Amantadine Hydrochloride

• Parkinson’s Disease: Management of Parkinsonism symptoms including rigidity, bradykinesia, and tremor.
• Drug-induced Extrapyramidal Symptoms (EPS): Treatment and prevention of EPS caused by neuroleptic agents.
• Influenza A Virus Infection: Prophylaxis and treatment of Influenza A virus infections (limited use due to resistance).
• Off-label Uses: May be used adjunctively for fatigue in multiple sclerosis and in some cases of traumatic brain injury-related disorders.

• Formulation: Oral tablets, capsules, and syrup.
• Adults (Parkinson’s disease and EPS):
• Initial dose: 100 mg orally once or twice daily.
• Maintenance dose: 100 mg twice or thrice daily (total 200–300 mg/day).
• Maximum dose: 400 mg/day in divided doses.
• Renal Impairment: Dose reduction required; adjust dose based on creatinine clearance due to renal excretion.
• Elderly: Use lower initial doses; careful monitoring advised.
• Pediatrics: Safety and efficacy not established; use only if clearly indicated.
• Influenza A: 200 mg daily for 5–7 days; treatment should start within 48 hours of symptom onset.

Amantadine hydrochloride acts through multiple mechanisms. It blocks the M2 proton channel of Influenza A virus, preventing viral uncoating and replication. In Parkinson’s disease, it enhances dopaminergic neurotransmission by increasing dopamine release and blocking dopamine reuptake in the synaptic cleft. Additionally, it exhibits anticholinergic and NMDA receptor antagonist activity, which contributes to its therapeutic effects by reducing excitatory glutamatergic neurotransmission and improving motor control.

• Absorption: Rapid and well absorbed orally with bioavailability of approximately 80-90%.
• Distribution: Widely distributed, crosses the blood-brain barrier; volume of distribution is about 3–8 L/kg.
• Metabolism: Minimally metabolized in the liver; majority excreted unchanged.
• Elimination: Primarily excreted unchanged in urine via glomerular filtration and tubular secretion.
• Half-life: Approximately 10–15 hours in individuals with normal renal function; prolonged in renal impairment.
• Onset: Clinical effects seen within 1–2 days of initiation.

• Pregnancy: FDA Pregnancy Category C. Animal studies have shown adverse effects; use only if potential benefit justifies the risk.
• Lactation: Excreted in breast milk; caution advised when administered to nursing mothers.

• Primary therapeutic class: Antiparkinsonian agent
• Additional class: Antiviral agent (Influenza A)

• Known hypersensitivity to amantadine or any formulation components.
• Severe renal impairment without appropriate dose adjustment.
• History of seizures or epilepsy without medical supervision.

• Use cautiously in patients with renal impairment; dose adjustment necessary.
• Monitor for neuropsychiatric symptoms including hallucinations, confusion, and suicidal ideation.
• Risk of orthostatic hypotension; caution in elderly and patients with cardiovascular disease.
• Abrupt withdrawal may exacerbate Parkinson’s symptoms or cause neuroleptic malignant syndrome-like symptoms.
• Monitor for signs of peripheral edema.

• Common: Dizziness, insomnia, nausea, dry mouth, constipation, headache.
• Neurological: Confusion, hallucinations, agitation, anxiety (especially in elderly).
• Cardiovascular: Orthostatic hypotension, peripheral edema.
• Rare but serious: Seizures, livedo reticularis, congestive heart failure exacerbation.

• Additive CNS effects with sedatives, alcohol, and other CNS depressants.
• May reduce efficacy of anticholinergic agents; caution when combined with other dopaminergic drugs.
• Interacts with trimethoprim or other drugs affecting renal clearance, potentially increasing amantadine levels.
• No significant CYP450 metabolism; minimal enzyme-mediated drug interactions.

• Increasing resistance has limited the use of amantadine for Influenza A treatment.
• Current guidelines recommend against routine use for influenza due to resistance and favor neuraminidase inhibitors.
• Ongoing evaluation of neuropsychiatric side effects has prompted updated monitoring recommendations in Parkinson’s treatment.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in tightly closed container, out of reach of children.