Amantadine is a synthetic antiviral and antiparkinsonian agent with a well-established clinical profile. Initially developed for prophylaxis against influenza A virus, its utility expanded following the serendipitous discovery of its efficacy in managing symptoms of Parkinson’s disease and drug-induced extrapyramidal reactions. Its dual mechanism of action, involving dopaminergic and antiglutamatergic pathways, underpins its therapeutic value in neurological and infectious contexts. This agent represents a versatile tool in the therapeutic arsenal for specific, well-defined indications.

Features

• Chemical Name: 1-Adamantanamine hydrochloride
• Molecular Formula: C₁₀H₁₇N•HCl
• Mechanism of Action: Dopaminergic activity (promotes release and inhibits reuptake); Anticholinergic effects; Antiviral activity via inhibition of the M2 ion channel of influenza A virus.
• Bioavailability: Well absorbed orally, approximately 86-94%
• Protein Binding: ~67%
• Metabolism: Minimally hepatic; majority excreted unchanged renally
• Half-life: Approximately 9-15 hours in adults with normal renal function; significantly prolonged in renal impairment
• Excretion: Primarily renal (≥90% unchanged)

Benefits

• Provides symptomatic relief of parkinsonian rigidity, tremor, and bradykinesia, often with a more rapid onset of effect than levodopa.
• Effective in reducing levodopa-induced dyskinesias in patients with Parkinson’s disease, improving functional mobility and quality of life.
• Serves as a prophylactic agent against influenza A virus infections, particularly in high-risk populations when vaccination is contraindicated or unavailable.
• Can be used to manage drug-induced extrapyramidal symptoms (EPS) caused by typical antipsychotic agents, facilitating continued necessary neuroleptic therapy.
• Offers an alternative therapeutic option with a different side effect profile compared to other antiparkinsonian medications.

Common use

Amantadine is primarily indicated for the treatment of idiopathic Parkinson’s disease (Parkinson’s syndrome), post-encephalitic parkinsonism, and drug-induced extrapyramidal reactions. It is used both as monotherapy in early disease and as an adjunct to levodopa/carbidopa therapy in more advanced stages, specifically for its beneficial effect on dyskinesia. Its second major indication is for the prophylaxis and symptomatic treatment of respiratory tract illnesses caused by influenza A virus strains. Off-label, it has been studied and used in the management of fatigue associated with multiple sclerosis.

Dosage and direction

Dosage must be individualized based on indication, efficacy, and tolerability, with paramount importance placed on renal function assessment.

For Parkinson’s Disease/Extrapyramidal Reactions:

• Adults: The initial dose is 100 mg orally once daily. The dose may be increased to 100 mg twice daily after one week, if necessary and well-tolerated. Some patients may benefit from 400 mg daily in divided doses, but doses exceeding 200 mg daily carry a significantly increased risk of adverse effects and require careful supervision. Doses must be reduced in patients with renal impairment.
• Elderly: Initiate therapy at 100 mg once daily with very cautious titration due to increased susceptibility to CNS and anticholinergic side effects. Renal function must guide dosing.

For Influenza A Prophylaxis:

• Adults & Children (12 years and older): 200 mg orally once daily or 100 mg twice daily.
• Children (9-12 years): 100 mg orally twice daily.
• Children (1-9 years): 4.4 to 8.8 mg/kg per day, not to exceed 150 mg per day, given in 2 or 3 divided doses.

Administration: Can be administered with or without food. For patients experiencing insomnia, administering the last dose of the day several hours before bedtime may be beneficial.

