcysteine is administered by instillation through a catheter into the trachea in adults or pediatric patients, 2-5 mL of the 20% solution may be given via a syringe attached to the catheter.102
Prior to diagnostic bronchial studies in adults or pediatric patients, 2 or 3 doses of 1-2 mL of the 20% solution or 2-4 mL of the 10% solution may be administered by nebulization or intratracheal instillation.102
When acetylcysteine is used in adults or pediatric patients for tracheostomy care, 1-2 mL of a 10-20% solution may be instilled into the tracheostomy every 1-4 hours.102
Prevention of Contrast Media-induced Nephropathy
For theprevention of nephropathy associated with administration of radiographic contrast media† in adults, an oral acetylcysteine dosage of 600 mg twice daily, given the day before and on the day of the administration of contrast media, has been used, for a total of 4 doses.100, 110, 117, 122 Other oral dosages have been investigated.110, 117, 126, 127 IV administration of acetylcysteine also has been investigated.110, 117, 122
Limited data in subjects with hepatic impairment suggest no clinically meaningful effects of hepatic impairment on acetylcysteine pharmacokinetics.108 The manufacturers make no specific dosage recommendations for patients with hepatic impairment.102, 108
The manufacturers make no specific dosage recommendations for patients with renal impairment.102, 108 Hemodialysis may remove some acetylcysteine.108
Encephalopathy Due to Hepatic Failure
If encephalopathy resulting from hepatic failure occurs during oral acetylcysteine therapy, discontinue the drug to avoid further administration of nitrogenous substances.102 There are no available data indicating that acetylcysteine adversely affects hepatic failure; however, this remains a theoretical possibility.102
An increased volume of liquefied bronchial secretions may develop following oral inhalation or intratracheal instillation and the airway may become occluded.102 If cough is inadequate to maintain an open airway, institute mechanical suction or endotracheal aspiration (with or without bronchoscopy).102 Observe asthmatic patients closely.102
Irritation of the tracheal and bronchial tracts and hemoptysis have occurred following administration of acetylcysteine; however, such findings are not uncommon in patients with bronchopulmonary disease and a causal relationship has not been established.102
Chest tightness and bronchoconstriction have been reported with acetylcysteine.102 Clinically overt acetylcysteine-induced bronchospasm occurs rarely and unpredictably, even in patients with asthmatic bronchitis or bronchitis complicating bronchial asthma.102 Occasionally, patients receiving oral inhalation of acetylcysteine develop increased airway obstruction of varying and unpredictable severity.102 Patients who have had such reactions to previous therapy with acetylcysteine may not react during subsequent therapy with the drug, and patients who have had inhalation treatments with acetylcysteine without incident may react to subsequent therapy.102
If bronchospasm occurs, give a bronchodilator by nebulization.102 If bronchospasm progresses, discontinue acetylcysteine immediately.102
When administered by IV infusion, use with caution in patients with asthma or history of bronchospasm.108
Serious hypersensitivity reactions (e.g., rash, hypotension, wheezing, dyspnea), including death in a patient with asthma, have been reported in patients receiving IV acetylcysteine.108
Acute flushing and erythema also have been reported; these reactions generally occur 30-60 minutes after initiation of the infusion and resolve despite continued infusion.108 Reactions to acetylcysteine that involve symptoms other than flushing and erythema should be considered anaphylactoid reactions and treated accordingly.108
If a severe hypersensitivity reaction occurs during IV acetylcysteine therapy, immediately discontinue IV acetylcysteine and initiate appropriate treatment.108 If less severe hypersensitivity reactions occur, manage according to the severity; management may include temporary interruption of acetylcysteine infusion and/or administration of antihistamines.108 Once treatment of the hypersensitivity reaction has been initiated, carefully reinstitute IV acetylcysteine.108 If the hypersensitivity reaction recurs or increases in severity, discontinue IV acetylcysteine and consider alternative management.108
Closely monitor patients with asthma during initiation of and throughout IV acetylcysteine therapy.108
Generalized urticaria has been reported rarely in patients receiving oral acetylcysteine for acetaminophen overdosage.102 If urticaria or other allergic symptoms occur during oral therapy, discontinue the drug unless it is considered essential and allergic symptoms can be otherwise controlled.102
