Class: Antidotes
- Sulfhydryl Donors
VA Class: RE400
CAS Number: 616-91-1
Brands: Acetadote, Mucomyst
Medically reviewed on Sep 3, 2018
Introduction
Antidote for acetaminophen overdosage; mucolytic agent and sulfhydryl donor.102 103 104 108
Uses for Acetylcysteine
Antidote for Acetaminophen Overdosage
Treatment of acetaminophen overdosage.102 103 104 108 Optimal if given within 8 hours of acetaminophen ingestion;109 may be effective when given ≥24 hours after ingestion.105 106
Prevention of Nephropathy Associated with Radiographic Contrast Media
Has been used to prevent radiographic contrast media-induced nephropathy†.100 101 110 111 112 113 114 116 117 Efficacy for this indication not established; additional study needed.110 115 117
Mucolytic Uses
Adjunctive treatment for patients with abnormal, viscid, or inspissated mucous secretions associated with conditions such 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 thoracic and cardiovascular surgery; and post-traumatic chest conditions.102 103 104
Used during anesthesia and in the preparation of patients for bronchograms, bronchospirometry, bronchial wedge catheterization, and other diagnostic bronchial studies.102 103 104
Acetylcysteine Dosage and Administration
General
-
Determine plasma or serum acetaminophen concentrations as soon as possible (but no sooner than 4 hours) after ingestion.107 May be appropriate to obtain an additional sample at 4–6 hours after initial sample if extended-release acetaminophen preparation was ingested.107
-
Use plasma or serum acetaminophen concentrations in conjunction with a nomogram to estimate potential for hepatotoxicity and necessity of acetylcysteine therapy.105 107
-
Full course of acetylcysteine therapy indicated if initial plasma or serum acetaminophen concentrations fall on or above the dashed line on the nomogram.105 (See nomogram.)106 107
-
Assistance available from a regional poison center at 800-222-1222 or an assistance line for acetaminophen overdosage at 800-525-6115.108
Multiple Supratherapeutic Acetaminophen Doses
-
Guidelines for the treatment of ingestions involving multiple, higher-than-recommended acetaminophen doses over an extended period of time currently are not available.118 Plasma AST/ALT concentrations and plasma or serum acetaminophen concentrations have been used to estimate potential for hepatotoxicity and necessity of acetylcysteine therapy.108 118
-
Assistance available from a regional poison center at 800-222-1222 or an assistance line for acetaminophen overdosage at 800-525-6115.108
Administration
Administer orally or by IV infusion as an antidote for acetaminophen overdosage; administer by oral inhalation or intracheal instillation for mucolytic uses.102 103 104 108
Has been administered orally100 110 117 or IV110 117 for prevention of radiographic contrast media-induced nephropathy†.
Oral Administration
Usually administered as a 5% solution.102 103 104 Dilute 20% solution 1:3 with diet soft drink.102 103 104
Initiate antiemetic therapy or administer via duodenal tube if persistently unable to retain orally administered drug.107
NG Tube
Administer as 5% solution; may use water as the diluent.102 103 104
IV Administration
For solution and drug compatibility information, see Compatibility under Stability.
Administer as a loading dose, followed by a first maintenance dose, then a second maintenance dose.108
Injection concentrate must be diluted prior to IV administration.108
Dilution
Dilute dose with an appropriate volume of 5% dextrose injection (see Table 1).108
Adjust total volume for patients who weigh <40 kg (see Table 1) and for those requiring fluid restriction.108
|
Volume of Diluent for Indicated Dose |
||
---|---|---|---|
Patient’s Weight (kg) |
Loading Dose |
First Maintenance Dose |
Second Maintenance Dose |
≥40 |
200 mL |
500 mL |
1 L |
30 |
100 mL |
250 mL |
500 mL |
25 |
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 |
Rate of Administration
Loading dose: Infuse over 60 minutes.108 109
First maintenance dose: Infuse over 4 hours.108
Second maintenance dose: Infuse over 16 hours.108
Oral Inhalation and Intratracheal Instillation
For drug compatibility information, see Compatibility under Stability.
