Great resource for drug information, reviews and discussions
Symmetrel (Antiviral) (Amantadine HCl)
How do you rate this drug's effectiveness?
Pharmacology
The antiviral activity of amantadine against influenza A virus in humans is not completely understood. The mode of action appears to be the prevention of the release of infectious viral nucleic acid into the host cell.
Pharmacokinetics: In man, amantadine is readily absorbed, passes the blood-brain barrier and appears in the saliva and nasal secretions. The drug can be detected in the blood and cerebrospinal fluid at relatively low, but dose-related, levels. No evidence of metabolites has been found and 90%or more of the dose can be recovered in the urine unchanged.
After oral administration of a single dose of 100mg, maximum blood levels are reached in approximately 4hours, based on mean time of the peak urinary excretion rate; the peak excretion rate is approximately 5mg/hour; the mean half-life of the excretion rate approximates 15hours.
Compared with otherwise healthy adult individuals, the clearance of amantadine is significantly reduced in adult patients with renal insufficiency. The elimination half-life increases 2 to 3fold when creatinine clearance is less than 40mL/min/1.73m 2 and averages 8days in patients on chronic maintenance hemodialysis.
The renal clearance of amantadine is reduced and plasma levels are increased in otherwise healthy elderly patients age 65years and older. The drug plasma levels in elderly patients receiving 100mg daily have been reported to approximate those determined in younger adults taking 200mg daily. Whether these changes are due to the normal decline in renal function or other age factors is not known.
The antiviral activity of amantadine against influenza A virus in humans is not completely understood. The mode of action appears to be the prevention of the release of infectious viral nucleic acid into the host cell.
Pharmacokinetics: In man, amantadine is readily absorbed, passes the blood-brain barrier and appears in the saliva and nasal secretions. The drug can be detected in the blood and cerebrospinal fluid at relatively low, but dose-related, levels. No evidence of metabolites has been found and 90%or more of the dose can be recovered in the urine unchanged.
After oral administration of a single dose of 100mg, maximum blood levels are reached in approximately 4hours, based on mean time of the peak urinary excretion rate; the peak excretion rate is approximately 5mg/hour; the mean half-life of the excretion rate approximates 15hours.
Compared with otherwise healthy adult individuals, the clearance of amantadine is significantly reduced in adult patients with renal insufficiency. The elimination half-life increases 2 to 3fold when creatinine clearance is less than 40mL/min/1.73m 2 and averages 8days in patients on chronic maintenance hemodialysis.
The renal clearance of amantadine is reduced and plasma levels are increased in otherwise healthy elderly patients age 65years and older. The drug plasma levels in elderly patients receiving 100mg daily have been reported to approximate those determined in younger adults taking 200mg daily. Whether these changes are due to the normal decline in renal function or other age factors is not known.
Indications
The Antiviral Activity Of Amantadine Against Influenza A Virus In Humans Is Not Completely Understood. The Mode Of Action Appears To Be The Prevention Of The Release Of Infectious Viral Nucleic Acid Into The Host Cell.
Pharmacokinetics: In Man, Amantadine Is Readily Absorbed, Passes The Blood-brain Barrier And Appears In The Saliva And Nasal Secretions. The Drug Can Be Detected In The Blood And Cerebrospinal Fluid At Relatively Low, But Dose-related, Levels. No Evidence Of Metabolites Has Been Found And 90%or More Of The Dose Can Be Recovered In The Urine Unchanged.
After Oral Administration Of A Single Dose Of 100mg, Maximum Blood Levels Are Reached In Approximately 4hours, Based On Mean Time Of The Peak Urinary Excretion Rate; The Peak Excretion Rate Is Approximately 5mg/hour; The Mean Half-life Of The Excretion Rate Approximates 15hours.
