Amantadine

Amantadine is a versatile antiviral and antiparkinsonian agent with a well-established clinical profile. Originally developed for prophylaxis against influenza A virus, its utility expanded significantly with the discovery of its efficacy in managing symptoms of Parkinson’s disease and drug-induced extrapyramidal reactions. This medication functions through dual mechanisms of action, providing both dopaminergic and antiglutamatergic effects that contribute to its therapeutic benefits across multiple neurological and infectious indications.

Features

• Chemical classification: Adamantane derivative
• Available formulations: 100 mg capsules and oral syrup (50 mg/5 mL)
• Mechanism: NMDA receptor antagonism and dopamine release facilitation
• Half-life: Approximately 12-18 hours in adults with normal renal function
• Administration: Oral route with or without food
• Pregnancy category: C (requires risk-benefit assessment)

Benefits

• Reduces rigidity, tremor, and bradykinesia in Parkinson’s disease
• Provides effective prophylaxis against influenza A viral infections
• Diminishes drug-induced extrapyramidal symptoms from neuroleptics
• May improve fatigue in multiple sclerosis patients
• Offers symptomatic relief in some cases of neuroleptic malignant syndrome
• Provides alternative therapeutic option when other antiparkinsonian agents are contraindicated

Common use

Amantadine is primarily indicated for the treatment of Parkinson’s disease, particularly in early-stage management and as adjunctive therapy with levodopa. It demonstrates efficacy in reducing the characteristic motor symptoms while potentially mitigating levodopa-induced dyskinesias. In virology, it serves as chemoprophylaxis against influenza A virus strains, though its use has declined with emerging resistance patterns. Off-label applications include management of fatigue in multiple sclerosis, treatment of certain drug-induced movement disorders, and adjunctive therapy in traumatic brain injury recovery.

Dosage and direction

For Parkinson’s disease: Initiate at 100 mg once daily, increasing to 100 mg twice daily after one week if tolerated. Maximum recommended dose is 400 mg daily in divided doses. For influenza prophylaxis: 200 mg once daily or 100 mg twice daily throughout exposure period. Renal impairment requires dosage adjustment—creatinine clearance 30-50 mL/min: 200 mg first day then 100 mg daily; 15-29 mL/min: 200 mg first day then 100 mg every other day; <15 mL/min: 200 mg every 7 days. Administer with food if gastrointestinal discomfort occurs.

Precautions

Monitor renal function regularly during therapy. Use caution in patients with history of seizures, as amantadine may lower seizure threshold. Elderly patients require careful dose titration due to increased susceptibility to CNS effects. Cardiovascular monitoring is advised in patients with pre-existing heart failure or peripheral edema. Psychiatric status should be assessed regularly due to potential neuropsychiatric adverse effects. Discontinuation should be gradual to avoid withdrawal symptoms or parkinsonian crisis.

Contraindications

Hypersensitivity to amantadine or any component of the formulation. Severe renal impairment (creatinine clearance <15 mL/min) without appropriate dosage adjustment. History of angle-closure glaucoma. Concurrent use of live attenuated influenza vaccine. Patients with uncontrolled psychosis or severe psychoneurosis not stabilized by antipsychotic medication.

Possible side effect

Common adverse reactions include nausea (5-10%), dizziness (5-7%), insomnia (5-10%), and peripheral edema (5-15%). Neuropsychiatric effects may include anxiety, depression, hallucinations, and confusion, particularly in elderly patients. Less frequently observed are livedo reticularis (mottling of skin), orthostatic hypotension, and urinary retention. Anticholinergic effects such as dry mouth and blurred vision may occur. Most side effects are dose-dependent and reversible upon dosage reduction or discontinuation.

Drug interaction

Concomitant use with anticholinergic agents may potentiate adverse effects. Alcohol may increase CNS depression. Co-administration with stimulants may exacerbate CNS stimulation. Thiazide diuretics may reduce renal clearance of amantadine. QT-prolonging agents require careful monitoring when used concurrently. Memantine should generally be avoided due to similar mechanism of action. Triamterene-hydrochlorothiazide combination may significantly increase amantadine plasma concentrations.

Missed dose

If a dose is missed, take it as soon as remembered unless it is nearly time for the next dose. Do not double the dose to make up for a missed administration. For twice-daily regimens, if remembered within 4 hours of scheduled time, take immediately then resume normal schedule. If beyond 4 hours, skip the missed dose and continue with next scheduled dose. Maintain regular dosing intervals to ensure stable plasma concentrations.

Overdose

Symptoms may include severe nausea, vomiting, agitation, hallucinations, seizures, cardiac arrhythmias, and respiratory depression. Management involves gastric lavage if presented early, activated charcoal administration, and supportive care. Acidification of urine may enhance elimination. Hemodialysis may be effective due to the drug’s relatively low molecular weight and partial protein binding. Cardiac monitoring is essential for 48 hours post-ingestion. Specific antidote is not available.

Storage

Store at controlled room temperature (20-25°C/68-77°F). Protect from light and moisture. Keep container tightly closed. Do not freeze oral solution. Keep out of reach of children and pets. Discard any unused medication after expiration date. Do not transfer capsules to other containers without proper labeling. Avoid storage in bathroom due to humidity fluctuations.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Individual response to amantadine may vary based on clinical status, concomitant medications, and other factors. Healthcare providers should exercise clinical judgment when prescribing, considering individual patient characteristics and current treatment guidelines. Always consult appropriate prescribing information and clinical guidelines before initiating therapy.

Reviews

Clinical studies demonstrate amantadine’s efficacy in improving Unified Parkinson’s Disease Rating Scale scores by 20-30% in mild to moderate disease. Systematic reviews support its utility in reducing levodopa-induced dyskinesias with effect sizes of 0.3-0.5. Influenza prophylaxis trials show 50-90% protective efficacy against susceptible strains. Patient-reported outcomes indicate meaningful improvements in quality of life measures, though individual experiences vary considerably based on disease severity and tolerance of side effects.