Class: Antidotes
- Sulfhydryl Donors
VA Class: RE400
CAS Number: 616-91-1
Brands: Acetadote, Mucomyst

Medically reviewed by Drugs.com on Aug 23, 2021. Written by ASHP.

• Uses
• Dosage
• Cautions
• Interactions
• Pharmacokinetics
• Patient advice
• Preparations

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†. 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.

Acetylcysteine Dosage and Administration

General

• 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.

Nomogram relating plasma or serum acetaminophen concentration and probability of hepatotoxicity at varying intervals following ingestion of a single toxic dose of acetaminophen. Modified from Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975; 55:871-6. American Academy of Pediatrics 1975. And from Rumack BH et al. Acetaminophen overdose. Arch Intern Med. 1981; 141:380-5. American Medical Association.

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†.

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.

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

Nebulization

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 Instillation

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 Instillation

1–2 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†

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

Nebulization

For 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 Instillation

For 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 Instillation

1–2 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.

Interactions for Acetylcysteine

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

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Drug Compatibility

Oral Inhalation, Intratracheal Instillation

Presence of light purple color in solution does not appreciably affect potency.

Drug Compatibility

Incompatible with oxidizing agents.

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).

• 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.

• 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

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• 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.

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