Amatoxin Toxicity

Updated: May 18, 2023
Author: Douglas S Lee, MD; Chief Editor: Stephen L Thornton, MD 


Practice Essentials

Amatoxin toxicity is caused by the ingestion of mushrooms containing these cyclopepeptide toxins, especially Amanita phalloides (see the image below), commonly known as the death cap. Amatoxins are also found in several other Amanita species (phalloides, bisporigera, hygroscopia, ocreata, suballiacea, tenuifolia, verna, and virosa), as well as in some species of the genera Galerina (autumnalis, marginata, and venenata) and Lepiota (brunneoincarnata, chlorophyllum, helveola, and josserandii).

Amanita phalloides.
				Amanita phalloides.

Amanita species are reputed to be responsible for 90% of fatal mushroom poisonings worldwide. Most reports of deadly mushroom ingestion come from central and eastern Europe; Amanita poisonings are uncommon in North America (see Epidemiology).[1]

Most fatalities resulting from mushroom ingestion are associated with amatoxins within the mushrooms (see Pathophysiology). Amatoxins (cyclic octapeptides) represent 1 of the 3 major groups of cyclopeptides (in addition to phallotoxins and virotoxins). They are heat-stable, insoluble in water, and not destroyed by drying. Although virotoxins are cyclopeptides, they have not been described to cause toxicity in humans. There are at least 5 subtypes of amatoxins; the most significant of these are the alpha and beta subtypes of amanitin.

Amatoxin toxicity occurs over several days and usually develops in 3 characteristic stages, with the examination approach and findings depending on the stage of the poisoning (see Presentation). The workup may include laboratory studies, diagnostic imaging (though specific studies are not indicated if there is already a clear history of mushroom ingestion), and analysis of mushroom specimens if available (see Workup).

Treatment approaches include aggressive intravenous (IV) fluid and electrolyte therapy, gastric decontamination, pharmacologic therapy, and, in selected cases, liver transplantation (see Treatment).

It is important to provide education regarding the dangers of amateur mushroom hunting. For patient education resources, see the Poisoning - First Aid and Injuries Center.


Amanita phalloides, commonly known as death cap, is generally considered the most toxic of the world’s cyclopeptide-containing mushrooms. The clinical manifestations of an A phalloides ingestion are caused by the cyclopeptide phallotoxins and amatoxins. Phalloidin, a cyclic heptapeptide, causes gastroenteritislike effects 6-12 hours after initial ingestion. It interrupts the actin polymerization-depolymerization cycle and impairs cell membrane function. Phalloidin has limited gastrointestinal (GI) absorption, and symptoms improve within hours of supportive care.

The cyclic octapeptide amanitins, primarily alpha-amanitin, are responsible for the hepatic, renal, and encephalopathic effects. Amatoxins inhibit RNA polymerase II, thereby interfering with DNA and RNA transcription. These toxins mainly affect tissues with high rates of protein synthesis, including the liver, kidneys, brain, pancreas, and testes.

About 60% of absorbed alpha-amanitin is excreted into the bile. The liver is exposed to high concentrations of toxin through the portal system and via the enterohepatic circulation. Hepatocytes are damaged early, with sparing of the hepatic sinusoids. In these cases, fatty degeneration of the hepatic parenchyma and patterns of centrilobular necrosis with hemorrhage are typical.

Amatoxin is eliminated in the urine, gastroduodenal fluids, and feces for several days after ingestion. A single gram of fresh A phalloides can yield approximately 0.2-0.4 mg of alpha-amanitin[2] . The lethal dose is estimated to be approximately 0.1 mg/kg but there are cases of survival with larger ingestions[3] . The toxins of A phalloides are stable to cooking and remain active in dried mushrooms.

The clinical course of amatoxin poisoning can be divided into 3 stages. The first stage is preceded by a characteristic latent period that lasts for 6-12 hours following ingestion. After this asymptomatic period, abdominal cramping, vomiting, and profuse watery diarrhea (rice-water or choleralike) occur. Fluid losses may be severe enough to cause profound dehydration and even circulatory collapse.

