Amantadine hydrochloride is indicated for the prophylaxis and treatment of signs and symptoms of infection caused by various strains of influenza A virus. Amantadine hydrochloride is also indicated in the treatment of parkinsonism and drug-induced extrapyramidal reactions.
Anti-Parkinson, Antiviral
Amantadine Hydrochloride has direct and indirect effects on dopamine neurons. It acts on the pre-synaptic membrane, enhancing the release of dopamine and inhibiting its reuptake. Post-synaptically, Amantadine acts directly on the dopamine receptor, and up regulates D2 receptors. This may be due to Amantadine-induced hypersensitivity of dopamine receptors. It has antimuscarinic properties. Amantadine also has antiglutamatergic properties, via non-competitive antagonism of NMDA receptors. Furthermore, potent, competitive, non-subunit selective NMDA receptor antagonists reduce the severity of levodopa-induced dyskinesias. NMDA receptor sensitization may be a key event in the genesis of levodopa-induced dyskinesias. It also has immunomodulatory properties. It restores the production of interleukin-2 (IL-2), which is defective in Parkinson’s disease patients. The mechanism by which Amantadine exerts its antiviral activity is not clearly understood. It appears to mainly prevent the release of infectious viral nucleic acid into the host cell by interfering with the function of the transmembrane domain of the viral M2 protein. Amantadine is also known to prevent virus assembly during virus replication. It does not appear to interfere with the immunogenicity of inactivated influenza A virus vaccine.
Parkinson’s disease BY MOUTH Adult: 100 mg daily for 1 week, then increased to 100 mg twice daily, usually administered in conjunction with other treatment. Some patients may require higher doses; maximum 400 mg per day Elderly: 100 mg daily, adjusted according to response Post-herpetic neuralgia BY MOUTH Adult: 100 mg twice daily for 14 days (continued for another 14 days if necessary) Treatment of influenza A (but not recommended) BY MOUTH Adult: 100 mg daily 4-5 days Prophylaxis of influenza A (but not recommended) BY MOUTH Adult: 100 mg daily usually for 6 weeks or with influenza vaccination for 2-3 weeks after vaccination
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.
Epilepsy . history of gastric ulceration Confused or hallucinatory states . congestive heart disease (may exacerbate oedema) . elderly . tolerance to the effects of amantadine may develop in Parkinson’s disease
Common or very common Anorexia . anxiety . dizziness . dry mouth . gastro-intestinal disturbances . hallucinations . headache . impaired concentration . insomnia, lethargy. livedo reticularis . mood changes . myalgia . palpitation . peripheral oedema . postural hypotension . slurred speech . sweating Uncommon Confusion . movement disorders . neuroleptic malignant syndrome . psychosis . rash . seizure . tremor . urinary incontinence . urinary retention . visual disturbances Frequency not known Heart failure . leucopenia . photosensitisation
PREGNANCY Avoid; toxicity in animal studies. BREAST FEEDING Avoid; present in milk; toxicity in infant reported.
Deaths have been reported from overdose with Amantadine Hydrochloride. The lowest reported acute lethal dose was 1 gram. Because some patients have attempted suicide by overdosing with Amantadine, prescriptions should be written for the smallest quantity consistent with good patient management.
Acute toxicity may be attributable to the anticholinergic effects of Amantadine. 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 have been reported; renal dysfunction including increased BUN, decreased creatinine clearance and renal insufficiency can occur. Central nervous system effects include insomnia, anxiety, agitation, aggressive behavior, hypertonia, hyperkinesia, ataxia, gait abnormality, tremor, confusion, disorientation, depersonalization, fear, delirium, hallucinations, psychotic reactions, lethargy, somnolence and coma. Seizures may be exacerbated in patients with prior history of seizure disorders. Hyperthermia has also been observed.
There is no specific antidote for an overdose of Amantadine Hydrochloride. However, slowly administered intravenous physostigmine in 1 and 2 mg doses in an adult at 1- to 2-hour intervals and 0.5 mg doses in a child at 5- to 10-minute intervals up to a maximum of 2 mg/hour have been reported to be effective in the control of central nervous system toxicity caused by Amantadine Hydrochloride. For acute overdosing, general supportive measures should be employed along with immediate gastric lavage or induction of emesis. Fluids should be forced, and if necessary, given intravenously. The pH of the urine has been reported to influence the excretion rate of Amantadine Hydrochloride. Since the excretion rate of Amantadine Hydrochloride increases rapidly when the urine is acidic, the administration of urine acidifying drugs may increase the elimination of the drug from the body. The blood pressure, pulse, respiration and temperature should be monitored. The patient should be observed for hyperactivity and convulsions; if required, sedation, and anticonvulsant therapy should be administered. The patient should be observed for the possible development of arrhythmias and hypotension; if required, appropriate antiarrhythmic and antihypotensive therapy should be given. Electrocardiographic monitoring may be required after ingestion, since malignant tachyarrhythmias can appear after overdose.
Keep away from the reach of children. Store in a cool & dry place. Protect from light.
.png&w=384&q=75)