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.