| GHS classification | DangerH302 (99.5%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P318, P319, P321, P330, P363, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 210 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
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| Regulatory information | Chemical: Tricyclo[3.3.1.13,7]decan-1-amine, hydrochlorideHazard Traits - Developmental ToxicityTricyclo[3.3.1.13,7]decan-1-amine, hydrochloride (1:1) is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Tricyclo[3.3.1.13,7]decan-1-amine, hydrochloride (1:1) are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)REACH registered substance: Amantadine hydrochloride (EC: 211-560-2)1-Adamantane ammonium chloride: Does not have an individual approval but may be used under an appropriate group standard |
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| Hazard Classes and Categories | Acute Tox. 4 (99.5%) |
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| Treatment | There is no specific antidote for an overdose of Amantadine. However, slowly administered intravenous physostigmine in 1 and 2 mg doses in an adult2 at 1- to 2-hour intervals and 0.5 mg doses in a child3 at 5- to 10-minute intervals up to a maximum of 2 mg/hour have been reported to be effective in the control of central nervous system toxicity caused by amantadine hydrochloride. For acute overdosing, general supportive measures should be employed along with immediate gastric lavage or induction of emesis. Fluids should be forced, and if necessary, given intravenously. The pH of the urine has been reported to influence the excretion rate of Amantadine. (L1744) |
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| Health effects | Acute overdosage of amantadine has resulted in cardiac dysfunction (e.g., arrhythmia, tachycardia, hypertension)pulmonary edema and respiratory distress (including adult respiratory distress syndrome)renal dysfunction (e.g., increased BUN, decreased creatinine clearance, renal insufficiency)or CNS toxicity (e.g., insomnia, anxiety, psychotic reactions, lethargy, somnolence, coma). Hyperthermia also has occurred with amantadine overdosage. In addition, seizures may be exacerbated in patients with a history of a seizure disorder (A620). |
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| Exposure routes | Inhalation.
Amantadine is well absorbed orally from the gastrointestinal tract. |
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| Toxicity summary | The mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response. It also has NMDA receptor antagonistic effects. The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, M2 (an ion channel), which is needed for the viral particle to become "uncoated" once it is taken inside the cell by endocytosis. |
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| Signs and Symptoms | Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 2 grams. Drug overdose has resulted in cardiac, respiratory, renal or central nervous system toxicity. Cardiac dysfunction includes arrhythmia, tachycardia and hypertension. Pulmonary edema and respiratory distress (including ARDS) have been reported. Renal dysfunction including increased BUN, decreased creatinine clearance and renal insufficiency can occur. Central nervous system effects that have been reported include insomnia, anxiety, aggressive behavior, hypertonia, hyperkinesia, tremor, confusion, disorientation, depersonalization, fear, delirium, hallucination, psychotic reactions, lethargy, somnolence and coma. Seizures may be exacerbated in patients with prior history of seizure disorders. Hyperthermia has also been observed in cases where a drug overdose has occurred. |
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| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
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| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)Amantadine hydrochlorideAmbiguous-DILI-concern3Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015 |
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| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
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| Toxicity Data | LD50: 800 mg/kg (Oral, Rat)
LD50: 700 mg/kg (Oral, Mouse) |
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