(For additional information see “Acetylcysteine: Patient drug information” and see “Acetylcysteine: Pediatric drug information”)
- Acetylcysteine Solution;
- Mucolytic Agent
Oral: Note: Consultation with a poison control center or clinical toxicologist is highly recommended when considering the discontinuation of oral acetylcysteine prior to the conclusion of a full 18-dose course of therapy.
72-hour regimen: Consists of 18 doses; total dose delivered: 1330 mg/kg
Loading dose: 140 mg/kg
Maintenance dose: 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration
21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg
Loading dose: 150 mg/kg (maximum: 15 g) infused over 60 minutes
Second dose: 50 mg/kg (maximum: 5 g) infused over 4 hours
Third dose: 100 mg/kg (maximum: 10 g) infused over 16 hours
Note: The fluid volume should be reduced in patients weighing <40 kg according to the following table:
150 mg/kg over 1 h
50 mg/kg over 4 h
100 mg/kg over 16 h
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to dose.
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours
Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment
Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours
Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter
Diagnostic bronchogram: Nebulization or intratracheal: 1-2 mL of 20% solution or 2-4 mL of 10% solution administered 2-3 times prior to procedure
Prevention of contrast-induced nephropathy (CIN) (unlabeled use): Oral: 600-1200 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules (some centers use solution, diluted in cola beverage or juice)
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use):I.V.: 1200 mg over 5-10 minutes prior to cardiac catheterization, followed by 1200 mg orally twice daily for 48 hours
Acetaminophen poisoning: Refer to adult dosing.
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted.
Infants: 1-2 mL of 20% solution or 2-4 mL 10% solution until nebulized given 3-4 times/day
Children: Refer to adult dosing.
Inhalation, nebulization (tent, croupette): Children: Refer to adult dosing.
Acetadote®: 20% [200 mg/mL] (30 mL [DSC]) [contains edetate disodium]
Injection, solution [preservative free]:
Acetadote®: 20% [200 mg/mL] (30 mL)
Solution, for inhalation/oral: 10% [100 mg/mL] (10 mL, 30 mL); 20% [200 mg/mL] (10 mL, 30 mL)
Solution, for inhalation/oral [preservative free]: 10% [100 mg/mL] (4 mL, 10 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
Oral: Treatment of acetaminophen poisoning, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).
Loading dose: Dilute in D5W 200 mL; administer over 60 minutes.
Second dose: Dilute in D5W 500 mL; administer over 4 hours.
Third dose: Dilute in D5W 1000 mL; administer over 16 hours.
Note: To avoid fluid overload in patients <40 kg and those requiring fluid restriction, decrease volume of D5W proportionally (see table in dosing section). Discard unused portion.
If the commercial I.V. form is unavailable, the solution for inhalation has been used; each dose should be infused through a 0.2 micron Millipore filter (in-line) over 60 minutes (Yip, 1998); intravenous administration of the solution for inhalation is not USP 797-compliant.
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use): Administer I.V. push over 5-10 minutes prior to contrast administration.
Intravenous: Y-site administration: Compatible with D5W, D5W 1/2NS. Incompatible with metals (particularly iron, copper, and nickel); cefepime, ceftazidime
Acetylcysteine may be confused with acetylcholine
Mucomyst® may be confused with Mucinex®
Central nervous system: Drowsiness, chills, fever
Gastrointestinal: Vomiting, nausea, stomatitis
Local: Irritation, stickiness on face following nebulization
Respiratory: Bronchospasm, rhinorrhea, hemoptysis
Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration
>10%: Miscellaneous: Anaphylactoid reaction (8% to 18%; shorter infusion periods [eg, <60 minutes] associated with increased incidence)
1% to 10%:
Cardiovascular: Flushing (1% to 8%), tachycardia (1% to 4%), edema (1% to 2%)
Dermatologic: Urticaria (6% to 8%), rash (2% to 4%), pruritus (1% to 4%)
Gastrointestinal: Vomiting (2% to 10%), nausea (1% to 6%)
Respiratory: Pharyngitis (≤1%), rhinorrhea (≤1%), rhonchi (≤1%), throat tightness (≤1%)
<1% (Limited to important or life-threatening): Anaphylaxis, bronchospasm, chest tightness, cough, dyspnea, hypotension, respiratory distress, stridor, wheezing
• Anaphylactoid reactions: Acute flushing and erythema have been reported; usually occurs within 30-60 minutes and may resolve spontaneously. Serious anaphylactoid reactions have also been reported and are more commonly associated with I.V. administration. When used for acetaminophen poisoning, the incidence is reduced when the initial loading dose is administered over 60 minutes. Acetylcysteine infusion may be interrupted until treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactoid reactions should be immediately available. Use caution in patients with asthma or history of bronchospasm as these patients may be at increased risk. Conversely, patients with high acetaminophen levels (>150 mg/dL) may be at a reduced risk for anaphylactoid reactions (Pakravan, 2008; Waring, 2008).
