Oral: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: 1330 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 60 minutes
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 kgBody Weight
(kg)
Loading Dose
150 mg/kg over 1 h
Second Dose
50 mg/kg over 4 h
Third Dose
100 mg/kg over 16 h
Acetadote
(mL)
D5W
(mL)
Acetadote
(mL)
D5W
(mL)
Acetadote
(mL)
D5W
(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 D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote 10 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote 20 mL in D5W 500 mL
Body weight 30 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote 22.5 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote 7.5 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote 15 mL in D5W 500 mL
Body weight 21 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote 15.75 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote 5.25 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote 10.5 mL in D5W 500 mL
Body weight 20 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote 15 mL in D5W 60 mL
Second dose (50 mg/kg over 4 hours): Acetadote 5 mL in D5W 140 mL
Third dose (100 mg/kg over 16 hours): Acetadote 10 mL in D5W 280 mL
Body weight 15 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote 11.25 mL in D5W 45 mL
Second dose (50 mg/kg over 4 hours): Acetadote 3.75 mL in D5W 105 mL
Third dose (100 mg/kg over 16 hours): Acetadote 7.5 mL in D5W 210 mL
Body weight 10 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote 7.5 mL in D5W 30 mL
Second dose (50 mg/kg over 4 hours): Acetadote 2.5 mL in D5W 70 mL
Third dose (100 mg/kg over 16 hours): Acetadote 5 mL in D5W 140 mL
Body weight 5 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote 3.75 mL in D5W 15 mL
Second dose (50 mg/kg over 4 hours): Acetadote 1.25 mL in D5W 35 mL
Third dose (100 mg/kg over 16 hours): Acetadote 2.5 mL in D5W 70 mL
Obesity: In patients who weigh >100 kg, the following dosing regimen is recommended: IV (Acetadote):
21-hour regimen: Consists of 3 doses; total dose delivered: 30 g
Loading dose: 15 g infused over 60 minutes
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]).
Refer to adult dosing.
Acetaminophen poisoning: Refer to adult dosing.
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
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.
Infants: 1-2 mL of 20% solution or 2-4 mL 10% solution until nebulized given 3-4 times/day
Children: Refer to adult dosing.
Inhalation, nebulization (tent, croupette): Children: Refer to adult dosing.
Oral, IV: No dosage adjustment provided in manufacturers labeling.
Oral: No dosage adjustment provided in manufacturers labeling.
IV: No dosage adjustment required.
Oral: Treatment of acetaminophen poisoning: Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink to prepare a 5% solution. Use within 1 hour of preparation.
Solution for injection (Acetadote): Acetaminophen poisoning: IV:
Loading dose: Dilute 150 mg/kg (maximum: 15 g) in D5W 200 mL.
Second dose: Dilute 50 mg/kg (maximum: 5 g) in D5W 500 mL
Third dose: Dilute 100 mg/kg (maximum: 10 g) in D5W 1000 mL
Note: To avoid fluid overload in patients <40 kg and those requiring fluid restriction, decrease volume of D5W proportionally (see table in dosing section). Discard unused portion.
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 (off-label route): Using D5W, dilute acetylcysteine 20% oral solution to a 3% solution.
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:
Treatment of acetaminophen poisoning: 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).
Prevention of contrast induced nephropathy (off-label use): Using the 20% solution, each 1200 mg dose should be diluted immediately prior to use in a minimum of 20 mL of a cola drink or other soft drink (or water if administered via NG tube); use within 1 hour of preparation (Massicotte 2008).
IV (Acetadote): Acetaminophen poisoning:
Loading dose: Administer over 60 minutes.
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 (Yip, 1998); intravenous administration of the solution for inhalation is not USP 797-compliant.
Note: Undiluted injection, solution (Acetadote) is hyperosmolar (2600 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 injection (Acetadote): Store unopened vials at room temperature, 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F). Following reconstitution with D5W, solution is stable for 24 hours at room temperature. A color change may occur in opened vials (light pink or purple) and does not affect the safety or efficacy.
