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N-Acetylcysteine

Generic Name: Acetylcysteine


JAN:

N-Acetyl- L-Cysteine

VA CLASSIFICATION
Primary: RE400
Secondary: DX900

Commonly used brand name(s): Mucomyst; Mucomyst-10; Mucosil.

Another commonly used name is
N-acetylcysteine .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Mucolytic—

diagnostic aid (bronchoscopy)—

Indications

Acceptance not established
Acetylcysteine is used in current medical practice in conjunction with chest physiotherapy as a mucolytic in patients who have viscid or thickened airway mucus {12}. When administered via direct instillation, it is used to loosen impacted mucus plugs during bronchoscopy {14} {15}. Acetylcysteine can irritate the airways and induce bronchospasm when given by inhalation; therefore, it should be administered simultaneously with or following administration of an inhaled beta-adrenergic bronchodilator {02} {07} {09}.

There are no controlled clinical studies showing that the drug improves mucus clearance {09}. Early reports indicating efficacy in clinical practice presented cases or used subjective information or nonspecific tests, such as sputum volume {08} {09} {13}. Additionally, there are other sources concluding that acetylcysteine is ineffective {02} {03} {06} {11}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
163.2 {01}

Mechanism of action/Effect:

Acetylcysteine exerts its mucolytic action through its free sulfhydryl group, which opens the disulfide bonds and lowers mucus viscosity. This action increases with increasing pH and is most significant at pH 7 to 9. The mucolytic action of acetylcysteine is not affected by the presence of DNA. {01}

Biotransformation:

Hepatic. Acetylcysteine undergoes rapid deacetylation in vivo to yield cysteine or oxidation to yield diacetylcystine. {01}

Onset of action:

In vitro—Within 1 minute {08}.

Time to peak effect:

In vitro—5 to 10 minutes {08}.


Precautions to Consider

Carcinogenicity

Studies have not been done to determine the carcinogenic potential of acetylcysteine {01}.

Mutagenicity

In the Ames test, both with and without metabolic activation, acetylcysteine was not shown to be mutagenic {01}.

Pregnancy/Reproduction
Fertility—
A reproduction toxicity study in rats given acetylcysteine with isoproterenol by inhalation showed no adverse effects on fertility. In reproduction toxicity studies in rats given acetylcysteine orally at doses up to 5.2 times the human dose, one study showed only a slight non–dose-related reduction in fertility. {01}

Pregnancy—
Adequate and well-controlled studies in humans have not been done.

Reproduction studies in rats given acetylcysteine with isoproterenol and in rabbits given acetylcysteine alone at doses up to 2.6 times the human dose have shown no evidence of teratogenicity or harm to the fetus {01}.

FDA Pregnancy Category B {01}.

Breast-feeding

It is not known whether acetylcysteine is distributed into breast milk. However, problems in humans have not been documented {01}.

Pediatrics

Appropriate studies on the relationship of age to the effects of acetylcysteine inhalation have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date.


Geriatrics


Appropriate studies on the relationship of age to the effects of acetylcysteine inhalation have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Asthma ( asthmatics may experience bronchospasm associated with the administration of nebulized acetylcysteine {01} {05}; therefore, it should be administered simultaneously with or following administration of an inhaled beta-adrenergic bronchodilator)


» Cough, inadequate ability to (after treatment with acetylcysteine, an increased mobilization of bronchial secretions may develop; when the ability to cough is inadequate, mechanical suctioning may be required to maintain open airways {01})


Sensitivity to acetylcysteine{01}


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent

Increased airways obstruction, {01}(difficulty in breathing; tightness in chest; wheezing)—especially in asthma patients

Note: Increased airways obstruction of varying and unpredictable severity has been reported following administration of acetylcysteine; however, it is not possible to identify those who will react. Patients who have developed increased airways obstruction following administration do not neccessarily react to a subsequent administration, and vice versa. {01}


Incidence rare

Sensitization (skin rash or other irritation)—with frequent and prolonged exposure{01}