Once this acute GI phase is over (usually after about 24 hours), the second stage begins. Although the patient appears to have improved clinically, ongoing liver damage is occurring, as indicated by laboratory abnormalities (eg, elevation of serum aminotransferase levels and lengthening of the prothrombin time [PT]). This stage may last as long as 2-3 days.

In the third and final phase, hepatic and renal injury become clinically apparent and may progress to fulminant hepatic failure (FHF). Death may occur in 3-7 days.


Amatoxin toxicity is caused by the ingestion of mushrooms containing the toxin (especially Amanita phalloides), such as may occur in any of the following circumstances:

  • Amateur mushroom hunters seeking a fresh-picked meal
  • Adults and adolescents seeking psychotropic mushrooms (eg, Amanita muscaria)
  • Unsupervised children in suburban or rural areas

Even experts can mistake A phalloides, also known as the death cap, for similar-looking nontoxic mushrooms (see the images below).

Amanita phalloides.
				Amanita phalloides.
Amanita muscaria.
				Amanita muscaria.

A phalloides has no characteristic odor or offensive taste. It is large, with a hemispherical cap 5-15 cm in diameter located on a central stem that is 8-15 cm long and 1-2 cm in diameter. The weight of an average intact mushroom is approximately 25 g. The cap is usually dry and shiny, with a light green-yellow color darkening towards the center. Gills are located under the cap and are not attached to the stem. Incomplete excavation of the entire mushroom may leave behind the volva, or cup, at the base of the stem.

In the United States, Amanita species are most commonly found in the Pacific Northwest and the Blue Ridge Mountains of the Northeast, but they are increasingly being identified in Pennsylvania, New Jersey, and Ohio. They tend to grow near filbert (hazelnut), chestnut, or oak trees. The peak season extends from late summer into fall; however, mushrooms can also be found in early winter.


In 2021, a total of 6458 single exposures to toxic mushrooms were reported to the National Poison Data System of the American Association of Poison Control Centers (AAPCC). In 4887 of those exposures, the mushroom type was unknown. Mushrooms containing cyclopeptides accounted for 86 exposures, with 6 major outcomes and one death.[4]

Over the course of 2 weeks in December 2016, California Poison Control System (CPCS) investigated 14 suspected A phalloides ingestions in five northern California counties. One of those patients, a child, developed cerebral edema and suffered permanent neurologic sequelae. All the remaining patients recovered completely, although 3 patients received liver transplants because of irreversible fulminant hepatic failure.[5]  

At present, there is no adequate database on which accurate estimates of worldwide exposures can be based. Mushroom foraging is known to be more common in parts of Europe and Russia than in other parts of the world. Between January 1995 and December 2009, 5638 inquiries concerning human exposures to mushrooms were reported to the Swiss Toxicological Information Centre, accounting for 1.2% of all inquiries. Death occurred in five of the 32 confirmed amatoxin poisonings.[6]  A review of mushroom toxicity globally found mortality rates were highest in China, Russia and the Ukraine.[7]

Of 67 cases of mushroom poisoning reported in Hong Kong between July 2005 and June 2015, 7 were confirmed amatoxin poisoning by consumption of A farinosa resulting in one death and 2 liver transplantations. This is the first report of this Amanita species in Hong Kong.[8]

Mycetismus commonly is due to amateur mushroom picking or accidental ingestions by unsupervised children. Most unintentional mushroom exposures occur in children younger than 6 years. Mortality is higher in children because they absorb a larger dose of toxins per kilogram of body weight.


The primary factor determining the prognosis is the quantity of mushroom that was eaten. In some cases, ingestion of a single A phalloides mushroom can be lethal. However, variations in individual susceptibility to amatoxin have been reported, and as noted, children absorb proportionally higher doses of toxins than adults do and are more likely to die of the poisoning.