Compared With Otherwise Healthy Adult Individuals, The Clearance Of Amantadine Is Significantly Reduced In Adult Patients With Renal Insufficiency. The Elimination Half-life Increases 2 To 3fold When Creatinine Clearance Is Less Than 40mL/min/1.73m 2 And Averages 8days In Patients On Chronic Maintenance Hemodialysis.
The Renal Clearance Of Amantadine Is Reduced And Plasma Levels Are Increased In Otherwise Healthy Elderly Patients Age 65years And Older. The Drug Plasma Levels In Elderly Patients Receiving 100mg Daily Have Been Reported To Approximate Those Determined In Younger Adults Taking 200mg Daily. Whether These Changes Are Due To The Normal Decline In Renal Function Or Other Age Factors Is Not Known.
The Antiviral Activity Of Amantadine Against Influenza A Virus In Humans Is Not Completely Understood. The Mode Of Action Appears To Be The Prevention Of The Release Of Infectious Viral Nucleic Acid Into The Host Cell.
Pharmacokinetics: In Man, Amantadine Is Readily Absorbed, Passes The Blood-brain Barrier And Appears In The Saliva And Nasal Secretions. The Drug Can Be Detected In The Blood And Cerebrospinal Fluid At Relatively Low, But Dose-related, Levels. No Evidence Of Metabolites Has Been Found And 90%or More Of The Dose Can Be Recovered In The Urine Unchanged.
After Oral Administration Of A Single Dose Of 100mg, Maximum Blood Levels Are Reached In Approximately 4hours, Based On Mean Time Of The Peak Urinary Excretion Rate; The Peak Excretion Rate Is Approximately 5mg/hour; The Mean Half-life Of The Excretion Rate Approximates 15hours.
Compared With Otherwise Healthy Adult Individuals, The Clearance Of Amantadine Is Significantly Reduced In Adult Patients With Renal Insufficiency. The Elimination Half-life Increases 2 To 3fold When Creatinine Clearance Is Less Than 40mL/min/1.73m 2 And Averages 8days In Patients On Chronic Maintenance Hemodialysis.
The Renal Clearance Of Amantadine Is Reduced And Plasma Levels Are Increased In Otherwise Healthy Elderly Patients Age 65years And Older. The Drug Plasma Levels In Elderly Patients Receiving 100mg Daily Have Been Reported To Approximate Those Determined In Younger Adults Taking 200mg Daily. Whether These Changes Are Due To The Normal Decline In Renal Function Or Other Age Factors Is Not Known.
Safety Information / Warning
A small number of suicidal attempts, some of which have been fatal, have been reported in patients treated with amantadine. The incidence of suicidal attempts is not known and the pathophysiologic mechanism is not understood. Suicidal attempts and suicidal ideation have been reported in patients with and without prior history of psychiatric illness. Amantadine can exacerbate mental problems in patients with a history of psychiatric disorders or substance abuse.
Patients who attempt suicide may exhibit abnormal mental states which include disorientation, confusion, depression, personality changes, agitation, aggressive behavior, hallucinations, paranoia, other psychotic reactions, and somnolence or insomnia. Because of the possibility of serious adverse effects, caution should be observed when prescribing amantadine to patients being treated with drugs having CNS effects, or for whom the potential risks outweigh the benefit of treatment. Because some patients have attempted suicide by overdosing with amantadine, prescriptions should be written for the smallest quantity consistent with good patient management.
Patients with a history of epilepsy or other seizures should be observed closely for possible increased seizure activity.
Patients with a history of CHF or peripheral edema should be followed closely as there are patients who developed congestive heart failure while receiving amantadine.
Occupational Hazards: Patients receiving amantadine who note CNS effects or blurring of vision should be cautioned against driving or working in situations where alertness and adequate motor coordination are important.
A small number of suicidal attempts, some of which have been fatal, have been reported in patients treated with amantadine. The incidence of suicidal attempts is not known and the pathophysiologic mechanism is not understood. Suicidal attempts and suicidal ideation have been reported in patients with and without prior history of psychiatric illness. Amantadine can exacerbate mental problems in patients with a history of psychiatric disorders or substance abuse.
