Acetylcysteine

Pronunciation
( N-Acetylcysteine )

Pronunciation: a-SEET-il-SIS-teen
Class: Antidote, Mucolytic

Trade Names

Acetadote
- Injection, solution 20% (200 mg/mL)

Acetylcysteine
- Solution, inhalation or oral 10%
- Solution, concentrate, inhalation or oral 20%

Acetylcysteine Solution (Canada)

Pharmacology

Decreases thickness of mucous secretions in lung; protects the liver by maintaining or restoring glutathione levels or by acting as an alternate substrate for conjugation with, and thus detoxification of, the acetaminophen reactive metabolite.

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Pharmacokinetics

Distribution

Vd is 0.47 L/kg, and 83% protein bound.

Metabolism

Acetylcysteine may form cysteine, disulfides, and conjugates in vivo (eg, N, N'-diacetylcysteine, N-acetylcysteine-cysteine, N-acetylcysteine-glutathione, N-acetylcysteine-protein).

Elimination

The half-life is 5.6 h (IV). The mean Cl is 0.11 L/h/kg and renal Cl is approximately 30% of total Cl (IV).

Special Populations

Renal Function Impairment

Pharmacokinetic information is not available.

Hepatic Function Impairment

In patients with severe liver impairment, half-life increased 80% and Cl decreased 30%.

Elderly

Pharmacokinetic information is not available.

Children

The half-life is increased to 11 h in newborns.

Gender

Adequate information is not available.

Indications and Usage

As adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in such conditions as chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis and primary amyloidosis of the lung), acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis), pulmonary complications of cystic fibrosis, tracheostomy care, pulmonary complications associated with surgery, during anesthesia, posttraumatic chest conditions, atelectasis caused by mucous obstruction, and diagnostic bronchial studies (eg, bronchograms, bronchospirometry, bronchial wedge catheterization) (inhalation); prevention or lessening of liver damage after potentially toxic quantity of acetaminophen (oral or IV).

Unlabeled Uses

Ophthalmic preparation for dry eyes; enema for bowel obstruction; prevention of radiocontrast-induced nephrotoxicity.

Contraindications

Sensitivity to acetylcysteine.

Dosage and Administration

Abnormal, Viscid, or Inspissated Mucous Secretions
Adults and Children

Inhalation 1 to 2 mL of a 10% solution may be given as often as every hour.

Direct instillation into a particular segment of the bronchopulmonary tree

Insert (under local anesthesia and direct vision) a small plastic catheter into the trachea. 2 to 5 mL of the 20% solution may then be instilled by means of a syringe connected to the catheter.

Direct instillation into percutaneous intratracheal catheter

1 to 2 mL of the 20% or 2 to 4 mL of the 10% solution every 1 to 4 h given by a syringe attached to the catheter.

Direct instillation for routine care of tracheostomy

1 to 2 mL of a 10% or 20% solution given every 1 to 4 h by instillation into the tracheostomy.

Nebulization with face mask, mouth piece, tracheostomy

The usual dosage is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times a day (alternative dosage is 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 h).

Nebulization with tent, croupette

The recommended dose is the volume of acetylcysteine (using 10% or 20%) that will maintain a very heavy mist in the tent or croupette for the desired period, occasionally as much as 300 mL during a single treatment period. Administration for intermittent or continuous prolonged periods, including overnight, may be desirable.

Acetaminophen Overdose
Adults and Children IV Patients weighing 40 kg or more Loading dose

150 mg/kg in 200 mL of diluent infused over 60 min.

Maintenance dose

50 mg/kg in 500 mL of diluent infused over 4 h followed by 100 mg/kg in 1,000 mL of diluent infused over 16 h.

Patients weighing more than 20 kg to less than 40 kg Loading dose

150 mg/kg in 100 mL of diluent infused over 60 min.

Maintenance dose

50 mg/kg in 250 mL of diluent infused over 4 h followed by 100 mg/kg in 500 mL of diluent infused over 16 h.

