Amantadine

Class
Antiparkinsonian agents
Subclass
Adamantanes
Substance name
Amantadine
Brand names
Gocovri®
Common formulations
Tablet, Solution, Capsule
See also
Amantadine ER (Osmolex ER®)
Dosage and administration
Adults patients
Treatment
Extrapyramidal symptoms • Drug-induced
•
Maintenance: 100 mg PO BID
•
Maximum: 300 mg per day
Influenza A virus infection • Uncomplicated
•
200 mg PO daily, in 1-2 divided doses, started within 24-48 hours after symptoms onset and continued for 24-48 hours after the disappearance of symptoms
Reduce the dose to 100 mg daily in patients aged ≥ 65 years.
Parkinson's disease
•
Start at: 100 mg PO daily
•
Maintenance: 100 mg PO BID
•
Maximum: 400 mg per day
Parkinsonism • Post-encephalitic or post-CO poisoning
•
Start at: 100 mg PO daily
•
Maintenance: 100 mg PO BID
•
Maximum: 400 mg per day
Fatigue in patients with multiple sclerosis • Off-label
•
100 mg PO BID
Neuroleptic malignant syndrome • Off-label
•
Start at: 100 mg PO daily
•
Maintenance: 200-400 mg PO daily, in 2-3 divided doses
Prevention
Prevention of influenza A infection
•
200 mg PO daily, started in anticipation of an influenza A outbreak and before or after contact with a patient with influenza A virus respiratory tract infection, and continued for at least 10 days and for 2-4 weeks if administered in conjunction with inactivated influenza A virus vaccine
Reduce the dose to 100 mg daily in patients aged ≥ 65 years.
Indications for use
Labeled indications
Adults
•
Treatment of Parkinson's disease
•
Treatment of extrapyramidal symptoms (drug-induced)
•
Treatment of influenza A virus infection (uncomplicated)
•
Treatment of parkinsonism (post-encephalitic or post-CO poisoning)
•
Prevention of influenza A infection
Off-label indications
Adults
•
Treatment of fatigue in patients with multiple sclerosis
•
Treatment of neuroleptic malignant syndrome
Safety risks
Contraindications
Hypersensitivity to amantadine or its components
Untreated angle-closure glaucoma
Warnings and precautions
Anticholinergic effects, death
•
Maintain a high level of suspicion, as acute toxicity from the anticholinergic effects of amantadine and deaths from overdose have been reported.
CNS adverse events
•
Use extreme caution in patients performing activities requiring mental alertness, such as driving or operating machinery.
Congestive HF
•
Use caution in patients with a history of congestive HF or peripheral edema.
Impulsivity, compulsive behavior
•
Maintain a high level of suspicion, as amantadine can cause intense urges to gamble, increased sexual urges, compulsive spending, binge eating, and other uncontrollable impulses.
Neuroleptic malignant syndrome
•
Do not discontinue abruptly, as rapid dose reduction or withdrawal has been associated with symptoms resembling neuroleptic malignant syndrome, as well as worsening of Parkinson's disease, delirium, agitation, delusions, hallucinations, paranoid reactions, stupor, anxiety, depression, and slurred speech.
Psychosis
•
Use caution in patients with a history of psychosis.
Reactivation of eczema
•
Use caution in patients with a history of recurrent eczematoid rash.
Seizure
•
Use caution in patients with a history of seizure disorder.
Suicidal ideation
•
Maintain a high level of suspicion, as suicidal ideation and suicide attempts have been reported with amantadine.
Specific populations
Renal impairment
eGFR > 50 mL/min/1.73 m²
•
Use acceptable. No dose adjustment required.
eGFR 35-50 mL/min/1.73 m²
•
Use with caution. 200 mg on the first day, followed by 100 mg daily.
eGFR 15-35 mL/min/1.73 m²
•
Use with caution. 200 mg on the first day, followed by 100 mg q48h.
eGFR < 15 mL/min/1.73 m²
•
Use with caution. 200 mg q1 week.
Renal replacement therapy
Continuous renal replacement
•
Use with caution. 200 mg q1 week.
Intermittent hemodialysis
•
Use with caution. 200 mg q1 week.
Peritoneal dialysis
•
No guidance available.
Hepatic impairment
Any severity
•
Use with caution.
Pregnancy and breastfeeding
Pregnancy
All trimesters • Australia Category: B3
•
Use only if benefits outweigh potential risks. Evidence of fetal harm in humans.
Breastfeeding
Do not use during breastfeeding.
Unknown amount excreted in breastmilk.
Unknown drug levels in breastfed infants.
Adverse reactions
Common 1-10%
•
Depression, anxiety, irritability, hallucination, confusion, loss of appetite, constipation, ataxia, dry mouth, peripheral edema, livedo reticularis, orthostatic hypotension, headache, somnolence, nervousness, nightmares, agitation, diarrhea, fatigue, dry nose, nausea, dizziness, lightheadedness, insomnia
Uncommon < 1%
•
Congestive heart failure, psychosis, optic nerve palsy, urinary retention, vomiting, skin rash, dyspnea, slurred speech, euphoria, weakness, memory impairment, hyperkinesia, hypertension, ↓ libido, visual disturbances, corneal edema, corneal opacity, photophobia, ↓ visual acuity
Rare < 0.1%
•
Congenital neutropenia, ↓ WBC count, ↓ blood neutrophil count, suicidal ideation, oculogyric crisis, dermatitis
Unknown frequency
•
Coma, delirium, stupor, hypokinesia, hypertonia, delusions, aggressive behavior, mania, paranoid ideation, gait disturbance, paresthesia, muscle twitching, tremor, cardiac arrest, cardiac arrhythmias, tachycardia, tachypnea, dysphagia, ↑ WBC count, agranulocytosis, keratitis, mydriasis, diaphoresis, pruritus, fever, edema, ↑ BUN, ↑ serum CK, ↑ serum ALP, ↑ serum creatinine, ↑ serum LDH, ↑ serum TBIL, ↑ serum transaminases, ↑ serum gamma-glutamyltransferase, respiratory failure, pulmonary edema, neuroleptic malignant syndrome, anaphylaxis
Interactions
Drug(s)
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