Acetylcysteine

U.S. BRAND NAMES — Acetadote®

PHARMACOLOGIC CATEGORY
Antidote
Mucolytic Agent

DOSING: ADULTS
Acetaminophen poisoning: Only the 72-hour oral and 21-hour I.V. regimens are FDA-approved. Ideally, in patients with an acute APAP ingestion, treatment should begin within 8 hours of ingestion. In patients who present following RSTI and treatment is deemed appropriate, acetylcysteine should be initiated immediately.
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
I.V. (Acetadote®):
21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg
Loading dose: 150 mg/kg infused over 60 minutes
Second dose: 50 mg/kg infused over 4 hours
Third dose: 100 mg/kg 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 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 25 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 18.75 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 6.25 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 12.5 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

Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 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: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours
Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment
Direct instillation:
Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours
Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter

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

Prevention of contrast-induced nephropathy (CIN) (unlabeled use): Oral: 600-1200 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules (some centers use solution, diluted in cola beverage or juice)

Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use):I.V.: 1200 mg over 5-10 minutes prior to cardiac catheterization, followed by 1200 mg orally twice daily for 48 hours

DOSING: PEDIATRIC

(For additional information see "Acetylcysteine: Pediatric drug information")
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.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL; contains disodium edetate]

Solution, inhalation/oral: 10% (4 mL, 10 mL, 30 mL) [100 mg/mL]; 20% (4 mL, 10 mL, 30 mL) [200 mg/mL]

DOSAGE FORMS: CONCISE
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL]

Solution, inhalation/oral: 10% [100 mg/mL]; 20% [200 mg/mL]

GENERIC EQUIVALENT AVAILABLE — Yes: Solution for inhalation

ADMINISTRATION
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 APAP poisoning, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).

I.V. (Acetadote®):
Acetaminophen poisoning:
Loading dose: Dilute in D5W 200 mL; administer over 60 minutes.
Second dose: Dilute in D5W 500 mL; administer over 4 hours.
Third dose: Dilute in D5W 1000 mL; administer over 16 hours.
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.
If the commercial I.V. 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.
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use): Administer 1200 mg I.V. push over 5-10 minutes prior to contrast administration.

COMPATIBILITY
Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, tetracycline, oxytetracycline, erythromycin.

Intravenous: Compatible with D5W, 1/2NS, SWFI. Incompatible with rubber, metals (particularly iron, copper, and nickel), cefepime, and ceftazidime.

USE — Antidote for acute acetaminophen (APAP) poisoning; repeated supratherapeutic ingestion (RSTI) of APAP; adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies

USE - UNLABELED / INVESTIGATIONAL — Prevention of contrast-induced renal dysfunction (oral, I.V.); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)

ADVERSE REACTIONS SIGNIFICANT
Inhalation: Frequency not defined.
Central nervous system: Drowsiness, chills, fever
Gastrointestinal: Vomiting, nausea, stomatitis
Local: Irritation, stickiness on face following nebulization
Respiratory: Bronchospasm, rhinorrhea, hemoptysis
Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration

Intravenous:

>10%: Miscellaneous: Anaphylactoid reaction (8% to 18%; shorter infusion periods [eg, <60 minutes] associated with increased incidence)

1% to 10%:
Cardiovascular: Flushing (1% to 8%), tachycardia (1% to 4%), edema (1% to 2%)
Dermatologic: Urticaria (6% to 8%), rash (2% to 4%), pruritus (1% to 4%)
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, bronchospasm, chest tightness, cough, dyspnea, hypotension, respiratory distress, stridor, wheezing

CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component of the formulation

WARNINGS / PRECAUTIONS
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 I.V. administration. When used for APAP poisoning, the incidence is reduced when the initial loading dose is administered over 60 minutes. Acetylcysteine infusion may be interrupted until 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 APAP levels (>150 mg/dL) may be at a reduced risk for anaphylactoid reactions (Pakravan, 2008; Waring, 2008).

Disease-related concerns: Acute APAP poisoning: Appropriate use: Acetylcysteine is indicated in patients with a serum APAP 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>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 APAP: Appropriate use: The Rumack-Matthew nomogram is not designed to be used following RSTIs. In general, an accurate past medical history, including a comprehensive APAP ingestion history, in conjunction with AST concentrations and serum APAP levels, may give the clinician insight as to the patient's risk of APAP toxicity. Some experts recommend that acetylcysteine be administered to any patient with "higher than expected" serum APAP levels or serum APAP 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.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — 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.

LACTATION — Excretion in breast milk unknown/use caution

PRICING — (data from drugstore.com)
Solution (Acetylcysteine)
10% (30): $17.99
10% (30): $25.99
20% (4): $7.99
20% (10): $22.99

Solution (Mucomyst-10)
10% (30): $18.99

MONITORING PARAMETERS — Acetaminophen poisoning: Monitor patient for the development of anaphylaxis or anaphylactoid reactions; monitor serum APAP 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.

Acute ingestion: Obtain the first APAP 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 APAP or have coingested an agent known to delay gastric emptying, obtain a repeat serum APAP 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.

CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®

INTERNATIONAL BRAND NAMES — ACC (AR, HU, LU, MX, PL, ZA); ACC 200 (EE, HN); Acemuk (AR); Acet (TW); Acetain (KP); Acetin (MY); Acetylcystein NM Pharma (SE); Acetylcystein Tika (SE); Acypront (HK, PL); Alistine Forte (TH); Bromuc (BR); Broncoflem (PH); Cystaline (TH); Drenaflen (EC); Ecomucyl (CH); Eloamin (CZ); Exomuc (FR, HK, LU); Fabrol (AT, GR); Flemex AC (TH); Fluimicil (CH, DE); Fluimiquil (LU); Fluimucil (AR, BG, BR, CL, CO, HK, HU, ID, IT, MA, NL, PE, PL, TH, TW); Fluimucil A (MY, PK); Fluimukan (HR); Flumil (ES); Flutafin (TW); Hidonac (ID, MY, PH, TH, TW); L-Cimexyl (SG); Libramucil (EC); Lubrisec (AR); Lysomucil (LU); Lysox (LU); Madame Pearl's Mucolytic (HK); Menaxol (CR, DO, GT, HN, NI, PA, SV); Mucofillin (JP); Mucolair (LU); Mucolator (LU, MY); Mucolitico (CN); Mucomiste (PT); Mucomyst (AT, AU, BE, DK, FI, FR, KP, LU, NO, SE); Mucomystendo (FR); Mucoserin (KP); Mucosof (CL); Mucosten (KP); Mucosys (IN); Mucoza (TH); Mukolit (ID); Muteran (KP); Muxatil (PY); NAC-ratiopharm (LU); Parvolex (GB, IE, NZ, PH); Pectocil (ID); Pectomucil (LU); Reolin (IL); Rumicil (LU); Siran (ID); Siran 200 (IL); Solmucol (HU, LU); Spatam (SG); Sputopur (HU); Stecin (KP); Stenac (TH); Syntemucol (PL); Touxium Mucolyticum (LU); Tussicom (PL); Viskoferm (SE)

MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity.

