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

Introduction

Antidote for acetaminophen overdosage; mucolytic agent and sulfhydryl donor.^{102 103 104 108}

Uses for Acetylcysteine

Antidote for Acetaminophen Overdosage

Treatment of acetaminophen overdosage.^{102 103 104 108} Optimal if given within 8 hours of acetaminophen ingestion;¹⁰⁹ may be effective when given ≥24 hours after ingestion.^{105 106}

Prevention of Nephropathy Associated with Radiographic Contrast Media

Has been used to prevent radiographic contrast media-induced nephropathy†.^{100 101 110 111 112 113 114 116 117} Efficacy for this indication not established; additional study needed.^{110 115 117}

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.^{102 103 104}

Used during anesthesia and in the preparation of patients for bronchograms, bronchospirometry, bronchial wedge catheterization, and other diagnostic bronchial studies.^{102 103 104}

Tracheostomy care.^{102 103 104}

Acetylcysteine Dosage and Administration

General

• Determine plasma or serum acetaminophen concentrations as soon as possible (but no sooner than 4 hours) after ingestion.¹⁰⁷ May be appropriate to obtain an additional sample at 4–6 hours after initial sample if extended-release acetaminophen preparation was ingested.¹⁰⁷

• Use plasma or serum acetaminophen concentrations in conjunction with a nomogram to estimate potential for hepatotoxicity and necessity of acetylcysteine therapy.^{105 107}

• Full course of acetylcysteine therapy indicated if initial plasma or serum acetaminophen concentrations fall on or above the dashed line on the nomogram.¹⁰⁵ (See nomogram.)^{106 107}

• Assistance available from a regional poison center at 800-222-1222 or an assistance line for acetaminophen overdosage at 800-525-6115.¹⁰⁸

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.¹¹⁸ Plasma AST/ALT concentrations and plasma or serum acetaminophen concentrations have been used to estimate potential for hepatotoxicity and necessity of acetylcysteine therapy.^{108 118}

• Assistance available from a regional poison center at 800-222-1222 or an assistance line for acetaminophen overdosage at 800-525-6115.¹⁰⁸

Administration

Administer orally or by IV infusion as an antidote for acetaminophen overdosage; administer by oral inhalation or intracheal instillation for mucolytic uses.^{102 103 104 108}

Has been administered orally^{100 110 117} or IV^{110 117} for prevention of radiographic contrast media-induced nephropathy†.

Oral Administration

Usually administered as a 5% solution.^{102 103 104} Dilute 20% solution 1:3 with diet soft drink.^{102 103 104}

Initiate antiemetic therapy or administer via duodenal tube if persistently unable to retain orally administered drug.¹⁰⁷

NG Tube

Administer as 5% solution; may use water as the diluent.^{102 103 104}

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.¹⁰⁸

Injection concentrate must be diluted prior to IV administration.¹⁰⁸

Dilution

Dilute dose with an appropriate volume of 5% dextrose injection (see Table 1).¹⁰⁸

Adjust total volume for patients who weigh <40 kg (see Table 1) and for those requiring fluid restriction.¹⁰⁸

Rate of Administration

Loading dose: Infuse over 60 minutes.^{108 109}

First maintenance dose: Infuse over 4 hours.¹⁰⁸

Second maintenance dose: Infuse over 16 hours.¹⁰⁸

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.^{102 103 104}

May use 10% acetylcysteine solution undiluted.^{102 103 104}

Dosage

Available as acetylcysteine and acetylcysteine sodium; dosage expressed in terms of acetylcysteine.^{102 103 103 108}

Pediatric Patients

Antidote for Acetaminophen Overdosage

Oral

Loading dose: 140 mg/kg, administered as soon as possible.^{102 103 104} Maintenance dosage, if indicated: 70 mg/kg every 4 hours for 17 doses.^{102 103 104}

If patient vomits a loading or maintenance dose within 1 hour of administration, repeat the dose.¹⁰⁷

IV

Loading dose: 150 mg/kg, administered as soon as possible.^{107 108}

First maintenance dose: 50 mg/kg.^{107 108}

Second maintenance dose: 100 mg/kg.^{107 108}

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.^{102 103 104}

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.^{102 103 104} Administer intermittently or for continuous prolonged periods.^{102 103 104}

Direct Instillation

1–2 mL of a 10–20% solution as often as every hour.^{102 103 104}

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.^{102 103 104}

Instillation through a catheter into the trachea: 2–5 mL of the 20% solution via a syringe attached to the catheter.^{102 103 104}

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.^{102 103 104}

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.^{102 103 104}

Tracheostomy Care

Intratracheal Instillation

1–2 mL of a 10–20% solution into the tracheostomy every 1–4 hours.^{102 103 104}

Adults

Antidote for Acetaminophen Overdosage

Oral

Loading dose: 140 mg/kg, administered as soon as possible.^{102 103 104} Maintenance dosage, if indicated: 70 mg/kg every 4 hours for 17 doses.^{102 103 104}

If patient vomits a loading or maintenance dose within 1 hour of administration, repeat the dose.¹⁰⁷

IV

Loading dose: 150 mg/kg, administered as soon as possible.¹⁰⁸

First maintenance dose: 50 mg/kg.¹⁰⁸

Second maintenance dose: 100 mg/kg.¹⁰⁸

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.^{100 110 117} Other dosage regimens have been investigated.^{110 117}

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.^{102 103 104}

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.^{102 103 104} Administer intermittently or for continuous prolonged periods.^{102 103 104}

Direct Instillation

1–2 mL of a 10–20% solution as often as every hour.^{102 103 104}

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.^{102 103 104}

Instillation through a catheter into the trachea: 2–5 mL of the 20% solution via a syringe attached to the catheter.^{102 103 104}

