Acetylcysteine

Generic name: Acetylcysteine (assah-teel-sis-tay-een) N-acetylcysteine, Mucomyst, NAC
Brand names: Mucomyst®: : 10% & 20% (as sodium) in 4 mL, 10 mL, & 30 mL vials
Dosage form: 
Drug class: Antidote, Mucolytic

Pharmacology and Mechanism of Action:

• When administered into the pulmonary tree, acetylcysteine reduces the viscosity of both purulent and nonpurulent secretions, facilitating their removal through coughing, suction, or postural drainage. The drug’s free sulfhydryl group is believed to break disulfide linkages in mucoproteins, with the most pronounced effect occurring at a pH of 7–9. Acetylcysteine does not affect living tissue or fibrin.

• Additionally, acetylcysteine can reduce liver injury or methemoglobinemia following the ingestion of acetaminophen or phenol by providing an alternative substrate for conjugation with the reactive metabolite of acetaminophen, thus helping to maintain or restore glutathione levels.

Pharmacokinetics: When administered orally, acetylcysteine is absorbed from the gastrointestinal tract. When given via nebulization or intratracheally into the pulmonary tract, most of the drug participates in the sulfhydryl-disulfide reaction, while the remaining portion is absorbed. The absorbed drug is then converted (deacetylated) into cysteine in the liver and further metabolized.

Indications and Clinical Uses:

• Acetylcysteine is used in veterinary medicine as a mucolytic agent for the pulmonary tree and as a treatment for acetaminophen, xylitol, or phenol toxicity in small animals. It is also being investigated as an anti-inflammatory for chronic upper respiratory disease in cats, as an adjunct in heavy metal detoxification, and topically in the eye to prevent the degradation of the cornea caused by collagenases and proteinases.
• Acetylcysteine enemas have been used in neonatal foals to help break up meconium that is resistant to repeated enemas.
• In horses with strangles, acetylcysteine instilled into the guttural pouch has been used to help break down chondroids, potentially avoiding the need for surgical removal.

Instructions for Use: When given orally for acetaminophen toxicity, acetylcysteine can cause GI effects (nausea, vomiting) and rarely, urticaria.

DOGS:

For acetaminophen toxicity:

• a) A 2–3 hour wait between activated charcoal and oral acetylcysteine (NAC) administration is necessary. Give an initial oral loading dose of 140 mg/kg (diluted to 5% in dextrose or sterile water), followed by 70 mg/kg orally every 6 hours for 7 doses. For massive ingestion, some recommend a 280 mg/kg loading dose and continuing treatment for 12–17 doses. Alternatively, acetylcysteine may be given intravenously, diluted to 5%, and administered slowly over 15–20 minutes. Additional therapies may include IV fluids, blood or Oxyglobin®, ascorbic acid, and SAMe. (Wismer, 2006)

• b) Initial dose of 150 mg/kg orally or intravenously, then 50 mg/kg every 4 hours for 17 additional doses. (Bailey, 1986)

• c) Initial oral loading dose of 140 mg/kg, then 70 mg/kg orally every 6 hours for 7 doses. (Grauer & Hjelle, 1988)

For phenol toxicity:

• 140 mg/kg orally or intravenously initially, followed by 50 mg/kg every 4 hours for 3 days. This may partially reduce hepatic and renal injury. Resultant methemoglobinemia should be treated with ascorbic acid or methylene blue. (Dorman & Dye, 2005)

For hepatotoxicity secondary to xylitol poisoning:

• Acetylcysteine at 140–280 mg/kg as an initial loading dose (oral or IV), followed by 70 mg/kg four times daily. Other treatments include vitamin K (phytonadione) at 1.25–2.5 mg/kg orally twice daily, plasma, SAMe at 20 mg/kg/day orally, vitamin E at 100–400 units twice daily, and silymarin at 20–50 mg/kg/day orally. (Talcott, 2008)

For degenerative myelopathy:

