Acetylcysteine

Pronunciation (a se teel SIS teen)

• Management of Overdosages

U.S. Brand Names Mucomyst®; Mucosil^TM

Synonyms Acetylcysteine Sodium; Mercapturic Acid; NAC; N-Acetylcysteine; N-Acetyl-L-cysteine

Generic Available Yes

Canadian Brand Names Mucomyst®; Parvolex®

Pharmacologic Category Antidote; Mucolytic Agent

Use Adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies; antidote for acute acetaminophen toxicity

Use - Unlabeled/Investigational Prevention of radiocontrast-induced renal dysfunction

Pregnancy Risk Factor B

Pregnancy Implications Based on limited reports using acetylcysteine to treat acetaminophen overdose in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective levels in the fetus.

Lactation Excretion in breast milk unknown/compatible

Contraindications Hypersensitivity to acetylcysteine or any component of the formulation

Warnings/Precautions 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

Inhalation:

>10%:

1% to 10%:

Systemic:

1% to 10%:

<1% (Limited to important or life-threatening): Bronchospastic allergic reaction, anaphylactoid reaction, EKG changes (transient)

Overdosage/Toxicology Treatment of acetylcysteine toxicity is usually aimed at reversing anaphylactoid symptoms or controlling nausea and vomiting. The use of epinephrine, antihistamines, and steroids may be beneficial.

Drug Interactions Adsorbed by activated charcoal; clinical significance is minimal, though, once a pure acetaminophen ingestion requiring N-acetylcysteine is established; further charcoal dosing is unnecessary once the appropriate initial charcoal dose is achieved (5-10 g:g acetaminophen)

Stability Store opened vials in the refrigerator, use within 96 hours; dilutions should be freshly prepared and used within 1 hour; light purple color of solution does not affect its mucolytic activity

Mechanism of Action Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity. The exact mechanism of action in acetaminophen toxicity is unknown; thought to act by providing substrate for conjugation with the toxic metabolite.

Onset of action: Inhalation: 5-10 minutes

Duration: Inhalation: >1 hour

Distribution: Oral: 0.33-0.47 L/kg

Protein binding, plasma: Oral: 50%

Half-life elimination: Reduced acetylcysteine: 2 hours; Total acetylcysteine: 5.5 hours

Time to peak, plasma: Oral: 1-2 hours

Acetaminophen poisoning: Children and Adults: Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until all doses are administered even though the acetaminophen plasma level has dropped below the toxic range

Inhalation: Acetylcysteine 10% and 20% solution (Mucomyst®) (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted

Meconium ileus equivalent: Children and Adults: 100-300 mL of 4% to 10% solution by irrigation or orally

Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Adults: Oral: 600 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). Hydrate patient with saline concurrently.

Administration For treatment of acetaminophen overdosage, 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

Reference Range Determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion (to ensure peak levels have been obtained); administer for acetaminophen level >150 g/mL at 4 hours following ingestion; toxic concentration with probable hepatotoxicity: >200 g/mL at 4 hours or 50 g at 12 hours

Patient Information Pulmonary treatment: Prepare solution (may dilute with sterile water to reduce concentrate from impeding nebulizer) and use as directed. Clear airway by coughing deeply before using aerosol. Wash face and face-mask after treatment to remove any residual. You may experience drowsiness (use caution when driving) or nausea or vomiting (small frequent meals may help). Report persistent chills or fever, adverse change in respiratory status, palpitations, or extreme anxiety or nervousness.

Nursing Implications Assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning; intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime

Dental Health: Effects on Dental Treatment Stomatitis has been reported in 1% to 10% of patients

Dental Health: Vasoconstrictor/Local Anesthetic Precautions No information available to require special precautions

Mental Health: Effects on Mental Status May cause drowsiness

Mental Health: Effects on Psychiatric Treatment Sedative effects may be potentiated by psychotropic agents

Dosage Forms Solution, as sodium: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL, 100 mL)

Douglas D and Smilkstein M, "Deferoxamine-Iron Induced Pulmonary Injury and N-Acetylcysteine,"J Toxicol Clin Toxicol, 1995, 33(5):495.

Harrison PM, Wendon JA, Gimson AE, et al, "Improvement by Acetylcysteine of Hemodynamics and Oxygen Transport in Fulminant Hepatic Failure,"N Engl J Med, 1991, 324(26):1852-7.

Henderson A and Hayes P, "Acetylcysteine as a Cytoprotective Antioxidant in Patients With Severe Sepsis: Potential New Use for an Old Drug,"Ann Pharmacother, 1994, 28(9):1086-8.

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.

