What are the uses and dosing recommendations for amantadine (Tab amantadine) in patients, including those with Parkinson's disease and the elderly?

Amantadine Uses and Dosing

Amantadine is FDA-approved for three primary indications: prophylaxis and treatment of influenza A virus infection, treatment of Parkinson's disease and related parkinsonian syndromes, and management of drug-induced extrapyramidal reactions. 1

FDA-Approved Indications

Influenza A Virus

• Prophylaxis: Amantadine prevents signs and symptoms of influenza A virus infection, though it does not completely prevent immune response development 1
• Treatment: Effective for uncomplicated respiratory tract illness caused by influenza A, particularly when administered early in the disease course 1
• Important limitation: No clinical evidence supports efficacy for viral respiratory illnesses other than influenza A 1

Parkinson's Disease and Parkinsonian Syndromes

• Approved for: Idiopathic Parkinson's disease (Paralysis Agitans), postencephalitic parkinsonism, and symptomatic parkinsonism following carbon monoxide intoxication 1
• Elderly patients: Indicated for parkinsonism associated with cerebral arteriosclerosis 1
• Comparative efficacy: Less effective than levodopa, with unclear efficacy compared to anticholinergic antiparkinson drugs 1

Drug-Induced Extrapyramidal Reactions

• Amantadine treats extrapyramidal reactions with lower incidence of anticholinergic side effects compared to traditional anticholinergic antiparkinson medications 1

Critical Dosing Guidelines

Elderly Patients (≥65 Years)

The daily dose must not exceed 100 mg for either prophylaxis or treatment in patients aged 65 years or older due to age-related decline in renal function and dose-dependent toxicity. 2

• Rationale: Renal function declines with increasing age, leading to drug accumulation 2
• Further reduction: Some elderly patients require doses below 100 mg/day, particularly elderly women who have smaller average body size and higher risk of side effects 3
• Monitoring: Close observation for CNS toxicity (confusion, hallucinations, agitation) is essential, especially during the first week 4, 3

Renal Impairment

Dose reduction is mandatory for patients with creatinine clearance <50 mL/min/1.73m² because amantadine is excreted unchanged in the urine. 2

• Consult package insert for specific dosing based on creatinine clearance 2
• Patients should be observed carefully for adverse reactions after dose adjustment 2
• Hemodialysis contributes minimally to amantadine clearance 2

Pediatric Dosing (Influenza A)

For children aged 1-9 years, prescribe 5 mg/kg/day (not to exceed 150 mg/day) to reduce toxicity risk. 2

• Children aged >10 years: Approved dose is 200 mg/day (100 mg twice daily) 2
• Weight-based adjustment: For children weighing <40 kg regardless of age, prescribe 5 mg/kg/day 2
• Safety note: Use in children <1 year has not been adequately evaluated 2

Safety Considerations and Toxicity Thresholds

CNS Toxicity Warning

Plasma amantadine concentrations >3000 ng/mL are associated with severe toxicity including myoclonus, hallucinations, and delirium, even in patients without prior psychiatric symptoms. 5

• Common side effects (at 200 mg/day): Nervousness, anxiety, insomnia, difficulty concentrating, lightheadedness occur in approximately 13% of patients versus 4% with placebo 3
• Serious CNS toxicity: Marked behavioral changes, delirium, hallucinations, agitation, and seizures occur particularly in high-risk populations 4, 3
• Time course: Most side effects are mild and cease after discontinuation or may diminish after the first week despite continued use 2, 3

High-Risk Populations Requiring Dose Reduction

• Patients with seizure disorders (may increase seizure activity) 4, 3
• Patients with psychiatric disorders (may worsen symptoms) 4, 3
• Patients with renal insufficiency of any degree 3
• Elderly patients, especially women 3

Management Algorithm for Side Effects

1. Verify renal function before initiating therapy in any elderly patient 3
2. Start at maximum 100 mg/day (not 200 mg/day) in elderly patients 3
3. Consider further reduction below 100 mg/day for elderly women, those with any renal impairment, or those with seizure/psychiatric history 3
4. Monitor closely for CNS toxicity, especially during the first week 4, 3
5. Reduce dose or discontinue immediately if serious side effects emerge 4, 3

Special Warnings

Pregnancy and Fertility

• Pregnancy Category C: Use only if potential benefit justifies potential risk to the fetus 1
• Teratogenicity: Human cases of cardiovascular malformations and limb defects have been reported with first-trimester exposure 1
• Fertility: Failed fertilization during IVF has been reported when sperm donor ingested amantadine 2 weeks prior to and during the IVF cycle 1

Nursing Mothers

• Amantadine is excreted in human milk; use is not recommended in nursing mothers 1

Anticholinergic Effects

• Amantadine has anticholinergic properties and can cause mydriasis 3
• Contraindication: Should not be used in patients with untreated angle-closure glaucoma 3
• Urinary retention may occur 3

Common Pitfalls to Avoid

• Failing to adjust dose for renal function in elderly patients, which significantly increases risk of adverse effects 4, 3
• Using standard 200 mg/day dosing in patients ≥65 years instead of the required maximum 100 mg/day 2
• Not monitoring for drug resistance when using amantadine for influenza treatment, as resistant viruses can emerge during therapy 2
• Overlooking the need for vaccination: Amantadine is not a substitute for annual influenza vaccination 1