Acetaminophen overdose: Note: Only the 72-hour oral and 21-hour IV regimens are FDA approved.
Initiation of therapy: Ideally, in patients with acute acetaminophen ingestion, treatment should begin within 8 hours of ingestion or as soon as possible after ingestion. If there will be a delay in obtaining a serum acetaminophen concentration, initiate treatment as soon as possible and re-evaluate the need for acetylcysteine upon receipt of the results. In patients who meet the criteria for acetylcysteine therapy based on the initial serum acetaminophen concentration, there is no reason to obtain additional acetaminophen concentrations, even in a patient who ingested an ER product. 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 repeated supratherapeutic ingestion and treatment is deemed appropriate, acetylcysteine should be initiated immediately. It is critical that there is no delay in the administration of the loading dose of acetylcysteine and no delay in the administration of bags 2 and 3 (Ref).
Note: There is no reason to withhold activated charcoal in a patient with an acetaminophen overdose. If activated charcoal is administered within 1 to 2 hours postingestion of acetaminophen, it may provide additional hepatoprotection in patients requiring N-acetylcysteine (NAC) treatment for acetaminophen overdose (Ref).
Duration of therapy: Discontinue treatment if the initial serum acetaminophen concentration indicates the patient is at "low" risk for hepatotoxicity when plotted on the Rumack-Matthew nomogram. In those patients who require a follow-up acetaminophen concentration, do not discontinue treatment if the follow-up serum acetaminophen concentration indicates the patient is at "low" risk for hepatotoxicity. In patients who continue to experience symptoms of hepatotoxicity or elevated LFTs 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 LFTs, 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 (Ref). 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. Some authors suggest continuing therapy until there are undetectable acetaminophen concentrations, improving hepatic aminotransferases, and improving prognostic markers (eg, creatinine, lactate pH, PT/INR, phosphate) (Ref). In patients with a low risk for acetaminophen-induced hepatotoxicity, an abbreviated 12-hour NAC dosing regimen has been compared to a 20-hour protocol; no difference was shown in measured acetaminophen metabolites or clinical outcomes (Ref). A 2-bag regimen with the same total dose of 300 mg/kg has been used but is not FDA approved (Ref). 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: Under certain circumstances, some experts may recommend a shortened course of oral acetylcysteine therapy (<72 hours of treatment) despite not being FDA approved (Ref). 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:
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.
Alternative recommendations : Note: Institution-specific regimens may exist; consultation with a poison control center or clinical toxicologist is highly recommended to determine optimal patient care. Clinicians should note that experience with these dosing methods is limited.
"Two bag method" (off-label dosing): Consists of 2 doses; total dose delivered: 300 mg/kg (Ref):
First dose: 200 mg/kg infused over 4 hours.
Second dose: 100 mg/kg infused over 16 hours.
Note: The "two bag method" has been associated with fewer and milder nonallergic anaphylactic reactions as compared to the manufacturer's labeled dosing (Ref).
"Single bag method" (off-label dosing): Total dose delivered 430 mg/kg: Initiate therapy with 150 mg/kg infused over 1 hour; then decrease the rate to 14 mg/kg/hour and infuse for an additional 20 hours (Ref).
Note: Patients weighing >69 kg will require a second bag to complete the dosing regimen.
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: For inhaled/nebulized/direct instillation therapy, may consider premedication with an aerosolized bronchodilator 10 to 15 minutes prior to dose in patients with reactive airway disease or in patients who develop bronchospasm.
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: Note: For inhaled/nebulized/direct instillation therapy, may consider premedication with an aerosolized bronchodilator 10 to 15 minutes prior to dose in patients with reactive airway disease or in patients who develop bronchospasm.
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.
Oral, IV: There are no dosage adjustments provided in the manufacturer's labeling.
Oral, IV: There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Acetylcysteine: Pediatric drug information")
Acetaminophen poisoning:
Note: Only the 72-hour oral and 21-hour IV regimens are FDA approved.
Initiation of therapy:
Ideally, in patients with an acute acetaminophen ingestion, treatment should begin within 8 hours of ingestion or as soon as possible after ingestion. If there will be a delay in obtaining a serum acetaminophen concentration, initiate treatment as soon as possible and reevaluate the need for continued acetylcysteine upon receipt of the results. In patients who meet the criteria for acetylcysteine therapy based on the initial serum acetaminophen concentration, there is no reason to obtain additional acetaminophen concentrations, even in a patient who ingested an extended-release product. In patients with a suspected acute ingestion where the time of ingestion is unknown, the serum acetaminophen 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 repeated supratherapeutic ingestions (RSTI) and treatment is deemed appropriate, acetylcysteine should be initiated immediately. It is critical that there is no delay in the administration of the loading dose of acetylcysteine and no delays in the administration of bags 2 and 3 (Ref).