In patients with APAP toxicity, acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of APAP.

The presumed mechanism in preventing contrast-induced nephropathy is its ability to scavenge oxygen-derived free radicals and improve endothelium-dependent vasodilation.

PHARMACODYNAMICS / KINETICS
Onset of action: Inhalation: 5-10 minutes

Duration: Inhalation: >1 hour

Distribution: 0.47 L/kg

Protein binding: 83%

Half-life elimination:
Reduced acetylcysteine: 2 hours
Total acetylcysteine: Adults: 5.6 hours; Newborns: 11 hours

Time to peak, plasma: Oral: 1-2 hours

Excretion: Urine

PATIENT INFORMATION — Clear airway by coughing deeply before using aerosol.

Acetylcysteine

U.S. BRAND NAMES — Acetadote®

PHARMACOLOGIC CATEGORY
Antidote
Mucolytic Agent

DOSING: ADULTS
Acetaminophen poisoning: Only the 72-hour oral and 21-hour I.V. regimens are FDA-approved. Ideally, in patients with an acute APAP ingestion, treatment should begin within 8 hours of ingestion. In patients who present following RSTI and treatment is deemed appropriate, acetylcysteine should be initiated immediately.
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
I.V. (Acetadote®):
21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg
Loading dose: 150 mg/kg infused over 60 minutes
Second dose: 50 mg/kg infused over 4 hours
Third dose: 100 mg/kg 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 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 25 kg:
Loading dose (150 mg/kg over 1 hour): Acetadote® 18.75 mL in D5W 100 mL
Second dose (50 mg/kg over 4 hours): Acetadote® 6.25 mL in D5W 250 mL
Third dose (100 mg/kg over 16 hours): Acetadote® 12.5 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

Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 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: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours
Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment
Direct instillation:
Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours
Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter

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

Prevention of contrast-induced nephropathy (CIN) (unlabeled use): Oral: 600-1200 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules (some centers use solution, diluted in cola beverage or juice)

Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use):I.V.: 1200 mg over 5-10 minutes prior to cardiac catheterization, followed by 1200 mg orally twice daily for 48 hours

DOSING: PEDIATRIC

(For additional information see "Acetylcysteine: Pediatric drug information")
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.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL; contains disodium edetate]

Solution, inhalation/oral: 10% (4 mL, 10 mL, 30 mL) [100 mg/mL]; 20% (4 mL, 10 mL, 30 mL) [200 mg/mL]

DOSAGE FORMS: CONCISE
Injection, solution:
Acetadote®: 20% (30 mL) [200 mg/mL]

Solution, inhalation/oral: 10% [100 mg/mL]; 20% [200 mg/mL]

GENERIC EQUIVALENT AVAILABLE — Yes: Solution for inhalation

ADMINISTRATION
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 APAP poisoning, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).

I.V. (Acetadote®):
Acetaminophen poisoning:
Loading dose: Dilute in D5W 200 mL; administer over 60 minutes.
Second dose: Dilute in D5W 500 mL; administer over 4 hours.
Third dose: Dilute in D5W 1000 mL; administer over 16 hours.
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.
If the commercial I.V. 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.
Prevention of CIN in acute MI patients requiring emergent cardiac catheterization (unlabeled use): Administer 1200 mg I.V. push over 5-10 minutes prior to contrast administration.

COMPATIBILITY
Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, tetracycline, oxytetracycline, erythromycin.

Intravenous: Compatible with D5W, 1/2NS, SWFI. Incompatible with rubber, metals (particularly iron, copper, and nickel), cefepime, and ceftazidime.

USE — Antidote for acute acetaminophen (APAP) poisoning; repeated supratherapeutic ingestion (RSTI) of APAP; adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies

USE - UNLABELED / INVESTIGATIONAL — Prevention of contrast-induced renal dysfunction (oral, I.V.); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)

ADVERSE REACTIONS SIGNIFICANT
Inhalation: Frequency not defined.
Central nervous system: Drowsiness, chills, fever
Gastrointestinal: Vomiting, nausea, stomatitis
Local: Irritation, stickiness on face following nebulization
Respiratory: Bronchospasm, rhinorrhea, hemoptysis
Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration

Intravenous:

>10%: Miscellaneous: Anaphylactoid reaction (8% to 18%; shorter infusion periods [eg, <60 minutes] associated with increased incidence)

1% to 10%:
Cardiovascular: Flushing (1% to 8%), tachycardia (1% to 4%), edema (1% to 2%)
Dermatologic: Urticaria (6% to 8%), rash (2% to 4%), pruritus (1% to 4%)
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, bronchospasm, chest tightness, cough, dyspnea, hypotension, respiratory distress, stridor, wheezing

CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component of the formulation

WARNINGS / PRECAUTIONS
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 I.V. administration. When used for APAP poisoning, the incidence is reduced when the initial loading dose is administered over 60 minutes. Acetylcysteine infusion may be interrupted until 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 APAP levels (>150 mg/dL) may be at a reduced risk for anaphylactoid reactions (Pakravan, 2008; Waring, 2008).

Disease-related concerns: Acute APAP poisoning: Appropriate use: Acetylcysteine is indicated in patients with a serum APAP 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>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 APAP: Appropriate use: The Rumack-Matthew nomogram is not designed to be used following RSTIs. In general, an accurate past medical history, including a comprehensive APAP ingestion history, in conjunction with AST concentrations and serum APAP levels, may give the clinician insight as to the patient's risk of APAP toxicity. Some experts recommend that acetylcysteine be administered to any patient with "higher than expected" serum APAP levels or serum APAP 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.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — 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.

LACTATION — Excretion in breast milk unknown/use caution

PRICING — (data from drugstore.com)
Solution (Acetylcysteine)
10% (30): $17.99
10% (30): $25.99
20% (4): $7.99
20% (10): $22.99

Solution (Mucomyst-10)
10% (30): $18.99

MONITORING PARAMETERS — Acetaminophen poisoning: Monitor patient for the development of anaphylaxis or anaphylactoid reactions; monitor serum APAP 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.

Acute ingestion: Obtain the first APAP 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 APAP or have coingested an agent known to delay gastric emptying, obtain a repeat serum APAP 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.

CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®

INTERNATIONAL BRAND NAMES — ACC (AR, HU, LU, MX, PL, ZA); ACC 200 (EE, HN); Acemuk (AR); Acet (TW); Acetain (KP); Acetin (MY); Acetylcystein NM Pharma (SE); Acetylcystein Tika (SE); Acypront (HK, PL); Alistine Forte (TH); Bromuc (BR); Broncoflem (PH); Cystaline (TH); Drenaflen (EC); Ecomucyl (CH); Eloamin (CZ); Exomuc (FR, HK, LU); Fabrol (AT, GR); Flemex AC (TH); Fluimicil (CH, DE); Fluimiquil (LU); Fluimucil (AR, BG, BR, CL, CO, HK, HU, ID, IT, MA, NL, PE, PL, TH, TW); Fluimucil A (MY, PK); Fluimukan (HR); Flumil (ES); Flutafin (TW); Hidonac (ID, MY, PH, TH, TW); L-Cimexyl (SG); Libramucil (EC); Lubrisec (AR); Lysomucil (LU); Lysox (LU); Madame Pearl's Mucolytic (HK); Menaxol (CR, DO, GT, HN, NI, PA, SV); Mucofillin (JP); Mucolair (LU); Mucolator (LU, MY); Mucolitico (CN); Mucomiste (PT); Mucomyst (AT, AU, BE, DK, FI, FR, KP, LU, NO, SE); Mucomystendo (FR); Mucoserin (KP); Mucosof (CL); Mucosten (KP); Mucosys (IN); Mucoza (TH); Mukolit (ID); Muteran (KP); Muxatil (PY); NAC-ratiopharm (LU); Parvolex (GB, IE, NZ, PH); Pectocil (ID); Pectomucil (LU); Reolin (IL); Rumicil (LU); Siran (ID); Siran 200 (IL); Solmucol (HU, LU); Spatam (SG); Sputopur (HU); Stecin (KP); Stenac (TH); Syntemucol (PL); Touxium Mucolyticum (LU); Tussicom (PL); Viskoferm (SE)

MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity.

In patients with APAP toxicity, acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of APAP.

The presumed mechanism in preventing contrast-induced nephropathy is its ability to scavenge oxygen-derived free radicals and improve endothelium-dependent vasodilation.

PHARMACODYNAMICS / KINETICS
Onset of action: Inhalation: 5-10 minutes

Duration: Inhalation: >1 hour

Distribution: 0.47 L/kg

Protein binding: 83%

Half-life elimination:
Reduced acetylcysteine: 2 hours
Total acetylcysteine: Adults: 5.6 hours; Newborns: 11 hours

Time to peak, plasma: Oral: 1-2 hours

Excretion: Urine

PATIENT INFORMATION — Clear airway by coughing deeply before using aerosol.

Acetylcysteine

U.S. BRAND NAMES — Acetadote®
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
SYNONYMS — N-Acetyl-L-Cysteine; N-Acetylcysteine; Mercapturic Acid; NAC
THERAPEUTIC CATEGORY Antidote, AcetaminophenMucolytic Agent
DOSING
(For additional information see "Acetylcysteine: Drug information")Acetaminophen poisoning: Children and Adults: Begin treatment within 8 hours of ingestion to optimize therapy in patients whose serum acetaminophen levels fall above the "possible" toxicity line on the Rumack-Matthew nomogram Treatment is also indicated in patients with a history of known or suspected acute acetaminophen ingestion of >150 mg/kg (child) or >7.5 g (adolescent or adult) total dose when plasma levels are not available within 8-10 hours of ingestion or in patients presenting >24 hours after acute ingestion who have a measurable acetaminophen level. See Warnings. I.V.: 150 mg/kg infused over 60 minutes; followed by a 4-hour infusion of 50 mg/kg; followed by a 16-hour infusion of 100 mg/kg; equivalent to a total dose of 300 mg/kg infused over 21 hours Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until all doses are administered even though the acetaminophen plasma level has dropped below the toxic range
Nebulized inhalation: Infants: 1-2 mL of 20% solution or 2-4 mL of 10% solution until nebulized, given 3-4 times/day Children: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized, given 3-4 times/day Adolescents: 5-10 mL of 10% to 20% solution until nebulized, given 3-4 times/day Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Intratracheal: Children and Adults: 1-2 mL of 10% to 20% solution every 1-4 hours as needed
Distal intestinal obstruction syndrome (previously known as meconium ileus equivalent): Varying regimens have been reported (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 Adults: 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; 100-300 mL of 4% to 6% solution 2-4 times/day; 50 mL of 20% solution 1-4 times/day and 5-30 mL of 10% to 20% solution 3-4 times/day have been used; rectal enemas appear to have less favorable results than oral administration (Mascarenhas, 2003) Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Adults: Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); hydrate patient concurrently
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
GENERIC AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION Parenteral: I.V.: Three infusions (See Usual Dosage) of different lengths: Dilute first dose (150 mg/kg) in 200 mL D5W and infuse over 60 minutes; dilute second dose (50 mg/kg) in 500 mL D5W and infuse over 4 hours; dilute third dose (100 mg/kg) in 1000 mL D5W and infuse over 16 hours; for children <40 kg and patients who are fluid restricted, the manufacturer recommends reducing the diluent to a "proportional" amount. See table for manufacturer's recommended infusion guideline for patients <40 kg. Or as an alternative to proportionally lower the diluent volume, a reasonable approach might be to utilize the concentrations resulting from using the recommended dilution for the dosage in a 50 kg patient. The calculated concentration would range between 5 mg/mL (maintenance infusion) to 37.5 mg/mL (loading dose).
