Amatoxin Toxicity Medication

Updated: Jul 17, 2018
  • Author: Douglas S Lee, MD; Chief Editor: Stephen L Thornton, MD  more...
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Medication

Medication Summary

Given the delay between ingestion and the development of clinical symptoms, the role of gastrointestinal (GI) decontaminants may be more limited with amatoxin poisoning than it is with other intoxications. However, multidose activated charcoal may still have a role in interrupting enterohepatic circulation of amatoxin. Clear benefit has not been established.

No US Food and Drug Administration (FDA)-approved specific antidote for cyclopeptide poisoning exists. Silibinin is the treatment of choice in Europe but is not available in the United States. Other therapies that have been suggested include benzylpenicillin (penicillin G), thioctic acid, and N -acetylcysteine (NAC).

Silibinin, also known as silymarin or silidianin, is a flavolignone isolated from the milk thistle Silybum marianum. It is thought to competitively antagonize toxin binding to liver cell membrane receptors in mushroom poisoning and other hepatotoxic exposure. Some recommend a water-soluble preparation of silymarin, which inhibits penetration of amatoxins into liver cells.

Penicillin G may displace amanitin from plasma proteins, thus increasing renal excretion. It may inhibit amanitin from entering hepatocytes and may bind to acid amanitin. Its use is based on animal studies in mice, rats, and dogs. Penicillin G is somewhat protective against lethal doses of amatoxin.

Thioctic acid is a coenzyme in cellular metabolism, a free radical scavenger, and an antioxidant used for diabetic neuropathies and various metabolic disorders. No controlled trials of this agent in amatoxin poisoning are known. Clinical efficacy has not been proven.

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Antidotes, Other

Class Summary

Activated charcoal binds toxin in the GI tract and thus may limit systemic adsorption. Repeat doses may effectively interrupt enterohepatic circulation.

Activated charcoal (Actidose-Aqua, CharcoCaps, EZ-Char, Requa Activated Charcoal)

Activated charcoal is used for emergency treatment in poisoning caused by drugs and chemicals. The network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Activated charcoal does not dissolve in water. For maximum effect, administer within 30 minutes of poison ingestion.

N-acetylcysteine

N-acetylcysteine (NAC) is given initially in a loading dose of 150 mg/kg IV infused over 15 minutes, diluted in 200 mL of 5% dextrose in water (D5W); some recommend giving the loading dose over 60 minutes to reduce the risk of an anaphylactoid reaction). Subsequently, the first maintenance dose of 50 mg/kg in 500 mL D5W is infused IV over 4 hours, followed by the second maintenance dose of 100 mg/kg in 1000 mL D5W infused IV over 16 hours. For continuation of NAC administration, consult with a poison control center or medical toxicologist.

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