Amantadine

Uses

Amantadine Hydrochloride is used for-

• Treatment of parkinsonism
• Treatment of drug-induced extrapyramidal reactions
• Prophylaxis and treatment of signs and symptoms of infection caused by various strains of influenza A virus

Amantadine is also used to associated treatment for these conditions: Cerebral Arteriosclerosis, Chorea, Extrapyramidal disorder caused by neuroleptic drugs without Tardive dyskinesia, Fatigue, Influenza A Virus Infection, Parkinson's Disease (PD), Parkinsonism, Parkinsonism post encephalitic, Restless Legs Syndrome (RLS)

How Amantadine works

The mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response. It also has NMDA receptor antagonistic effects. The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, M2 (an ion channel), which is needed for the viral particle to become "uncoated" once it is taken inside the cell by endocytosis.

Dosage

Amantadine dosage

Parkinson's disease:

• Adult: Initially, 100 mg/day, increased to 100 mg bid after a wk or more. Max dose: 400 mg daily.
• Elderly: >65 yr: Lowest effective dose.

Prophylaxis of influenza A:

• Adult: 100 mg daily for up to 6 wk; when used with influenza vaccination: only up to 3 wk after vaccination.
• Child: 10-15 yr: 100 mg daily.

Influenza A:

• Adult: 100 mg daily for 5 days.
• Elderly: >65 yr: Daily dose of 1 day.

Herpes zoster in immunocompromised patients:

• Adult: 100 mg bid for 14 days, continued for another 14 days if pain persists.

Side Effects

The adverse effects of Amantadine are generally mild and, when they occur, may diminish or cease after a week or more on the medication. The most commonly reported side effects include nausea, dizziness/ lightheadedness, and insomnia.

Other side effects may include edema of ankles, livedo reticularis; anxiety, elevation of mood, headache, lethargy, hallucinations, ataxia, slurred speech, blurred vision, loss of concentration, nervousness, depression, myalgia, palpitations, orthostatic hypotension, dry mouth, anorexia, constipation and diaphoresis.

Toxicity

Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 2 grams. Drug overdose has resulted in cardiac, respiratory, renal or central nervous system toxicity. Cardiac dysfunction includes arrhythmia, tachycardia and hypertension. Pulmonary edema and respiratory distress (including ARDS) have been reported. Renal dysfunction including increased BUN, decreased creatinine clearance and renal insufficiency can occur. Central nervous system effects that have been reported include insomnia, anxiety, aggressive behavior, hypertonia, hyperkinesia, tremor, confusion, disorientation, depersonalization, fear, delirium, hallucination, psychotic reactions, lethargy, somnolence and coma. Seizures may be exacerbated in patients with prior history of seizure disorders. Hyperthermia has also been observed in cases where a drug overdose has occurred.

Precaution

Amantadine should not be discontinued abruptly in patients with Parkinson's disease since a few patients have experienced a parkinsonian crisis, i.e., a sudden marked clinical deterioration, when this medication was suddenly stopped. The dose of anticholinergic drugs or of Amantadine Hydrochloride should be reduced if atropine-like effects appear when these drugs are used concurrently. Abrupt discontinuation may also precipitate delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression and slurred speech.

Interaction

Concurrent administration of Amantadine and anticholinergic agents or levodopa may increase confusion, hallucinations, nightmares, gastro-intestinal disturbances, or other atropine-like side effects. Psychotic reactions have been observed in patients receiving Amantadine and Levodopa.

Concurrent administration of Amantadine and drugs or substances (e.g. alcohol) acting on the CNS may result in additive CNS toxicity. Close observation is recommended.

Food Interaction

• Avoid alcohol.
• Take with or without food. The absorption is unaffected by food.

Amantadine Drug Interaction

Unknown: aspirin, aspirin, rasagiline, rasagiline, duloxetine, duloxetine, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, carbidopa / levodopa, carbidopa / levodopa, levothyroxine, levothyroxine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Amantadine Disease Interaction

Major: psychoses/depression, renal dysfunction, seizure disorders, hypotension, psychosisModerate: CHF/edema, hypotension

Volume of Distribution

• 3 to 8 L/kg [healthy subjects]

Elimination Route

Amantadine is well absorbed orally from the gastrointestinal tract.

Half Life

Mean half-lives ranged from 10 to 14 hours, however renal function impairment causes a severe increase in half life to 7 to 10 days.

Clearance

• 0.2 - 0.3 L/hr/kg
• 0.10 +/- 0.04 L/hr/kg [healthy, elderly male]

Elimination Route

It is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion.

Pregnancy & Breastfeeding use

Pregnancy category C. No well-controlled studies have been done in pregnant women to evaluate Amantadine's safety. Amantadine may be used during pregnancy when the potential benefits outweigh the potential but unknown risks to the fetus.

Amantadine is excreted into breast milk in low concentrations. As no information is available on the effects in infants, therefore amantadine should be used cautiously in women who are breastfeeding.

Contraindication

Amantadine is contraindicated in patients with known hypersensitivity to the active substances or to any of the excipients.

Special Warning

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. For example:

• CrCl <15 ml/min: Contraindicated
• CrCl 15-35 ml/min: 100 mg every 2 to 3 days
• CrCl >35 ml/min: 100mg every day

Patients with hepatic impairment: Use with caution

Storage Condition

Store at 20-25°C in dry place. Protect from light.

Innovators Monograph

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