With good supportive care, mortality from amatoxin toxicity is now lower than it once was. Worldwide, most mushroom fatalities are ascribed to amatoxins. Most mortality statistics for amatoxin poisoning are from Europe, where the number of victims is larger.[6] Figures of 10-60% have been reported. With current therapies, mortality from A phalloides poisoning is 10-20%.[9]  

Liver failure is the most serious complication of amatoxin ingestion. It may be complicated by hepatic coma and hypoglycemia. Various studies have shown that some who recover from acute liver failure may go on to develop chronic liver disease. The mechanism of development of related chronic liver disease is unknown, but it is thought that changes in hepatocyte structure may induce autoimmunity, leading to chronic hepatitis with potential progression to end-stage liver disease.[10]

Liver transplantation can save the life of a patient with the most severe amatoxin poisoning. A retrospective study concluded that the prothrombin index in combination with the serum creatinine level from day 3 to day 10 after ingestion may help predict those patients needing liver transplantation.[11] In this study, an international normalized ratio (INR) of 2.5 or higher along with a serum creatinine level greater than 106 µmol/L was predictive of a fatal outcome.




In patients with suspected amatoxin poisoning it is important to attempt to collect the following information:

  • Time of mushroom ingestion - Patiens who develop GI symptoms (abdominal cramping, nausea, vomiting, and diarrhea) within 5 hours of the ingestion of the mushroom are unlikely to have ingested an amatoxin containing mushroom.  GI symtpoms which manifest more the 6 hours from ingestion should make health care providers suspicious for ingestion of a possible amatoxin containing mushroom.

  • Time of onset of symptoms – Phalloidin causes gastrointestinal (GI) symptoms about 6-12 hours after ingestion; renal and liver toxicity caused by amanitin is evident 24-48 hours after ingestion, though a pattern of delayed-onset renal toxic mushroom ingestion has been seen in western North America[12]

  • Description of the mushrooms ingested – If a mushroom sample is available, place it in a dry paper bag (do not moisten or refrigerate it)

  • Location at which the mushrooms were obtained

  • Other mushrooms or toxins concurrently ingested – GI symptoms occurring earlier than 6-12 hours after ingestion suggest that another mushroom is responsible, but if the patient’s meal included several different mushrooms, earlier onset of symptoms does not rule out concomitant amatoxin ingestion; if the setting is an attempted suicide, every effort should be made to identify any other toxins that may have been ingested

Toxicity from amatoxin and other cyclopeptides occurs over several days and usually develops in the following stages:

  • Stage I – Sudden onset of nausea, vomiting, watery diarrhea, and cramping abdominal pain between 6 and 12 hours after ingestion, potentially resulting in dehydration and hypotension; patients often present during this stage and, if misdiagnosed, may be erroneously discharged without further care.  There is some evidence that in the development of early diarrhea (within 8 hours of ingestion) may protend more serious outcomes[13]

  • Stage II – Clinical improvement with supportive care; however, despite the resolution of symptoms, hepatic and renal damage is ongoing, as evidenced by rising laboratory test values

  • Stage III – If discharged, patients may return to the hospital 2-6 days later with severe hepatica injury or failure, severe coagulopathy, renal failure, and encephalopathy

Physical Examination

The examination findings depend on the stage of the poisoning. As a consequence of profuse vomiting and watery diarrhea, the patient may present in hypovolemic shock during the GI phase. Accordingly, assessing the patient’s volume status is an important component of the initial evaluation. With delayed presentations, it is important to look for signs of hepatic dysfunction (eg, jaundice, lethargy, or bruising), renal injury, or central nervous system (CNS) dysfunction.

Examination findings may include the following:

  • Vital signs – Tachycardia, hypotension

  • Skin – Poor turgor, jaundice, bruising (with hepatic failure)

  • Head, ears, eyes, nose, and throat – Epistaxis or scleral icterus that is related to hepatic failure may appear in a patient with delayed presentation

  • Abdomen – The patient can have mild diffuse tenderness, and a rectal examination reveals occult bloody stool. Hepatomegaly results from hepatitis late in the course of the disease.

  • Nervous system – Neurologic effects are related to hepatic failure; depending on the time elapsed since ingestion, the examination findings may range from normal to confusion, agitation, lethargy, somnolence, seizures, or coma.


