Amantadine Hydrochloride 100mg Information
Amantadine hydrochloride 100mg (Amantadine hydrochloride)
Amantadine hydrochloride 100mg (Amantadine hydrochloride) Description
Amantadine hydrochloride is designated chemically as 1-adamantanamine hydrochloride.
Amantadine hydrochloride is a stable white or nearly white crystalline powder, freely soluble in water and soluble in alcohol and in chloroform.
Amantadine hydrochloride has pharmacological actions as both an anti-Parkinson and an antiviral drug.
Amantadine Hydrochloride Oral Solution USP for oral administration contains 50 mg of amantadine hydrochloride per 5 mL and has the following inactive ingredients: citric acid (anhydrous), methylparaben, propylene glycol, propylparaben, purified water, sorbitol solution, and natural and artificial flavoring.
Amantadine hydrochloride 100mg (Amantadine hydrochloride) Clinical Pharmacology
Amantadine Hydrochloride is well absorbed orally. Maximum plasma concentrations are directly related to dose for doses up to 200 mg/day. Doses above 200 mg/day may result in a greater than proportional increase in maximum plasma concentrations. It is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. Eight metabolites of amantadine have been identified in human urine. One metabolite, an N-acetylated compound, was quantified in human urine and accounted for 5-15% of the administered dose. Plasma acetylamantadine accounted for up to 80% of the concurrent amantadine plasma concentration in 5 of 12 healthy volunteers following the ingestion of a 200 mg dose of amantadine. Acetylamantadine was not detected in the plasma of the remaining seven volunteers. The contribution of this metabolite to efficacy or toxicity is not known.
There appears to be a relationship between plasma amantadine concentrations and toxicity. As concentration increases toxicity seems to be more prevalent, however absolute values of amantadine concentrations associated with adverse effects have not been fully defined.
Amantadine pharmacokinetics were determined in 24 normal adult male volunteers after the oral administration of a single amantadine hydrochloride 100 mg soft gel capsule. The mean ± SD maximum plasma concentration was 0.22 ± 0.03 µg/mL (range: 0.18 to 0.32 µg/mL). The time to peak concentration was 3.3 ± 1.5 hours (range: 1.5 to 8.0 hours). The apparent oral clearance was 0.28 ± 0.11 L/hr/kg (range: 0.14 to 0.62 L/hr/kg). The half-life was 17 ± 4 hours (range: 10 to 25 hours). Across other studies, amantadine plasma half-life has averaged 16 ± 6 hours (range: 9 to 31 hours) in 19 healthy volunteers.
After oral administration of a single dose of 100 mg of amantadine oral solution to five healthy volunteers, the mean SD maximum plasma concentration C was 0.24 0.04 μg/mL and ranged from 0.18 to 0.28 μg/mL. After 15 days of amantadine 100 mg b.i.d. the C was 0.47 ± 0.11 μg/mL in four of five volunteers.
Plasma amantadine clearance ranged from 0.2 to 0.3 L/hr/kg after the administration of 5 mg to 25 mg intravenous doses of amantadine to 15 healthy volunteers.
In six healthy volunteers, the ratio of amantadine renal clearance to apparent oral plasma clearance was 0.79 0.17 (mean SD).
The volume of distribution determined after the intravenous administration of amantadine to 15 healthy subjects was 3 to 8 L/kg, suggesting tissue binding. Amantadine, after single oral 200 mg doses to 6 healthy young subjects and to 6 healthy elderly subjects has been found in nasal mucus at mean ± SD concentrations of 0.15 0.16, 0.28 0.26, and 0.39 0.34 μg/g at 1, 4, and 8 hours after dosing, respectively. These concentrations represented 31 ± 33%, 59 61%, and 95 86% of the corresponding plasma amantadine concentrations. Amantadine is approximately 67% bound to plasma proteins over a concentration range of 0.1 to 2.0 μg/mL. Following the administration of amantadine 100 mg as a single dose, the mean ± SD red blood cell to plasma ratio ranged from 2.7 ± 0.5 in 6 healthy subjects to 1.4 ± 0.2 in 8 patients with renal insufficiency.
The apparent oral plasma clearance of amantadine is reduced and the plasma half-life and plasma concentrations are increased in healthy elderly individuals age 60 and older. After single dose administration of 25 to 75 mg to 7 healthy, elderly male volunteers, the apparent plasma clearance of amantadine was 0.10 ± 0.04 L/hr/kg (range 0.06 to 0.17 L/hr/kg) and the half-life was 29 ± 7 hours (range 20 to 41 hours). Whether these changes are due to decline in renal function or other age related factors is not known.