• Acute acetaminophen poisoning: Appropriate use: Acetylcysteine is indicated in patients with a serum acetaminophen level that indicates they are at “possible” risk or greater for hepatotoxicity when plotted on the Rumack-Matthew nomogram. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained <4 hours postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, despite having received a toxic dose. The nomogram is less predictive of hepatic injury following an acute overdose with an extended release acetaminophen product or in patients who have coingested acetaminophen with an agent known to delay gastric emptying. The nomogram also does not take into account patients who may be at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients). Nevertheless, acetylcysteine should be administered to any patient with signs of hepatotoxicity, even if the serum acetaminophen level is low or undetectable. Patients who present >24 hours after an acute ingestion or patients who present following an acute ingestion at an unknown time may be candidates for acetylcysteine therapy; consultation with a poison control center or clinical toxicologist is highly recommended.
• Repeated supratherapeutic ingestion (RSTI) of acetaminophen: Appropriate use: The Rumack-Matthew nomogram is not designed to be used following RSTIs. In general, an accurate past medical history, including a comprehensive acetaminophen ingestion history, in conjunction with AST concentrations and serum acetaminophen levels, may give the clinician insight as to the patient’s risk of acetaminophen toxicity. Some experts recommend that acetylcysteine be administered to any patient with “higher than expected” serum acetaminophen levels or serum acetaminophen level >10 mcg/mL, even in the absence of hepatic injury; others recommend treatment for patients with laboratory evidence and/or signs and symptoms of hepatotoxicity (Hendrickson, 2006; Jones, 2000). Consultation with a poison control center or a clinical toxicologist is highly recommended.
Dosage form specific issues:
• Inhalation: Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow. If bronchospasm occurs, administer a bronchodilator; discontinue acetylcysteine if bronchospasm progresses.
There are no known significant interactions.
10% (30): $20.58
10% (30): $25.99
20% (4): $16.99
20% (10): $22.99
Acute ingestion: Obtain the first acetaminophen level 4 hours postingestion (or as soon as possible thereafter); plot on the Rumack-Matthew nomogram. In patients who have ingested an extended release formulation of acetaminophen or have coingested an agent known to delay gastric emptying, obtain a repeat serum acetaminophen measurement 4-6 hours following the first measurement if the original level (taken at 4-8 hours postingestion) when plotted on the Rumack-Matthew nomogram indicated that treatment was not necessary.
- ACC (AR, HU, LU, MX, RU, ZA);
- ACC 200 (EE);
- Acemuk (AR);
- Acetadote (NZ);
- Acetain (KP);
- Acetin (MY);
- Acetylcystein NM Pharma (SE);
- Acetylcystein Tika (SE);
- Acypront (HK);
- Aerosolv (AT);
- Alistine Forte (TH);
- Bromuc (BR);
- Broncoflem (PH);
- Cystaline (TH);
- Drenaflen (EC);
- Ecomucyl (CH);
- Eloamin (CZ);
- Exomuc (FR, HK, LU);
- Fabrol (AT, GR);
- Flemex AC (TH);
- Flucil (TH);
- Fluimicil (CH, DE);
- Fluimiquil (LU);
- Fluimucil (AR, BG, BR, CL, CO, CZ, HK, HU, ID, IT, MA, NL, PE, PL, RU, TH, TW);
- Fluimucil A (MY, PK);
- Fluimukan (HR);
- Flumil (ES);
- Flutafin (TW);
- Hidonac (ID, MY, PH, TH, TW);
- Icystein (TW);
- L-Cimexyl (SG);
- Lubrisec (AR);
- Lysomucil (LU);
- Lysox (LU);
- Madame Pearl’s Mucolytic (HK);
- Menaxol (CR, DO, GT, HN, NI, PA, SV);
- Menaxol Forte (CR, DO, GT, HN, NI, PA, SV);
- Mucofillin (JP);
- Mucolair (LU);
- Mucolator (LU, MY);
- Mucolitico (CN);
- Mucomiste (PT);
- Mucomyst (AT, AU, BE, DK, FI, FR, KP, LU, NL, NO, SE);
- Mucomystendo (FR);
- Mucoserin (KP);
- Mucosof (CL);
- Mucosten (KP);
- Mucosys (IN);
- Mucoza (TH);
- Mucylin (ID);
- Mukolit (ID);
- Muterin (KP);
- Muxatil (PY);
- Mysoven (TH);
- NAC (TR);
- NAC-ratiopharm (LU);
- Parvolex (GB, IE, PH);
- Pectocil (ID);
- Pectomucil (LU);
- Reolin (IL);
- Rumicil (LU);
- Sebron (KP);
- Simucil (ID);
- Simucin (TH);
- Siran 200 (IL);
- Solmucol (HU, LU);
- Spatam (SG);
- Sputopur (HU);
- Stecin (KP);
- Stenac (TH);
- Tancore (TW);
- Touxium Mucolyticum (LU);
- Viskoferm (SE)
In patients with acetaminophen toxicity, acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of acetaminophen.