Infusion Guide by Weight for Patients <40 kg Body Weight = 10 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 30 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 500 mg (2.5 mL) 5% dextrose: 70 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL Body Weight = 15 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 2250 mg (11.25 mL) 5% dextrose: 45 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 750 mg (3.75 mL) 5% dextrose: 105 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 210 mL Body Weight = 20 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 60 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2000 mg (10 mL) 5% dextrose: 280 mL Body Weight = 25 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3750 mg (18.75 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1250 mg (6.25 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2500 mg (12.5 mL) 5% dextrose: 500 mL Body Weight = 30 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 4500 mg (22.5 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 500 mL
Oral: For treatment of acetaminophen overdosage, administer as a 5% solution; dilute the 20% solution (inhalation formulation) 1:3 with a cola, orange juice, or other soft drink; use within 1 hour of preparation
Oral inhalation: May be administered by nebulization either undiluted (both 10% and 20%) or diluted in NS
Rectal: Dilute the inhalation solution in NS to the desired final concentration and administer rectally
USE Inhalation: Adjunctive therapy in patients with abnormal or viscid mucous secretions in bronchopulmonary diseases, pulmonary complications of surgery, and cystic fibrosis; diagnostic bronchial studies
Injection, Oral: Antidote for acute acetaminophen toxicity; prevention of radiocontrast-induced renal dysfunction
Oral, rectal: Treatment of distal intestinal obstruction syndrome (previously known as "meconium ileus or its equivalent")
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypotension, syncope, chest tightness, vasodilation, hypertension (after large oral doses)
Central nervous system: Drowsiness, chills, dysphoria
Dermatologic: Generalized urticaria, rash, pruritus, erythema, angioedema
Gastrointestinal: Stomatitis, nausea, vomiting, dyspepsia, hemoptysis
Hepatic: Mild elevations in liver function tests have occurred after oral therapy
Ocular: Eye pain
Respiratory: Bronchospasm, rhinorrhea, cough
Miscellaneous: Anaphylactoid reactions (I.V. use; 17% in an open label study; 1% reported as severe or moderate in 10% of patients within 15 minutes of the first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after the 60 minute infusion); diaphoresis, unpleasant odor during administration
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component
PRECAUTIONS — Use with caution in patients with asthma or previous history of bronchospasm
WARNINGS — Serious anaphylactoid reactions including death in a patient with asthma have been reported after I.V. use; acute flushing and erythema may occur 30-60 minutes into an I.V. infusion, resolving spontaneously; the infusion may be interrupted until treatment of allergic symptoms is initiated; if acute hypersensitivity reactions occur which do not respond to medical management (eg, antihistamines, H2 blockers) or temporarily halting infusion, discontinue use and pursue alternative management. Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow.
Acetaminophen overdose: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients) or individuals ingesting higher than recommended acetaminophen doses for extended periods of time (repeated supratherapeutic ingestion).
DRUG INTERACTIONS — May potentiate the hemodynamic effects of nitroglycerin; acetylcysteine is adsorbed by activated charcoal
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — When used in acetaminophen overdose, determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion of immediate release formulations or 2 hours after ingestion of liquid formulations (to ensure peak levels have been obtained); coingestion of acetaminophen with other medications which may delay GI peristalsis eg, antihistamines, opioids, may require repeated serum levels to determine the peak serum level; liver function tests
STABILITY — Store at room temperature; I.V. formulation is preservative free and stable 24 hours after dilution at room temperature; opened inhalation solution vials may be stored in the refrigerator; use within 96 hours; contact with rubber, copper, iron, and cork may inactivate the drug; the light purple color of solution does not affect its activity. I.V. acetylcysteine is hyperosmolar (2600 mOsm/L) and is compatible with 5% dextrose, 0.45% sodium chloride, and SWI.
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering the viscosity. The exact mechanism of action in acetaminophen toxicity is unknown. It may act by maintaining or restoring glutathione levels or by acting as an alternative substrate for conjugation with the acetaminophen's toxic metabolite.
PHARMACODYNAMICS Onset of action: Upon inhalation, mucus liquefaction occurs maximally within 5-10 minutes
Duration of mucus liquefaction: More than 1 hour
PHARMACOKINETICS Distribution: Vd: 0.47 L/kg
Protein binding: 83%
Half-life: Reduced acetylcysteine: 2 hours Total acetylcysteine: Newborns: 11 hours Adults: 5.6 hours
Time to peak serum concentration: Oral: 1-2 hours
Elimination: Clearance: Adults: 0.11 L/hour/kg
PATIENT INFORMATION — Clear airway by coughing deeply before aerosol treatment
(For additional information see "Acetylcysteine: Patient drug information")
NURSING IMPLICATIONS — Anaphylactoid reactions following I.V. administration have been reported; have emergency treatments such as antihistamines and H2 blockers readily available for potential adverse effects; assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning; intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime

