Acetylcysteine

Name: Acetylcysteine

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

Commonly used brand name(s)

In the U.S.

  • Acys-5
  • Cetylev

In Canada

  • Acetylcysteine

Available Dosage Forms:

  • Powder
  • Tablet, Effervescent
  • Capsule
  • Capsule, Extended Release
  • Tablet
  • Solution

Therapeutic Class: Amino Acid Supplement

Chemical Class: Amino Acid

Index Terms

  • N Acetylcysteine
  • N-Acetyl-L-cysteine
  • N-Acetylcysteine
  • Acetylcysteine Sodium
  • Cetylev
  • Mercapturic Acid
  • Mucomyst
  • NAC

Use Labeled Indications

Acetaminophen overdose: To prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in patients with acute ingestion or from repeated supratherapeutic ingestion (RSTI).

Mucolytic: Adjunct therapy in patients with abnormal, viscid, or inspissated mucous secretions in conditions such as: chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis, primary amyloidosis of the lung); acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis); pulmonary complications of cystic fibrosis; tracheostomy care; pulmonary complications associated with surgery; use during anesthesia; posttraumatic chest conditions; atelectasis due to mucous obstruction; diagnostic bronchial studies (bronchograms, bronchospirometry, bronchial wedge catheterization).

Dosing Adult

Acetaminophen overdose: Only the 72-hour oral and 21-hour IV regimens are FDA approved. Ideally, in patients with acute acetaminophen ingestion, treatment should begin within 8 hours of ingestion or as soon as possible after ingestion. In patients with a suspected acute ingestion where the time of ingestion is unknown, the concentration is unobtainable or uninterpretable within 8 hours of ingestion, the patient presents >8 hours after ingestion, or there is clinical evidence of toxicity, initiate treatment immediately and re-evaluate the need for acetylcysteine upon receipt of the results (if applicable). In patients who present following RSTI and treatment is deemed appropriate, acetylcysteine should be initiated immediately. Regardless of the treatment regimen selected, serum acetaminophen concentrations, liver function, and clinical status should be evaluated during and prior to the end of the treatment regimen to determine if treatment discontinuation is appropriate. In patients who continue to experience symptoms of hepatotoxicity or elevated liver function tests at the conclusion of a 72-hour oral or 21-hour IV regimen, extending the treatment course may be appropriate; however, when and to which patients additional doses should be administered is unclear. Possible candidates for extended therapy include patients with a suspected massive overdose, concomitant ingestion of other substances, or patients with preexisting liver disease. In patients with persistently elevated acetaminophen concentrations, persistently elevated liver function tests, or an elevated INR, additional acetylcysteine should be administered. Typically, an additional "third dose" or "third bag" (IV: 100 mg/kg [maximum: 10 g] infused over 16 hours) is administered; however, this dose may be inadequate in some patients (Rumack 2012). Consultation with a poison control center or clinical toxicologist is highly recommended to determine optimal patient care.

Oral: (Effervescent tablets [Cetylev]; solution for oral administration): Note: Consultation with a poison control center or clinical toxicologist is highly recommended when considering the discontinuation of oral acetylcysteine prior to the conclusion of a full 18-dose course of therapy.

72-hour regimen: Consists of 18 doses; total dose delivered: 1,330 mg/kg

Loading dose: 140 mg/kg

Maintenance dose: 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration

IV (Acetadote):

21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg

Loading dose: 150 mg/kg (maximum: 15 g) infused over 1 hour

Second dose: 50 mg/kg (maximum: 5 g) infused over 4 hours

Third dose: 100 mg/kg (maximum: 10 g) infused over 16 hours

Note: The fluid volume should be reduced in patients weighing ≤40 kg according to the following table:

Acetadote Dosing / Fluid Volume Guidelines for Patients ≤40 kg

Body Weight

(kg)

Loading Dose

150 mg/kg over 1 hour

Second Dose

50 mg/kg over 4 hours

Third Dose

100 mg/kg over 16 hours

Acetadote

(mL)

Diluent

(mL)

Acetadote

(mL)

Diluent

(mL)

Acetadote

(mL)

Diluent

(mL)

40

30

100

10

250

20

500

30

22.5

100

7.5

250

15

500

21

15.75

100

5.25

250

10.5

500

20

15

60

5

140

10

280

15

11.25

45

3.75

105

7.5

210

10

7.5

30

2.5

70

5

140

5

3.75

15

1.25

35

2.5

70

Table has been converted to the following text.

