Acetylcysteine (Monograph)
Brand names: Acetadote, Mucomyst
Drug class: Antidotes
- Sulfhydryl Donors
VA class: RE400
CAS number: 616-91-1
Introduction
Antidote for acetaminophen overdosage; mucolytic agent and sulfhydryl donor.
Uses for Acetylcysteine
Antidote for Acetaminophen Overdosage
Treatment of acetaminophen overdosage. Optimal if given within 8 hours of acetaminophen ingestion; may be effective when given ≥24 hours after ingestion.
Prevention of Nephropathy Associated with Radiographic Contrast Media
Has been used to prevent radiographic contrast media-induced nephropathy† [off-label]. Efficacy for this indication not established; additional study needed.
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.
Used during anesthesia and in the preparation of patients for bronchograms, bronchospirometry, bronchial wedge catheterization, and other diagnostic bronchial studies.
Tracheostomy care.
Related/similar drugs
ambroxol, ascorbic acid, biotin, Vitamin C, multivitamin, Dextrose, niacin
Acetylcysteine Dosage and Administration
General
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Determine plasma or serum acetaminophen concentrations as soon as possible (but no sooner than 4 hours) after ingestion. May be appropriate to obtain an additional sample at 4–6 hours after initial sample if extended-release acetaminophen preparation was ingested.
-
Use plasma or serum acetaminophen concentrations in conjunction with a nomogram to estimate potential for hepatotoxicity and necessity of acetylcysteine therapy.
-
Full course of acetylcysteine therapy indicated if initial plasma or serum acetaminophen concentrations fall on or above the dashed line on the nomogram. (See nomogram.)
-
Assistance available from a regional poison center at 800-222-1222 or an assistance line for acetaminophen overdosage at 800-525-6115.
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. Plasma AST/ALT concentrations and plasma or serum acetaminophen concentrations have been used to estimate potential for hepatotoxicity and necessity of acetylcysteine therapy.
-
Assistance available from a regional poison center at 800-222-1222 or an assistance line for acetaminophen overdosage at 800-525-6115.
Administration
Administer orally or by IV infusion as an antidote for acetaminophen overdosage; administer by oral inhalation or intracheal instillation for mucolytic uses.
Has been administered orally or IV for prevention of radiographic contrast media-induced nephropathy† [off-label].
Oral Administration
Usually administered as a 5% solution. Dilute 20% solution 1:3 with diet soft drink.
Initiate antiemetic therapy or administer via duodenal tube if persistently unable to retain orally administered drug.
NG Tube
Administer as 5% solution; may use water as the diluent.
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.
Injection concentrate must be diluted prior to IV administration.
Dilution
Dilute dose with an appropriate volume of 5% dextrose injection (see Table 1).
Adjust total volume for patients who weigh <40 kg (see Table 1) and for those requiring fluid restriction.
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.
First maintenance dose: Infuse over 4 hours.
Second maintenance dose: Infuse over 16 hours.
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.
May use 10% acetylcysteine solution undiluted.
Dosage
Available as acetylcysteine and acetylcysteine sodium; dosage expressed in terms of acetylcysteine.
Pediatric Patients
Antidote for Acetaminophen Overdosage
Oral
Loading dose: 140 mg/kg, administered as soon as possible. Maintenance dosage, if indicated: 70 mg/kg every 4 hours for 17 doses.
If patient vomits a loading or maintenance dose within 1 hour of administration, repeat the dose.
IV
Loading dose: 150 mg/kg, administered as soon as possible.
First maintenance dose: 50 mg/kg.
Second maintenance dose: 100 mg/kg.
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.
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. Administer intermittently or for continuous prolonged periods.
Direct Instillation
1–2 mL of a 10–20% solution as often as every hour.
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.
Instillation through a catheter into the trachea: 2–5 mL of the 20% solution via a syringe attached to the catheter.
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.
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.
Tracheostomy Care
Intratracheal Instillation1–2 mL of a 10–20% solution into the tracheostomy every 1–4 hours.
Adults
Antidote for Acetaminophen Overdosage
Oral
Loading dose: 140 mg/kg, administered as soon as possible. Maintenance dosage, if indicated: 70 mg/kg every 4 hours for 17 doses.
If patient vomits a loading or maintenance dose within 1 hour of administration, repeat the dose.
IV
Loading dose: 150 mg/kg, administered as soon as possible.
First maintenance dose: 50 mg/kg.
Second maintenance dose: 100 mg/kg.
Prevention of Nephropathy Associated with Radiographic Contrast Media† [off-label]
Oral
600 mg twice daily, given the day before and the day of contrast media administration (total of 4 doses), has been used. Other dosage regimens have been investigated.
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.
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. Administer intermittently or for continuous prolonged periods.
Direct Instillation
1–2 mL of a 10–20% solution as often as every hour.