Note: There is no reason to withhold activated charcoal in a patient with an acetaminophen overdose. If activated charcoal is administered within 1 to 2 hours postingestion of acetaminophen, it may provide additional hepatoprotection in patients requiring N-acetylcysteine treatment for acetaminophen overdose (Ref).
Duration of therapy:
Discontinue treatment if the initial serum acetaminophen concentration indicates the patient is at "low" risk for hepatotoxicity when plotted on the Rumack-Matthew nomogram. In those patients who require a follow-up acetaminophen concentration, do not discontinue treatment if the follow-up serum acetaminophen concentration indicates the patient is at "low" risk for hepatotoxicity. 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 dose: 10 g/dose] infused over 16 hours) is administered; however, this dose may be inadequate in some patients (Ref). 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. Some experts suggest continuing therapy until there are undetectable acetaminophen concentrations, improving hepatic aminotransferases, and improving prognostic markers (eg, creatinine, lactate pH, prothrombin time/INR, phosphate) (Ref). In patients with a low risk for acetaminophen-induced hepatotoxicity, an abbreviated 12-hour N-acetylcysteine dosing regime has been compared to a 20-hour protocol; no difference was shown in measured acetaminophen metabolites or clinical outcomes (Ref). A two-bag regimen with the same total dose of 300 mg/kg has been used, but is not FDA-approved (Ref). Consultation with a poison control center or clinical toxicologist is highly recommended to determine optimal patient care.
Oral: Effervescent tablet (Cetylev) or solution for oral administration (using injectable/nebulizer formulation):
Note: There is no data for use of the OTC supplement tablets for acetaminophen poisoning. Dosing below is based on effervescent tablet (Cetylev) or a solution for oral administration that is prepared from the solution for oral inhalation:
Infants, Children, and Adolescents: 72-hour regimen: Consists of 18 doses; total dose delivered: 1,330 mg/kg.
Loading dose: Oral: 140 mg/kg; maximum dose: 15 g/dose.
Maintenance dose: Oral: 70 mg/kg every 4 hours for 17 doses; maximum dose: 7.5 g/dose; repeat dose if emesis occurs within 1 hour of administration; Note: Although not FDA approved, some experts may recommend a shortened course of oral acetylcysteine therapy (<72 hours of treatment) under certain circumstances (Ref). 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.
IV: Acetadote:
Three-bag method: Infants, Children, and Adolescents: 21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg.
Loading dose: IV: 150 mg/kg infused over 60 minutes; maximum dose: 15 g/dose.
Second dose: IV: 50 mg/kg infused over 4 hours; maximum dose: 5 g/dose.
Third dose: IV: 100 mg/kg infused over 16 hours; maximum dose: 10 g/dose.
Two-bag method: Limited data available: Note: The "two-bag method" has been associated with fewer and milder nonallergic anaphylactic reactions as compared to the manufacturer's labeled dosing (Ref).
Children ≥12 years and Adolescents: 20-hour regimen: Consists of 2 doses; total dose delivered: 300 mg/kg; maximum total dose: 30 g (Ref):
First dose: IV: 200 mg/kg infused over 4 hours.
Second dose: IV: 100 mg/kg infused over 16 hours.
Respiratory conditions, adjuvant therapy: Note: Patients should receive an aerosolized bronchodilator 10 to 15 minutes prior to acetylcysteine:
Nebulized inhalation:
Face mask, mouthpiece, tracheostomy:
Infants: 1 to 2 mL of 20% solution (may be further diluted with sodium chloride or sterile water for inhalation) or 2 to 4 mL of 10% solution (undiluted); administer 3 to 4 times daily.
Children: 3 to 5 mL of 20% solution (may be further diluted with sodium chloride or sterile water for inhalation) or 6 to 10 mL of 10% solution (undiluted); administer 3 to 4 times daily.
Adolescents: 3 to 5 mL of 20% solution (may be further diluted with sodium chloride or sterile water for inhalation) or 6 to 10 mL of 10% solution (undiluted); administer 3 to 4 times daily; usual dosing range: 20% solution: 1 to 10 mL or 10% solution: 2 to 20 mL every 2 to 6 hours.
Tent, croupette: 10% or 20% solution: Dose must be individualized; dose is volume of solution necessary to maintain a very heavy mist in tent or croupette; in some cases, may require up to 300 mL solution/treatment.
Direct instillation: Children and Adolescents:
Endotracheal: 1 to 2 mL of 10% to 20% solution every 1 to 4 hours as needed.
Percutaneous endotracheal 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: Children and Adolescents: Nebulization or endotracheal: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution administered 2 to 3 times prior to procedure.
