Amantadine

Amantadine is a versatile antiviral and antiparkinsonian agent with a well-established clinical profile. Originally developed for influenza prophylaxis, its utility in managing parkinsonian symptoms, particularly drug-induced extrapyramidal effects, has made it a valuable therapeutic option. This medication functions through dual mechanisms of action, offering both dopaminergic and antiglutamatergic effects, which contribute to its efficacy in movement disorders and certain fatigue states. Its favorable pharmacokinetics allow for convenient once- or twice-daily dosing in most patient populations.

Features

• Chemical class: 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
• Metabolism: Minimal hepatic metabolism, primarily renal excretion
• Bioavailability: Nearly complete oral absorption

Benefits

• Reduces parkinsonian tremor, rigidity, and bradykinesia through enhanced dopaminergic activity
• Mitigates levodopa-induced dyskinesias via NMDA receptor blockade
• Provides prophylaxis against influenza A viral strains when administered appropriately
• Demonstrates efficacy in treating fatigue associated with multiple sclerosis
• Offers flexible dosing options suitable for geriatric populations
• Shows rapid onset of action for parkinsonian symptoms, often within 48 hours

Common use

Amantadine is primarily indicated for the treatment of Parkinson’s disease, particularly for patients experiencing motor fluctuations and dyskinesias associated with long-term levodopa therapy. It serves as both monotherapy in early disease stages and as adjunctive treatment in advanced Parkinsonism. Additionally, it maintains FDA approval for influenza A prophylaxis and treatment in individuals over one year of age. Off-label applications include management of drug-induced extrapyramidal symptoms, fatigue in multiple sclerosis, and cognitive enhancement in traumatic brain injury cases. The medication has shown particular utility in addressing akinetic crises and neuroleptic-induced parkinsonism.

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, though most patients respond to 100-300 mg daily. For influenza prophylaxis: 200 mg once daily or 100 mg twice daily for at least 10 days following exposure. For influenza treatment: 200 mg once daily or 100 mg twice daily for 3-5 days, initiated within 24-48 hours of symptom onset. Renal impairment requires dosage adjustment: CrCl 30-50 mL/min: 200 mg first day, then 100 mg daily; CrCl 15-29 mL/min: 200 mg first day, then 100 mg every other day; CrCl <15 mL/min: 200 mg every 7 days. Administration with food may minimize gastrointestinal upset.

Precautions

Monitor renal function periodically during therapy, particularly in elderly patients. Gradual titration is recommended to minimize CNS side effects. Use caution in patients with history of seizures, as amantadine may lower seizure threshold. Orthostatic hypotension may occur, requiring blood pressure monitoring. Psychiatric manifestations including depression, anxiety, and hallucinations warrant close observation. Peripheral edema, often reversible with dose reduction, may develop. Abrupt discontinuation may precipitate parkinsonian crisis or neuroleptic malignant syndrome. Patients should avoid alcohol consumption due to increased risk of CNS effects.

Contraindications

Hypersensitivity to amantadine or other adamantane derivatives. Severe renal impairment (CrCl <15 mL/min) without appropriate dosage adjustment. History of angle-closure glaucoma. Concurrent use of live attenuated influenza vaccine. Pregnancy category C: not recommended unless potential benefit justifies risk. Breastfeeding is contraindicated due to secretion in human milk. Patients with uncontrolled psychosis or severe psychoneurosis should not receive amantadine therapy.

Possible side effect

Common reactions include nausea (5-10%), dizziness (5-8%), and dry mouth (5-7%). CNS effects such as insomnia, anxiety, and impaired concentration occur in 5-15% of patients. Livedo reticularis develops in approximately 5% of long-term users. Peripheral edema affects 5-10% of patients, typically dose-dependent. Less frequent adverse effects include visual hallucinations (2-5%), confusion (2-4%), and orthostatic hypotension (3-5%). Rare but serious reactions include neuroleptic malignant syndrome, suicidal ideation, and cardiomyopathy. Most side effects are dose-related and reversible upon discontinuation.

Drug interaction

Concomitant use with anticholinergic agents may potentiate CNS and peripheral anticholinergic effects. Co-administration with CNS stimulants increases risk of nervousness, insomnia, and seizures. Thiazide diuretics may reduce amantadine clearance by 20-30%. QT-prolonging agents require careful monitoring when combined with amantadine. Memantine should be avoided due to similar mechanism of action. Drugs affecting renal tubular secretion (cimetidine, quinidine) may alter amantadine concentrations. Alcohol potentiates CNS depression and orthostatic hypotension.

Missed dose

If a dose is missed, administer as soon as remembered unless within 4 hours of next scheduled dose. Do not double doses. For twice-daily regimens, if missed for more than 4 hours, skip and resume regular schedule. Maintain consistent timing to minimize fluctuation in symptom control. Patients experiencing missed doses should monitor for return of parkinsonian symptoms or influenza manifestations. Consult healthcare provider if multiple doses are missed consecutively.

Overdose

Manifests as exaggerated pharmacological effects: severe nausea, vomiting, cardiac arrhythmias, hypertension or hypotension, hyperthermia, and neuropsychiatric symptoms including agitation, hallucinations, and seizures. Management includes gastric lavage if within 1 hour of ingestion, activated charcoal, and supportive care. Acidification of urine may enhance elimination. Hemodialysis removes approximately 40-60% of circulating drug over 8 hours. Cardiac monitoring is essential for 24-48 hours. No specific antidote exists; treatment remains symptomatic and supportive.

Storage

Store at controlled room temperature (20-25°C/68-77°F). Protect from light and moisture. Keep bottle tightly closed. Do not freeze oral suspension. Discard any unused portion after 14 days of opening. Keep out of reach of children and pets. Do not transfer capsules to other containers unless specifically designed for medication storage. Check expiration date before administration.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Individual response to amantadine may vary based on genetic factors, renal function, and concomitant medications. Healthcare providers should review full prescribing information before initiating therapy. Patients should not adjust dosage without medical supervision. Regular monitoring of renal function and neurological status is recommended during treatment.

Reviews

Clinical studies demonstrate 60-70% efficacy in reducing parkinsonian symptoms when used as monotherapy. As adjunct to levodopa, amantadine reduces dyskinesia severity by 40-60% in responsive patients. Influenza prophylaxis studies show 70-90% effectiveness against susceptible strains when initiated prior to exposure. Multiple sclerosis fatigue trials indicate moderate improvement in 50-60% of treated patients. Long-term data suggests maintained efficacy for parkinsonian symptoms for 6-12 months, with some patients developing tolerance thereafter. Most reviews note favorable tolerability profile compared to other antiparkinsonian agents.