Acetadote Dosing / Fluid Volume Guidelines for Patients ≤40 kg

Body weight 40 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 30 mL in 100 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 10 mL in 250 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 20 mL in 500 mL diluent

Body weight 30 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 22.5 mL in 100 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 7.5 mL in 250 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 15 mL in 500 mL diluent

Body weight 21 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 15.75 mL in 100 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 5.25 mL in 250 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 10.5 mL in 500 mL diluent

Body weight 20 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 15 mL in 60 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 5 mL in 140 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 10 mL in 280 mL diluent

Body weight 15 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 11.25 mL in 45 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 3.75 mL in 105 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 7.5 mL in 210 mL diluent

Body weight 10 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 7.5 mL in 30 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 2.5 mL in 70 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 5 mL in 140 mL diluent

Body weight 5 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 3.75 mL in 15 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 1.25 mL in 35 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 2.5 mL in 70 mL diluent

Obesity: In patients who weigh >100 kg, the following dosing regimen is recommended:

Oral: Effervescent tablets (Cetylev): Limited information exists regarding the oral dosing requirements of patients >100 kg

72-hour regimen: Consists of 18 doses; total dose delivered: 142.5 g

Loading dose: 15 g

Maintenance dose: 7.5 g every 4 hours

IV (Acetadote): 21-hour regimen: Consists of 3 doses; total dose delivered: 30 g

Loading dose: 15 g infused over 1 hour

Second dose: 5 g infused over 4 hours

Third dose: 10 g infused over 16 hours

Adjuvant therapy in respiratory conditions:

Note: Patients should receive an aerosolized bronchodilator 10 to 15 minutes prior to dose.

Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted: 3 to 5 mL of 20% solution or 6 to 10 mL of 10% solution until nebulized given 3 to 4 times/day; dosing range: 1 to 10 mL of 20% solution or 2 to 20 mL of 10% solution every 2 to 6 hours

Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment

Direct instillation:

Into tracheostomy: 1 to 2 mL of 10% to 20% solution every 1 to 4 hours

Through percutaneous intratracheal catheter: 1 to 2 mL of 20% or 2 to 4 mL of 10% solution every 1 to 4 hours via syringe attached to catheter

Diagnostic bronchogram: Nebulization or intratracheal: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution administered 2 to 3 times prior to procedure

Prevention of contrast-induced nephropathy (off-label use): Oral: 1,200 mg every 12 hours starting the day prior to the procedure and on the day of procedure for a total of 4 doses. (ACT Investigators 2011). Note: No longer recommended for use prior to left ventricular angiography or percutaneous coronary intervention; instead adequate hydration is preferred (ACCF/AHA/SCAI [Levine 2011]; AHA/ACC [Amsterdam 2014]).

Dosing Geriatric

Refer to adult dosing.

Reconstitution

Effervescent tablets (Cetylev): Dissolve the effervescent tablets in the volume of water indicated below based upon patient weight; administer immediately:

1 to <20 kg: Dissolve two 2.5 g tablets in 100 mL of water to create a 50 mg/mL solution; administer an appropriate amount of this solution to deliver the calculated dose.

20 to <60 kg: Dissolve an appropriate number of tablets to deliver the calculated dose in 150 mL of water.

≥60 kg: Dissolve an appropriate number of tablets to deliver the calculated dose in 300 mL of water.

Solution for inhalation: The 20% solution may be diluted with sodium chloride or sterile water; the 10% solution may be used undiluted.

Intravenous administration of solution for inhalation/oral (off-label route): Using D5W, dilute acetylcysteine 20% inhalation/oral solution to a 3% solution.

Solution for injection (Acetadote): Note: Volume of diluent based on weight; compatible diluents include D5W, 1/2NS, or SWFI:

Patient weight 5 to 20 kg:

Loading dose: Dilute dose in 3 mL/kg diluent

Second dose: Dilute dose in 7 mL/kg diluent

Third dose: Dilute dose in 14 mL/kg diluent

Patient weight 21 to 40 kg:

Loading dose: Dilute dose in 100 mL diluent

Second dose: Dilute dose in 250 mL diluent

Third dose: Dilute dose in 500 mL diluent

Patient weight: ≥41 kg: Note: In patients requiring fluid restriction, decrease diluent volume.

Loading dose: Dilute dose in 200 mL diluent

Second dose: Dilute dose in 500 mL diluent

Third dose: Dilute dose in 1,000 mL diluent

Note: Clinicians should be aware that undiluted injection solution (Acetadote) is hyperosmolar (2,600 mOsmol/L); when the diluent volume is decreased for patients ≤40 kg or requiring fluid restriction, the osmolarity of the solution may remain higher than desirable for intravenous infusion. To ensure tolerance of the infusion, osmolarity should be adjusted to a physiologically safe level (eg, ≥150 mOsmol/L in children).

