What are the indications for amantadine?

Indications for Amantadine

Amantadine is FDA-approved for three primary indications: prophylaxis and treatment of influenza A virus infection, treatment of Parkinson's disease/parkinsonism, and treatment of drug-induced extrapyramidal reactions—however, it should NOT be used for influenza due to widespread viral resistance. 1

Current Clinical Reality: Do Not Use for Influenza

The CDC explicitly recommends against using amantadine for influenza treatment or prevention due to resistance rates exceeding 90-99% among circulating strains. 2

• Resistance among influenza A (H3N2) viruses skyrocketed from 0.4% in 1994-1995 to 92% by 2005-2006, with approximately 99% of H3N2 isolates and 10% of H1N1 isolates demonstrating resistance by 2007-2008. 2
• The Advisory Committee on Immunization Practices (ACIP) states amantadine should not be used until susceptibility is reestablished among circulating viruses. 2
• Use oseltamivir or zanamivir instead—these neuraminidase inhibitors are effective against both influenza A and B, with resistance remaining <1%. 2

Critical Pitfall to Avoid

Do not prescribe amantadine based on FDA labeling alone or older literature—current resistance patterns have rendered it clinically ineffective for influenza despite its continued FDA approval for this indication. 2, 1

FDA-Approved Indications (Current Clinical Use)

1. Parkinson's Disease and Related Conditions

Amantadine is indicated for treatment of: 1

• Idiopathic Parkinson's disease (Paralysis Agitans)
• Postencephalitic parkinsonism
• Symptomatic parkinsonism following carbon monoxide intoxication
• Parkinsonism in elderly patients associated with cerebral arteriosclerosis

Important limitation: Amantadine is less effective than levodopa for Parkinson's disease, and its efficacy compared to anticholinergic antiparkinson drugs has not been established. 1

2. Drug-Induced Extrapyramidal Reactions

Amantadine is indicated for treatment of extrapyramidal symptoms caused by medications (typically antipsychotics). 1

3. Influenza A (Historical Indication—No Longer Clinically Appropriate)

While FDA-approved for influenza A prophylaxis and treatment, this indication is obsolete in clinical practice: 1, 2

Historical context when it was effective (pre-2005):

• Prophylaxis was 70-90% effective against influenza A when viruses were susceptible. 3
• Treatment reduced illness duration by approximately 1 day when started within 48 hours of symptom onset. 3
• Required administration for 2 weeks after vaccination during outbreaks to bridge the antibody response period. 3

Why it no longer works:

• Resistant strains emerge in approximately one-third of patients within 2-3 days of treatment. 2, 4
• A single point mutation in the M2 protein confers complete cross-resistance to both amantadine and rimantadine. 2
• Amantadine has no activity against influenza B viruses. 3

Dosing Considerations for Current Indications

Renal Impairment (Critical for All Indications)

Dose reduction is mandatory in renal dysfunction to prevent severe toxicity: 3

• Normal renal function: elimination half-life is 11.8 hours. 5
• Renal impairment: half-life extends from 18.5 hours to 33.8 days depending on severity. 5
• Hemodialysis patients: mean half-life is 8.3 days, with <5% removed per dialysis session. 5
• For patients ≥65 years, do not exceed 100 mg/day due to age-related decline in renal function. 3

CNS Toxicity Warnings

Minor CNS side effects (nervousness, anxiety, insomnia, difficulty concentrating, lightheadedness) occur in 5-10% of patients at 200 mg/day. 3

Serious CNS toxicity (seizures, confusion, hallucinations, delirium) occurs more frequently in: 3

• Elderly patients
• Patients with renal disease
• Patients with seizure disorders
• Patients with altered mental status or neuropsychiatric disorders

Reducing dosage to ≤100 mg/day decreases CNS side effects without compromising efficacy. 3

Absolute Contraindication: Cocaine Use

Do not prescribe amantadine to patients using cocaine due to additive CNS stimulation and cardiovascular risks. 6

• If cocaine use is disclosed in a patient on amantadine, immediately discontinue the drug and monitor for seizures, psychosis, agitation, and cardiovascular instability. 6

Key Takeaway Algorithm

For influenza symptoms: Use oseltamivir or zanamivir, NOT amantadine. 2

For Parkinson's disease or drug-induced extrapyramidal reactions:

• Start with ≤100 mg/day, especially in elderly or renally impaired patients. 3
• Screen for substance use (particularly cocaine) before prescribing. 6
• Adjust dose based on creatinine clearance. 5
• Monitor closely for CNS side effects in the first week. 3