Precautions

• Renal Impairment: Dose reduction is mandatory. Dosing intervals must be prolonged based on creatinine clearance (e.g., CrCl 30-50 mL/min: 200 mg first day, 100 mg daily thereafter; CrCl 15-29 mL/min: 200 mg first day, 100 mg on alternate days; CrCl <15 mL/min: 200 mg every 7 days). Serum levels should be monitored if possible.
• Suicidal Ideation: Patients with a history of psychiatric disorders, especially depression, should be monitored closely. Amantadine has been associated with suicidal ideation.
• Seizure Disorders: May lower seizure threshold; use with caution in patients with a history of seizures.
• Congestive Heart Failure/Peripheral Edema: Amantadine can cause or exacerbate peripheral edema. Monitor patients, especially those on concomitant levodopa therapy.
• Orthostatic Hypotension: Can occur; advise patients to rise slowly from a sitting or lying position.
• Abrupt Discontinuation: A gradual dose reduction is recommended to avoid a potentially severe parkinsonian hyperpyrexia or neuroleptic malignant syndrome-like event.
• Pregnancy & Lactation: Use only if the potential benefit justifies the potential risk to the fetus (Pregnancy Category C). Excreted in breast milk; a decision should be made to discontinue nursing or discontinue the drug.

Contraindications

Hypersensitivity to amantadine or any component of the formulation. Use is also contraindicated in patients with end-stage renal disease.

Possible side effect

Adverse reactions are often dose-related and may include:

• Common (>10%): Nausea, dizziness (lightheadedness), insomnia, anxiety, irritability, livedo reticularis (a purplish, net-like mottling of the skin, usually on the legs).
• Less Common (1-10%): Depression, confusion, hallucinations, anorexia, constipation, dry mouth, peripheral edema, orthostatic hypotension, visual disturbances.
• Rare (<1%): Suicidal ideation, psychosis, seizures, leukopenia, neutropenia, heart failure, neuroleptic malignant syndrome (upon withdrawal).

Drug interaction

• Anticholinergic Agents: Concurrent use with other drugs possessing anticholinergic properties (e.g., trihexyphenidyl, benztropine, some antidepressants, antihistamines) may potentiate anticholinergic side effects (e.g., dry mouth, blurred vision, urinary retention, constipation, confusion).
• CNS Stimulants/Depressants: May potentiate the effects of CNS stimulants. Effects may be additive with alcohol and other CNS depressants, impairing mental or physical abilities.
• QT-Prolonging Agents: Theoretical risk of additive effect on QT interval; use with caution.
• Thioridazine: Concurrent use may increase the risk of Parkinsonian symptoms and/or other extrapyramidal symptoms.
• Drugs Affecting Renal Secretion: Cimetidine and triamterene may reduce the renal clearance of amantadine, potentially increasing plasma levels and the risk of toxicity.
• Dopaminergic Agents: Additive therapeutic and adverse effects when used with levodopa.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The regular dosing schedule should be resumed. Do not double the dose to make up for a missed one.

Overdose

Symptoms: Overdose is serious and can be fatal. Symptoms are primarily related to CNS and cardiac effects and may include agitation, aggressive behavior, hallucinations, cardiac arrhythmias (including tachycardia and bradycardia), hypertension or hypotension, hyperthermia, respiratory distress, and acute renal failure. Convulsions and coma may occur. Management: There is no specific antidote. Management is supportive and symptomatic. Ensure a patent airway and assist ventilation if needed. ECG monitoring is essential. Gastric lavage may be considered if presentation is early. Forced diuresis or hemodialysis may be beneficial in severe cases due to the drug’s primary renal excretion. Acidification of the urine increases elimination.

Storage

Store at room temperature (20°C to 25°C or 68°F to 77°F), in a tight, light-resistant container. Keep out of reach of children and pets. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any specific health or allergy needs that may require medical supervision and are not liable for any damages or negative consequences from any treatment, action, application, or preparation, to any person reading or following the information in this document.

Reviews

• “As a movement disorder specialist, I find amantadine to be an invaluable tool, particularly for managing troublesome levodopa-induced dyskinesias. The rapid onset of effect is a notable advantage in certain clinical scenarios.” – Neurologist, 15 years experience.
• “Its utility in influenza prophylaxis in our immunocompromised pediatric patients, when the vaccine is not an option, is well-documented in our practice. Monitoring for CNS side effects is key.” – Infectious Disease Pharmacist.
• “The side effect profile, particularly the neuropsychiatric manifestations and livedo reticularis, requires diligent patient education and monitoring. It’s effective but demands respect.” – General Practitioner.
• “While newer agents exist, amantadine remains a cost-effective and evidence-based option for early Parkinson’s disease and EPS management, provided renal function is carefully considered.” – Clinical Pharmacologist.