Complications of amatoxin poisoning include:

  • Volume depletion and shock from GI distress
  • Hepatotoxicity
  • Hepatic failure 
  • Acute kidney injury
  • Encephalopathy
  • Pancreatitis
  • Polyneuropathy


Diagnostic Considerations

In addition to poisoning by Amanita phalloides, poisoning by the following cyclopeptide-containing mushrooms should also be considered:

  • A verna
  • A virosa
  • A tenuiflolia
  • Galerina autumnalis
  • G marginata
  • G venenata
  • Lepiota brunneoincarnata
  • L chlorophyllum
  • L helveola
  • L josserandi

Differential Diagnoses



Approach Considerations

Evaluation of the potentially amatoxin poisoned patient requires a high index of suspicion in the appropriate patient population and will be based primarly on history and physical with laboratory analysis primarly serving to confirm clinical suspicion.

Laboratory Studies

Various laboratory studies may be indicated in patients with suspected amatoxin poisoning.[14]

Abnormalities in electrolyte, glucose, blood urea nitrogen (BUN), and creatinine levels may be due to vomiting, diarrhea, and dehydration. Progression to renal failure causes a further rise in BUN and creatinine levels. Glucose levels should be monitored very closely in patients with hepatic failure.

Because hepatic damage is the main concern with amatoxin poisoning, liver function tests (LFTs) should be performed, including the following:

LFT results may be normal upon presentation; however, elevation may occur after 24-48 hours.

The prothrombin time (PT), the activated partial thromboplastin time (aPTT), or both should be evaluated. Severe coagulopathy may develop as the toxicity progresses to later stages. PT is considered a reliable prognostic indicator for Amanita poisoning.

Urinalysis is indicated, with hematuria and proteinuria signifying renal involvement. Microscopic hematuria may occur in stage I. Oliguria and anuria develop with renal failure. According to a pilot study, urinary amanitin analysis may have high specificity and positive predictive value, but it is not clinically feasible in most cases.  Amatoxins may be detected in the urine prior to the onset of symptoms but are only detectable for a short time.[15]

Because A phalloides can directly induce pancreatitis, amylase and lipase levels should be measured.

Leves of amatoxin and other cyclopeptides in serum or urine are not routinely obtained and have no clinical utility. 

Radiography, Ultrasonography, and CT

Specific diagnostic imaging studies are not indicated with a history of amatoxin ingestion. Mushrooms are not radiopaque and thus will not be seen on abdominal radiographs. However, in the absence of such a history, abdominal radiography may be performed if bowel obstruction or ileus appears in the differential diagnosis.

Ultrasonography and computed tomography (CT) scanning may be considered for the purpose of narrowing the differential diagnosis, but they do not yield positive findings.

Analysis of Mushroom Specimen

Meixner test

If a specimen of the ingested mushroom is available for analysis, the Meixner test can be performed. This test can detect amatoxin concentrations as low as 0.2 mg/mL; however, the number of false-negative and false-positive test results (eg, from the presence of psilocybin) reported raises questions about its reliability in clinical use.

Uneaten mushrooms should be placed in a dry paper bag for transport. A drop of liquid from a fresh mushroom is expressed onto a lignin-containing paper (ie, paper derived from wood pulp, such as newspaper but not filter paper). After the paper has dried, a drop of concentrated hydrochloride (10-12 N) is added. If amatoxins are present, a blue color develops within 2 minutes. Delayed appearance of a blue color suggests that amatoxin is present but in lower concentrations.

A dried mushroom may be tested by crushing it in pure methanol and using a drop of the methanol before adding the hydrochloride. It should be kept in mind that gastric contents are not suitable for the Meixner test; the results will not be valid.

The Meixner test should never be used to rule in or out a potential amatoxin mushroom ingestion.

Spore analysis in stomach contents

An experienced mycologist may analyze and identify spores in gastric contents. The spores can be examined by light microscopy using an oil immersion lens after isolation and concentration via centrifuge. The spores are examined in both water and Melzer solution. The spores of amatoxin-containing Amanita mushrooms are smooth and turn blue in Melzer solution.

Whether the spores of Amanita species survive the digestive process and pass into the stool is unknown.

Other Tests

Radioimmunoassay, thin-layer chromatography, and high-performance liquid chromatography can measure the toxin in the serum, although these methods are generally not available. Amatoxins are eliminated very rapidly from the serum. Levels have no prognostic significance.