Acetylcysteine

U.S. BRAND NAMES — Acetadote®
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
SYNONYMS — N-Acetyl-L-Cysteine; N-Acetylcysteine; Mercapturic Acid; NAC
THERAPEUTIC CATEGORY Antidote, AcetaminophenMucolytic Agent
DOSING
(For additional information see "Acetylcysteine: Drug information")Acetaminophen poisoning: Children and Adults: Begin treatment within 8 hours of ingestion to optimize therapy in patients whose serum acetaminophen levels fall above the "possible" toxicity line on the Rumack-Matthew nomogram Treatment is also indicated in patients with a history of known or suspected acute acetaminophen ingestion of >150 mg/kg (child) or >7.5 g (adolescent or adult) total dose when plasma levels are not available within 8-10 hours of ingestion or in patients presenting >24 hours after acute ingestion who have a measurable acetaminophen level. See Warnings. I.V.: 150 mg/kg infused over 60 minutes; followed by a 4-hour infusion of 50 mg/kg; followed by a 16-hour infusion of 100 mg/kg; equivalent to a total dose of 300 mg/kg infused over 21 hours Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until all doses are administered even though the acetaminophen plasma level has dropped below the toxic range
Nebulized inhalation: Infants: 1-2 mL of 20% solution or 2-4 mL of 10% solution until nebulized, given 3-4 times/day Children: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized, given 3-4 times/day Adolescents: 5-10 mL of 10% to 20% solution until nebulized, given 3-4 times/day Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine
Intratracheal: Children and Adults: 1-2 mL of 10% to 20% solution every 1-4 hours as needed
Distal intestinal obstruction syndrome (previously known as meconium ileus equivalent): Varying regimens have been reported (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 Adults: 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; 100-300 mL of 4% to 6% solution 2-4 times/day; 50 mL of 20% solution 1-4 times/day and 5-30 mL of 10% to 20% solution 3-4 times/day have been used; rectal enemas appear to have less favorable results than oral administration (Mascarenhas, 2003) Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Adults: Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); hydrate patient concurrently
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
GENERIC AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION Parenteral: I.V.: Three infusions (See Usual Dosage) of different lengths: Dilute first dose (150 mg/kg) in 200 mL D5W and infuse over 60 minutes; dilute second dose (50 mg/kg) in 500 mL D5W and infuse over 4 hours; dilute third dose (100 mg/kg) in 1000 mL D5W and infuse over 16 hours; for children <40 kg and patients who are fluid restricted, the manufacturer recommends reducing the diluent to a "proportional" amount. See table for manufacturer's recommended infusion guideline for patients <40 kg. Or as an alternative to proportionally lower the diluent volume, a reasonable approach might be to utilize the concentrations resulting from using the recommended dilution for the dosage in a 50 kg patient. The calculated concentration would range between 5 mg/mL (maintenance infusion) to 37.5 mg/mL (loading dose).
Infusion Guide by Weight for Patients <40 kg Body Weight = 10 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 30 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 500 mg (2.5 mL) 5% dextrose: 70 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL Body Weight = 15 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 2250 mg (11.25 mL) 5% dextrose: 45 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 750 mg (3.75 mL) 5% dextrose: 105 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 210 mL Body Weight = 20 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 60 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1000 mg (5 mL) 5% dextrose: 140 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2000 mg (10 mL) 5% dextrose: 280 mL Body Weight = 25 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 3750 mg (18.75 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1250 mg (6.25 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 2500 mg (12.5 mL) 5% dextrose: 500 mL Body Weight = 30 kg: LOADING Dose 150 mg/kg over 60 minutes: Acetylcysteine dose: 4500 mg (22.5 mL) 5% dextrose: 100 mL SECOND Dose 50 mg/kg over 4 hours: Acetylcysteine dose: 1500 mg (7.5 mL) 5% dextrose: 250 mL THIRD Dose 100 mg/kg over 16 hours: Acetylcysteine dose: 3000 mg (15 mL) 5% dextrose: 500 mL
Oral: For treatment of acetaminophen overdosage, administer as a 5% solution; dilute the 20% solution (inhalation formulation) 1:3 with a cola, orange juice, or other soft drink; use within 1 hour of preparation
Oral inhalation: May be administered by nebulization either undiluted (both 10% and 20%) or diluted in NS
Rectal: Dilute the inhalation solution in NS to the desired final concentration and administer rectally
USE Inhalation: Adjunctive therapy in patients with abnormal or viscid mucous secretions in bronchopulmonary diseases, pulmonary complications of surgery, and cystic fibrosis; diagnostic bronchial studies
Injection, Oral: Antidote for acute acetaminophen toxicity; prevention of radiocontrast-induced renal dysfunction
Oral, rectal: Treatment of distal intestinal obstruction syndrome (previously known as "meconium ileus or its equivalent")
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypotension, syncope, chest tightness, vasodilation, hypertension (after large oral doses)
Central nervous system: Drowsiness, chills, dysphoria
Dermatologic: Generalized urticaria, rash, pruritus, erythema, angioedema
Gastrointestinal: Stomatitis, nausea, vomiting, dyspepsia, hemoptysis
Hepatic: Mild elevations in liver function tests have occurred after oral therapy
Ocular: Eye pain
Respiratory: Bronchospasm, rhinorrhea, cough
Miscellaneous: Anaphylactoid reactions (I.V. use; 17% in an open label study; 1% reported as severe or moderate in 10% of patients within 15 minutes of the first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after the 60 minute infusion); diaphoresis, unpleasant odor during administration
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component
PRECAUTIONS — Use with caution in patients with asthma or previous history of bronchospasm
WARNINGS — Serious anaphylactoid reactions including death in a patient with asthma have been reported after I.V. use; acute flushing and erythema may occur 30-60 minutes into an I.V. infusion, resolving spontaneously; the infusion may be interrupted until treatment of allergic symptoms is initiated; if acute hypersensitivity reactions occur which do not respond to medical management (eg, antihistamines, H2 blockers) or temporarily halting infusion, discontinue use and pursue alternative management. Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow.
Acetaminophen overdose: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients) or individuals ingesting higher than recommended acetaminophen doses for extended periods of time (repeated supratherapeutic ingestion).
DRUG INTERACTIONS — May potentiate the hemodynamic effects of nitroglycerin; acetylcysteine is adsorbed by activated charcoal
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — When used in acetaminophen overdose, determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion of immediate release formulations or 2 hours after ingestion of liquid formulations (to ensure peak levels have been obtained); coingestion of acetaminophen with other medications which may delay GI peristalsis eg, antihistamines, opioids, may require repeated serum levels to determine the peak serum level; liver function tests
STABILITY — Store at room temperature; I.V. formulation is preservative free and stable 24 hours after dilution at room temperature; opened inhalation solution vials may be stored in the refrigerator; use within 96 hours; contact with rubber, copper, iron, and cork may inactivate the drug; the light purple color of solution does not affect its activity. I.V. acetylcysteine is hyperosmolar (2600 mOsm/L) and is compatible with 5% dextrose, 0.45% sodium chloride, and SWI.
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering the viscosity. The exact mechanism of action in acetaminophen toxicity is unknown. It may act by maintaining or restoring glutathione levels or by acting as an alternative substrate for conjugation with the acetaminophen's toxic metabolite.
PHARMACODYNAMICS Onset of action: Upon inhalation, mucus liquefaction occurs maximally within 5-10 minutes
Duration of mucus liquefaction: More than 1 hour
PHARMACOKINETICS Distribution: Vd: 0.47 L/kg
Protein binding: 83%
Half-life: Reduced acetylcysteine: 2 hours Total acetylcysteine: Newborns: 11 hours Adults: 5.6 hours
Time to peak serum concentration: Oral: 1-2 hours
Elimination: Clearance: Adults: 0.11 L/hour/kg
PATIENT INFORMATION — Clear airway by coughing deeply before aerosol treatment
(For additional information see "Acetylcysteine: Patient drug information")
NURSING IMPLICATIONS — Anaphylactoid reactions following I.V. administration have been reported; have emergency treatments such as antihistamines and H2 blockers readily available for potential adverse effects; assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning; intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime

Acetylcysteine

U.S. BRAND NAMES — Acetadote®
PHARMACOLOGIC CATEGORY AntidoteMucolytic Agent
DOSING: ADULTS Acetaminophen poisoning: Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until acetaminophen levels are undetectable and there is no evidence of hepatotoxicity. I.V. (Acetadote®): Loading dose: 150 mg/kg over 60 minutes; Note: Extended infusion time recommended by manufacturer as of February, 2006. Loading dose is followed by 2 additional infusions: Initial maintenance dose of 50 mg/kg infused over 4 hours, followed by a second maintenance dose of 100 mg/kg infused over 16 hours. Total dosage: 300 mg/kg administered over 21 hours. Patients <40 kg: Reduce fluid volume according to the following table.
Acetadote® Dosing / Fluid Volume Guidelines for Patients <40 kg
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 25 kg: Loading dose (150 mg/kg over 1 hour): Acetadote® 18.75 mL in D5W 100 mL Second dose (50 mg/kg over 4 hours): Acetadote® 6.25 mL in D5W 250 mL Third dose (100 mg/kg over 16 hours): Acetadote® 12.5 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 130 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 Note: If commercial I.V. form is unavailable, the following dose has been reported using solution for oral inhalation (unlabeled): Loading dose: 140 mg/kg, followed by 70 mg/kg every 4 hours, for a total of 13 doses (loading dose and 48 hours of treatment); infuse each dose over 1 hour through a 0.2 micron Millipore filter (in-line). Experts suggest that the duration of acetylcysteine administration may vary depending upon serial acetaminophen levels and liver function tests obtained during treatment. In general, patients without measurable acetaminophen levels and without significant LFT elevations (>3 times the ULN) can safely stop acetylcysteine after 24 hours of treatment. The patients who still have detectable levels of acetaminophen, and/or LFT elevations (>1000 units/L) continue to benefit from additional acetylcysteine administration.
Adjuvant therapy in respiratory conditions: Note: Patients should receive bronchodilator 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: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment Direct instillation: Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter
Diagnostic bronchogram: Nebulization or intratracheal: 1-2 mL of 20% solution or 2-4 mL of 10% solution administered 2-3 times prior to procedure
Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules, some centers use solution (diluted in cola beverage or juice). Hydrate patient with saline concurrently.
DOSING: PEDIATRIC
(For additional information see "Acetylcysteine: Pediatric drug information")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.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
DOSAGE FORMS: CONCISE Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL)
Solution, inhalation/oral: 10% [100 mg/mL]; 20% [200 mg/mL]
GENERIC EQUIVALENT AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION 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: For treatment of acetaminophen overdosage, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister.
I.V.: Intravenous formulation (Acetadote®): Administer loading dose of 150 mg/kg over 60 minutes (see "Note"), followed by 2 separate maintenance infusions: 50 mg/kg over 4 hours followed by 100 mg/kg over 16 hours. If not using commercially available I.V. formulation, use a 0.2-µ millipore filter (in-line). Note: Extended infusion time recommended by manufacturer as of February, 2006.
COMPATIBILITY Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, tetracycline, oxytetracycline, erythromycin.
Intravenous: Compatible with D5W, 1/2NS, SWFI. Incompatible with rubber and metals (particularly iron, copper, and nickel).
USE — Adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies; antidote for acute acetaminophen toxicity
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiocontrast-induced renal dysfunction (oral, I.V.); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)
ADVERSE REACTIONS SIGNIFICANT Inhalation: Frequency not defined. Central nervous system: Drowsiness, chills, fever Gastrointestinal: Vomiting, nausea, stomatitis Local: Irritation, stickiness on face following nebulization Respiratory: Bronchospasm, rhinorrhea, hemoptysis Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration
Intravenous:
>10%: Miscellaneous: Anaphylactoid reaction (~17%; reported as severe in 1% or moderate in 10% of patients within 15 minutes of first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after 60-minute infusion)
1% to 10%: Cardiovascular: Angioedema (2% to 8%), vasodilation (1% to 6%), hypotension (1% to 4%), tachycardia (1% to 4%), syncope (1% to 3%), chest tightness (1%), flushing (1%) Central nervous system: Dysphoria (<1% to 2%) Dermatologic: Urticaria (2% to 7%), rash (1% to 5%), facial erythema (1%), palmar erythema (1%), pruritus (1% to 3%), pruritus with rash and vasodilation (2% to 9%) Gastrointestinal: Vomiting (<1% to 10%), nausea (1% to 10%), dyspepsia (1%) Neuromuscular & skeletal: Gait disturbance (<1% to 2%) Ocular: Eye pain (<1% to 3%) Otic: Ear pain (1%) Respiratory: Bronchospasm (1% to 6%), cough (1% to 4%), dyspnea (<1% to 3%), pharyngitis (1%), rhinorrhea (1%), rhonchi (1%), throat tightness (1%) Miscellaneous: Diaphoresis (1%)
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component of the formulation
WARNINGS / PRECAUTIONS Disease-related concerns: Acetaminophen overdose: Appropriate use: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients).
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. Intravenous: Acute flushing and erythema have been reported; usually occurs within 30-60 minutes and may resolve spontaneously. Serious anaphylactoid reactions have also been reported. Acetylcysteine infusion may be interrupted until treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactic reactions should be immediately available. Use caution with asthma or history of bronchospasm.
DRUG INTERACTIONS — Adsorbed by activated charcoal; clinical significance is minimal, though, once a pure acetaminophen ingestion requiring N-acetylcysteine is established; further charcoal dosing is unnecessary once the appropriate initial charcoal dose is achieved (5-10 g:g acetaminophen)
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Based on limited reports using acetylcysteine to treat acetaminophen overdose in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective levels in the fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)Solution (Acetylcysteine) 10% (30): $19.56 20% (4): $7.99 20% (10): $14.99
Solution (Mucomyst) 20% (30): $18.99
Solution (Mucomyst-10) 10% (10): $11.74 10% (30): $18.99
MONITORING PARAMETERS — Acetaminophen overdose: AST, ALT, bilirubin, PT, serum creatinine, BUN, serum glucose, and electrolytes. Acetaminophen levels at ~4 hours postingestion (every 4-6 hours if extended release acetaminophen; plot on the nomogram) and every 4-6 hours to assess serum levels, and LFTs for possible hepatotoxicity. Assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning. If administered I.V., monitor for anaphylaxis/anaphylactoid reactions.
