Amantadine Hydrochloride is used for:

• Treatment of Parkinson’s disease and Parkinsonism
• Treatment of drug-induced extrapyramidal symptoms (movement disorders caused by medications)
• Prevention and treatment of symptoms caused by various strains of influenza A virus.

Amantadine Hydrochloride works by affecting dopamine neurons both directly and indirectly. It enhances the release of dopamine and reduces its reuptake at the pre-synaptic membrane. After synaptic transmission, it acts directly on dopamine receptors and increases the activity of D2 receptors, possibly by making them more sensitive. Amantadine also has antimuscarinic effects and reduces glutamate activity through non-competitive NMDA receptor antagonism, which may help reduce levodopa-induced involuntary movements. Additionally, Amantadine has immunomodulatory properties. It helps restore interleukin-2 (IL-2) production, which is often reduced in Parkinson’s disease. The antiviral mechanism of Amantadine is not fully understood, but it appears to block the release of viral genetic material into host cells by interfering with the M2 protein of influenza A virus and may also prevent virus assembly during replication. It does not affect the effectiveness of inactivated influenza A vaccines.

Parkinson's disease-

• Adults: The usual dose is 100 mg twice a day when used alone.
• The initial dose of Amantadine is 100 mg daily for patients with serious associated medical illnesses or who are receiving high doses of other antiparkinson drugs. After one to several weeks at 100 mg once daily, the dose may be increased to 100 mg twice daily, if necessary.
• Occasionally, patients whose responses are not optimal with Amantadine at 200 mg daily may benefit from an increase up to 400 mg daily in divided doses.
• Dosage for Concomitant Therapy: Some patients who do not respond to anticholinergic antiparkinson drugs may respond to Amantadine.
• When Amantadine or anticholinergic antiparkinson drugs are each used with marginal benefit, concomitant use may produce additional benefit. When Amantadine and levodopa therapy are initiated concurrently, the patient can exhibit rapid therapeutic benefits. Amantadine dose, should be held constant at 100 mg daily or twice daily while the daily dose of levodopa is gradually increased to optimal benefit.
• When Amantadine is added to optimal well-tolerated doses of levodopa, additional benefit may result, including smoothing out the fluctuations in improvement which sometimes occur in patients on levodopa alone. Patients who require a reduction in their usual dose of levodopa because of development of side effects may possibly regain lost benefit with the addition of Amantadine.

Drug-induced extrapyramidal reactions

• Adults: The usual dose is 100 mg twice a day.
• Occasionally, patients whose responses are not optimal with Amantadine at 200 mg daily may benefit from an increase up to 300 mg daily in divided doses.

Prophylaxis and treatment of Influenza A virus illness:

• Adults: 200 mg/day as single dose or 100 mg twice daily. If CNS effects develop on a once- daily dosage, split dosage schedule may reduce complaints.
• Elderly over 65 years of age: 100 mg every day.
• Children: 1 to 9 years of age: 4.4 to 8.8 mg/kg/day; not to exceed 150 mg/day. 9 to 12 years of age: 100 mg twice daily

Method of administration: Each capsule is to be taken orally either with or without food.

Patients with renal impairment: The dose should be reduced. This can be achieved by either reducing the total daily
dose, or by increasing the dosage interval in accordance with the creatinine clearance.

Patients with hepatic impairment: Use with caution.

Taking Amantadine together with anticholinergic drugs or levodopa may increase the risk of confusion, hallucinations, nightmares, gastrointestinal problems, or other atropine-like side effects. Psychotic reactions have been reported in patients receiving both Amantadine and levodopa. Using Amantadine with other drugs or substances that affect the central nervous system (e.g., alcohol) may add to CNS side effects. Close monitoring of the patient is recommended in such cases.

Amantadine should not be used in patients who are allergic to the active ingredient or any of the other components in the medication.

The side effects of Amantadine are usually mild and often decrease or disappear after a week or more of treatment. The most common side effects include nausea, dizziness or lightheadedness, and difficulty sleeping. Other possible side effects may include swelling of the ankles, skin mottling (livedo reticularis), anxiety, elevated mood, headache, fatigue, hallucinations, uncoordinated movements (ataxia), slurred speech, blurred vision, difficulty concentrating, nervousness, depression, muscle pain (myalgia), rapid heartbeat (palpitations), low blood pressure when standing (orthostatic hypotension), dry mouth, loss of appetite, constipation, and excessive sweating (diaphoresis).

Amantadine is classified as Pregnancy Category C. There are no well-controlled studies in pregnant women to confirm its safety. It may be used during pregnancy only if the potential benefits outweigh the possible but unknown risks to the fetus. Amantadine passes into breast milk in small amounts. Since the effects on infants are not well known, it should be used with caution in women who are breastfeeding.

Amantadine should not be stopped suddenly in patients with Parkinson’s disease, as some patients have experienced a parkinsonian crisis—a rapid and severe worsening of symptoms—when the medication was abruptly discontinued. If atropine-like effects appear while using Amantadine together with anticholinergic drugs, the dose of one or both medications should be reduced. Sudden discontinuation of Amantadine may also trigger delirium, agitation, delusions, hallucinations, paranoia, stupor, anxiety, depression, and slurred speech.

Fatalities have been reported following overdose of Amantadine Hydrochloride. The lowest documented acute lethal dose is 1 gram. As some individuals have attempted self-harm using excessive doses of Amantadine, prescriptions should be limited to the minimum quantity necessary for proper patient care.

Acute toxicity is likely related to the anticholinergic properties of Amantadine. Overdose may lead to toxic effects on the cardiovascular, respiratory, renal, and central nervous systems. Cardiac complications may include arrhythmia, tachycardia, and hypertension. Cases of pulmonary edema and respiratory distress have also been noted. Renal impairment may present with elevated BUN, reduced creatinine clearance, and possible renal failure. Central nervous system symptoms may include insomnia, anxiety, agitation, aggressive behavior, hypertonia, hyperkinesia, ataxia, abnormal gait, tremors, confusion, disorientation, depersonalization, fear, delirium, hallucinations, psychotic reactions, lethargy, drowsiness, and coma. Seizures may worsen in individuals with a prior history of seizure disorders. Hyperthermia has also been reported.

There is no specific antidote for Amantadine Hydrochloride overdose. However, slow intravenous administration of physostigmine (1–2 mg doses in adults at 1–2 hour intervals, or 0.5 mg doses in children every 5–10 minutes up to a maximum of 2 mg/hour) has been found helpful in managing central nervous system toxicity. In cases of acute overdose, general supportive care should be initiated along with prompt gastric lavage or induction of emesis. Adequate fluid administration, including intravenous fluids if required, should be ensured. Urinary pH affects drug elimination; since excretion increases in acidic urine, acidifying agents may enhance drug removal. Vital signs such as blood pressure, pulse, respiration, and temperature must be closely monitored. Patients should be observed for hyperactivity and seizures; if necessary, sedation and anticonvulsant therapy should be provided. Monitoring for arrhythmias and hypotension is essential, and appropriate antiarrhythmic or antihypertensive treatment should be given if needed. Electrocardiographic monitoring may be required after ingestion, as serious tachyarrhythmias can occur following overdose.

Used for respiratory viral infections, including Influenza.

Keep out of reach of children. Store in a cool, dry place, and protect from light.