On histologic analysis, excised livers from patients with Amanita poisoning reveal massive hepatic centrilobular necrosis with resultant hemorrhage. If allowed to progress, the poisoning causes lobular collapse and regenerative changes.



Approach Considerations

Before arrival at the emergency department (ED), supportive measures, such as intravenous (IV) access and oxygen, should be instituted if needed. Suspected amatoxin ingestion should be aggressively treated because mortality after amatoxin ingestion may be as high as 60%. All patients with amatoxin poisoning should be admitted for aggressive supportive care, monitoring of liver function, and observation for progression to later stages of poisoning.

The mainstays of treatment of amatoxin ingestion include aggressive IV fluid and electrolyte therapy to correct deficiencies and maintain adequate hydration. Serum electrolyte and glucose levels should be closely monitored. Gastric decontamination may be helpful if instituted promptly (within 1 hour after ingestion) but patients rarely present in this time frame. Liver transplantation may be indicated in selected cases, though the precise indications remain controversial.

Consider transferring any patient with amatoxin poisoning to a facility with a medical toxicologist. Consultation with a regional poison control center is recommended. Consider transferring any patient with progressive liver dysfunction to a facility with liver transplantation capability in order to minimize delays in procuring an appropriate organ.

Supportive Measures

Airway and fluid support

Early management of airway, breathing, and circulation (the ABCs) and prompt institution of IV access are vital in the treatment of Amanita poisoning. Supportive care with IV hydration and correction of electrolyte abnormalities leads to symptomatic improvement.

A retrospective review of 105 patients with amatoxin poisoning treated from 1988 to 2002 in Italy showed that all patients treated within 36 hours after ingestion were cured without sequelae. Only 2 of the 105 patients died, and both of them were admitted more than 60 hours after ingestion. Their treatment protocols included intensive fluid and supportive therapy, restitution of altered coagulation factors, multiple-dose activated charcoal, mannitol, dexamethasone, glutathione, and penicillin G.[16]

Gastric decontamination

If the patient presents less than 1 hour after known ingestion of cyclopeptide-containing mushrooms and has not already vomited, consider gastric decontamination via gastric lavage or nasoduodenal suctioning. Patients who present with nausea and vomiting within 1-2 hours of ingestion of a mushroom most likely have consumed a less toxic mushroom. 

Administer activated charcoal in all patients who are asymptomatic with suspected Amanita ingestion. Patients who are asymptomatic afer ingesting unknown or unidentified mushrooms may receive activated charcoal and observation for 6-12 hours. Most patients with confirmed Amanita poisoning arrive later than 6 hours after ingestion and are usually vomiting at presentation, which may eliminate the need for lavage. Control nausea and vomiting with antiemetics, preferably ondansetron.

Activated charcoal (1 g/kg) is recommended if the patient is not vomiting and has a protected airway. Multidose activated charcoal (typically 1 g/kg given every 2-4 hours) should be given as it may disrupt enterohepatic circulation and reduce toxicity.[17]

Hemodialysis and hemoperfusion

Hemodialysis and hemoperfusion have been proposed as methods for removing circulating amatoxin from the blood. Clear recommendations cannot be made, but hemodialysis may be necessary in those patients who develop renal failure.

The Molecular Adsorbent Recirculation System (MARS), a form of hepatic albumin dialysis, may have a role in bridging critically ill patients to liver transplantation or to spontaneous recovery of liver function. 

One tertiary center reported successful treatment of six patients with acute liver injury caused by ingestion of amanita mushrooms. Four were listed on admission for liver transplantation. All received extracorporeal albumin dialysis (ECAD) using the MARS system in addition to standard medical treatment. Overall 16 dialysis sessions were performed and all six patients recovered fully without the need for transplantation. No severe adverse events were reported during treatment.[18]  

Pharmacologic Therapy

No US Food and Drug Administration (FDA)–approved specific antidote for cyclopeptide poisoning exists. Several drugs have been postulated to reduce uptake of amatoxin into hepatocytes; animal data support the use of some of these drugs, but only anecdotal support is available for humans.[19]

