Amantadine is a versatile antiviral and antiparkinsonian agent with a well-established clinical profile. Initially developed for influenza prophylaxis, its utility expanded significantly with the discovery of its efficacy in managing Parkinson’s disease symptoms and drug-induced extrapyramidal reactions. This synthetic tricyclic amine demonstrates unique pharmacological properties, offering both symptomatic relief and potential neuroprotective benefits through multiple mechanisms of action. Its favorable pharmacokinetic profile allows for convenient once or twice-daily dosing in most clinical scenarios.

Features

• Chemical classification: Adamantane derivative
• Available formulations: 100mg capsules, 50mg/5mL syrup
• Mechanism: NMDA receptor antagonism and dopamine modulation
• Half-life: Approximately 12-18 hours in adults
• Protein binding: 67% bound to plasma proteins
• Metabolism: Minimal hepatic metabolism (90% excreted unchanged)
• Administration: Oral route with or without food

Benefits

• Provides rapid symptomatic improvement in Parkinson’s disease within 48 hours
• Reduces severity and duration of influenza A viral infections when administered early
• Decreases drug-induced extrapyramidal symptoms in antipsychotic therapy
• Offers potential neuroprotective effects through glutamate modulation
• Demonstrates lower risk of long-term complications compared to levodopa
• May improve fatigue symptoms in multiple sclerosis patients

Common use

Amantadine is primarily indicated for the treatment of Parkinson’s disease, particularly in early-stage management where it can delay the need for levodopa therapy. It effectively addresses tremor, rigidity, and bradykinesia through its dopaminergic and antiglutamatergic actions. In virology, it serves as chemoprophylaxis against influenza A virus strains, though resistance patterns should be considered. Off-label applications include management of neuroleptic-induced extrapyramidal symptoms, fatigue in multiple sclerosis, and cognitive enhancement in traumatic brain injury. The medication has also shown promise in addressing negative symptoms in schizophrenia when combined with antipsychotic regimens.

Dosage and direction

For Parkinson’s disease: Initiate with 100mg once daily, increasing to 100mg twice daily after one week. Maximum recommended dose is 400mg daily in divided doses, though most patients respond to 100-200mg daily. For influenza prophylaxis: 200mg once daily or 100mg twice daily throughout exposure period. For treatment of established influenza A infection: 200mg once daily or 100mg twice daily for 3-5 days. Renal impairment requires significant dose adjustment—creatinine clearance 30-50 mL/min: 200mg first day then 100mg daily; 15-29 mL/min: 200mg first day then 100mg every other day; <15 mL/min: 200mg every 7 days. Administration with food may minimize gastrointestinal discomfort.

Precautions

Monitor renal function regularly during therapy, particularly in elderly patients. Gradual dose titration is essential to minimize CNS side effects. Use caution in patients with history of seizures, as amantadine may lower seizure threshold. Cardiovascular monitoring is recommended in patients with congestive heart failure or peripheral edema. Psychiatric status should be assessed regularly due to potential for hallucinations, confusion, or mood disturbances. Ophthalmologic examinations are advised for patients developing visual changes. Avoid abrupt discontinuation to prevent rebound parkinsonism or neuroleptic malignant syndrome-like reactions.

Contraindications

Hypersensitivity to amantadine or any component of the formulation. Severe renal impairment (creatinine clearance <15 mL/min) without appropriate dose adjustment. End-stage renal disease requiring dialysis. History of angle-closure glaucoma. Concurrent use of live attenuated influenza vaccine. Pregnancy unless potential benefit justifies potential risk to fetus. Breastfeeding is not recommended due to secretion in human milk. Patients with untreated psychosis or severe psychoneurosis should avoid amantadine therapy.

Possible side effect

Common reactions include nausea (5-10%), dizziness (5-15%), and insomnia (5-10%). Less frequent effects comprise livedo reticularis (2-5%), peripheral edema (2-5%), and orthostatic hypotension (1-3%). Neuropsychiatric manifestations may include anxiety, depression, hallucinations, and confusion, particularly in elderly patients. Rare but serious adverse events include suicidal ideation, neuroleptic malignant syndrome, and congestive heart failure. Gastrointestinal disturbances typically diminish with continued therapy. Dose-related side effects often respond to dosage reduction rather than complete discontinuation.

Drug interaction

Significant interactions occur with anticholinergic agents, potentially causing additive CNS effects. Concurrent use with other dopaminergic drugs may enhance efficacy but also increase side effect risk. QT-prolonging agents may have additive effects on cardiac repolarization. Alcohol may potentiate CNS depression. Thiazide diuretics reduce amantadine clearance by 20-30%. Memantine should be avoided due to similar mechanism of action. Triamterene-hydrochlorothiazide combination particularly affects renal excretion. Monitor closely when co-administering with drugs that affect renal tubular secretion.

Missed dose

If a dose is missed, take it as soon as remembered unless it is nearly time for the next scheduled dose. Do not double doses to make up for a missed dose. If multiple doses are missed, contact healthcare provider for guidance on resumption, as abrupt restart at full dose may cause increased side effects. For patients on twice-daily dosing, if more than 4 hours have passed since the missed dose, skip and resume with next scheduled dose. Maintain consistent timing to ensure stable plasma concentrations.

Overdose

Symptoms include severe nausea, vomiting, blurred vision, hallucinations, agitation, and cardiac arrhythmias. Life-threatening overdose may cause respiratory depression, hypertension or hypotension, and convulsions. Management involves gastric lavage if presented within 1 hour of ingestion. Activated charcoal may be effective. Supportive care includes IV fluids, cardiac monitoring, and symptomatic treatment. Physostigmine (1-2 mg IV slowly) may reverse CNS toxicity but requires careful monitoring for cholinergic crisis. Hemodialysis effectively removes amantadine (50-70% clearance in 4 hours). Monitor renal function and electrolyte status during recovery.

Storage

Store at controlled room temperature (20-25°C or 68-77°F). Protect from light and moisture. Keep container tightly closed. Do not freeze liquid formulation. Keep out of reach of children and pets. Do not transfer capsules to other containers unless specifically designed for medication storage. Discard any unused medication after expiration date. Do not flush medications down toilet or pour into drain unless instructed to do so. Consult pharmacist regarding proper disposal methods.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Individual response to amantadine may vary based on genetic factors, concomitant medications, and underlying health conditions. Always consult with a qualified healthcare professional before initiating or modifying any treatment regimen. Dosage adjustments should only be made under medical supervision. The full prescribing information should be reviewed before administration. Report any adverse reactions to healthcare provider promptly.

Reviews

Clinical studies demonstrate 60-70% efficacy in reducing Parkinson’s disease symptoms within the first month of therapy. Influenza prophylaxis studies show 70-90% effectiveness against susceptible strains when initiated before exposure. Patient-reported outcomes indicate significant improvement in quality of life measures, particularly regarding motor function and fatigue. Long-term follow-up studies suggest maintained efficacy for 6-12 months in Parkinson’s disease, though some patients develop tolerance requiring dose adjustment or adjunct therapy. Overall satisfaction rates range from 65-80% in various patient populations, with best outcomes seen in early-stage Parkinson’s patients and those using for specific influenza prophylaxis.