Mohammed S, Jamal AZ, and Robison LR, "Serum Sickness-Like Illness Associated With N-Acetylcysteine Therapy,"Ann Pharmacother, 1994, 28(2):285.

Mroz L, Benitez JG, and Krenzelok E, "Angioedema With Oral Acetylcysteine,"Clin Toxicol, 1995, 33(5):554-5

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.

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.

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.

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.

Walson PD and Groth JF Jr, "Acetaminophen Hepatotoxicity After Prolonged Ingestion,"Pediatrics, 1993, 91(5):1021-2.

Woo OF, Anderson IB, Kim SY, et al, "Shorter Duration of N-Acetylcysteine (NAC) for Acute Acetaminophen Poisoning,"Clin Toxicol, 1995, 33(5):508.

International Brand Names ACC® (AR, AT, DE, HU, LU, PL, ZA, CH); ACC eco® (CH); ACC injekt® (DE); acebraus® (DE); Acedyn® (AT); Acemuc (DE); Acemucol® (CH); Acemuk® (AR); Acetabs (DE); Acetein® (JP); Acetylcystein acis® (DE); Acetylcystein AL® (DE); Acetylcystein Atid® (DE); Acetylcystein Basics® (DE); Acetylcystein-Cophar® (CH); Acetylcystein Genericon® (AT); Acetylcystein Heumann® (DE); Acetylcystein-Mepha® (CH); Acetylcystein NM Pharma® (SE); Acetylcystein Nycomed® (AT); Acetylcystein Tika® (SE); Acetylcystein Trom® (DE, TR); Acetylin® (DE); Acetylocysteina® (PL); Acetyst® (DE); Acétylcystéine GNR® (FR); Aeromuc (AT); Airbron® (GB); Alveolex (IE); Asist® (TR); Azubronchin (DE); Bisolapid® (CH); Bisolbruis (NL); Bisolvon NAC (DE); Bromuc (DE); Broncho-Fips® (DE); Broncholysin® (CZ); Broncoclar (FR); Bronkyl® (NO); Brunac® (IT); Cimelin (AT); Cimexyl (AT); Codotussyl® (FR); Codotussyl Expectorant (FR); Cordes Granulat (DE); Cystamucil® (NL); Dampo Mucopect® (NL); Demolibral (CH); durabronchal® (DE); Dynamucil® (CH); Ecomucyl (CH); Ecomucyl® [inj.] (CH); Euronac® (MC); Exomuc (FR, LU); Fabrol® (GB); Fabrol (IE, SE); Fluimiquil® (LU); Fluimucil® (AR); Fluimucil (AT, BR, FR, DE, HK, HU, IT, NL, PT, ES, CH, YU); Fluimucil Solucao Nasal (BR); Fluimukan® (HR, SI); Fluprowit (DE); Freka (DE); Frekatuss (DE); Genac (FR); Génac® (FR); Granon (DK); Hidonac (IT); Hoestil® (NL); Hostop (DK); Humex® (FR); Humex Expectorant (FR); Husten ACC (AT); Ilube® (GB, IE); L-Cimexyl® (HK); L-Cimexyl (CH); Librochin acetylcysteine® (NL); Libronchin (NL); Locomucil (ES); Lubrisec® (AR); Lysodrop (BE); Lysomucil (BE, LU); Lysox® (BE, LU); M-Pectil® (NL); Mucisol® (IT, PL); Mucobene® (AT, HU); Mucocil (NL); Mucofim (BE); Mucofluid® (CH); Mucolair (BE, LU); Mucolator (BE, FR, HK, LU); Mucolysin (DK); Muco-Mepha® (CH); Mucomist (IT); Mucomyst (AU, AT, BE, CA, DK, FI, FR, LU, NL, NO, SE); Mucomyst® [inhal./inj.] (NL); Mucoporetta® (FI); Mucospire (FR); Mucostop® (CH); Mucret® (AT); Mukinex (NL); Mu-Off® (HK); NAC-ratiopharm® (LU); Neo Expectan (CH); Neo-Fluimucil® (BE); No-Muc® (CH); Oxxa® (TR); Parvolex (AU, CA, GB, IE, ZA); Pectomucil (BE, LU); Pharcetil® (HK); Pharcetil (NL); Pulmovent® (AT); Robitussin Expectorant (CH); Rumicil® (LU); Secresol (CH); Siccoral® (AT); Siran® (ID); Siran (CH); Solmucol (FR, HU, IT, LU, ZA, ES, CH); Solvomed® (AT); Sputopur® (HU); Tirocular® (IT); Tixair® (FR); Touxium Mucolyticum® (BE, LU); Tussicom® (PL); Viskoferm® (SE)