Acetylcysteine

U.S. BRAND NAMES — Acetadote®
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
SYNONYMS — N-Acetyl-L-Cysteine; N-Acetylcysteine; Mercapturic Acid; NAC
THERAPEUTIC CATEGORY Antidote, AcetaminophenMucolytic Agent
DOSING
(For additional information see "Acetylcysteine: Drug information")Acetaminophen poisoning: Children and Adults: Begin treatment within 8 hours of ingestion to optimize therapy in patients whose serum acetaminophen levels fall above the "possible" toxicity line on the Rumack-Matthew nomogram Treatment is also indicated in patients with a history of known or suspected acute acetaminophen ingestion of >150 mg/kg (child) or >7.5 g (adolescent or adult) total dose when plasma levels are not available within 8-10 hours of ingestion or in patients presenting >24 hours after acute ingestion who have a measurable acetaminophen level. See Warnings. I.V.: 150 mg/kg infused over 60 minutes; followed by a 4-hour infusion of 50 mg/kg; followed by a 16-hour infusion of 100 mg/kg; equivalent to a total dose of 300 mg/kg infused over 21 hours 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
Nebulized inhalation: Infants: 1-2 mL of 20% solution or 2-4 mL of 10% solution until nebulized, given 3-4 times/day Children: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized, given 3-4 times/day Adolescents: 5-10 mL of 10% to 20% solution until nebulized, given 3-4 times/day Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Intratracheal: Children and Adults: 1-2 mL of 10% to 20% solution every 1-4 hours as needed
Distal intestinal obstruction syndrome (previously known as meconium ileus equivalent): Varying regimens have been reported (polyethylene glycol has become more widely used for this indication): Oral: Children <10 years: 30 mL of 10% solution diluted in 30 mL juice or soda 3 times/day for 24 hours Children 10 years and Adults: 60 mL of 10% solution diluted in 60 mL juice or soda 3 times/day for 24 hours Note: Prior to treatment, administer a phosphosoda enema. A clear liquid diet should be used during the 24-hour acetylcysteine treatment Rectal enema: Children: Varying dosages; 100-300 mL of 4% to 6% solution 2-4 times/day; 50 mL of 20% solution 1-4 times/day and 5-30 mL of 10% to 20% solution 3-4 times/day have been used; rectal enemas appear to have less favorable results than oral administration (Mascarenhas, 2003) Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Adults: Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); hydrate patient concurrently
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
GENERIC AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION Parenteral: I.V.: Three infusions (See Usual Dosage) of different lengths: Dilute first dose (150 mg/kg) in 200 mL D5W and infuse over 60 minutes; dilute second dose (50 mg/kg) in 500 mL D5W and infuse over 4 hours; dilute third dose (100 mg/kg) in 1000 mL D5W and infuse over 16 hours; for children <40 kg and patients who are fluid restricted, the manufacturer recommends reducing the diluent to a "proportional" amount. See table for manufacturer's recommended infusion guideline for patients <40 kg. Or as an alternative to proportionally lower the diluent volume, a reasonable approach might be to utilize the concentrations resulting from using the recommended dilution for the dosage in a 50 kg patient. The calculated concentration would range between 5 mg/mL (maintenance infusion) to 37.5 mg/mL (loading dose).