The presumed mechanism in preventing contrast-induced nephropathy is its ability to scavenge oxygen-derived free radicals and improve endothelium-dependent vasodilation.
Duration: Inhalation: >1 hour
Distribution: 0.47 L/kg
Protein binding: 83%
Reduced acetylcysteine: 2 hours
Total acetylcysteine: Adults: 5.6 hours; Newborns: 11 hours
Time to peak, plasma: Oral: 1-2 hours
ACT Investigators, “Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography: Main Results from the Randomized Acetylcysteine for Contrast-induced Nephropathy Trial (ACT),” Circulation, 2011, 124(11):1250-9. [PubMed 21859972]
Allaqaband S, Tumuluri R, Malik AM, et al, “Prospective Randomized Study of N-Acetylcysteine, Fenoldopam, and Saline for Prevention of Radiocontrast-Induced Nephropathy,” Catheter Cardiovasc Interv, 2002, 57(3):279-83. [PubMed 12410497]
Appelboam AV, Dargan PI, and Knighton J, “Fatal Anaphylactoid Reaction to N-Acetylcysteine: Caution in Patients With Asthma,” Emerg Med J, 2002, 19(6):594-5. [PubMed 12410497]
Bailey B and McGuigan MA, “Management of Anaphylactoid Reactions to Intravenous N-Acetylcysteine,” Ann Emerg Med, 1998, 31(6):710-5. [PubMed 12421803]
Baker CS, Wragg A, Kumar S, et al, “A Rapid Protocol for the Prevention of Contrast-Induced Renal Dysfunction: The RAPPID Study,” J Am Coll Cardiol, 2003, 41(12):2114-8. [PubMed 9624310]
Briguori C, Airoldi F, D’Andrea D, et al, “Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL). A Randomized Comparison of 3 Preventive Strategies,” Circulation, 2007, 115(10):1211-17. [PubMed 17309916]
Curhan GC, “Prevention of Contrast Nephropathy,” JAMA, 2003, 289(5):606-8. [PubMed 12821233]
Dart RC, Erdman AR, Olson KR, et al, “Acetaminophen Poisoning: An Evidence-Based Consensus Guideline for Out-of-Hospital Management,” Clin Toxicol (Phila), 2006, 44(1):1-18. [PubMed 12578494]
Douglas D and Smilkstein M, “Deferoxamine-Iron Induced Pulmonary Injury and N-Acetylcysteine,” J Toxicol Clin Toxicol, 1995, 33(5):495. [PubMed 16496488]
Falk JL, “Oral N-Acetylcysteine Given Intravenously for Acetaminophen Overdose: We Shouldn’t Have To, But We Must,” Crit Care Med, 1998, 26(1):7. [PubMed 9428532]
Harrison PM, Keays R, Bray BP, et al, “Improved Outcome of Paracetamol-Induced Fulminant Hepatic Failure by Late Administration of Acetylcysteine,” Lancet, 1990, 335(8705):1572-3. [PubMed 9428532]
Hendrickson RG and Bizovi KE, “Acetaminophen,” Goldfrank’s Toxicologic Emergencies, 8th edition, Flomenbaum NE, Goldfrank LR, Hoffman RS, et al, eds, New York: The McGraw-Hill Companies, Inc, 2006, 523-43.
Jones AL, “Mechanism of Action and Value of N-Acetylcysteine in the Treatment of Early and Late Acetaminophen Poisoning: A Critical Review,” J Toxicol Clin Toxicol, 1998, 36(4):277-85. [PubMed 9711192]
Jones AL, “Recent Advances in the Management of Late Paracetamol Poisoning,” Emerg Med, 2000, 12(1):14-21.