Distal intestinal obstruction syndrome (previously known as meconium ileus equivalent): Limited data available; dosing regimens variable (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 Adolescents: 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 to 300 mL of 4% to 6% solution 2 to 4 times daily; 50 mL of 20% solution 1 to 4 times daily and 5 to 30 mL of 10% to 20% solution 3 to 4 times daily have been used; rectal enemas appear to have less favorable results than oral administration (Ref). Note: Higher concentrations (10% to 20%) appear to increase fluid in the bowel and lead to increased incidence of adverse effects (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
Refer to indication-specific dosing for obesity-related information (may not be available for all indications).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Inhalation:
Generic: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (10 mL, 30 mL)
Solution, Inhalation [preservative free]:
Generic: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
Solution, Intravenous [preservative free]:
Acetadote: 200 mg/mL (30 mL)
Generic: 200 mg/mL (30 mL)
Tablet Effervescent, Oral:
Cetylev: 500 mg [DSC], 2.5 g [DSC] [contains edetate (edta) disodium]
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Inhalation:
Parvolex: 20% [200 mg/mL] ([DSC])
Generic: 20% [200 mg/mL] (10 mL, 30 mL)
Inhalation: Acetylcysteine is incompatible with tetracyclines, erythromycin, amphotericin B, iodized oil, chymotrypsin, trypsin, and hydrogen peroxide. Administer separately. Intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime.
Oral:
Effervescent tablets (Cetylev): Use within 2 hours of preparation. If the patient vomits within 1 hour of administration, repeat that dose. If the patient is persistently unable to retain the orally administered acetylcysteine, acetylcysteine may be administered by nasoduodenal tube. An intravenous formulation of acetylcysteine may also be considered.
Solution for oral administration: For the treatment of acetaminophen overdose, administer orally as a 5% solution. Use within 1 hour of preparation. The unpleasant odor (sulfur-like) becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put the acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).
IV (Acetadote): Acetaminophen overdose:
Loading dose: Administer over 1 hour.
Second dose: Administer over 4 hours.
Third dose: Administer over 16 hours.
If the commercial IV form is unavailable, the solution for inhalation has been used; each dose should be infused through a 0.2 micron Millipore filter (in-line) over 60 minutes (Ref); intravenous administration of the solution for inhalation is not USP 797-compliant.
Alternative recommendations (off-label):
"Two bag method" (off-label dosing): Administer first dose (200 mg/kg) over 4 hours, then administer the second dose (100 mg/kg) over 16 hours (Ref).
"Single bag method" (off-label dosing): Administer initial dose (150 mg/kg) over 60 minutes, then decrease the rate and administer the remaining dose (14 mg/kg/hour) over 20 hours (Ref). Note: Patients weighing >69 kg will require a second bag to complete the dosing regimen.
Oral: Differs based on use.
Acetaminophen poisoning:
Effervescent tablets: Cetylev: Use within 2 hours of preparation. If the patient vomits within 1 hour of administration, repeat that dose. If the patient is persistently unable to retain the orally administered acetylcysteine, acetylcysteine may be administered by nasoduodenal tube.
Solution for oral administration: Administer as a 5% solution (see Preparation for Administration); use within 1 hour of preparation. If patient vomits within 1 hour of dose, readminister. Note: The unpleasant odor (sulfur-like) becomes less noticeable as treatment progresses. It is helpful to put the acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube.
Parenteral: Acetaminophen poisoning:
IV: Acetadote:
Three-bag method: Neonates, Infants, Children, and Adolescents:
Loading dose: Administer IV over 60 minutes.
Second dose: Administer IV over 4 hours.
Third dose: Administer IV over 16 hours.
Note: If the commercial IV form is unavailable, the solution for inhalation has been used; each dose should be infused through a 0.2 micron Millipore filter (in-line) over 60 minutes (Ref); intravenous administration of the solution for inhalation is not USP 797-compliant.
Two-bag method: Children ≥12 years and Adolescents:
First dose: Administer IV over 4 hours.
Second dose: Administer IV over 16 hours.
Inhalation solution: May be administered by nebulization either undiluted (both 10% and 20%) or diluted in NS. Acetylcysteine solution for inhalation is incompatible with tetracyclines, erythromycin, amphotericin B, iodized oil, chymotrypsin, trypsin, and hydrogen peroxide. Administer separately. Intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime.
Rectal: Inhalation solution may be given undiluted (10% to 20%) or diluted to 4% to 6% solution and administer rectally (Ref).
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).
