ACETYLCYSTEINE

By | 2010-05-08

Chemistry

The N-acetyl derivative of L-cysteine, acetylcysteine occurs as a white, crystalline powder with a slight acetic odor. It is freely soluble in water or alcohol. Acetylcysteine may also be known as N-acetylcysteine or N-Acetyl-L-cysteine.

Storage – Stability – Compatibility

When unopened, vials of sodium acetylcysteine should be stored at room temperature (15-30°C). After opening, vials should be kept refrigerated and used within 96 hours.

Acetylcysteine is incompatible with oxidizing agents and solutions can become discolored and liberate hydrogen sulfide when exposed to rubber, copper, iron, and during autoclaving. It does not react to aluminum, stainless steel, glass or plastic. If the solution becomes light purple in color, potency is not appreciably affected, but it is best to use non-reactive materials when giving the drug via nebulization. Acetylcysteine solutions are incompatible with amphotericin B, ampicillin sodium, erythromycin lactobionate, tetracycline, oxtetracycline, iodized oil, hydrogen peroxide and trypsin.

Pharmacology

When administered into the pulmonary tree, acetylcysteine reduces the viscosity of both purulent and nonpurulent secretions and expedites the removal of these secretions via coughing, suction, or postural drainage. The free sulfhydryl group on the drug is believed to reduce disulfide linkages in mucoproteins. This effect is most pronounced at a pH from 7-9. The drug has no effect on living tissue or fibrin.

Acetylcysteine also can reduce the extent of liver injury or methemoglobinemia after ingestion of acetominophen, by providing an alternate substrate for conjugation with the reactive metabolite of acetominophen, thus maintaining or restoring glutathione levels.

Uses – Indications

Acetylcysteine is used in veterinary medicine as both a mucolytic agent for pulmonary and ophthalmic use and a treatment for acetominophen toxicity in small animals.

Pharmacokinetics

When given orally, acetylcysteine is absorbed from the GI tract. When administered via nebulization or intratracheally into the pulmonary tract, most of the drug is involved in the sulfhydryl-disulfide reaction and the remainder is absorbed. Absorbed drug is converted (deacetylated) into cysteine in the liver and then further metabolized.

Contraindications – Precautions – Reproductive Safety

Acetylcysteine is contraindicated (for pulmonary indications) in animals hypersensitive to it. There are no contraindications for its use as an antidote.

Because acetylcysteine may cause bronchospasm in some patients when used in the pulmonary system, animals with bronchospastic diseases should be monitored carefully when using this agent.

Reproduction studies in rabbits and rats have not demonstrated any evidence of teratogenic or embryotoxic effects when used in doses up to 17 times normal. It is unknown if acetylcysteine enters milk.

Adverse Effects – Warnings

When given orally for acetominophen toxicity, acetylcysteine can cause GI effects (nausea, vomiting) and rarely, urticaria. Because the taste of the solution is very bad, use of taste masking agents (e.g., colas, juices) have been used. Because oral dosing of these drugs may be very difficult in animals, gastric or duodenal tubes may be necessary. When administered into the pulmonary tract, acetylcysteine hypersensitivity has been reported rarely. Chest tightness, bronchoconstriction, and bronchial or tracheal irritation have also been reported, but these effects are also considered to occur rarely.

Overdosage – Acute Toxicity

The LD50 of acetylcysteine in dogs is 1 g/kg (PO) and 700 mg/kg (IV). It is believed that acetylcysteine is quite safe (with the exception of the adverse effects listed above) in most overdose situations.

Drug Interactions, Drug/Laboratory Interactions

The use of activated charcoal as a gut adsorbent of acetominophen is controversial, as charcoal may also adsorb acetylcysteine. In humans, at least 3 hours should pass between giving activated charcoal and the first dose of acetylcysteine. Because cats can develop methemoglobinemia very rapidly after ingestion of acetominophen, delay in treating with acetylcysteine cannot be recommended.

Doses

Doses for dogs:

For acetominophen toxicity:

a) 150 mg/kg PO or IV initially, then 50 mg/kg q4h for 17 additional doses.

b) Loading dose of 140 mg/kg PO or IV (as a 5% solution), then 70 mg/kg every 4 hours for 3-5 treatments.

c) Loading dose of 140 mg/kg PO, then 70 mg/kg PO every 6 hours for 7 treatments.

For respiratory use:

a) 50 ml/hr for 30-60 minutes every 12 hours by nebulization.

Doses for cats:

For acetaminophen toxicity:

a) 140 mg/kg PO or IV (as a 5% solution) initially, then 70 mg/kg q4h PO or IV for 3-5 additional treatments.

b) 150 mg/kg PO or IV initially, then 50 mg/kg q4h for 17 additional doses.

c) For methemoglobinemia secondary to acetaminophen or other toxins: Using a 10% solution give 1.4 ml/kg (0.7 ml/kg if using 20% solution) PO q8h for a total of 3-7 treatments.

d) Loading dose of 140 mg/kg PO, then 70 mg/kg PO every 6 hours for 7 treatments.

e) 140 mg/kg PO initially (as a 5% solution in water (isotonic) or in 5-10% dextrose), then 70 mg/kg PO for 3-5 treatments.

For respiratory use: a) 50 ml/hr for 30-60 minutes every 12 hours by nebulization.

Monitoring Parameters

When used for acetaminophen poisoning:

1) Hepatic enzymes (particularly in dogs)

2) Acetaminophen level, if available (particularly in dogs)

3) Hemogram, with methemoglobin value (particularly in cats)

4) Serum electrolytes, hydration status

Client Information

This agent should be used in a clinically supervised setting only.

Dosage Forms – Preparations – FDA Approval Status – Withholding Times

Veterinary-Approved Products:

None

Human-Approved Products:

Acetylcysteine (as sodium) 10% (100 mg/ml) and 20% (200 mg/ml) in 4 ml, 10 ml and 30 ml vials for oral inhalation, oral solution, or intratracheal instillation.; Mucomyst® (Apothecon); Mucosil-10 ®(Dey Labs); Mucosil-20 ®(Dey Labs); Generic. (Rx)