| Indication |
For the chemoprophylaxis, prophylaxis, and treatment of signs and
symptoms of infection caused by various strains of influenza A virus.
Also for the treatment of parkinsonism and drug-induced extrapyramidal
reactions. |
| Pharmacodynamics |
Amantadine is an antiviral drug which also acts as an
antiparkinson agent, for which it is usually combined with L-DOPA when
L-DOPA responses decline (probably due to tolerance). It is a derivate
of adamantane, like a similar drug rimantadine. The mechanism of action
of amantadine in the treatment of Parkinson's disease and drug-induced
extrapyramidal reactions is not known. It has been shown to cause an
increase in dopamine release in the animal brain, and does not possess
anticholinergic activity. |
| Mechanism of action |
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. |
| Absorption |
Amantadine is well absorbed orally from the gastrointestinal tract. |
| Volume of distribution |
- 3 to 8 L/kg [healthy subjects]
|
| Protein binding |
Approximately 67% bound to plasma proteins over a concentration range of 0.1 to 2.0 µg/mL. |
| Metabolism |
No appreciable metabolism, although negligible amounts of an acetyl metabolite have been identified. |
| Route of elimination |
It is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. |
| 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]
|
| 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. |