Acetadote concentration: 7 mg/mL

Osmolarity in D5W: 343 mOsmol/L

Osmolarity in 1/2NS: 245 mOsmol/L

Osmolarity in SWFI: 91 mOsmol/L

Acetadote concentration: 24 mg/mL

Osmolarity in D5W: 564 mOsmol/L

Osmolarity in 1/2NS: 466 mOsmol/L

Osmolarity in SWFI: 312 mOsmol/L

Solution for oral administration: Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink to prepare a 5% solution. If being administered via a nasogastric tube or Miller-Abbott tube, water may be used as the diluent. Use within 1 hour of preparation.

Drug Interactions

There are no known significant interactions.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Acute flushing and erythema have been reported; usually occurs within 30 to 60 minutes and may resolve spontaneously. Serious anaphylactoid reactions (some fatal) have also been reported and are more commonly associated with IV administration, but also occur with oral administration (Mroz 1997). When used for acetaminophen overdose, the incidence is reduced when the initial intravenous loading dose is administered over 60 minutes. The acetylcysteine infusion may be interrupted until the treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactoid reactions should be immediately available. Conversely, patients with high acetaminophen concentrations (>150 mg/L) may be at a reduced risk for anaphylactoid reactions (Pakravan 2008; Sandilands 2009; Waring 2008).

• Fluid overload: IV administration can cause fluid overload, potentially resulting in hyponatremia, seizure and death. To avoid fluid overload in patients ≤40 kg and those requiring fluid restriction, decrease volume of diluent proportionally (see table in dosing section).

Disease-related concerns:

• Asthma/bronchospasm: Use caution in patients with asthma or history of bronchospasm; these patients may be at increased risk of hypersensitivity reactions.

Other warnings/precautions:

• Acute acetaminophen overdose: Appropriate use: Acetylcysteine is indicated in patients with a serum acetaminophen concentration that indicates they are at "possible" risk or greater for hepatotoxicity when plotted on the Rumack-Matthew nomogram. There are several situations where the nomogram is of limited use. Serum acetaminophen concentrations obtained <4 hours postingestion are not reliable, except to document the presence of acetaminophen (Seifert 2015). Patients presenting late may have undetectable serum concentrations, despite having received a toxic dose. The nomogram is less predictive of hepatic injury following an acute overdose with an extended release acetaminophen product. The nomogram also does not take into account patients who may be at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients, concurrent use of CYP2E1 enzyme-inducing agents [eg, isoniazid]). Nevertheless, acetylcysteine should be administered to any patient with signs of hepatotoxicity, even if the serum acetaminophen concentration is low or undetectable. Patients who present >24 hours after an acute ingestion or patients who present following an acute ingestion at an unknown time may be candidates for acetylcysteine therapy; consultation with a poison control center or clinical toxicologist is highly recommended.

• Repeated supratherapeutic ingestion (RSTI) of acetaminophen: Appropriate use: The Rumack-Matthew nomogram is not designed to be used following RSTIs. In general, an accurate past medical history, including a comprehensive acetaminophen ingestion history, in conjunction with AST concentrations and serum acetaminophen concentrations, may give the clinician insight as to the patient's risk of acetaminophen toxicity. Some experts recommend that acetylcysteine be administered to any patient with "higher than expected" serum acetaminophen concentrations or serum acetaminophen concentration >10 mcg/mL, even in the absence of hepatic injury; others recommend treatment for patients with laboratory evidence and/or signs and symptoms of hepatotoxicity (Hendrickson 2006; Jones 2000). Consultation with a poison control center or a clinical toxicologist is highly recommended.

Dosage form specific issues:

• Effervescent tablets (Cetylev): Contains sodium; consider acetylcysteine treatment as a source of sodium in patients who may be sensitive to excess sodium intake (eg, heart failure, hypertension, renal impairment).

• Oral administration: Gastrointestinal hemorrhage: Oral administration of acetylcysteine may result in nausea and vomiting, which may exacerbate vomiting associated with acetaminophen overdose. Therefore, patients at risk of gastrointestinal hemorrhage (eg, esophageal varices, peptic ulcer) may experience an even higher risk of gastrointestinal hemorrhage during therapy.

• Inhalation: 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.

Acetylcysteine Drug Class

Acetylcysteine is part of the drug class:

  • Antidotes

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