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent

Clammy skin {01}

fever {01}

increase in bronchial secretions {01}

irritation of throat or lungs {01}—more frequent with a 20% solution{08}

nausea {01}

rhinorrhea {01}(runny nose)

stomatitis {01}(irritation or soreness of mouth)

vomiting {01}



Those not indicating need for medical attention
Incidence more frequent

Stickiness on face, after nebulization using a face mask

unpleasant odor during administration, transient





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Acetylcysteine (Inhalation).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
» Conditions affecting use, especially:
Sensitivity to acetylcysteine
Other medical problems, especially asthma or decreased ability to cough

Proper use of this medication
» Importance of not using more medication than the amount prescribed

Proper administration: Knowing correct administration technique; checking with physician if necessary

After using medication, coughing up loosened mucus to prevent excessive accumulation in lungs; mechanical suction may be necessary if cough inadequate to remove mucus

» Proper dosing
Missed dose: Using as soon as possible; using any remaining doses for that day at regularly spaced intervals

» Proper storage

Precautions while using this medication
» Checking with physician if condition does not improve or if it becomes worse


Side/adverse effects
Signs of potential side effects, especially increased airways obstruction and sensitization

Possibility of stickiness on face after nebulization using a face mask; removing by washing with water

Possibility of acetylcysteine having a transient unpleasant odor during administration


General Dosing Information
The method of acetylcysteine administration depends on the condition being treated. Acetylcysteine, usually as a 10 to 20% solution, may be administered by nebulization or direct instillation. {01}

Acetylcysteine usually is administered by nebulization, using conventional nebulizers made of plastic or glass. Certain materials used in nebulization equipment react with acetylcysteine, especially iron, copper, and rubber. {01}

Acetylcysteine should not be placed directly into the chamber of a heated (hot pot) nebulizer. A heated nebulizer may be part of the nebulization assembly to provide a warm saturated atmosphere if the acetylcysteine aerosol is introduced by means of a separate unheated nebulizer. The usual precautions for administration of warm saturated nebulae should be followed. {01}

The nebulizing equipment should be cleaned immediately after use because the residues may clog the smaller orifices or corrode metal parts {01}.

Hand bulb nebulizers are not recommended for nebulizing acetylcysteine because their output is generally too small and some deliver particles that are larger than optimum for inhalation therapy {01}.

Nebulization with a face mask may leave a sticky residue on the face. This can be removed by washing with water. {01}

For treatment of adverse effects
Bronchospasm may be relieved by the administration of a bronchodilator by nebulization. If bronchospasm continues, acetylcysteine should be discontinued. {01}


Inhalation or Direct Instillation Dosage Forms

ACETYLCYSTEINE SOLUTION USP

Usual adult and adolescent dose
Mucolytic


Nebulization via face mask, mouthpiece, or tracheostomy:
Inhalation, 3 to 5 (range, 1 to 10) mL of a 20% solution or 6 to 10 (range, 2 to 20) mL of a 10% solution three or four times a day (range, every two to six hours) {01}.



Nebulization via tent or croupette:
Inhalation, a sufficient volume of a 10 or 20% solution to maintain a very heavy mist in the tent or croupette for the period of time necessary {01}.

Note: The method of nebulization, via tent or croupette, must be individualized according to the available equipment and the patient's condition. Very large volumes of the solution are required, occasionally as much as 300 mL during a single treatment period. {01}




Instillation, direct:
1 to 2 mL of a 10 to 20% solution every hour, if necessary {01}.

For routine care of patients with tracheostomy—Intratracheal, 1 to 2 mL of a 10 to 20% solution every one to four hours {01}.

For instillation into a particular segment of bronchopulmonary tree via small plastic catheter into trachea—Intratracheal, 2 to 5 mL of a 20% solution instilled by means of a syringe connected to the catheter {01}.

For instillation via percutaneous intratracheal catheter—Intratracheal, 2 to 4 mL of a 10% solution or 1 to 2 mL of a 20% solution every one to four hours administered by a syringe attached to the catheter {01}.


Diagnostic aid (bronchoscopy)
Inhalation or intratracheal instillation, 1 to 2 mL of a 20% solution or 2 to 4 mL of a 10% solution for two or three doses prior to the procedure {01}.

Note: Acetylcysteine can irritate the airways and induce bronchospasm when given by inhalation; therefore, it should be administered simultaneously with or following administration of an inhaled beta-adrenergic bronchodilator {02} {07} {09}.



Usual pediatric dose
See Usual adult and adolescent dose {01}.

Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


10% (Rx) [Mucomyst-10] [Mucosil][Generic]


20% (Rx) [Mucomyst] [Mucosil][Generic]

Canada—


20% (Rx) [Mucomyst]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container {04}.

Preparation of dosage form:
The 10% solution may be used undiluted.

The 20% solution may be used undiluted or diluted to a lesser concentration with 0.9% sodium chloride injection, sodium chloride inhalation solution, sterile water for injection, or sterile water for inhalation. {01}

Stability:
Acetylcysteine solution does not contain an antimicrobial agent; therefore, care must be taken to minimize contamination of the sterile solution {01}.

After opening, the vial should be stored in the refrigerator; the opened vial should be discarded after 96 hours {01}.

A color change may occur in acetylcysteine after the bottle has been opened. The light purple color results from a chemical reaction that does not significantly affect the safety or mucolytic efficacy of acetylcysteine. {01}

Acetylcysteine has been shown to be physically and chemically compatible with cromolyn sodium inhalation solution for up to 60 minutes {10} and with isoproterenol {16}. Although the admixture of albuterol inhalation solution and acetylcysteine is common medical practice, there is no information about the stability of this combination. If an admixture with acetylcysteine is necessary, it should be administered as soon as possible after preparation; unused admixtures should not be stored. {12}

Incompatibilities:
Acetylcysteine reacts with certain materials, such as iron, copper, and rubber, used in nebulization equipment. Where materials may come into contact with acetylcysteine solution, parts made of the following materials should be used: glass, plastic, aluminum, anodized aluminum, chromed metal, tantalum, sterling silver, or stainless steel. Silver may become tarnished after exposure but this does not affect the efficacy of acetylcysteine or harm the patient. {01}

Auxiliary labeling:
• Store in refrigerator after opening.
• Discard opened vial after 96 hours.



Revised: 05/14/1997


References
  1. Mucosil package insert (Dey—US), Rev 3/91.
  1. Nelson JD. Management of acute pulmonary exacerbations in cystic fibrosis: a critical appraisal. J Pediatr 1985; 106: 1030-4.
  1. American Thoracic Society. Inpatient management of COPD. Am J Resp Crit Care Med 1995; 152: S100.
  1. The United States pharmacopeia. The national formulary. USP 23rd revision NF 18th ed. (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1995.
  1. Mucomyst (Roberts). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 31st ed. Ontario: Canadian Pharmaceutical Assoc, 1996: 922-3.
  1. Barton AD. Aerosolized detergents and mucolytic agents in the treatment of stable chronic obstructive pulmonary disease. Am Rev Respir Dis 1974; 110(Suppl): 104-8.
  1. Ziment I. Hydration, humidification, and mucokinetic therapy. In: Weiss EB, Stein M, editors. Bronchial asthma—mechanisms and therapeutics. Boston: Little, Brown and Co., 1993. p. 926.
  1. Webb WR. New mucolytic agents for sputum liquefaction. Postgrad Med 1964; 36: 449-53.
  1. Salathe M, O'Riordan TG, Wanner A. Treatment of mucociliary dysfunction. Chest 1996; 110: 1048-57.
  1. Lesko LJ, Miller AK. Physical-chemical compatibility of cromolyn sodium nebulizer solution–bronchodilator inhalant solution admixtures. Ann Allergy 1984; 53: 236-8.
  1. Ziment I. Drugs used in respiratory therapy. In: Burton GG, Hodgkin JE, editors. Respiratory care: a guide to clinical practice. Philadelphia: JB Lippincott, 1984: 456-92.
  1. Reviewers' comments, 1/97.
  1. Tsai SH, Jenne JW. Mucoid impaction of the bronchi. Am J Roentgenology 1965; 96: 953-61.
  1. Millman M, Goodman AH, Goldstein IM, et al. Treatment of a patient with chronic bronchial asthma with many bronchoscopies and lavage using acetylcysteine: a case report. J Asthma. 1985; 22: 13-35.
  1. Perruchoud A, Ehrsam R, Heitz M, et al. Atelectasis of the lung: bronchoscopic lavage with acetylcysteine; experience in 51 patients. Eur J Respir Dis. 1980; 61(suppl 111): 163-8.
  1. Panel comment 2/97.

Further information

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