Friday, February 29, 2008

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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