• 25 mg/kg orally every 8 hours for 2 weeks, then every 8 hours every other day. The 20% solution should be diluted to 5% with chicken broth or a suitable diluent. This is used in conjunction with aminocaproic acid (500 mg per dog orally every 8 hours indefinitely). Other treatments may include prednisone (0.25–0.5 mg/kg orally daily for 10 days, then every other day), Vitamin C (1000 mg orally every 12 hours), and Vitamin E (1000 units orally every 12 hours). Note: No treatment has been shown to be effective in published trials. (Shell, 2003)

Cats:

For acetaminophen toxicity:

• A 2–3 hour wait between activated charcoal and oral acetylcysteine (NAC) administration is necessary. Administer NAC as an initial oral loading dose of 140 mg/kg (diluted to 5% in dextrose or sterile water), followed by 70 mg/kg orally every 6 hours for 7 doses. In cases of massive ingestion, some recommend a 280 mg/kg loading dose and continuing treatment for 12–17 doses. NAC may also be given intravenously after dilution to 5% and administered slowly via IV over 15–20 minutes. Additional therapy may include IV fluids, blood or Oxyglobin®, ascorbic acid, and SAMe. (Wismer, 2006)

For phenol toxicity:

• 140 mg/kg orally or intravenously initially, followed by 50 mg/kg every 4 hours for 3 days. This may help reduce hepatic and renal injury. Resulting methemoglobinemia should be treated with ascorbic acid or methylene blue. (Dorman & Dye, 2005)

For adjunctive treatment of hepatic lipidosis (see also Carnitine):

• Identify the underlying cause of anorexia and provide a protein-rich feline diet. Administer acetylcysteine (NAC) at 140 mg/kg IV over 20 minutes, then 70 mg/kg IV every 12 hours. Dilute 10% NAC with saline (1:4) and administer via IV using a 0.25-micron filter. Correct hypokalemia and hypophosphatemia, and be cautious of electrolyte changes due to the re-feeding phenomenon. (Center, 2006)

Horse:

To help break up chondroids in the guttural pouch:

• Instill a 20% acetylcysteine solution (Foreman, 1999).

In neonatal foals to break up meconium refractory to repeated enemas:

• • a) Mix 8 grams of acetylcysteine in 20 grams of sodium bicarbonate in 200 mL of water (pH 7.6) and administer as an enema as needed to achieve effect (Freeman, 1999).

  • b) With the foal in lateral recumbency, insert a 30 French Foley catheter with a 30 cc bulb for retention. Using gravity flow, slowly infuse 100–200 mL of 4% acetylcysteine solution and retain for 30–45 minutes. IV fluids and pain medication should be considered, and bladder distention should be monitored (Pusterla et al., 2003).

Contraindications: Acetylcysteine is contraindicated for pulmonary indications in animals that are hypersensitive to the drug.

Patient Monitoring and Laboratory Tests:

When used for acetaminophen poisoning, monitor the following:

• Hepatic enzymes (particularly in dogs)

• Acetaminophen level, if available (particularly in dogs)

• Hemogram, with methemoglobin value (particularly in cats)

• Serum electrolytes and hydration status

Stability and Storage : Unopened vials of sodium acetylcysteine should be stored at room temperature (15–30°C). Once opened, vials should be kept refrigerated and used within 96 hours. The product labeled for IV use should be used within 24 hours.

Drug Compatibility:

• Acetylcysteine is incompatible with oxidizing agents; solutions can become discolored and release hydrogen sulfide when exposed to rubber, copper, iron, or during autoclaving. It does not react with aluminum, stainless steel, glass, or plastic. If the solution turns light purple, its potency is not significantly affected, but it is best to use non-reactive materials when administering the drug via nebulization. Acetylcysteine solutions are also incompatible with amphotericin B, ampicillin sodium, erythromycin lactobionate, tetracycline, oxytetracycline, iodized oil, hydrogen peroxide, and trypsin.
• ACTIVATED CHARCOAL: The use of activated charcoal as a gut adsorbent for acetaminophen is controversial, as charcoal may also adsorb acetylcysteine. Since cats can develop methemoglobinemia rapidly after acetaminophen ingestion, acetylcysteine treatment should not be delayed, and the first dose is preferably given intravenously. If using the solution (which is not labeled for injectable use), it is recommended to use a 0.2 micron in-line filter.