Solution for inhalation: Store unopened vials at room temperature; once opened, store under refrigeration and use within 96 hours. A color change may occur in opened vials (light purple) and does not affect the safety or efficacy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 20% (30 mL)
Acetadote: 20% [200 mg/mL] (30 mL)
Solution, for inhalation/oral: 10% [100 mg/mL] (10 mL, 30 mL); 20% [200 mg/mL] (10 mL, 30 mL)
Solution, for inhalation/oral [preservative free]: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
Tablet Effervescent, Oral:
Cetylev: 500 mg, 2.5 g [contains edetate disodium; lemon mint flavor]
Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, oxytetracycline, erythromycin.
Intravenous: Stable in D5W, 1/2 NS, SWFI.
Y-site administration: Incompatible: Metals (particularly iron, copper, and nickel); cefepime, ceftazidime
There are no known significant interactions.
Acetaminophen poisoning: Monitor patient for the development of anaphylaxis or anaphylactoid reactions; monitor serum acetaminophen levels, 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 4-6 hours. An early elevation in the INR may be related to acetylcysteine therapy (Schmidt, 2002).
Acute ingestion: Obtain the first acetaminophen level 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 4-6 hours following the first measurement if the original level (taken at 4-8 hours postingestion) when plotted on the Rumack-Matthew nomogram indicated that treatment was not necessary.
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% (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 2008)
Dermatologic: Rash (with or without fever), urticaria
Gastrointestinal: Gastrointestinal symptoms, nausea, vomiting
Hypersensitivity: Hypersensitivity reaction
Respiratory: Bronchospasm, bronchitis
<1% (Limited to important or life-threatening): Angioedema (Bebarta 2010), tachycardia (Bebarta 2010)
In patients with severe liver impairment, half-life increased 80% and clearance decreased 30%.
Concerns related to adverse effects:
- Anaphylactoid reactions: Acute flushing and erythema have been reported; usually occurs within 30-60 minutes and may resolve spontaneously. Serious anaphylactoid reactions have also been reported and are more commonly associated with IV administration, but also occur with oral administration (Mroz, 1997). When used for acetaminophen poisoning, 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. Use caution in patients with asthma or history of bronchospasm as these patients may be at increased risk. Conversely, patients with high acetaminophen levels (>150 mg/L) may be at a reduced risk for anaphylactoid reactions (Pakravan, 2008; Sandilands, 2009; Waring, 2008).
Disease-related concerns:
- Acute acetaminophen poisoning: Appropriate use: Acetylcysteine is indicated in patients with a serum acetaminophen level 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 levels obtained <4 hours postingestion are not interpretable; 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 level 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 levels, may give the clinician insight as to the patients risk of acetaminophen toxicity. Some experts recommend that acetylcysteine be administered to any patient with higher than expected" serum acetaminophen levels or serum acetaminophen level >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:
- 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.
B
Adverse events have not been observed in animal reproduction studies. Based on limited reports using acetylcysteine to treat acetaminophen poisoning in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective levels in the fetus.
Acetylcysteine may be used to treat acetaminophen overdose in during pregnancy (Wilkes, 2005). 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).
Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity.
In patients with acetaminophen toxicity, acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of acetaminophen.
The presumed mechanism in preventing contrast-induced nephropathy is its ability to scavenge oxygen-derived free radicals and improve endothelium-dependent vasodilation.
0.47 L/kg
Urine
Inhalation: 5-10 minutes
Plasma: Oral: 1-2 hours
Inhalation: >1 hour
Reduced acetylcysteine: 2 hours; Total acetylcysteine: Adults: 5.6 hours, Newborns: 11 hours
83%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience mouth sores, rhinorrhea, fatigue, clammy skin, or flushing. Have patient report immediately to prescriber shortness of breath; severe nausea; black, tarry, or bloody stools; severe vomiting; vomiting blood; severe dizziness; or passing out (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.