Acetylcysteine

Trade Names:Acetadote- Injection 20% (200 mg/mL)

Trade Names:Mucomyst- Solution 10% (as sodium)- Solution 20% (as sodium)

Pharmacology

Decreases thickness of mucous secretions in lung.

Pharmacokinetics

Absorption

C _max is 0.35 to 4 mg/L; T _max is 1 to 2 h.

Distribution

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

About 50% protein bound. Vd is 0.33 to 0.47 L/kg.

Metabolism

Undergoes rapid deacetylation to yield cysteine or oxidation to yield diacetylcysteine.

Elimination

The t _½ is 5.6 h. The mean Cl is 0.11 L/h/kg, renally about 30% of total Cl.

The t _½ is 6.25 h. About 70% is excreted by nonrenal mechanisms.

Special Populations

For severe liver impairment, primary and/or secondary biliary cirrhosis, t _½ increased 80%, Cl decreased 30%.

The t _½ is increased to 11 h.

Indications and Usage

Reduction of viscosity of bronchopulmonary mucous secretions in patients with chronic or acute lung diseases, pulmonary complications associated with cystic fibrosis, surgery, anesthesia, or atelectasis caused by mucous obstruction; diagnostic bronchial studies; tracheostomy care, posttraumatic chest conditions (oral solution); 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.

Contraindications

Standard considerations.

Dosage and Administration

Nebulization (face mask, mouthpiece, tracheostomy) 1 to 10 mL (usually 3 to 5 mL) of 20% solution or 2 to 20 mL (usually 6 to 10 mL) of 10% solution every 2 to 6 h (usually twice daily or 4 times daily); (nebulization tent) large volumes (up to 300 mL) during treatment period.

1 to 2 mL of 10% to 20% solution as often as every 1 h.

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.

After appropriate overdose procedures (eg, lavage, induction of emesis), PO 140 mg/kg as oral loading dose (diluted with diet soft drink). Then 70 mg/kg orally 4 h after loading dose and repeated at 4-h intervals for total of 17 doses, unless acetaminophen assay indicates otherwise. IV 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 acetylcysteine treatment. If patient presents 4 h post-ingestion, determine acetylcysteine serum 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 has elapsed from the time of the reported overdose ingestion of acetaminophen, regardless of quantity reported to have been ingested. Critical ingestion-treatment interval for max protection against severe hepatic injury is 0 to 8 h. Efficacy diminishes progressively after 8 h and treatment initiated 15 h postingestion of acetaminophen yields limited efficacy. However, it does not appear to worsen the condition and should not be withheld.

150 mg/kg in 200 mL of 5% dextrose; infuse over 15 min.

50 mg/kg in 500 mL of 5% dextrose; infuse over 4 h followed by 100 mg/kg in 1,000 mL of 5% dextrose infused over 16 h.

General Advice

• Mucolytic
• Because compatibility with other medications may vary between manufacturers of acetylcysteine, refer to individual manufacturer's guidelines before combining with other medications or solvents. If an admixture is prepared, administer as soon as possible after preparation. Do not store admixtures for future use.
• 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.
• Clean nebulizing equipment immediately after use to prevent clogging of small orifices or corrosion of metal parts.
• To prevent concentration of medication during prolonged nebulization add sterile water for injection to canister when three fourths of initial volume of acetylcysteine has been administered. The amount of sterile water for injection added should be approximately equal to the volume of solution remaining.

• Injection for acetaminophen overdose
• Dilute injection concentrate with 5% dextrose for loading dose and maintenance doses following manufacturer's guidelines.
• Do not mix with other IV medications or dilute with any IV solution other than 5% dextrose.
• Do not administer injection if particulate matter, cloudiness, or discoloration noted.
• Discard any remaining injection concentrate from single dose vial. Do not save for future use or use if vial has been previously opened.

Oral solution for acetaminophen overdose

• To reduce propensity of oral acetylcysteine to cause or aggravate vomiting, dilute 10% and 20% 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.

Storage/Stability

Store unopened vials at controlled room temperature (59° to 86°F). Once opened, store any unused solution in refrigerator (36° to 46°F). Discard any unused solution after 96 h.

Store unopened vials at controlled room temperature (68° to 77°F). Diluted solution is stable for up to 24 h at controlled room temperature.

Drug Interactions

None well documented.

Incompatibility

Do not mix with tetracycline, chlortetracycline, oxytetracycline, erythromycin lactobionate, amphotericin B, ampicillin sodium, iodized oil, chymotrypsin, trypsin, or hydrogen peroxide.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Tachycardia, hypotension, hypertension, chest tightness (oral); tachycardia, chest tightness (greater than 1%; IV).

CNS

Drowsiness (oral).

Dermatologic

Rash, pruritus, angioedema (oral); pruritus, rash, flushing (greater than 1%; IV).

EENT

Rhinorrhea (oral); ear pain, pharyngitis, throat tightness (greater than 1%; IV).

GI

Nausea, vomiting, stomatitis (oral); nausea, vomiting (greater than 1%; IV).

Hypersensitivity

Anaphylactoid reactions (greater than 1%; IV).

Respiratory

Bronchospasm, bronchial irritation (oral); rhinorrhea, rhonchi (greater than 1%; IV).

Miscellaneous

Fever, clamminess (oral).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Anaphylactoid reaction

Serious anaphylactoid reactions, including death, 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. 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.

Cutaneous reactions

Acute flushing and erythema may occur with IV use.

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 or allergic reaction, new or worsening wheezing, chest tightness or difficulty breathing, persistent nausea or vomiting, coughing up blood, fever, or other signs of respiratory infection.

• Acetaminophen Overdose
• Advise patient, family, or caregiver that medication will be prepared and administered by a health care professional in a hospital setting.

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