Use 20% acetylcysteine solution undiluted or dilute with 0.9% sodium chloride injection or inhalation solution or sterile water for injection or inhalation.102 103 104
May use 10% acetylcysteine solution undiluted.102 103 104
Dosage
Available as acetylcysteine and acetylcysteine sodium; dosage expressed in terms of acetylcysteine.102 103 103 108
Pediatric Patients
Antidote for Acetaminophen Overdosage
Oral
Loading dose: 140 mg/kg, administered as soon as possible.102 103 104 Maintenance dosage, if indicated: 70 mg/kg every 4 hours for 17 doses.102 103 104
If patient vomits a loading or maintenance dose within 1 hour of administration, repeat the dose.107
IV
Loading dose: 150 mg/kg, administered as soon as possible.107 108
First maintenance dose: 50 mg/kg.107 108
Second maintenance dose: 100 mg/kg.107 108
Mucolytic Uses
Nebulization
Face mask, mouthpiece, or tracheostomy: 3–5 mL of the 20% solution or 6–10 mL of the 10% solution 3 or 4 times daily; alternatively, 1–10 mL of the 20% solution or 2–20 mL of the 10% solution every 2–6 hours.102 103 104
Tent or croupette: Volume of acetylcysteine solution should be sufficient to maintain a very heavy mist in the tent or croupette for the desired period; maintenance of heavy mist may require up to 300 mL of the 10 or 20% solution for a single, continuous treatment.102 103 104 Administer intermittently or for continuous prolonged periods.102 103 104
Direct Instillation
1–2 mL of a 10–20% solution as often as every hour.102 103 104
Intratracheal Instillation
Instillation through a percutaneous intratracheal catheter: 1–2 mL of the 20% solution or 2–4 mL of the 10% solution every 1–4 hours via a syringe attached to the catheter.102 103 104
Instillation through a catheter into the trachea: 2–5 mL of the 20% solution via a syringe attached to the catheter.102 103 104
Diagnostic Bronchial Studies
Nebulization2 or 3 doses of 1–2 mL of the 20% solution or 2–4 mL of the 10% solution prior to the procedure.102 103 104
Intratracheal Instillation2 or 3 doses of 1–2 mL of the 20% solution or 2–4 mL of the 10% solution prior to the procedure.102 103 104
Tracheostomy Care
Intratracheal Instillation1–2 mL of a 10–20% solution into the tracheostomy every 1–4 hours.102 103 104
Adults
Antidote for Acetaminophen Overdosage
Oral
Loading dose: 140 mg/kg, administered as soon as possible.102 103 104 Maintenance dosage, if indicated: 70 mg/kg every 4 hours for 17 doses.102 103 104
If patient vomits a loading or maintenance dose within 1 hour of administration, repeat the dose.107
IV
Loading dose: 150 mg/kg, administered as soon as possible.108
First maintenance dose: 50 mg/kg.108
Second maintenance dose: 100 mg/kg.108
Prevention of Nephropathy Associated with Radiographic Contrast Media†
Oral
600 mg twice daily, given the day before and the day of contrast media administration (total of 4 doses), has been used.100 110 117 Other dosage regimens have been investigated.110 117
Mucolytic Uses
Nebulization
Face mask, mouthpiece, tracheostomy: 3–5 mL of the 20% solution or 6–10 mL of the 10% solution 3 or 4 times daily; alternatively, 1–10 mL of the 20% solution or 2–20 mL of the 10% solution every 2–6 hours.102 103 104
Tent or croupette: Volume of acetylcysteine solution should be sufficient to maintain a very heavy mist in the tent or croupette for the desired period; maintenance of heavy mist may require up to 300 mL of the 10 or 20% solution for a single, continuous treatment.102 103 104 Administer intermittently or for continuous prolonged periods.102 103 104
Direct Instillation
1–2 mL of a 10–20% solution as often as every hour.102 103 104
Intratracheal Instillation
Instillation through a percutaneous intratracheal catheter: 1–2 mL of the 20% solution or 2–4 mL of the 10% solution every 1–4 hours via a syringe attached to the catheter.102 103 104
Instillation through a catheter into the trachea: 2–5 mL of the 20% solution via a syringe attached to the catheter.102 103 104
