From the Guidelines
Amantadine can cause a range of side effects, from mild to severe, including marked behavioral changes, delirium, hallucinations, agitation, and seizures, particularly in older persons, those with renal insufficiency, seizure disorders, or certain psychiatric disorders 1. The most common side effects of amantadine are usually mild and may cease soon after discontinuing the drug, but can include:
- Behavioral changes
- Delirium
- Hallucinations
- Agitation
- Seizures
- CNS, renal, respiratory, and cardiac toxicity, including arrhythmias, have been reported in cases of acute overdosage 1. It is essential to note that the incidence and severity of side effects can be reduced by lowering the dosage of amantadine, particularly in older persons or those with certain medical conditions 1. Elderly patients should not exceed a daily dosage of 100 mg for prophylaxis or treatment, as renal function declines with age, and the dose may need to be further reduced in some cases 1. In general, patients should be aware of the potential side effects of amantadine and contact their healthcare provider immediately if severe side effects occur, rather than stopping the medication abruptly, as sudden discontinuation can worsen symptoms of the underlying condition.
From the FDA Drug Label
The adverse reactions reported most frequently at the recommended dose of amantadine hydrochloride (5 to 10%) are: nausea, dizziness (lightheadedness), and insomnia Less frequently (1 to 5%) reported adverse reactions are: depression, anxiety and irritability, hallucinations, confusion, anorexia, dry mouth, constipation, ataxia, livedo reticularis, peripheral edema, orthostatic hypotension, headache, somnolence, nervousness, dream abnormality, agitation, dry nose, diarrhea and fatigue. Infrequently (0. 1 to 1%) occurring adverse reactions are: congestive heart failure, psychosis, urinary retention, dyspnea, skin rash, vomiting, weakness, slurred speech, euphoria, thinking abnormality, amnesia, hyperkinesia, hypertension, decreased libido, and visual disturbance, including punctate subepithelial or other corneal opacity, corneal edema, decreased visual acuity, sensitivity to light, and optic nerve palsy. Rare (less than 0. 1%) occurring adverse reactions are: instances of convulsion, leukopenia, neutropenia, eczematoid dermatitis, oculogyric episodes, suicidal attempt, suicide, and suicidal ideation
The side effects of Amantadine (Adamantane) include:
- Common side effects (5-10%):
- Nausea
- Dizziness
- Insomnia
- Less common side effects (1-5%):
- Depression
- Anxiety
- Irritability
- Hallucinations
- Confusion
- Infrequent side effects (0.1-1%):
- Congestive heart failure
- Psychosis
- Urinary retention
- Rare side effects (less than 0.1%):
- Convulsion
- Leukopenia
- Neutropenia
- Suicidal attempt
- Suicide
- Suicidal ideation 2
From the Research
Side Effects of Amantadine
The side effects of Amantadine are primarily related to the central nervous system and include:
- Hallucinations 3, 4, 5, 6, 7
- Confusion 3, 4, 5, 6, 7
- Nightmares 3
- Delirium 4, 6, 7
- Acute psychosis 3, 6
- Coma 3
- Cardiovascular toxicity 3
- Death 3
- Constipation 5
- Cardiovascular dysfunction including QT prolongation 5
- Orthostatic hypotension 5
- Edema 5
- Nausea 5
- Livedo reticularis 5
- Corneal degeneration 5
- Apathy 5
- Fatigue 5
Amantadine Withdrawal Syndrome
Amantadine withdrawal syndrome is a rare adverse event that may present with severe delirium, even in patients without cognitive impairment 4, 7. The symptoms of amantadine withdrawal syndrome are thought to be related to a cortical and limbic dopamine shortage, which may be reversed with electroconvulsive therapy or reintroduction of amantadine 7. The clinical presentation of amantadine withdrawal syndrome may occur on a spectrum and may include features suggestive of delirium, catatonia, or neuroleptic malignant syndrome 7.
Special Considerations
Amantadine toxicity is a particular problem in patients with renal insufficiency because 90% of an oral dose is excreted unchanged in the urine 3. Therefore, patients with renal insufficiency should be closely monitored for signs of amantadine toxicity. Additionally, amantadine withdrawal syndrome may be under-recognized by mental health clinicians, which has the potential to lead to protracted hospital courses and suboptimal outcomes 7.