REFERENCE RANGE — Determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion (to ensure peak levels have been obtained); administer for acetaminophen level >150 mcg/mL at 4 hours following ingestion; toxic concentration with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg at 12 hours
TOXICOLOGY / OVERDOSE COMPREHENSIVE — The treatment of acetylcysteine toxicity is usually aimed at reversing anaphylactoid symptoms or controlling nausea and vomiting. The use of epinephrine, antihistamines, and steroids may be beneficial.
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
INTERNATIONAL BRAND NAMES — ACC (MX, PL); ACC 200 (EE, HU); Acetain (KR); Acetylcysteine Solution (CA); Acypront (HK, PL); Alveolex (IE); Bromuc (BR); Drenaflen (EC); Ecomucyl (CH); Eloamin (CZ); Exomuc (FR, HK); Fabrol (AT, GR); Flemex AC (TH); Fluimicil (CH); Fluimucil (BR, CN, CO, EC, HK, ID, MA, NL, PE, PL, SG, TH, TW); Fluimucil A (MY, PK); Fluimukan (HR); Flutafin (TW); Hidonac (ID, PH, TH); Libramucil (EC); Menaxol (CR, DO, GT, HN, NI, PA, SV); Mucofillin (JP); Mucolator (MY); Mucolitico (CL); Mucomiste (PT); Mucomyst (AT, AU, BE, CA, DK, FI, FR, KR, NL); Mucoserin (KR); Mucosof (CN); Mucosten (KR); Mucosys (IN); Mucoza (TH); Mukolit (ID); Muteran (KR); Parvolex (CA, GB, IE, NZ, PH); Parvolex DBL (MY); Reolin (IL); Simucin (TH); Siran 200 (IL); Solmucol (SG); Spatam (SG); Stecin (KR); Syntemucol (PL); Tussicom (PL); Zifluvis (CO)
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity. The exact mechanism of action in acetaminophen toxicity is unknown; thought to act by providing substrate for conjugation with the toxic metabolite.
PHARMACODYNAMICS / KINETICS Onset of action: Inhalation: 5-10 minutes
Duration: Inhalation: >1 hour
Distribution: 0.47 L/kg
Protein binding, plasma: 83%
Half-life elimination: Reduced acetylcysteine: 2 hours Total acetylcysteine: Adults: 5.5 hours; Newborns: 11 hours
Time to peak, plasma: Oral: 1-2 hours
Excretion: Urine
PATIENT INFORMATION — Clear airway by coughing deeply before using aerosol.
(For additional information see "Acetylcysteine: Patient drug information")
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Allaqaband, S, Tumuluri, R, Malik, AM, et al. Prospective Randomized Study of N-Acetylcysteine, Fenoldopam, and Saline for Prevention of Radiocontrast-Induced Nephropathy. Catheter Cardiovasc Interv 2002; 57:279. 2. Appelboam, AV, Dargan, PI, Knighton, J. Fatal Anaphylactoid Reaction to N-Acetylcysteine: Caution in Patients With Asthma. Emerg Med J 2002; 19:594. 3. Bailey, B, McGuigan, MA. Management of Anaphylactoid Reactions to Intravenous N-Acetylcysteine. Ann Emerg Med 1998; 31:710. 4. Baker, CS, Wragg, A, Kumar, S, et al. A Rapid Protocol for the Prevention of Contrast-Induced Renal Dysfunction: The RAPPID Study. J Am Coll Cardiol 2003; 41:2114. 5. Curhan, GC. Prevention of Contrast Nephropathy. JAMA 2003; 289:606. 6. Douglas, D, Smilkstein, M. Deferoxamine-Iron Induced Pulmonary Injury and N-Acetylcysteine. J Toxicol Clin Toxicol 1995; 33:495. 7. Falk, JL. Oral N-Acetylcysteine Given Intravenously for Acetaminophen Overdose: We Shouldn't Have To, But We Must. Crit Care Med 1998; 26:7. 8. Harrison, PM, Keays, R, Bray, BP, et al. Improved Outcome of Paracetamol-Induced Fulminant Hepatic Failure by Late Administration of Acetylcysteine. Lancet 1990; 335:1572. 9. Harrison, PM, Wendon, JA, Gimson, AE, et al. Improvement by Acetylcysteine of Hemodynamics and Oxygen Transport in Fulminant Hepatic Failure. N Engl J Med 1991; 324:1852. 10. Henderson, A, Hayes, P. Acetylcysteine as a Cytoprotective Antioxidant in Patients With Severe Sepsis: Potential New Use for an Old Drug. Ann Pharmacother 1994; 28:1086. 11. Kay, J, Chow, WH, Chan, TM, et al. Acetylcysteine for Prevention of Acute Deterioration of Renal Function Following Elective Coronary Angiography and Intervention: A Randomized Controlled Trial. JAMA 2003; 289:553. 12. Keays, R, Harrison, PM, Wendon, JA, et al. Intravenous Acetylcysteine in Paracetamol Induced Fulminant Hepatic Failure: A Prospective Controlled Trial. BMJ 1991; 303:1026. 13. Mascarenhas, MR. Treatment of Gastrointestinal Problems in Cystic Fibrosis. Curr Treat Options Gastroenterol 2003; 6:427. 14. Mohammed, S, Jamal, AZ, Robison, LR. Serum Sickness-Like Illness Associated With N-Acetylcysteine Therapy. Ann Pharmacother 1994; 28:285. 15. Mokhlesi, B, Leikin, JB, Murray, P, et al. Adult Toxicology in Critical Care: Part II: Specific Poisonings. Chest 2003; 123:897. 16. Mroz, L, Benitez, JG, Krenzelok, E. Angioedema With Oral Acetylcysteine. Clin Toxicol 1995; 33:554. 17. Prescott, LF, Donovan, JW, Jarvie, DR, et al. The Disposition and Kinetics of Intravenous N-acetylcysteine in Patients With Paracetamol Overdosage. Eur J Clin Pharmacol 1989; 37:501. 18. Prescott, LF, Illingworth, RN, Critchley, JA, et al. Intravenous N-Acetylcysteine: The Treatment of Choice for Paracetamol Poisoning. BMJ 1979; 2:1097. 19. Rashid, ST, Salman, M, Myint, F, et al. Prevention of Contrast-Induced Nephropathy in Vascular Patients Undergoing Angiography: A Randomized Controlled Trial of Intravenous N-Acetylcysteine. J Vasc Surg 2004; 40:1136. 20. Rodgers, G, Matyunas, N, Ross, M, et al. Sulfhemoglobinemia Associated With N-Acetylcysteine (NAC) Therapy of Acetaminophen (APAP) Overdose: A Case Report. Clin Toxicol 1995; 33:530. 21. Smilkstein, MJ, Bronstein, AC, Linden, C. Acetaminophen Overdose: A 48-Hour Intravenous N-Acetylcysteine Treatment Protocol. Ann Emerg Med 1991; 20:1058. 22. Smilkstein, MJ, Knapp, GL, Kulig, KW, et al. Efficacy of N-Acetylcysteine in the Treatment of Acetaminophen Overdose: Analysis of the National Multicenter Study (1976 to 1985). N Engl J Med 1988; 319:1557. 23. Tepel, M, van der Giet, M, Schwarzfeld, C, et al. Prevention of Radiographic-Contrast-Agent-Induced Reductions in Renal Function by Acetylcysteine. N Engl J Med 2000; 343:180. 24. Walson, PD, Groth JF, Jr. Acetaminophen Hepatotoxicity After Prolonged Ingestion. Pediatrics 1993; 91:1021. 25. Webb, JG, Pate, GE, Humphries, KH, et al. A Randomized Controlled Trial of Intravenous N-Acetylcysteine for the Prevention of Contrast-Induced Nephropathy After Cardiac Catheterization: Lack of Effect. Am Heart J 2004; 148:422. 26. Woo, OF, Anderson, IB, Kim, SY, et al. Shorter Duration of N-Acetylcysteine (NAC) for Acute Acetaminophen Poisoning. Clin Toxicol 1995; 33:508. 27. Woo, OF, Mueller, PD, Olson, KR, et al. Shorter Duration of Oral N-Acetylcysteine Therapy for Acute Acetaminophen Overdose. Ann Emerg Med 2000; 35:363. 28. Yankaskas, JR, Marshall, BC, Sufian, B, et al. Cystic Fibrosis Adult Care: Consensus Conference Report. Chest 2004; 125(1 Suppl):1. 29. Yip, L, Dart, RC, Hurlbut, KM. Intravenous Administration of Oral N-Acetylcysteine. Crit Care Med 1998; 26:40.

