amantadine
Brand: Symmetrel, Gocovri (ER for dyskinesia), Osmolex ER
Beers Criteria Prototype: levodopa-carbidopa
Drug Class: antiviral / antiparkinson agent
Drug Family: antiviral
Subclass: NMDA receptor antagonist / dopamine releaser
Organ Systems: cns
Mechanism of Action
Multiple mechanisms: blocks NMDA receptors (reducing glutamatergic excitotoxicity), promotes dopamine release from presynaptic terminals, and inhibits dopamine reuptake. The NMDA antagonism is responsible for its use in levodopa-induced dyskinesia (LID). Originally discovered as an antiviral for influenza A.
NMDA glutamate receptorDAT (dopamine transporter)sigma receptor
Indications
- Parkinson's disease (adjunct for motor symptoms)
- levodopa-induced dyskinesia (ER formulation)
- influenza A prophylaxis/treatment (historical; now largely replaced by oseltamivir)
- drug-induced extrapyramidal symptoms
Contraindications
- end-stage renal disease
- concurrent live influenza vaccine
Adverse Effects
Common
- nausea
- dizziness
- insomnia
- confusion
- livedo reticularis (mottled skin discoloration)
- edema
- hallucinations
Serious
- psychosis (especially in elderly)
- QT prolongation
- suicidal ideation (extended-release)
- neuroleptic malignant syndrome-like syndrome on abrupt discontinuation
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~86-90%; ER Gocovri formulation has delayed absorption designed for bedtime dosing |
| Distribution | protein binding ~67%; Vd ~6.6 L/kg; crosses BBB |
| Metabolism | minimal hepatic metabolism; primarily excreted unchanged |
| Excretion | renal (>90% unchanged); dose adjustment critical in renal impairment |
| Half-life | 10-14 hours (varies with age and renal function) |
| Onset | days for antiparkinson effect |
| Peak | 2-4 hours |
| Duration | 8-12 hours |
| Protein Binding | 67% |
| Vd | 6.6 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| anticholinergics | additive anticholinergic CNS effects; confusion and hallucinations | moderate |
| live influenza vaccine | amantadine may inhibit replication of vaccine virus | moderate |
| trimethoprim/sulfamethoxazole | decreases renal tubular secretion of amantadine; increases levels | moderate |
Nursing Considerations
- Dose adjustment is critical and proportional to renal function; creatinine clearance determines maximum safe dose (CrCl <15 mL/min: alternate-day dosing; dialysis patients: 200 mg after each dialysis session).
- Livedo reticularis — a mottled, blueish-purple lace-like skin discoloration primarily on the legs — is a benign but concerning-appearing adverse effect; reassure patients this is not a serious finding.
- Gocovri ER (extended-release amantadine) is specifically designed for levodopa-induced dyskinesia at doses higher than traditional amantadine; do not substitute IR amantadine for Gocovri without dose conversion.
- Do not abruptly stop amantadine in Parkinson's patients; withdrawal can precipitate NMS-like syndrome with fever, rigidity, and altered consciousness.
Clinical Pearls
- Amantadine was discovered in 1966 when a patient taking it for influenza prophylaxis noticed improvement in her Parkinson's symptoms — a classic serendipitous pharmacological discovery.
- Extended-release amantadine (Gocovri) at 274 mg once daily at bedtime is the only FDA-approved treatment specifically for levodopa-induced dyskinesia; its delayed-release design achieves peak plasma levels during the hours when levodopa-related dyskinesias are most prominent (late morning through evening).
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.