Acetylcysteine
Antidote
View Brand Names (12)Dose and dosage
For acetaminophen (Paracetamol) toxicity:
a) A 2–3 hour wait between activated charcoal and PO administration of acetylcysteine (NAC) is necessary. Give NAC as an initial oral loading dose of 140 mg/kg (dilute to 5% in dextrose or sterile water), followed by 70 mg/kg PO four times daily (q6h) for 7 treatments. With ingestion of massive quantities, some authors suggest using a 280 mg/kg loading dose and continuing treatment for 12–17 doses. May also be given IV after diluting to 5% and given via slow IV over 15–20 minutes. Additional therapy may include IV fluids, blood or Oxyglobin®, ascorbic acid and SAMe. (Wismer 2006)
b) 150 mg/kg PO or IV initially, then 50 mg/kg q4h for 17 additional doses (Bailey 1986)
c) Loading dose of 140 mg/kg PO, then 70 mg/kg PO every 6 hours for 7 treatments (Grauer & Hjelle 1988)
For phenol toxicity:
a) 140 mg/kg PO or IV initially, then 50 mg/kg q4h for 3 days. May be partially effective to 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:
a) Acetylcysteine at 140–280 mg/kg loading dose IV, PO; followed by 70 mg/kg four times daily; vitamin K (phytonadione) at 1.25–2.5 mg/kg PO twice daily; plasma, SAMe at 20 mg/kg/day PO; vitamin E at 100–400 Units twice daily PO; and silymarin 20–50 mg/kg/day PO. (Talcott 2008)
For degenerative myelopathy:
a) 25 mg/kg PO q8h for 2 weeks, then q8h every other day. The 20% solution should be diluted to 5% with chicken broth or suitable diluent.
Used in conjunction with aminocaproic acid (500 mg per dog PO q8h indefinitely). Other treatments may include prednisone (0.25–0.5 mg/kg PO daily for 10 days then every other day), Vitamin C (1000 mg PO q12h) and Vitamin E (1000 Units PO q12h). Note: No treatment has been shown to be effective in published trials. (Shell 2003)
For acetaminophen toxicity:
a) A 2–3 hour wait between activated charcoal and PO administration of acetylcysteine (NAC) is necessary. Give NAC as an initial oral loading dose of 140 mg/kg (dilute to 5% in dextrose or sterile water), followed by 70 mg/kg PO four times daily (q6h) for 7 treatments. With ingestion of massive quantities, some authors suggest using a 280 mg/kg loading dose and continuing treatment for 12–17 doses. May also be given IV after diluting to 5% and given via slow IV over 15–20 minutes. Additional therapy may include IV fluids, blood or Oxyglobin®, ascorbic acid and SAMe. (Wismer 2006)
For phenol toxicity:
a) 140 mg/kg PO or IV initially, then 50 mg/kg q4h for 3 days. May be partially effective to reduce hepatic and renal injury. Resultant methemoglobinemia should be treated with ascorbic acid or methylene blue. (Dorman & Dye 2005)
For adjunctive treatment of hepatic lipidosis (see also Carnitine):
a) Identify underlying cause of anorexia and provide a protein replete feline diet, give acetylcysteine (NAC) at 140 mg/kg IV over 20 minutes, then 70 mg/kg IV q12h; dilute 10% NAC with saline 1:4 and administer IV using a 0.25 micron filter; correct hypokalemia and hypophosphatemia, beware of electrolyte changes with re-feeding phenomenon (Center 2006)
To help break up chondroids in the gutteral pouch:
a) Instill 20% solution (Foreman 1999) In neonatal foals to break up meconium refractory to repeated enemas:
a) 8 grams in 20 g sodium bicarbonate in 200 mL water (pH of 7.6), give as enema as needed to effect (Freeman 1999)
b) With foal in lateral recumbency, insert a 30 french foley catheter with a 30 cc bulb for a retention enema. Using gravity flow, infuse slowly 100– 200 mL of 4% acetylcysteine solution and retain for 30–45 minutes. IV fluids and pain medication should be considered. Monitor for possible bladder distention. (Pusterla et al. 2003)
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Acetylcysteine is used in veterinary medicine as both a mucolytic agent in the pulmonary tree and as a treatment for acetaminophen, xylitol, or phenol toxicity in small animals. Acetylcysteine is used investigatively as an antiinflammatory for chronic upper respiratory disease in cats, as an adjunct in heavy metal removal, and topically in the eye to halt the melting effect of collagenases and proteinases on the cornea.
It has been used anecdotally with aminocaproic acid to treat degenerative myelopathy in dogs, but data is lacking showing efficacy.
In horses with strangles, acetylcysteine instilled into the gutteral pouch has been used to help break up chondroids and avoid the need for surgical removal. Acetylcysteine enemas have been used in neonatal foals to break up meconium refractory to repeated enemas.
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.
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 can reduce the extent of liver injury or methemoglobinemia after ingestion of acetaminophen or phenol, by providing an alternate substrate for conjugation with the reactive metabolite of acetaminophen, thus maintaining or restoring glutathione levels.
ACTIVATED CHARCOAL: The use of activated charcoal as a gut adsorbent of acetaminophen is controversial, as charcoal may also adsorb acetylcysteine. Because cats can develop methemoglobinemia very rapidly after ingestion of acetaminophen, do not delay acetylcysteine treatment and preferably give the first dose intravenously. If using the solution (not labeled for injectable use), it is preferable to use a 0.2 micron in-line filter.
When given orally for acetaminophen toxicity, acetylcysteine can cause GI effects (nausea, vomiting) and rarely, urticaria. Because the taste of the solution is very bad, taste-masking agents (e.g., colas, juices) have been used. Since oral dosing of these drugs may be very difficult in animals, gastric or duodenal tubes may be necessary.
Intravenous administration appears to be very well tolerated in veterinary patients. IV boluses in humans have caused changes in blood pressure (hyper-, hypo-tension), GI effects and allergic reactions.
Rare adverse effects reported when acetylcysteine is administered into the pulmonary tract, include: hypersensitivity, chest tightness, bronchoconstriction, and bronchial or tracheal irritation.
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.
Monitoring:
When used for acetaminophen poisoning:
- Hepatic enzymes (particularly in dogs)
- Acetaminophen level, if available (particularly in dogs)
- Hemogram, with methemoglobin value (particularly in cats)
- Serum electrolytes, hydration status