Infusion Guide by Weight for Patients <40 kg Body Weight = 10 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 30 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 500 mg (2.5 mL) 5% dextrose: 70 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL Body Weight = 15 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 2250 mg (11.25 mL) 5% dextrose: 45 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 750 mg (3.75 mL) 5% dextrose: 105 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 210 mL Body Weight = 20 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 60 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2000 mg (10 mL) 5% dextrose: 280 mL Body Weight = 25 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3750 mg (18.75 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1250 mg (6.25 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2500 mg (12.5 mL) 5% dextrose: 500 mL Body Weight = 30 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 4500 mg (22.5 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 500 mL
Oral: For treatment of acetaminophen overdosage, administer as a 5% solution; dilute the 20% solution (inhalation formulation) 1:3 with a cola, orange juice, or other soft drink; use within 1 hour of preparation
Oral inhalation: May be administered by nebulization either undiluted (both 10% and 20%) or diluted in NS
Rectal: Dilute the inhalation solution in NS to the desired final concentration and administer rectally
USE Inhalation: Adjunctive therapy in patients with abnormal or viscid mucous secretions in bronchopulmonary diseases, pulmonary complications of surgery, and cystic fibrosis; diagnostic bronchial studies
Injection, Oral: Antidote for acute acetaminophen toxicity; prevention of radiocontrast-induced renal dysfunction
Oral, rectal: Treatment of distal intestinal obstruction syndrome (previously known as "meconium ileus or its equivalent")
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypotension, syncope, chest tightness, vasodilation, hypertension (after large oral doses)
Central nervous system: Drowsiness, chills, dysphoria
Dermatologic: Generalized urticaria, rash, pruritus, erythema, angioedema
Gastrointestinal: Stomatitis, nausea, vomiting, dyspepsia, hemoptysis
Hepatic: Mild elevations in liver function tests have occurred after oral therapy
Ocular: Eye pain
Respiratory: Bronchospasm, rhinorrhea, cough
Miscellaneous: Anaphylactoid reactions (I.V. use; 17% in an open label study; 1% reported as severe or moderate in 10% of patients within 15 minutes of the first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after the 60 minute infusion); diaphoresis, unpleasant odor during administration
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component
PRECAUTIONS — Use with caution in patients with asthma or previous history of bronchospasm
WARNINGS — Serious anaphylactoid reactions including death in a patient with asthma have been reported after I.V. use; acute flushing and erythema may occur 30-60 minutes into an I.V. infusion, resolving spontaneously; the infusion may be interrupted until treatment of allergic symptoms is initiated; if acute hypersensitivity reactions occur which do not respond to medical management (eg, antihistamines, H2 blockers) or temporarily halting infusion, discontinue use and pursue alternative management. Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow.
Acetaminophen overdose: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients) or individuals ingesting higher than recommended acetaminophen doses for extended periods of time (repeated supratherapeutic ingestion).
DRUG INTERACTIONS — May potentiate the hemodynamic effects of nitroglycerin; acetylcysteine is adsorbed by activated charcoal
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — When used in acetaminophen overdose, determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion of immediate release formulations or 2 hours after ingestion of liquid formulations (to ensure peak levels have been obtained); coingestion of acetaminophen with other medications which may delay GI peristalsis eg, antihistamines, opioids, may require repeated serum levels to determine the peak serum level; liver function tests
STABILITY — Store at room temperature; I.V. formulation is preservative free and stable 24 hours after dilution at room temperature; opened inhalation solution vials may be stored in the refrigerator; use within 96 hours; contact with rubber, copper, iron, and cork may inactivate the drug; the light purple color of solution does not affect its activity. I.V. acetylcysteine is hyperosmolar (2600 mOsm/L) and is compatible with 5% dextrose, 0.45% sodium chloride, and SWI.
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering the viscosity. The exact mechanism of action in acetaminophen toxicity is unknown. It may act by maintaining or restoring glutathione levels or by acting as an alternative substrate for conjugation with the acetaminophen's toxic metabolite.
PHARMACODYNAMICS Onset of action: Upon inhalation, mucus liquefaction occurs maximally within 5-10 minutes
Duration of mucus liquefaction: More than 1 hour
PHARMACOKINETICS Distribution: Vd: 0.47 L/kg
Protein binding: 83%
Half-life: Reduced acetylcysteine: 2 hours Total acetylcysteine: Newborns: 11 hours Adults: 5.6 hours
Time to peak serum concentration: Oral: 1-2 hours
Elimination: Clearance: Adults: 0.11 L/hour/kg
PATIENT INFORMATION — Clear airway by coughing deeply before aerosol treatment
(For additional information see "Acetylcysteine: Patient drug information")
NURSING IMPLICATIONS — Anaphylactoid reactions following I.V. administration have been reported; have emergency treatments such as antihistamines and H2 blockers readily available for potential adverse effects; 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