Diagnostic Bronchial Studies
NebulizationFor diagnostic bronchial studies: 2 or 3 doses of 1–2 mL of the 20% solution or 2–4 mL of the 10% solution prior to the procedure.102 103 104
Intratracheal InstillationFor diagnostic bronchial studies: 2 or 3 doses of 1–2 mL of the 20% solution or 2–4 mL of the 10% solution prior to the procedure.102 103 104
Tracheostomy Care
Intratracheal Instillation1–2 mL of a 10–20% solution into the tracheostomy every 1–4 hours.102 103 104
Special Populations
Hepatic Impairment
Antidote for Acetaminophen Overdosage
IV
Published reports do not indicate that the dose should be reduced in patients with hepatic impairment.108 Data are not available to determine whether dosage adjustment is needed in patients with hepatic cirrhosis.108
Renal Impairment
Antidote for Acetaminophen Overdosage
IV
Data are not available to determine whether dosage adjustment is needed in patients with moderate or severe renal impairment.108
Cautions for Acetylcysteine
Contraindications
-
When administered orally as an antidote, no contraindications.102 103 104
-
For other uses (including IV administration as an antidote), hypersensitivity to acetylcysteine or any ingredient in the formulation.102 103 104 108
Warnings/Precautions
Warnings
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.102 103 104
Respiratory Effects
Volume of liquefied bronchial secretions may increase following oral inhalation or intratracheal instillation; potential for airway occlusion.102 103 104 If cough is inadequate to maintain an open airway, institute mechanical suction or endotracheal aspiration.102 103 104
Observe asthmatic patients closely.102 103 104
If bronchospasm occurs, give a bronchodilator by nebulization.102 103 104 If bronchospasm progresses, discontinue acetylcysteine immediately.102 103 104
When administered IV, caution in patients with asthma or history of bronchospasm.108
Sensitivity Reactions
Anaphylactoid Reactions
Serious anaphylactoid reactions (i.e., acute hypersensitivity reactions such as rash, hypotension, wheezing, dyspnea), including death in a patient with asthma, reported in patients receiving IV acetylcysteine.108
Acute flushing and erythema also 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 as such.108
If an anaphylactoid reaction occurs, temporarily interrupt IV acetylcysteine to administer antihistamines and, in severe reactions, epinephrine.108 Once treatment of the anaphylactoid reaction has been initiated, carefully reinstitute IV acetylcysteine.108 If the anaphylactoid reaction recurs or increases in severity, discontinue IV acetylcysteine and consider alternative management.108
Other Allergic Reactions
Generalized urticaria reported rarely in patients receiving oral acetylcysteine for acetaminophen overdosage.102 103 104 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.102 103 104
Sensitization
Sensitization reported rarely.102 103 104
Major Toxicities
GI Effects
Oral administration may result in vomiting or may aggravate vomiting associated with acetaminophen overdosage.102 103 104
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.102 103 104
Specific Populations
Pregnancy
Lactation
Not known whether acetylcysteine is distributed into milk; caution advised.102 103 104 108
Pediatric Use
Efficacy of IV acetylcysteine as an antidote for acetaminophen overdosage appears to be similar to that in adults.108
Geriatric Use
Insufficient experience with IV acetylcysteine in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.108
Common Adverse Effects
Oral administration: Nausea, vomiting, other GI symptoms, rash with or without fever.102 103 104
IV administration: Rash, urticaria, pruritus.108
Oral inhalation/intratracheal instillation: Stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess.102 103 104
Interactions for Acetylcysteine
Activated Charcoal
Possible interference with absorption of oral acetylcysteine; 119 however, usual dosage of acetylcysteine is appropriate in patients given activated charcoal (higher dosages not necessary).105 106 107