Acquired sensitization to acetylcysteine has been reported rarely.102 Sensitization has not been confirmed by patch testing.102 Sensitization to acetylcysteine and dermal eruptions have been reported by several inhalation therapists after frequent and extended exposure to the drug.102
Oral administration may result in vomiting or may aggravate vomiting associated with acetaminophen overdosage.102 Administration of dilute acetylcysteine solutions may minimize the tendency of the drug to aggravate vomiting.102 Acetylcysteine solutions have a slight, disagreeable odor.102
Evaluate patients at risk of gastric hemorrhage (e.g., those with esophageal varices or peptic ulcers) with regard to relative risks of upper GI hemorrhage and acetaminophen-induced hepatotoxicity; provide acetylcysteine treatment accordingly.102
IV administration of acetylcysteine can cause fluid overload, possibly resulting in hyponatremia, seizures, and death.108 To avoid fluid overload, follow recommendations for dilution and reduce the volume of diluent as needed.108
Nebulization Administration Precautions
A slight disagreeable odor that tends to become unnoticeable, and stickiness on the face with use of a face mask (easily removed with water) can occur with administration by nebulization.102
An increased concentration of the drug in the nebulizer due to evaporation of the solvent occurs with continued nebulization of acetylcysteine solution with a dry gas.102 If extreme concentration impedes nebulization and efficient delivery of the drug, dilute the nebulizing solution with appropriate amounts of sterile water for injection as concentration occurs to resolve this problem.102
Reproductive studies in rabbits using oral acetylcysteine dosages of 500 mg/kg daily (2.6 times the human mucolytic dose) on days 6 through 16 of gestation revealed no teratogenicity.102 Studies in rabbits exposed for 30-35 minutes twice daily to a nebulized solution containing acetylcysteine and isoproterenol hydrochloride on days 6 through 18 of pregnancy revealed no teratogenicity.102 Perinatal and postnatal studies in rats exposed to a nebulized solution containing acetylcysteine and isoproterenol did not reveal harm to the fetus or newborns.102 Acetylcysteine has been reported to cross the placenta in humans following oral or IV administration.108 However, there are no adequate and controlled studies to date using acetylcysteine in pregnant women, and the drug should be used during pregnancy only when clearly needed.102
Limited published case reports and case series of pregnant women exposed to acetylcysteine during various trimesters are not sufficient to inform any drug-associated risk.108 Delaying treatment of acetaminophen overdose may increase the risk of maternal or fetal morbidity and mortality.108 Reproduction studies in rats and rabbits following oral administration of acetylcysteine during the period of organogenesis at doses similar to the total IV dose (based on body surface area) did not result in any adverse effects to the fetus.108
It is not known whether acetylcysteine is distributed into human milk;105, 108 the drug's effects on the breast-fed infant or on milk production also are not known.108 Consider the developmental and health benefits of breast-feeding along with the mother's need for acetylcysteine and any potential adverse effects on the breast-fed child from acetylcysteine or from the underlying maternal condition.108 Use acetylcysteine with caution in nursing women.108
Based on pharmacokinetic data, acetylcysteine should be nearly completely cleared 30 hours after IV administration of the drug.108 Breast-feeding women may consider pumping and discarding their milk for 30 hours after administration.108
Efficacy of IV acetylcysteine as an antidote for acetaminophen overdosage in pediatric patients appears to be similar to that in adults.108 Safety and efficacy of IV acetylcysteine in pediatric patients have not been established by adequate and well-controlled studies; use of IV acetylcysteine as an antidote for acetaminophen overdosage in pediatric patients ≥5 kg is based on clinical practice.108
Insufficent experience with IV acetylcysteine in patients 65 years of age or older in order to determine whether these patients respond differently than younger adults.108
Common adverse effects following oral administration of acetylcysteine include nausea, vomiting, and other GI symptoms.102
Common adverse effects following IV administration of acetylcysteine reported in >2% of patients include rash, urticaria/facial flushing, and pruritus.108
Common adverse effects following oral inhalation or intratracheal instillation of acetylcysteine include stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction.102
