Neuroleptic Malignant Syndrome (NMS): (Cont.)
The management of NMS should include: Intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
Patients with Special Diseases and Conditions:
Because amantadine is not metabolized and is mainly excreted in the urine, it may accumulate in the plasma and in the body when renal function declines.
The dose of amantadine should be reduced in patients with renal impairment and in patients who are 65 years of age or older (see Dosage). The dose of amantadine may need careful adjustment in patients with congestive heart failure, peripheral edema, or orthostatic hypotension.
Care shoud be exercised when administering amantadine to patients with liver disease, a history of recurrent eczematoid rash, or to patients with psychosis or severe psychoneurosis not controlled by chemotherapeutic agents.
Rare instances of reversible elevation of liver enzyme levels have been reported in patients receiving amantadine, though a specific relationship between the drug and such changes has not been established.
Amantadine has been shown to be embryotoxic and teratogenic in rats at 50 mg/kg/day, approximately 12 times the recommended human dose, but not at 37 mg/kg/day.
Embryotoxic and teratogenic drug effects were not seen in rabbits that received up to 25 times the recommended human dose.
There are not adequate and well controlled studies in pregnant women. Therefore, amantadine should not be used in women with childbearing potential, unless in the opinion of the physician, the expected benefit to the patient outweighs the possible risk to the fetus.
Since amantadine is secreted in human milk, its use is not recommended in nursing mothers.
The safety and efficacy of use of amantadine in neonates and infants less than 1 year old have not been established.
The dose of anticholinergic drugs or of amantadine should be reduced if atropine-like effects appear when these drugs are used concurrently.Careful observation is required when amantadine is administered concurrently with CNS stimulants.
Adverse reactions reported below have occurred in patients while receiving amantadine alone or in combination with anticholinergic antiparkinsonian drugs and/or levodopa.
The adverse reactions reported most frequently (5 to 10%) are: nausea, dizziness (lightheadedness) and insomnia.Less frequently reported (1 to 5%) are: depression, anxiety and irritability, hallucinations, confusion, anorexia, dry mouth, constipation, ataxia, livedo reticularis, peripheral edema, orthostatic hypotension, headache, somnolence, nervousness, dream abnormality, agitation, dry nose, diarrhea and fatigue.
Infrequently occurring adverse reaction (0.1 to 1%) are: CHF, psychosis, urinary retention, dyspnea, skin rash, vomiting, weakness, slurred speech, euphoria, confusion, thinking abnormality, amnesia, hyperkinesia, hypertension, decreased libido, and visual disturbance, including punctuate subepithelial or other corneal opacity, corneal edema, decreased visual acuity, sensitivity to light, and optic nerve palsy.
Rarely occurring adverse reactions (less than 0.1%) are: instances of convulsion, leukopenia, neutropenia, ezcematoid dermatitis and oculogyric episodes. Other rare occurring adverse reactions are: suicidal attempt, suicide, and suicidal ideation (see Warnings).
Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 2 g.
An elderly patient with Parkinson's syndrome who took an overdose of 2.8 g of amantadine in a suicidal attempt, developed acute toxic psychosis, urinary retention, and a mixed acid-base disturbance.
The toxic psychosis was manifested by disorientation, confusion, visual hallucinations and aggressive behavior. Convulsions did not occur, possibly because the patient had been receiving phenytoin prior to the acute ingestion of amantadine.
There is no specific antidote. Slowly administered i.v. physostigmine in 1 and 2 mg doses at 1 to 2 hour intervals in an adult, and 0.5 mg doses at 5 to 10 minute intervals in a child up to a maximum of 2 mg/hour, have been reported to be effective in the control of CNS 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 i.v.Hemodialysis does not remove significant amounts of amantadine hydrochloride in patients with renal failure; a 4 hour hemodialysis removed 7 to 15 mg after a single 300 mg oral dose.
The pH of the urine has been reported to influence the excretion rate of amantadine. Since the excretion rate of the drug increases rapidly when the urine is acidic, the administration of urine-acidifying fluids 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 the possible development of arrhythmias, hypotension, hyperactivity, and convulsions; if required, appropriate therapy should be administered.
The blood electrolytes,
urine pH and urinary output should be monitored. If there is no record of recent voiding, catheterization should be done. The possibility of multiple drug ingestion by the patient should be considered.
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.
When amantadine and levodopa are initiated concurrently, amantadine should be held constant at 100 mg daily or twice daily while the daily dose of levodopa is gradually increased to optimal dose. When used alone, the usual dose of amantadine is 100 mg twice a day.
Patients whose responses are not optimal with amantadine at 200 mg daily may benefit from an increase to 300 mg daily in divided doses.
Patients who experience a fall-off of effectiveness may regain benefit by increasing the dose to 300 mg daily; such patients should be supervised closely by their physicians.
Drug-Induced Extrapyramidal Symptoms:
In the Presence of Impaired Renal Function:
The usual dose of amantadine 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.
Table I outlines the recommended dosage adjustments dependent upon creatinine clearance, based upon the current National Advisory Committee on Immunization (NACI) Canada Communicable Disease Report, May 29, 1992.----------------------------------------------------------------
---------------------------------=80 100 mg twice daily
60-79 Alternating daily doses of 200 and 100 mg
40-59 100 mg once daily
30-39 200 mg twice weekly
20-29 100 mg thrice weekly
10-19 Alternating weekly doses of 200 and 100 mg
The recommended dosage for patients on hemodialysis is 20 mg every 7 days.
Each red, soft gelatin capsule contains: Amantadine HCl 100 mg. Also contains parabens. Alcohol-free, lactose-free, sodium-free, sulfite-free and tartrazine-free. Bottles of 100. Store at room temperature (15 to 30°C).
Each 5 mL of clear colorless syrup contains: Amantadine HCl 50 mg. Also contains parabens. Alcohol-free, lactose-free, sodium-free, sulfite-free and tartrazine-free. Bottles of 500 mL. Store at room temperature (15 to 30°C).
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