Acetylcysteine Pharmacokinetics
Absorption
Bioavailability
Absorbed following oral administration, with peak plasma concentrations achieved within 1–2 hours.a 119
Absorbed from the pulmonary epithelium.a
Distribution
Extent
Crosses the placenta following oral or IV administration.108
Plasma Protein Binding
Elimination
Metabolism
Deacetylated in the liver to cysteine.a
Elimination Route
Principally (70%) nonrenal.119
Half-life
6.25 hours after oral administration.119
5.6 hours after IV administration in adults.108
11 hours after IV administration in neonates.108
Special Populations
In patients with hepatic cirrhosis, plasma concentrations following IV administration are threefold higher.108 Half-life increased by 80% in patients with severe liver damage (i.e., alcoholic cirrhosis [Child-Pugh score of 7–13] or primary and/or secondary biliary cirrhosis [Child-Pugh score of 5–7]).108
Stability
Storage
Oral, Oral Inhalation, Intratracheal Instillation
Solution
15–30°C.102 103 104 Use diluted solutions within 1 hour.102 103 104 Store undiluted solution in opened vials in refrigerator; use within 96 hours.102 103 104 Do not store admixtures.102 103 104
Parenteral
Injection Concentrate for IV Infusion
20–25°C.108
Presence of light pink to light purple color in solution does not affect the quality of the product.108
Following dilution with 5% dextrose, stable at controlled room temperature for 24 hours.108
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Solution Compatibility
Compatible108 |
---|
Dextrose 5% in water |
Sodium chloride 0.45% |
Drug Compatibility
Incompatible |
---|
Cefepime HCl |
Ceftazidime |
Oral Inhalation, Intratracheal Instillation
Presence of light purple color in solution does not appreciably affect potency.102 103 104 a
Drug Compatibility
Incompatible with oxidizing agents.a
Compatible |
---|
Cocaine HCl |
Dexamethasone sodium phosphate |
Epinephrine HCl |
Gentamicin sulfate |
Halothane |
Isoetharine HCl |
Isoproterenol HCl |
Lidocaine HCl |
Lincomycin HCl |
Nitrous oxide |
Phenylephrine HCl |
Polymyxin B sulfate |
Tetracaine HCl |
Vancomycin HCl |
Incompatible |
Amphotericin B |
Ampicillin sodium |
Erythromycin lactobionate |
Actions
-
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 (N-acetyl-p-benzoquinoneimine; NAPQI).102 103 104
-
Thiol-containing antioxidant.100 May act as an oxygen free-radical scavenger to prevent radiographic contrast media-induced renal toxicity;100 also may increase the biologic effects of nitric oxide by combining with the oxide to form S-nitrosothiol, a potent vasodilator.101
-
Reduces viscosity of purulent and nonpurulent pulmonary secretions and facilitates their removal by coughing, postural drainage, or mechanical means.102 103 104 Mucolytic effect depends on the free sulfhydryl group, which appears to reduce disulfide linkages of mucoproteins through an interchange reaction.102 103 104
Advice to Patients
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.102 103 104
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.102 103 104
-
Importance of informing patients of other important precautionary information.102 103 104 (See Cautions.)
Preparations
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 (of acetylcysteine) per mL (10%) |
Acetylcysteine Sodium Solution |
Abbott, American Regent, Bedford, Dey, Mayne, Roxane |
Mucomyst |
Sandoz |
|||
200 mg (of acetylcysteine) per mL (20%) |
Acetylcysteine Sodium Solution |
Abbott, American Regent, Bedford, Dey, Mayne, Roxane |
||
Mucomyst |
Sandoz |
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
For injection concentrate, for IV infusion |
200 mg/mL |
Acetadote |
Cumberland |
AHFS DI Essentials™. © Copyright 2019, Selected Revisions September 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
Only references cited for selected revisions after 1984 are available electronically.