Patients who attempt suicide may exhibit abnormal mental states which include disorientation, confusion, depression, personality changes, agitation, aggressive behavior, hallucinations, paranoia, other psychotic reactions, and somnolence or insomnia. Because of the possibility of serious adverse effects, caution should be observed when prescribing amantadine to patients being treated with drugs having CNS effects, or for whom the potential risks outweigh the benefit of treatment. Because some patients have attempted suicide by overdosing with amantadine, prescriptions should be written for the smallest quantity consistent with good patient management.
Patients with a history of epilepsy or other seizures should be observed closely for possible increased seizure activity.
Patients with a history of CHF or peripheral edema should be followed closely as there are patients who developed congestive heart failure while receiving amantadine.
Occupational Hazards: Patients receiving amantadine who note CNS effects or blurring of vision should be cautioned against driving or working in situations where alertness and adequate motor coordination are important.
Precautions
Neuroleptic Malignant Syndrome (NMS): Sporadic cases of possible Neuroleptic Malignant Syndrome (NMS) have been reported in association with dose reduction or withdrawal of amantadine therapy. NMS is an uncommon but life-threatening syndrome characterized by fever or hyperthermia; neurologic findings including muscle rigidity, involuntary movements, altered consciousness; other disturbances such as autonomic dysfunction, tachycardia, tachypnea, hyper- or hypotension; laboratory findings such as creatinine phosphokinase elevation, leukocytosis, and increased serum myoglobin.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary CNS pathology.
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 65years 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 should 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.
Pregnancy: Amantadine has been shown to be embryotoxic and teratogenic in rats at 50mg/kg/day, approximately 12times the recommended human dose, but not at 37mg/kg/day. Embryotoxic and teratogenic drug effects were not seen in rabbits that received up to 25times the recommended human dose.
There are no 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.
Lactation: Since amantadine is secreted in human milk, its use is not recommended in nursing mothers.
Children: The safety and efficacy of use of amantadine in neonates and infants less than 1year old have not been established.
Drug Interactions : 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.
Neuroleptic Malignant Syndrome (NMS): Sporadic cases of possible Neuroleptic Malignant Syndrome (NMS) have been reported in association with dose reduction or withdrawal of amantadine therapy. NMS is an uncommon but life-threatening syndrome characterized by fever or hyperthermia; neurologic findings including muscle rigidity, involuntary movements, altered consciousness; other disturbances such as autonomic dysfunction, tachycardia, tachypnea, hyper- or hypotension; laboratory findings such as creatinine phosphokinase elevation, leukocytosis, and increased serum myoglobin.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary CNS pathology.
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 65years 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 should 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.
Pregnancy: Amantadine has been shown to be embryotoxic and teratogenic in rats at 50mg/kg/day, approximately 12times the recommended human dose, but not at 37mg/kg/day. Embryotoxic and teratogenic drug effects were not seen in rabbits that received up to 25times the recommended human dose.
There are no 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.
Lactation: Since amantadine is secreted in human milk, its use is not recommended in nursing mothers.
Children: The safety and efficacy of use of amantadine in neonates and infants less than 1year old have not been established.
Drug Interactions : 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.
Side Effects / Adverse Effects
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 reactions (0.1 to 1%) are: congestive heart failure, 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.
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 reactions (0.1 to 1%) are: congestive heart failure, 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.
Overdose
Symptoms: Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 2g. An elderly patient with Parkinson's syndrome who took an overdose of 2.8g 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.
Treatment: There is no specific antidote. Slowly administered i.v. physostigmine in 1 and 2mg doses at 1 to 2hour intervals in an adult, and 0.5mg doses at 5 to 10minute intervals in a child up to a maximum of 2mg/hour, have been reported to be effective in the control of CNS toxicity caused by amantadine. 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 in patients with renal failure; a 4hour hemodialysis removed 7 to 15mg after a single 300mg 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.