Acetylcysteine

U.S. BRAND NAMES — Acetadote®
PHARMACOLOGIC CATEGORY AntidoteMucolytic Agent
DOSING: ADULTS Acetaminophen poisoning: Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until acetaminophen levels are undetectable and there is no evidence of hepatotoxicity. I.V. (Acetadote®): Loading dose: 150 mg/kg over 60 minutes; Note: Extended infusion time recommended by manufacturer as of February, 2006. Loading dose is followed by 2 additional infusions: Initial maintenance dose of 50 mg/kg infused over 4 hours, followed by a second maintenance dose of 100 mg/kg infused over 16 hours. Total dosage: 300 mg/kg administered over 21 hours. Patients <40 kg: Reduce fluid volume according to the following table.
Acetadote® Dosing / Fluid Volume Guidelines for Patients <40 kg
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 25 kg: Loading dose (150 mg/kg over 1 hour): Acetadote® 18.75 mL in D5W 100 mL Second dose (50 mg/kg over 4 hours): Acetadote® 6.25 mL in D5W 250 mL Third dose (100 mg/kg over 16 hours): Acetadote® 12.5 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 130 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 Note: If commercial I.V. form is unavailable, the following dose has been reported using solution for oral inhalation (unlabeled): Loading dose: 140 mg/kg, followed by 70 mg/kg every 4 hours, for a total of 13 doses (loading dose and 48 hours of treatment); infuse each dose over 1 hour through a 0.2 micron Millipore filter (in-line). Experts suggest that the duration of acetylcysteine administration may vary depending upon serial acetaminophen levels and liver function tests obtained during treatment. In general, patients without measurable acetaminophen levels and without significant LFT elevations (>3 times the ULN) can safely stop acetylcysteine after 24 hours of treatment. The patients who still have detectable levels of acetaminophen, and/or LFT elevations (>1000 units/L) continue to benefit from additional acetylcysteine administration.
Adjuvant therapy in respiratory conditions: Note: Patients should receive bronchodilator 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: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment Direct instillation: Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter
Diagnostic bronchogram: Nebulization or intratracheal: 1-2 mL of 20% solution or 2-4 mL of 10% solution administered 2-3 times prior to procedure
Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules, some centers use solution (diluted in cola beverage or juice). Hydrate patient with saline concurrently.
DOSING: PEDIATRIC
(For additional information see "Acetylcysteine: Pediatric drug information")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.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
DOSAGE FORMS: CONCISE Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL)
Solution, inhalation/oral: 10% [100 mg/mL]; 20% [200 mg/mL]
GENERIC EQUIVALENT AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION 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: For treatment of acetaminophen overdosage, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister.
I.V.: Intravenous formulation (Acetadote®): Administer loading dose of 150 mg/kg over 60 minutes (see "Note"), followed by 2 separate maintenance infusions: 50 mg/kg over 4 hours followed by 100 mg/kg over 16 hours. If not using commercially available I.V. formulation, use a 0.2-µ millipore filter (in-line). Note: Extended infusion time recommended by manufacturer as of February, 2006.
COMPATIBILITY Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, tetracycline, oxytetracycline, erythromycin.
Intravenous: Compatible with D5W, 1/2NS, SWFI. Incompatible with rubber and metals (particularly iron, copper, and nickel).
USE — Adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies; antidote for acute acetaminophen toxicity
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiocontrast-induced renal dysfunction (oral, I.V.); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)
ADVERSE REACTIONS SIGNIFICANT Inhalation: Frequency not defined. Central nervous system: Drowsiness, chills, fever Gastrointestinal: Vomiting, nausea, stomatitis Local: Irritation, stickiness on face following nebulization Respiratory: Bronchospasm, rhinorrhea, hemoptysis Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration
Intravenous:
>10%: Miscellaneous: Anaphylactoid reaction (~17%; reported as severe in 1% or moderate in 10% of patients within 15 minutes of first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after 60-minute infusion)
1% to 10%: Cardiovascular: Angioedema (2% to 8%), vasodilation (1% to 6%), hypotension (1% to 4%), tachycardia (1% to 4%), syncope (1% to 3%), chest tightness (1%), flushing (1%) Central nervous system: Dysphoria (<1% to 2%) Dermatologic: Urticaria (2% to 7%), rash (1% to 5%), facial erythema (1%), palmar erythema (1%), pruritus (1% to 3%), pruritus with rash and vasodilation (2% to 9%) Gastrointestinal: Vomiting (<1% to 10%), nausea (1% to 10%), dyspepsia (1%) Neuromuscular & skeletal: Gait disturbance (<1% to 2%) Ocular: Eye pain (<1% to 3%) Otic: Ear pain (1%) Respiratory: Bronchospasm (1% to 6%), cough (1% to 4%), dyspnea (<1% to 3%), pharyngitis (1%), rhinorrhea (1%), rhonchi (1%), throat tightness (1%) Miscellaneous: Diaphoresis (1%)
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component of the formulation
WARNINGS / PRECAUTIONS Disease-related concerns: Acetaminophen overdose: Appropriate use: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients).
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. Intravenous: Acute flushing and erythema have been reported; usually occurs within 30-60 minutes and may resolve spontaneously. Serious anaphylactoid reactions have also been reported. Acetylcysteine infusion may be interrupted until treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactic reactions should be immediately available. Use caution with asthma or history of bronchospasm.
DRUG INTERACTIONS — Adsorbed by activated charcoal; clinical significance is minimal, though, once a pure acetaminophen ingestion requiring N-acetylcysteine is established; further charcoal dosing is unnecessary once the appropriate initial charcoal dose is achieved (5-10 g:g acetaminophen)
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Based on limited reports using acetylcysteine to treat acetaminophen overdose in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective levels in the fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)Solution (Acetylcysteine) 10% (30): $19.56 20% (4): $7.99 20% (10): $14.99
Solution (Mucomyst) 20% (30): $18.99
Solution (Mucomyst-10) 10% (10): $11.74 10% (30): $18.99
MONITORING PARAMETERS — Acetaminophen overdose: AST, ALT, bilirubin, PT, serum creatinine, BUN, serum glucose, and electrolytes. Acetaminophen levels at ~4 hours postingestion (every 4-6 hours if extended release acetaminophen; plot on the nomogram) and every 4-6 hours to assess serum levels, and LFTs for possible hepatotoxicity. Assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning. If administered I.V., monitor for anaphylaxis/anaphylactoid reactions.
REFERENCE RANGE — Determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion (to ensure peak levels have been obtained); administer for acetaminophen level >150 mcg/mL at 4 hours following ingestion; toxic concentration with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg at 12 hours
TOXICOLOGY / OVERDOSE COMPREHENSIVE — The treatment of acetylcysteine toxicity is usually aimed at reversing anaphylactoid symptoms or controlling nausea and vomiting. The use of epinephrine, antihistamines, and steroids may be beneficial.
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
INTERNATIONAL BRAND NAMES — ACC (MX, PL); ACC 200 (EE, HU); Acetain (KR); Acetylcysteine Solution (CA); Acypront (HK, PL); Alveolex (IE); Bromuc (BR); Drenaflen (EC); Ecomucyl (CH); Eloamin (CZ); Exomuc (FR, HK); Fabrol (AT, GR); Flemex AC (TH); Fluimicil (CH); Fluimucil (BR, CN, CO, EC, HK, ID, MA, NL, PE, PL, SG, TH, TW); Fluimucil A (MY, PK); Fluimukan (HR); Flutafin (TW); Hidonac (ID, PH, TH); Libramucil (EC); Menaxol (CR, DO, GT, HN, NI, PA, SV); Mucofillin (JP); Mucolator (MY); Mucolitico (CL); Mucomiste (PT); Mucomyst (AT, AU, BE, CA, DK, FI, FR, KR, NL); Mucoserin (KR); Mucosof (CN); Mucosten (KR); Mucosys (IN); Mucoza (TH); Mukolit (ID); Muteran (KR); Parvolex (CA, GB, IE, NZ, PH); Parvolex DBL (MY); Reolin (IL); Simucin (TH); Siran 200 (IL); Solmucol (SG); Spatam (SG); Stecin (KR); Syntemucol (PL); Tussicom (PL); Zifluvis (CO)
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity. The exact mechanism of action in acetaminophen toxicity is unknown; thought to act by providing substrate for conjugation with the toxic metabolite.
PHARMACODYNAMICS / KINETICS Onset of action: Inhalation: 5-10 minutes
Duration: Inhalation: >1 hour
Distribution: 0.47 L/kg
Protein binding, plasma: 83%
Half-life elimination: Reduced acetylcysteine: 2 hours Total acetylcysteine: Adults: 5.5 hours; Newborns: 11 hours
Time to peak, plasma: Oral: 1-2 hours
Excretion: Urine
PATIENT INFORMATION — Clear airway by coughing deeply before using aerosol.
(For additional information see "Acetylcysteine: Patient drug information")
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