Patients weighing 20 kg or less Loading dose

150 mg/kg in 3 mL/kg of diluent infused over 60 min.

Maintenance dose

50 mg/kg in 7 mL/kg of diluent infused over 4 h followed by 100 mg/kg in 14 mL/kg of diluent infused over 16 h.

PO

140 mg/kg loading dose administered immediately if 24 h or less have elapsed from the reported time of ingestion of an acetaminophen overdose, then 70 mg/kg 4 h after loading dose and repeated at 4-h intervals for total of 17 doses, unless acetaminophen assay indicates otherwise.

Diagnostic Bronchograms
Adults and children

Inhalation 2 to 3 administrations of 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution by nebulization or tracheal instillation before procedure.

General Advice

  • Mucolytic
  • For oral inhalation via nebulizer only. Not for injection.
  • The 20% solution may be diluted to a lesser concentration with sodium chloride inhalation solution or injection, or sterile water for injection or inhalation. The 10% solution may be used undiluted.
  • If an admixture is prepared, administer as soon as possible after preparation. Do not store admixtures for future use.
  • Refer to individual manufacturer's guidelines before combining with other medications or solvents. Do not mix with erythromycin lactobionate or tetracycline.
  • When three-fourths of the initial volume of acetylcysteine solution has been nebulized, a quantity of sterile water for injection (approximately equal to the volume of solution remaining), should be added to the nebulizer. This obviates any concentration of the agent in the residual solvent remaining after prolonged nebulization.
  • Do not use nebulization equipment that contains iron, copper, or rubber because of potential for corrosion. Use glass, plastic, aluminum, anodized aluminum, chromed metal, tantalum, sterling silver, or stainless steel equipment. Silver may become tarnished after exposure to acetylcysteine, but this is not harmful to the patient and does not reduce the effectiveness of the medication.
  • Take care to minimize contamination of the sterile solution.
  • Clean nebulizing equipment immediately after use to prevent clogging of small orifices or corrosion of metal parts.
  • Injection
  • For IV use.
  • On admission, draw a serum blood sample at least 4 h after ingestion to determine the acetaminophen level, which will serve as a basis for determining the need for treatment. If patient presents 4 h postingestion, determine serum acetaminophen sample immediately. Administer acetylcysteine within 8 h from acetaminophen ingestion for max protection against hepatic injury. If time of ingestion is unknown, or acetaminophen level is not available, administer acetylcysteine immediately if 24 h or less have elapsed from the time of the reported overdose ingestion of acetaminophen, regardless of quantity reported to have been ingested.
  • Acetylcysteine is compatible with dextrose 5%, sodium chloride 0.45% injection, and water for injection.
  • In patients requiring fluid restriction, reduce the volume of diluent needed.
  • Oral solution
  • For oral administration. Not for parenteral injection.
  • Plasma or serum acetaminophen concentrations, determined as early as possible but no sooner than 4 h following an acute overdose, are essential in assessing the potential risk of hepatotoxicity. If an assay for acetaminophen cannot be obtained, it is necessary to assume that the overdose is potentially toxic. Acetaminophen levels drawn less than 4 h postingestion may be misleading. Do not await results of assay for acetaminophen level before initiating treatment.
  • Empty the stomach by lavage before administration. In case of mixed drug overdose, activated charcoal may be indicated. However, if activated charcoal has been administered, lavage before administering treatment.
  • Dilute the acetylcysteine solution with diet cola or other diet soft drink to provide an oral solution with a final concentration of 5%. Administer diluted solution within 1 h of preparation.
  • If the patient vomits within 1 h of administration, repeat that dose.
  • If the patient persistently is unable to retain the orally administered acetylcysteine, administer by duodenal intubation.

Storage/Stability

Inhalation or oral solution

Store unopened vials at 59° to 86°F. Use freshly prepared solutions within 1 h. Once opened, store any unused solution in refrigerator (36° to 46°F). Discard any unused solution after 96 h.