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.
Instillation through a catheter into the trachea: 2–5 mL of the 20% solution via a syringe attached to the catheter.
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.
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.
Tracheostomy Care
Intratracheal Instillation1–2 mL of a 10–20% solution into the tracheostomy every 1–4 hours.
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. Data are not available to determine whether dosage adjustment is needed in patients with hepatic cirrhosis.
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.
Cautions for Acetylcysteine
Contraindications
-
When administered orally as an antidote, no contraindications.
-
For other uses (including IV administration as an antidote), hypersensitivity to acetylcysteine or any ingredient in the formulation.
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.
Respiratory Effects
Volume of liquefied bronchial secretions may increase following oral inhalation or intratracheal instillation; potential for airway occlusion. If cough is inadequate to maintain an open airway, institute mechanical suction or endotracheal aspiration.
Observe asthmatic patients closely.
If bronchospasm occurs, give a bronchodilator by nebulization. If bronchospasm progresses, discontinue acetylcysteine immediately.
When administered IV, caution in patients with asthma or history of bronchospasm.
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.
Acute flushing and erythema also reported; these reactions generally occur 30–60 minutes after initiation of the infusion and resolve despite continued infusion. Reactions to acetylcysteine that involve symptoms other than flushing and erythema should be considered anaphylactoid reactions and treated as such.
If an anaphylactoid reaction occurs, temporarily interrupt IV acetylcysteine to administer antihistamines and, in severe reactions, epinephrine. Once treatment of the anaphylactoid reaction has been initiated, carefully reinstitute IV acetylcysteine. If the anaphylactoid reaction recurs or increases in severity, discontinue IV acetylcysteine and consider alternative management.
Other Allergic Reactions
Generalized urticaria reported rarely in patients receiving oral acetylcysteine for acetaminophen overdosage. 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.
Sensitization
Sensitization reported rarely.
Major Toxicities
GI Effects
Oral administration may result in vomiting or may aggravate vomiting associated with acetaminophen overdosage.
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.
Specific Populations
Pregnancy
Category B.
Lactation
Not known whether acetylcysteine is distributed into milk; caution advised.
Pediatric Use
Efficacy of IV acetylcysteine as an antidote for acetaminophen overdosage appears to be similar to that in adults.
Geriatric Use
Insufficient experience with IV acetylcysteine in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.
Common Adverse Effects
Oral administration: Nausea, vomiting, other GI symptoms, rash with or without fever.
IV administration: Rash, urticaria, pruritus.
Oral inhalation/intratracheal instillation: Stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess.
Activated Charcoal
Possible interference with absorption of oral acetylcysteine; however, usual dosage of acetylcysteine is appropriate in patients given activated charcoal (higher dosages not necessary).
Acetylcysteine Pharmacokinetics
Absorption
Bioavailability
Absorbed following oral administration, with peak plasma concentrations achieved within 1–2 hours.
Absorbed from the pulmonary epithelium.
Distribution
Extent
Crosses the placenta following oral or IV administration.
Plasma Protein Binding
50–83%.
Elimination
Metabolism
Deacetylated in the liver to cysteine.
Elimination Route
Principally (70%) nonrenal.
Half-life
6.25 hours after oral administration.
5.6 hours after IV administration in adults.
11 hours after IV administration in neonates.
Special Populations
In patients with hepatic cirrhosis, plasma concentrations following IV administration are threefold higher. 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]).
Stability
Storage
Oral, Oral Inhalation, Intratracheal Instillation
Solution
15–30°C. Use diluted solutions within 1 hour. Store undiluted solution in opened vials in refrigerator; use within 96 hours. Do not store admixtures.
Parenteral
Injection Concentrate for IV Infusion
20–25°C.
Presence of light pink to light purple color in solution does not affect the quality of the product.
Following dilution with 5% dextrose, stable at controlled room temperature for 24 hours.
Compatibility
Parenteral
Solution Compatibility
Compatible |
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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.
Drug Compatibility
Incompatible with oxidizing agents.
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
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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).
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Thiol-containing antioxidant. May act as an oxygen free-radical scavenger to prevent radiographic contrast media-induced renal toxicity; also may increase the biologic effects of nitric oxide by combining with the oxide to form S-nitrosothiol, a potent vasodilator.
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Reduces viscosity of purulent and nonpurulent pulmonary secretions and facilitates their removal by coughing, postural drainage, or mechanical means. Mucolytic effect depends on the free sulfhydryl group, which appears to reduce disulfide linkages of mucoproteins through an interchange reaction.
Advice to Patients
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Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
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Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
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Importance of informing patients of other important precautionary information. (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 |
Mucomyst |
Sandoz |
|||
200 mg (of acetylcysteine) per mL (20%) |
Acetylcysteine Sodium Solution |
Abbott |
||
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 2024, Selected Revisions September 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
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