In a study of young healthy subjects (n=20), mean renal clearance of amantadine, normalized for body mass index, was 1.5 fold higher in males compared to females (p
Compared with otherwise healthy adult individuals, the clearance of amantadine is significantly reduced in adult patients with renal insufficiency. The elimination half-life increases two to three fold or greater when creatinine clearance is less than 40 mL/min/1.73 m and averages eight days in patients on chronic maintenance hemodialysis. Amantadine is removed in negligible amounts by hemodialysis.
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.
Amantadine hydrochloride 100mg (Amantadine hydrochloride) Indications And Usage
Amantadine Hydrochloride Oral Solution USP 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.
Amantadine Hydrochloride is also indicated in the treatment of uncomplicated respiratory tract illness caused by influenza A virus strains especially when administered early in the course of illness. There are no well-controlled clinical studies demonstrating that treatment with Amantadine Hydrochloride will avoid the development of influenza A virus pneumonitis or other complications in high risk patients.
There is no clinical evidence indicating that Amantadine Hydrochloride is effective in the prophylaxis or treatment of viral respiratory tract illnesses other than those caused by influenza A virus strains.
Amantadine hydrochloride 100mg (Amantadine hydrochloride) Contraindications
Amantadine Hydrochloride is contraindicated in patients with known hypersensitivity to amantadine hydrochloride or to any of the other ingredients in Amantadine Hydrochloride Oral Solution.
Amantadine hydrochloride 100mg (Amantadine hydrochloride) Warnings
Patients with a history of epilepsy or other “seizures” should be observed closely for possible increased seizure activity.
Patients receiving Amantadine Hydrochloride who note central nervous system effects or blurring of vision should be cautioned against driving or working in situations where alertness and adequate motor coordination are important.
Patients with a history of congestive heart failure or peripheral edema should be followed closely as there are patients who developed congestive heart failure while receiving Amantadine Hydrochloride. Patients with Parkinson’s disease improving on Amantadine Hydrochloride should resume normal activities gradually and cautiously, consistent with other medical considerations, such as the presence of osteoporosis or phlebothrombosis.
Because Amantadine Hydrochloride has anticholinergic effects and may cause mydriasis, it should not be given to patients with untreated angle closure glaucoma.
Amantadine hydrochloride 100mg (Amantadine hydrochloride) Precautions
Amantadine Hydrochloride 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.
Sporadic cases of possible Neuroleptic Malignant Syndrome (NMS) have been reported in association with dose reduction or withdrawal of Amantadine Hydrochloride therapy. Therefore, patients should be observed carefully when the dosage of Amantadine Hydrochloride is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
NMS is an uncommon but life-threatening syndrome characterized by fever or hyperthermia; neurologic findings including muscle rigidity, involuntary movements, altered consciousness; mental status changes; other disturbances such as autonomic dysfunction, tachycardia, tachypnea, hyper - or hypotension; laboratory findings such as creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin. The early diagnosis of this condition is important for the appropriate management of these patients. Considering NMS as a possible diagnosis and ruling out other acute illnesses (e.g., pneumonia, systemic infection, etc.) is essential. This may be especially complex if the clinical presentation includes both serious medical illness 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 central nervous system (CNS) pathology.
The management of NMS should include: 1) intense symptomatic treatment and medical monitoring, and 2) treatment of any concomitant serious medical problems for which specific treatments are available. Dopamine agonists, such as bromocriptine, and muscle relaxants, such as dantrolene are often used in the treatment of NMS, however, their effectiveness has not been demonstrated in controlled studies.
Patients should be advised of the following information:
Blurry vision and/or impaired mental acuity may occur.
Gradually increase physical activity as the symptoms of Parkinson’s disease improve.
Avoid excessive alcohol usage, since it may increase the potential for CNS effects such as dizziness, confusion, lightheadedness and orthostatic hypotension.
Avoid getting up suddenly from a sitting or lying position. If dizziness or lightheadedness occurs, notify physician.
Notify physician if mood/mental changes, swelling of extremities, difficulty urinating and/or shortness of breath occur.
Do not take more medication than prescribed because of the risk of overdose. If there is no improvement in a few days, or if medication appears less effective after a few weeks, discuss with a physician.
Consult physician before discontinuing medication.
Seek medical attention immediately if it is suspected that an overdose of medication has been taken.