Kay J, Chow WH, Chan TM, et al, “Acetylcysteine for Prevention of Acute Deterioration of Renal Function Following Elective Coronary Angiography and Intervention: A Randomized Controlled Trial,” JAMA, 2003, 289(5):553-8. [PubMed 7803886]
Keays R, Harrison PM, Wendon JA, et al, “Intravenous Acetylcysteine in Paracetamol Induced Fulminant Hepatic Failure: A Prospective Controlled Trial,” BMJ, 1991, 303(6809):1026-9. [PubMed 12578487]
Marenzi G, Assanelli E, Marana I, et al, “N-Acetylcysteine and Contrast-Induced Nephropathy in Primary Angioplasty,” N Engl J Med, 2006, 354(26):2773-82. [PubMed 6807414]
Mascarenhas MR, “Treatment of Gastrointestinal Problems in Cystic Fibrosis,” Curr Treat Options Gastroenterol, 2003, 6(5):427-41. [PubMed 1954453]
Mohammed S, Jamal AZ, and Robison LR, “Serum Sickness-Like Illness Associated With N-Acetylcysteine Therapy,” Ann Pharmacother, 1994, 28(2):285. [PubMed 12954149]
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922. [PubMed 12628894]
Mroz L, Benitez JG, and Krenzelok E, “Angioedema With Oral Acetylcysteine,” Clin Toxicol, 1995, 33(5):554-5 [PubMed 12628894]
Pakravan N, Waring WS, Sharma S, et al, “Risk Factors and Mechanisms of Anaphylactoid Reactions to Acetylcysteine in Acetaminophen Overdose,” Clin Toxicol, 2008, 46(8):697-702. [PubMed 18803085]
Prescott LF, Donovan JW, Jarvie DR, et al, “The Disposition and Kinetics of Intravenous N-acetylcysteine in Patients With Paracetamol Overdosage,” Eur J Clin Pharmacol, 1989, 37(5):501-6. [PubMed 2598989]
Prescott LF, Illingworth RN, Critchley JA, et al, “Intravenous N-Acetylcysteine: The Treatment of Choice for Paracetamol Poisoning,” BMJ, 1979, 2:1097-1100. [PubMed 2598989]
Rashid ST, Salman M, Myint F, et al,“Prevention of Contrast-Induced Nephropathy in Vascular Patients Undergoing Angiography: A Randomized Controlled Trial of Intravenous N-Acetylcysteine,” J Vasc Surg, 2004, 40(6):1136-41. [PubMed 15622367]
“Rationale, Design, and Baseline Characteristics of the Acetylcystein for Contrast-Induced NephropaThy (ACT) Trial: A Pragmatic Randomized Controlled Trial to Evaluate the Efficacy of Acetylcysteine for the Prevention of Contrast-Induced Nephropathy,” Trials, 2009, 10:38-45. [PubMed 19497091]
Rodgers G, Matyunas N, Ross M, et al, “Sulfhemoglobinemia Associated With N-Acetylcysteine (NAC) Therapy of Acetaminophen (APAP) Overdose: A Case Report,” Clin Toxicol, 1995, 33(5):530. [PubMed 15622367]
Smilkstein MJ, Bronstein AC, Linden C, “Acetaminophen Overdose: A 48-Hour Intravenous N-Acetylcysteine Treatment Protocol,” Ann Emerg Med, 1991, 20(10):1058-63. [PubMed 1928874]
Smilkstein MJ, Knapp GL, Kulig KW, et al, “Efficacy of N-Acetylcysteine in the Treatment of Acetaminophen Overdose: Analysis of the National Multicenter Study (1976 to 1985),” N Engl J Med, 1988, 319(24):1557-62. [PubMed 1928874]
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(3):180-4. [PubMed 3059186]
Walson PD and Groth JF Jr, “Acetaminophen Hepatotoxicity After Prolonged Ingestion,” Pediatrics, 1993, 91(5):1021-2. [PubMed 10900277]
Waring WS, Stephen AF, Robinson OD, et al,“Lower Incidence of Anaphylactoid Reactions to N-Acetylcysteine in Patients With High Acetaminophen Concentrations After Overdose,” Clin Toxicol (Phila), 2008, 46(6):496-500. [PubMed 18584360]
Webb JG, Pate GE, Humphries KH, et al, “A Randomized Controlled Trial of Intravenous N-Acetylcysteine for the Prevention of Contrast-Induced Nephropathy After Cardiac Catheterization: Lack of Effect,” Am Heart J, 2004, 148(3):422-9. [PubMed 15389228]
Woo OF, Anderson IB, Kim SY, et al, “Shorter Duration of N-Acetylcysteine (NAC) for Acute Acetaminophen Poisoning,” Clin Toxicol, 1995, 33(5):508. [PubMed 15389228]
Woo OF, Mueller PD, Olson KR, et al, “Shorter Duration of Oral N-Acetylcysteine Therapy for Acute Acetaminophen Overdose,” Ann Emerg Med, 2000, 35(4):363-8. [PubMed 10736123]
Yankaskas JR, Marshall BC, Sufian B, et al, “Cystic Fibrosis Adult Care: Consensus Conference Report,” Chest, 2004, 125(1 Suppl):1-39. [PubMed 10736123]
Yip L, Dart RC, and Hurlbut KM, “Intravenous Administration of Oral N-Acetylcysteine,” Crit Care Med, 1998, 26(1):40-3. [PubMed 14718408]