Symptoms: Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 2g. An elderly patient with Parkinson's syndrome who took an overdose of 2.8g 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.
Treatment: There is no specific antidote. Slowly administered i.v. physostigmine in 1 and 2mg doses at 1 to 2hour intervals in an adult, and 0.5mg doses at 5 to 10minute intervals in a child up to a maximum of 2mg/hour, have been reported to be effective in the control of CNS toxicity caused by amantadine. 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 in patients with renal failure; a 4hour hemodialysis removed 7 to 15mg after a single 300mg 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.
Recommended Dosage
Dosage for Prophylaxis and Treatment of Influenza A Respiratory Infections: Adults: 200mg: 2capsules of 100mg each or 20mL of syrup as a single daily dose, or the daily dosage may be split into 1 capsule of 100mg or 10mL of syrup twice a day. If CNS effects develop on once-a-day dosage, a split dosage schedule may reduce such complaints.
Geriatrics: In persons 65 years of age or older, the daily dosage is 100mg.
Children: 1 to 9 years: The total daily dose should be calculated on the basis of 4.5 to 9.0mg/kg of body weight/day (but not to exceed 150mg/day). The daily dose, given as the syrup, should be given in 2 or 3 equal portions. 9 to 12 years: The total daily dose is 200mg given as 1 capsule of 100mg or 10mL of syrup twice a day.
The recommended dosage for patients on hemodialysis is 200mg every 7 days.
Dosage for Prophylaxis and Treatment of Influenza A Respiratory Infections: Adults: 200mg: 2capsules of 100mg each or 20mL of syrup as a single daily dose, or the daily dosage may be split into 1 capsule of 100mg or 10mL of syrup twice a day. If CNS effects develop on once-a-day dosage, a split dosage schedule may reduce such complaints.
Geriatrics: In persons 65 years of age or older, the daily dosage is 100mg.
Children: 1 to 9 years: The total daily dose should be calculated on the basis of 4.5 to 9.0mg/kg of body weight/day (but not to exceed 150mg/day). The daily dose, given as the syrup, should be given in 2 or 3 equal portions. 9 to 12 years: The total daily dose is 200mg given as 1 capsule of 100mg or 10mL of syrup twice a day.
The recommended dosage for patients on hemodialysis is 200mg every 7 days.
Supplied / Packaging
Capsules: Each red, soft gelatin capsule contains: amantadine HCl USP 100mg. Nonmedicinal ingredients: FD&C Red No.40, gelatin, glycerin, hydrogenated soybean oil, lecithin, methylparaben, propylparaben, soybean oil, titanium dioxide, vegetable shortening and yellow wax. Alcohol-, lactose-, sodium-, sulfite- and tartrazine-free. Bottles of100.
Syrup: Each 5mL of clear colorless syrup contains: amantadine HCl 50mg. Nonmedicinal ingredients: citric acid, methylparaben, propylparaben, purified water, raspberry flavor and sorbitol solution. Alcohol-, lactose-, sodium-, sulfite- and tartrazine-free. Bottles of 500mL.
Store at controlled room temperature (15to30°C) in a tightly closed container.
Capsules: Each red, soft gelatin capsule contains: amantadine HCl USP 100mg. Nonmedicinal ingredients: FD&C Red No.40, gelatin, glycerin, hydrogenated soybean oil, lecithin, methylparaben, propylparaben, soybean oil, titanium dioxide, vegetable shortening and yellow wax. Alcohol-, lactose-, sodium-, sulfite- and tartrazine-free. Bottles of100.
Syrup: Each 5mL of clear colorless syrup contains: amantadine HCl 50mg. Nonmedicinal ingredients: citric acid, methylparaben, propylparaben, purified water, raspberry flavor and sorbitol solution. Alcohol-, lactose-, sodium-, sulfite- and tartrazine-free. Bottles of 500mL.
Store at controlled room temperature (15to30°C) in a tightly closed container.