100. Tepel M, van der Giet M, Schwarzfeld C et al. Prevention of radiographic-contrast -agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000; 343:180-4. http://www.ncbi.nlm.nih.gov/pubmed/10900277?dopt=AbstractPlus
101. Safirstein R, Andrade L, Vieira JM. Acetylcysteine and nephrotoxic effects of radiographic contrast agents—a new use for an old drug. N Engl J Med. 2000; 343: 210-2. http://www.ncbi.nlm.nih.gov/pubmed/10900284?dopt=AbstractPlus
102. Roxane Laboratories. Acetylcysteine solution USP prescribing information. Columbus, OH; 2001 Oct.
103. Dey. Acetylcysteine solution USP 10% and 20% prescribing information. Napa, CA; 1999 Nov.
104. Apothecon. Mucomyst (acetylcysteine) prescribing information. Princeton, NJ; 2001 Jan.
105. Acetaminophen (paracetamol). In: Ellenhorn MJ, Schonwald S, Ordog G et al., eds. Ellenhorn’s medical toxicology: diagnosis and treatment of human poisoning. 2nd ed. Baltimore, MD: Williams & Wilkens; 1997:180-95.
106. Zed PJ, Krenzelok EP. Treatment of acetaminophen overdose. Am J Health-Syst Pharm. 1999; 56:1081-93. http://www.ncbi.nlm.nih.gov/pubmed/10385455?dopt=AbstractPlus
107. Poisindex Managements: Acetaminophen-Acute. 26 Jul 2002. From website. http://www.micromedex.com/products/poisindex
108. Cumberland Pharmaceuticals. Acetadote (acetylcysteine) injection prescribing information. Nashville, TN; 2006 Feb.
109. N-acetylcysteine. In: Goldfrank LR, Flomenbaum NE, Lewin NA et al., eds. Goldfrank’s Toxicologic Emergencies. 7th ed. McGraw-Hill; 2002:502-6.
110. Pannu N, Wiebe N, Tonelli M et al. Prophylaxis strategies for contrast-induced nephropathy. JAMA. 2006; 295:2765-79. http://www.ncbi.nlm.nih.gov/pubmed/16788132?dopt=AbstractPlus
111. Coyle LC, Rodriguez A, Jeschke RE et al. Acetylcysteine In Diabetes (AID): a randomized study of acetylcysteine for the prevention of contrast nephropathy in diabetics. Am Heart J. 2006; 151:1032.e9-12.
112. Carbonell N, Blasco M, Sanjuán R et al. Intravenous N-acetylcysteine for preventing contrast-induced nephropathy: A randomised trial. Int J Cardiol. 2007; 115:57-62 (Epub 2006 Jun 30). http://www.ncbi.nlm.nih.gov/pubmed/16814414?dopt=AbstractPlus
113. Bartholomew BA, Harjai KJ, Dukkipati S et al. Impact of nephropathy after percutaneous coronary intervention and a method for risk stratification. Am J Cardiol. 2004; 93:1515-9. http://www.ncbi.nlm.nih.gov/pubmed/15194023?dopt=AbstractPlus
114. McCullough PA, Adam A, Becker CR et al. Risk prediction of contrast-induced nephropathy. Am J Cardiol. 2006; 98 (suppl 6A):27K-36K.
115. McCullough PA, Stacul F, Davidson C et al. Overview. Am J Cardiol. 2006; 98 (suppl 6A):2K-4K.
116. Davidson C, Stacul F, McCullough PA et al. Contrast medium use. Am J Cardiol. 2006; 98 (suppl 6A):42K-58K. http://www.ncbi.nlm.nih.gov/pubmed/16949380?dopt=AbstractPlus
117. Stacul F, Adam A, Becker CR et al. Strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol. 2006; 98 (suppl 6A):59K-77K.
118. Daly FF, O’Malley GF, Heard K et al. Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. Ann Emerg Med. 2004; 44:393-400. http://www.ncbi.nlm.nih.gov/pubmed/15459622?dopt=AbstractPlus
119. Holdiness MR. Clinical pharmacokinetics of N-acetylcysteine. Clin Pharmacokinet. 1991; 20:123-34. http://www.ncbi.nlm.nih.gov/pubmed/2029805?dopt=AbstractPlus
a. AHFS drug information 2003. McEvoy GK, ed. Acetylcysteine. Bethesda, MD: American Society of Health-System Pharmacists; 2003: page 2582-5.
HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:6.
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Other brands: Mucomyst, Acetadote, Cetylev