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.^{102 103 104}

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.^{102 103 104}

Tracheostomy Care

Intratracheal Instillation

1–2 mL of a 10–20% solution into the tracheostomy every 1–4 hours.^{102 103 104}

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.¹⁰⁸ Data are not available to determine whether dosage adjustment is needed in patients with hepatic cirrhosis.¹⁰⁸

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.¹⁰⁸

Cautions for Acetylcysteine

Contraindications

• When administered orally as an antidote, no contraindications.^{102 103 104}

• For other uses (including IV administration as an antidote), hypersensitivity to acetylcysteine or any ingredient in the formulation.^{102 103 104 108}

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.^{102 103 104}

Respiratory Effects

Volume of liquefied bronchial secretions may increase following oral inhalation or intratracheal instillation; potential for airway occlusion.^{102 103 104} If cough is inadequate to maintain an open airway, institute mechanical suction or endotracheal aspiration.^{102 103 104}

Observe asthmatic patients closely.^{102 103 104}

If bronchospasm occurs, give a bronchodilator by nebulization.^{102 103 104} If bronchospasm progresses, discontinue acetylcysteine immediately.^{102 103 104}

When administered IV, caution in patients with asthma or history of bronchospasm.¹⁰⁸

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.¹⁰⁸

Acute flushing and erythema also reported; these reactions generally occur 30–60 minutes after initiation of the infusion and resolve despite continued infusion.¹⁰⁸ Reactions to acetylcysteine that involve symptoms other than flushing and erythema should be considered anaphylactoid reactions and treated as such.¹⁰⁸

If an anaphylactoid reaction occurs, temporarily interrupt IV acetylcysteine to administer antihistamines and, in severe reactions, epinephrine.¹⁰⁸ Once treatment of the anaphylactoid reaction has been initiated, carefully reinstitute IV acetylcysteine.¹⁰⁸ If the anaphylactoid reaction recurs or increases in severity, discontinue IV acetylcysteine and consider alternative management.¹⁰⁸

Other Allergic Reactions

Generalized urticaria reported rarely in patients receiving oral acetylcysteine for acetaminophen overdosage.^{102 103 104} 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.^{102 103 104}

Sensitization

Sensitization reported rarely.^{102 103 104}

Major Toxicities

GI Effects

Oral administration may result in vomiting or may aggravate vomiting associated with acetaminophen overdosage.^{102 103 104}

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.^{102 103 104}

Specific Populations

Pregnancy

Category B.^{102 103 104 108}

Lactation

Not known whether acetylcysteine is distributed into milk; caution advised.^{102 103 104 108}

Pediatric Use

Efficacy of IV acetylcysteine as an antidote for acetaminophen overdosage appears to be similar to that in adults.¹⁰⁸

Geriatric Use

Insufficient experience with IV acetylcysteine in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹⁰⁸

Common Adverse Effects

Oral administration: Nausea, vomiting, other GI symptoms, rash with or without fever.^{102 103 104}

IV administration: Rash, urticaria, pruritus.¹⁰⁸

Oral inhalation/intratracheal instillation: Stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess.^{102 103 104}

Interactions for Acetylcysteine

Activated Charcoal

Possible interference with absorption of oral acetylcysteine; ¹¹⁹ however, usual dosage of acetylcysteine is appropriate in patients given activated charcoal (higher dosages not necessary).^{105 106 107}

Acetylcysteine Pharmacokinetics

Absorption

Bioavailability

Absorbed following oral administration, with peak plasma concentrations achieved within 1–2 hours.^{a 119}

Absorbed from the pulmonary epithelium.^a

Distribution

Extent

Crosses the placenta following oral or IV administration.¹⁰⁸

Plasma Protein Binding

50–83%.^{108 119}

Elimination

Metabolism

Deacetylated in the liver to cysteine.^a

Elimination Route

Principally (70%) nonrenal.¹¹⁹

Half-life

6.25 hours after oral administration.¹¹⁹

5.6 hours after IV administration in adults.¹⁰⁸

11 hours after IV administration in neonates.¹⁰⁸

Special Populations

In patients with hepatic cirrhosis, plasma concentrations following IV administration are threefold higher.¹⁰⁸ 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]).¹⁰⁸

Stability

Storage

Oral, Oral Inhalation, Intratracheal Instillation

Solution

15–30°C.^{102 103 104} Use diluted solutions within 1 hour.^{102 103 104} Store undiluted solution in opened vials in refrigerator; use within 96 hours.^{102 103 104} Do not store admixtures.^{102 103 104}

Parenteral

Injection Concentrate for IV Infusion

20–25°C.¹⁰⁸

Presence of light pink to light purple color in solution does not affect the quality of the product.¹⁰⁸

Following dilution with 5% dextrose, stable at controlled room temperature for 24 hours.¹⁰⁸

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.^{102 103 104 a}

Drug Compatibility

Incompatible with oxidizing agents.^a

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).^{102 103 104}

• Thiol-containing antioxidant.¹⁰⁰ May act as an oxygen free-radical scavenger to prevent radiographic contrast media-induced renal toxicity;¹⁰⁰ also may increase the biologic effects of nitric oxide by combining with the oxide to form S-nitrosothiol, a potent vasodilator.¹⁰¹

• Reduces viscosity of purulent and nonpurulent pulmonary secretions and facilitates their removal by coughing, postural drainage, or mechanical means.^{102 103 104} Mucolytic effect depends on the free sulfhydryl group, which appears to reduce disulfide linkages of mucoproteins through an interchange reaction.^{102 103 104}

Advice to Patients

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{102 103 104}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{102 103 104}

• Importance of informing patients of other important precautionary information.^{102 103 104} (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.