Careful observation is required when Amantadine Hydrochloride is administered concurrently with central nervous system stimulants.
Agents with anticholinergic properties may potentiate the anticholinergic-like side effects of amantadine.
Coadministration of thioridazine has been reported to worsen the tremor in elderly patients with Parkinson's disease, however, it is not known if other phenothiazines produce a similar response.
Coadministration of Dyazide (triamterene/hydrochlorothiazide) resulted in a higher plasma amantadine concentration in a 61-year-old man receiving Amantadine Hydrochloride 100 mg TID for Parkinson's disease. It is not known which of the components of Dyazide contributed to the observation or if related drugs produce a similar response.
Coadministration of quinine or quinidine with amantadine was shown to reduce the renal clearance of amantadine by about 30%.
The effect of amantadine on fertility has not been adequately tested, that is, in a study conducted under Good Laboratory Practices (GLP) and according to current recommended methodology. In a three litter, non-GLP, reproduction study in rats, Amantadine Hydrochloride at a dose of 32 mg/kg/day (equal to the maximum recommended human dose on a mg/m basis) administered to both males and females slightly impaired fertility. There were no effects on fertility at a dose level of 10 mg/kg/day (or 0.3 times the maximum recommended human dose on a mg/m basis); intermediate doses were not tested.
Failed fertility has been reported during human fertilization (IVF) when the sperm donor ingested amantadine 2 weeks prior to, and during the IVF cycle.
Amantadine hydrochloride 100mg (Amantadine hydrochloride) Adverse Reactions
The adverse reactions reported most frequently at the recommended dose of Amantadine Hydrochloride (5-10%) are: nausea, dizziness (lightheadedness), and insomnia.
Less frequently (1-5%) reported adverse reactions 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 (0.1-1%) occurring adverse reactions are: congestive heart failure, psychosis, urinary retention, dyspnea, fatigue, skin rash, vomiting, weakness, slurred speech, euphoria, 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.
Rare (less than 0.1%) occurring adverse reactions are: instances of convulsion, leukopenia, neutropenia, eczematoid dermatitis, oculogyric episodes, suicidal attempt, suicide, and suicidal ideation (see ).
Other adverse reactions reported during postmarketing experience with Amantadine Hydrochloride usage include:
Amantadine hydrochloride 100mg (Amantadine hydrochloride) Overdosage
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 (including adult respiratory distress syndrome – 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, 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 in cases where a drug overdose has occurred.
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 childat 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.
Care should be exercised when administering adrenergic agents, such as isoproterenol, to patients with a Amantadine Hydrochloride overdose, since the dopaminergic activity of Amantadine Hydrochloride has been reported to induce malignant arrhythmias.
The blood electrolytes, urine pH and urinary output should be monitored. If there is no record of recent voiding, catheterization should be done.
Amantadine hydrochloride 100mg (Amantadine hydrochloride) Dosage And Administration
The dose of Amantadine Hydrochloride may need reduction in patients with congestive heart failure, peripheral edema, orthostatic hypotension, or impaired renal function (see ).
Some patients who do not respond to anticholinergic antiparkinson drugs may respond to Amantadine Hydrochloride. When Amantadine Hydrochloride or anticholinergic antiparkinson drugs are each used with marginal benefit, concomitant use may produce additional benefit.
When Amantadine Hydrochloride and levodopa are initiated concurrently, the patient can exhibit rapid therapeutic benefits. Amantadine Hydrochloride should be held constant at 100 mg daily or twice daily while the daily dose of levodopa is gradually increased to optimal benefit.
When Amantadine Hydrochloride is added to optimal well-tolerated doses of levodopa, additional benefit may result, including smoothing out the fluctuations in improvement which sometimes occur in patients on levodopa alone. Patients who require a reduction in their usual dose of levodopa because of development of side effects may possibly regain lost benefit with the addition of Amantadine Hydrochloride.
Depending upon creatinine clearance, the following dosage adjustments are recommended:
The recommended dosage for patients on hemodialysis is 200 mg every 7 days.
Amantadine hydrochloride 100mg (Amantadine hydrochloride) How Supplied
Amantadine Hydrochloride Oral Solution USP is available as a clear, fruit punch flavored oral solution containing 50 mg amantadine hydrochloride per 5 mL (1 teaspoonful). It is supplied in containers of 16 fl oz (473 mL).
Store at 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
Dispense in a tight container as defined in the USP, with a child-resistant closure (as required).
Amantadine hydrochloride 100mg (Amantadine hydrochloride)