Silibinin (derived from the Mediterranean milk thistle plant, Silybum marianum) is the pharmacologic treatment of choice in Europe, but it is not available in the United States. Milk thistle is hypothesized to provide hepatoprotective effects via interruption of the enterohepatic circulation of amanitin and inhibition of penetration into liver cells.[9]

Other suggested therapies include benzylpenicillin (penicillin G), N-acetylcysteine (NAC), indocyanine green (ICG), thioctic acid, vitamin K, cimetidine, cytochrome C, and hyperbaric oxygen. Given the rarity of toxic mushroom ingestion and the difficulties in designing prospective trials, evidence is limited to animal studies and retrospective analysis in humans. Because these suggested therapies are unapproved, consult with a medical toxicologist from the nearest regional poison control center before undertaking a course of therapy.

NAC is given initially in an intravenous (IV) 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.

In a retrospective analysis, the lowest mortality was reported in patients treated with NAC and silibinin, both of which were administered as monotherapy.[20] The polytherapy with the lowest mortality was a combination of high-dose penicillin G with silibinin. Notably, an isolated administration of high-dose penicillin did not yield improved survival.

In a subsequent retrospective analysis of 367 patients with suspected amatoxin poisoning, of whom 118 received silibinin alone and 249 silibinin plus penicillin, the investigators reported lower death and transplantation rates in the silibinin group than in the silibinin-penicillin group, though the difference did not prove statistically significant.[21]

Research by Wang et al identified ICG as a potential specific antidote to alpha-amatinin toxicity. Using a genome-wide CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) loss-of-function screen, these investigators found that N-Glycan biosynthesis and its catalytic enzyme STT3B were required for alpha-amatinin toxicity. A computerized scan of FDA-approved agents then identified ICG—a fluorescent dye used in ocular angiography and liver function assessment—as an inhibitor of STT3B. ICG proved effective in blocking the toxic effect of alpha-amanitin in human cells, mouse liver organoids, and male mice, resulting in an overall increase in animal survival.[22]

Liver Transplantation

Some patients recover liver function with medical therapy alone, but some do not. Efforts have been made to facilitate early identification of those patients who will require transplantation, thus expediting location of donors and avoiding unnecessary transplants.

Precise indications for liver transplantation are controversial. The American Association for the Study of Liver Diseases has released guidelines for the evaluation of patients for liver transplantation.[23] Proposed criteria have included graded hepatic encephalopathy, prothrombin time (PT), and creatinine level.

Consider orthotopic liver transplantation in patients who develop any of the following:

  • A 2-fold prolongation of PT despite administration of fresh frozen plasma
  • Persistent hypoglycemia
  • Serum bilirubin levels higher than 25 mg/dL
  • Azotemia
  • Grade III or grade IV hepatic encephalopathy


Ingestion of cyclopeptide-containing mushrooms can be reduced by closely monitoring young children in rural or suburban areas and by educating mushroom pickers about the dangers of amateur mushroom hunting.

No single test can be used to determine the edibility of wild mushrooms. Foragers should abide by the following dictum: “No rule is the only rule.” Immigrants, even if very experienced with the mushrooms that grow in their countries of origin, may not be able to distinguish poisonous mushrooms from edible mushrooms in the United States.


Consultation with a regional poison control center or toxicologist for assistance in case management is often valuable.

Contacting a mycologist for possible mushroom identification may be helpful. Possible sources for mushroom identification include the following:

  • North American Mycological Association
  • Local botanical garden
  • Local mycology club
  • Regional poison control center

If hepatic dysfunction is present, a gastroenterologist should be consulted. If hepatic failure is present, medical personnel who work with a liver transplant program should be consulted to facilitate a preoperative evaluation should spontaneous recovery not occur. If fulminant hepatic failure (FHF) has developed, a liver transplant service should be consulted.

Long-Term Monitoring

Patients who remain asymptomatic for 12 hours after ingestion of unknown mushrooms may be safely discharged. Results of the following laboratory studies should be monitored for signs of deterioration:

  • Liver function tests (LFTs)
  • Electrolytes and glucose levels
  • Kidney function testing—blood urea nitrogen (BUN) and creatinine levels
  • Prothrombin time (PT)


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.

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 (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.