Acetylcysteine may be confused with acetylcholine
Mucomyst may be confused with Mucinex
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Intravenous:
>10%:
Immunologic: Autoimmune disease (14% to 18%)
Miscellaneous: Anaphylactoid reaction (1% to 18%)
1% to 10%:
Cardiovascular: Flushing (1% to 3%), tachycardia (1% to 4%), edema (1% to 2%)
Dermatologic: Urticaria (≤21%), rash (2% to ≤21%), pruritus (1% to ≤21%)
Gastrointestinal: Vomiting (2% to 10%), nausea (1% to 6%)
Respiratory: Pharyngitis (≤1%), rhinorrhea (≤1%), rhonchi (≤1%), throat tightness (≤1%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Anaphylaxis, angioedema, bronchospasm, chest tightness, cough, dizziness (Sandilands 2008), dyspnea (Sandilands 2008), hypotension, respiratory distress, stridor, wheezing
Oral: Frequency not defined.
Cardiovascular: Chest tightness, hypotension (Bebarta 2010; Sandilands 2009)
Dermatologic: Rash (with or without fever), urticaria
Gastrointestinal: Gastrointestinal symptoms, nausea, vomiting
Hypersensitivity: Hypersensitivity reaction
Respiratory: Bronchospasm, bronchitis
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Angioedema (Bebarta 2010), pruritus (Bebarta 2010), tachycardia (Bebarta 2010)
Hypersensitivity to acetylcysteine or any component of the formulation.
Effervescent tablet (Cetylev): There are no contraindications listed in the manufacturer's labeling.
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.
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.
• Route of administration: Both oral and IV acetylcysteine are effective in reducing the risk of acetaminophen-related hepatotoxicity (Yarema 2009). A comprehensive review concurred that acetylcysteine therapy appears to reduce acetaminophen-related hepatotoxicity; however, it is also concluded that there is paucity of quality data to determine which route of administration or dosing regimen is superior (Chiew 2018). Consultation with a poison control center or a clinical toxicologist is highly recommended to determine the preferred route and duration of administration.
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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Charcoal, Activated: May decrease the serum concentration of Acetylcysteine. Risk C: Monitor therapy
Acetylcysteine crosses the placenta.
Acetylcysteine may be used to treat acetaminophen overdose during pregnancy (Wilkes 2005). Delaying treatment to pregnant women with acetaminophen toxicity may increase the risk of adverse maternal and fetal outcomes. In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003).
It is not known if acetylcysteine is excreted in breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of infant exposure, the benefits of breast-feeding to the infant, and benefits of treatment to the mother. Based on pharmacokinetics, acetylcysteine should be nearly completely cleared 30 hours after administration; breast-feeding women may consider pumping and discarding breast milk for 30 hours after administration.
Acetaminophen overdose: Monitor patient for the development of anaphylaxis or anaphylactoid reactions; monitor serum acetaminophen concentrations, AST, ALT, bilirubin, PT, INR, serum creatinine, BUN, serum glucose, hemoglobin, hematocrit, and electrolytes. Assess patient for nausea, vomiting, and skin rash following oral administration. Reassess LFTs for possible hepatotoxicity every 4 to 6 hours. An early elevation in the INR may be related to acetylcysteine therapy (Schmidt 2002).
Acute ingestion: Obtain the first acetaminophen concentration 4 hours postingestion (or as soon as possible thereafter); plot on the Rumack-Matthew nomogram. In patients who have ingested an extended release formulation of acetaminophen or have coingested an agent known to delay gastric emptying, obtain a repeat serum acetaminophen measurement 4 to 6 hours following the first measurement if the original concentration (taken at 4 to 8 hours postingestion) when plotted on the Rumack-Matthew nomogram indicated that treatment was not necessary.
Acetaminophen overdose: Acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of acetaminophen.
Mucolytic: Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity.
Onset of action: Inhalation: 5 to 10 minutes
Duration: Inhalation: >1 hour
Distribution: Vdss: 0.47 L/kg
Protein binding: 66% to 87%
Metabolism: Undergoes extensive first pass metabolism to form cysteine and disulfides (N,N-diacetylcysteine and N-acetylcysteine); cysteine is further metabolized to form glutathione and other metabolites
Half-life elimination:
Reduced acetylcysteine: 2 hours
Total acetylcysteine: Adults: 5.6 hours; Newborns: 11 hours
Effervescent tablets: Terminal half-life: 18.1 hours
Time to peak, plasma: Oral solution: 1 to 2 hours; Effervescent tablets: 1 to 3.5 hours (median: 2 hours)
Excretion: Urine (13% to 38%)
Solution (Acetadote Intravenous)
200 mg/mL (per mL): $9.14
Solution (Acetylcysteine Inhalation)
10% (per mL): $2.59 - $3.36
20% (per mL): $1.80 - $4.20
Solution (Acetylcysteine Intravenous)
200 mg/mL (per mL): $1.48 - $7.52
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