Injection

Store unopened vials at 68° to 77°F. Diluted solution is stable for up to 24 h at controlled room temperature. Discard any remaining injection concentrate from single-dose vial. Do not save for future use; do not use if vial has been previously opened.

Drug Interactions

None well documented.

Adverse Reactions

Cardiovascular

Tachycardia (4%); hypotension (postmarketing).

Dermatologic

Rash (4%); flushing, pruritus (3%); urticaria (postmarketing).

EENT

Pharyngitis, rhinorrhea, throat tightness (1%).

GI

Vomiting (10%); nausea (6%); stomatitis.

Respiratory

Rhonchi (1%); bronchoconstriction; bronchospasm; irritation to the tracheal and bronchial tracts; hemoptysis; edema, respiratory symptoms (postmarketing).

Miscellaneous

Anaphylaxis, immune system disorder (18%); chest tightness; clamminess; drowsiness; fever; acquired acetylcysteine sensitization (rare).

Precautions

Monitor

Acetaminophen overdose

Ensure that blood for baseline acetaminophen plasma level, liver enzymes, bilirubin, PT, electrolytes, blood sugar, BUN, and creatinine have been drawn before initiating therapy, and then daily for duration of therapy.

Mucolytic

Monitor for development of airway obstruction.


Pregnancy

Category B .

Lactation

Undetermined. Acetylcysteine is nearly completely cleared 30 h after administration. Breast-feeding women may consider resuming breast-feeding 30 h after administration.

Hypersensitivity

Serious anaphylactoid reactions, including death in a patient with asthma, have been reported with IV administration.

Antidotal use

If allergic reaction, encephalopathy, or severe, persistent vomiting occurs, discontinuation of drug may be necessary.

Asthmatic bronchospasm

Use with caution in patients with asthma or a history of bronchospasm. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, medication must be discontinued immediately.

Bronchial secretions

Increased secretion volume may occur. When cough is inadequate, open airway may need to be maintained by mechanical suction. When there is a mechanical block caused by a foreign body or local accumulation, clear the airway via endotracheal aspiration, with or without bronchoscopy.

Fluid overload

When administering IV, adjust the total volume administered for patients less than 40 kg and for those requiring fluid restriction.

Patient Information

  • Mucolytic
  • Instruct patient or caregiver not to change the dose or stop taking unless advised by health care provider.
  • Advise patient or caregiver that medication has a disagreeable odor (rotten eggs), but that this should become unnoticeable after continued use.
  • Advise patient or caregiver that treatment is expected to increase volume of respiratory secretions and that effective coughing will be required to clear the secretions. Advise patient or caregiver to immediately notify health care provider if respiratory secretions cannot be adequately removed by coughing.
  • Advise patient or caregiver that administration using face mask may leave a sticky residue on the face that can be easily removed by washing with water.
  • Advise patient that medication may turn a light purple color after opening bottle. Advise patient that this is normal and does not alter the safety or effectiveness of the medication.
  • Caution patient or caregiver to dilute the nebulizer solution with sterile water for injection to prevent the solution from becoming concentrated and plugging the nebulizer.
  • Caution patient or caregiver not to add other medications or solutions to nebulizer canister unless advised by health care provider.
  • Advise patient or caregiver to notify health care provider if any of the following occur: rash or other signs of allergic reaction, new or worsening wheezing, chest tightness or difficulty breathing, persistent nausea or vomiting, coughing up blood, fever, other signs of respiratory infection.
  • Acetaminophen overdose
  • Advise patient, family, or caregiver that medication will be prepared and administered by a health care provider in a hospital setting.
  • Advise patients to report any history of asthma to their health care provider.
  • Inform patients that serious anaphylactoid reactions, including death in a patient with asthma, and severe and persistent vomiting may occur.

Copyright © 2009 Wolters Kluwer Health.

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