Possible interference with absorption of oral acetylcysteine;102, 119 however, usual dosage of acetylcysteine is appropriate in patients given activated charcoal (higher dosages not necessary).105, 106 The manufacturer recommends that if activated charcoal has been administered, lavage should be performed before administering oral acetylcysteine treatment.102
The exact mechanism(s) by which acetylcysteine prevents or minimizes acetaminophen-induced hepatotoxicity has not been fully determined.108 Acetylcysteine may protect the liver following acetaminophen overdosage by maintaining or restoring glutathione levels or by acting as an alternate substrate for conjugation with (and detoxification of) a toxic intermediate metabolite of acetaminophen.102
Acetylcysteine reduces the viscosity of purulent and nonpurulent pulmonary secretions and facilitates their removal by coughing, postural drainage, or mechanical means.102 The mucolytic effect of the drug has been shown to depend on the free sulfhydryl group, which is thought to reduce disulfide linkages of mucoproteins.102
The exact mechanism(s) by which acetylcysteine might prevent radiographic contrast media-associated nephrotoxicity is unclear.100, 101, 110, 125 It has been suggested that since radiographic contrast media-induced renal toxicity may be related to formation of reactive oxygen species or to reduced antioxidant activity; acetylcysteine, a thiol-containing antioxidant, may reduce the ability of the generated oxygen free radicals to damage cells by acting as an oxygen free-radical scavenger.100, 123, 125, 129 In addition, the drug also may increase the biologic effects of nitric oxide by combining with the oxide to form S -nitrosothiol, a potent vasodilator.101, 123, 129 The interaction of acetylcysteine and nitric oxide may limit the production of the damaging peroxinitrate radical, because acetylcysteine would compete with the superoxide radical for nitric oxide.101 Acetylcysteine also increases the expression of nitric oxide synthase and therefore may improve blood flow.101, 123, 125 Evidence suggesting the possibility that decreases in serum creatinine associated with acetylcystine may occur in the absence of any actual effect on kidney function has been observed.129
Following oral administration (e.g., when used as an antidote for acetaminophen overdosage), acetylcysteine is absorbed from the GI tract, with peak plasma concentrations achieved within 1-2 hours.119 The drug is 50-87% bound to plasma proteins.108, 119 Acetylcysteine is deacetylated to cysteine and oxidized to yield diacetylcysteine;102, 108 cysteine is further metabolized to form glutathione and other metabolites.108 Following oral administration of acetylcysteine, a mean elimination half-life of 6.25 hours has been reported.119 Following IV administration of acetylcysteine, a mean elimination half-life of 5.6 hours has been reported in adults.108 Elimination of acetylcysteine is principally (70%) nonrenal.108, 119 Following IV administration of acetylcysteine in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), or severe (Child-Pugh class C) hepatic impairment, mean elimination half-life is increased by 80% compared with normal subjects.108 Mean clearance is decreased by 30% and systemic exposure increased 1.6-fold in subjects with hepatic impairment compared to subjects with normal hepatic function.108 These changes are not considered clinically meaningful.108 Hemodialysis may remove some of total acetylcysteine.108
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral Inhalation, Intratracheal Instillation, and Oral | Solution | 100 mg/mL (10%)* | Acetylcysteine Solution | |
200 mg/mL (20%)* | Acetylcysteine Solution | |||
Parenteral | For injection concentrate, for IV infusion | 200 mg/mL | Acetadote® | Cumberland |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | For oral solution | 500 mg (of acetylcysteine) | Legubeti® | Galephar |
2.5 g (of acetylcysteine) | Legubeti® | Galephar |
Only references cited for selected revisions after 1984 are available electronically.
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102. Fresenius Kabi. Acetylcysteine solution USP prescribing information. Lake Zurich, IL; 2018 Sep.
103. Galephar Pharmaceutical Research Inc. Legubeti (acetylcysteine) for oral solution prescribing information. Puerto Rico; 2024 Feb
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108. Cumberland Pharmaceuticals. Acetadote® (acetylcysteine) injection prescribing information. Nashville, TN; 2021 Oct.
109. N-acetylcysteine. In: Goldfrank LR, Flomenbaum NE, Lewin NA et al., eds. Goldfrank's Toxicologic Emergencies. 7th ed. McGraw-Hill; 2002:502-6.
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115. McCullough PA, Stacul F, Davidson C et al. Overview. Am J Cardiol . 2006; 98 (suppl 6A): 2K-4K.
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