amantadine SYMMETREL
Class: Antiviral/AntiparkinsonianFDA Indications: Influenza A (Prophylaxis And Treatment), Parkinson's Disease, Drug-induced Extrapyramidal Reactions
Off-Label Use: Catatonia, Treatment Resistant Depression, SSRI-induced Sexual Dysfunction, Intermittent Explosive Outbursts Seen In Context Of FASD, Drug-induced Weight Gain, Cocaine Withdrawal, Enuresis, Dementia, OCD, Tardive Dyskinesia, ADHD, Autism Spectrum Disorder, Antipsychotic-drug-induced Hyperprolactinemia, Fatigue Due To Multiple Sclerosis, Concussion-related Cognitive Deficits, Recovery From Severe TBI
Prescribing
Forms: 100mg tablet; 100mg capsule; 50mg/5mL (syrup) po solnDose Range: 100-400 mg/day
Starting: 100-400 mg qd for EPS; 100 mg bid-tid for cocaine withdrawal
Stopping: Recommend cautiously tapering off as there have been cases of NMS associatio with withdrawal of amantadine, especially in patients who are coprescribed neuroleptics
Precautions
Contraindications: Seizures may be exacerbated in patients with prior history of seizure disordersSerious Side Effects: Some patients experience intense urges (e.g. gambling, sex) while taking dopaminergic agents; exposure amantadine has been implicated as a major cause of psychosis in PD
Side Effects: dizziness, nausea, lightheadedness, insomnia, xerostomia, ataxia, constipation, confusion, orthostatic hypotension, headache, sedation/somnolence, nervousness, anxiety, depression, irritability, livedo reticularis
Pharmacodynamics
1° MOA: Inhibits penetration of RNA virus particles into the host cell; inhibits the early stages of viral replication by blocking the uncoating of the viral genome2° MOA: antiglutamatergic & pro-dopaminergic; NMDA receptor blockade ↓'s glutamatergic neurotransmission (thought to play a role in many psychiatric disorders); also ↑'s DA release, has direct & indirect effects on DA receptors, & ↓'s DA reuptake
Target: NMDA antagonist, indirect DA agonist, Matrix protein 2 (on Influenza A virus)
Pharmacokinetics
t½: 17 (10-25)° TMAX: 2-4°Substrate of: Renally cleared
Inhibits: ∅ ; Induces: ∅
Active Metabolites: ∅
DDIs
- - use caution when coprescribing with CNS stimulants
- - anticholinergic agents may potentiate the anticholinergic-like side effects of amantadine
Misc
- - originally developed as an antiviral agent, and its use in PD patients with influenza revealed unexpected improvement in PD symptoms
- - might provide neuroprotective effects
- - can be "activating" d/t its dopaminergic activity, to be cautious in patients with bipolar disorder
- - has been shown to safely improve arousal and cognitive function in patients with moderate to severe TBI
- - psychotic symptoms develop in 20-30% of patients with PD receiving chronic anti-PD medications, and amantadine is a major offender
Special Populations
Category C—Teratogenic and embryotoxic in one animal species, but human pregnancy data are too limited for a better assessment of the embryo-fetal risk. Complex cardiac defects were reported in three cases, and five other outcomes involved various malformations. The drug is best avoided in the 1st trimester.
Excreted into breast milk in low concentrations. No reports of adverse effects in nursing infants have been located hoqwcwe manufacturer recommends to not use during breastfeeding
Oral plasma clearance of amantadine is reduced and the plasma half-life and plasma concentrations are increased in healthy elderly individuals age 60 and older
Patients with kidney problems or poor renal clearance may require a lower starting and daily dose
No increase in adverse reactions to amantadine has been observed among persons with liver disease