The P-I-E-N-O Parkinsn's List Drug Database
amantadine / SymmetrelTM
ANTIPARKINSON:
Antiviral
Description: Amantadine is a synthetic antiviral agent. It was introduced as an agent for prophylaxis of influenza A and was later found to cause symptomatic improvement in parkinsonism. It is used for the prophylactic or symptomatic treatment of influenza A virus, especially for high-risk patients such as those in critical public-service positions, immunosuppressed patients, nursing home residents, contacts of high-risk patients, and those with severe influenza A viral infection. Although it inhibits replication of all types of the influenza A virus, it should not be used as a substitute for vaccination. Rimantadine is a related antiviral compound that reaches higher concentrations in respiratory secretions after oral administration and has fewer CNS effects. Amantadine was approved by the FDA in 1966.
Mechanism of Action: Amantadine's mechanism of action is not fully understood. Antiparkinsonian actions are unrelated to the antiviral effects. Amantadine appears to potentiate CNS dopaminergic responses. It may release dopamine and norepinephrine from storage sites and inhibit the reuptake of dopamine and norepinephrine. Amantadine is clearly less effective than levodopa but can offer additional benefit in patients experiencing maximal or waning effects from levodopa.
As an antiviral, amantadine can inhibit viral replication within the viral cell. Amantadine appears to block the uncoating of the virus particle and subsequent release of viral nucleic acid into the host cell. It also may interfere with penetration of the cell wall by adsorbed virus. To prevent a viral infection, the drug should be present before exposure to the virus, but, if given within 24-48 hours of onset of symptoms, the influenza may be less severe.
Pharmacokinetics: Amantadine is administered orally. Absorption from the GI tract appears to be rapid and complete. Bioavailability is 86% in the elderly and greater than 90% in young adults. Peak plasma concentrations are achieved in about 2-4 hours following oral administration. Steady-state concentrations following daily dosage are obtained in 2-4 days. Amantadine crosses the blood-brain barrier and the placenta; distributes into tears, saliva, and nasal secretions; and is excreted into breast milk.
Ninety percent of amantadine is excreted in the urine via glomerular filtration and tubular secretion. Renal impairment reduces protein binding. The elimination half-life in patients with normal renal function is about 11-15 hours but can be as long as 7-10 days for those with severe renal impairment. Half- life in elderly patients is 24-29 hours. Acidifying the urine increases the rate of excretion. Only a small amount of amantadine is removed by dialysis.
CONTRAINDICATIONS/PRECAUTIONS: Because amantadine is primarily excreted unchanged in the urine, patients with renal impairment should receive lower doses. Renal function should be monitored closely and the dose adjusted accordingly. The elderly require lower dosages, because delayed clearance of amantadine in the elderly can increase toxic effects (see Dosage).
Peripheral edema and congestive heart failure can be precipitated by amantadine, which is thought to induce a redistribution of fluid within the body rather than an increase in total body water. Patients at risk should be treated with caution. Peripheral edema can be preceded by or can accompany livedo reticularis and may require dose reduction or drug discontinuation.
Amantadine can increase seizure activity in patients with a seizure disorder. Patients with a history of seizures should be monitored closely when amantadine is initiated.
Amantadine is contraindicated in patients with a known rimantadine hypersensitivity, amantadine hypersensitivity, or hypersensitivity to any agent in the adamantane class.
Patients with eczema should receive amantadine with caution. Recurrent eczema or rash can be aggravated during treatment. Amantadine can produce CNS disturbance. Psychosis can be exacerbated, and confusion, hallucinations, or nightmares can result. The psychotic effects may be dose-related, but patients with preexisiting psychoses should be treated with caution.
Abrupt withdrawal of amantadine should be avoided in patients with Parkinson's disease since this may precipitate symptoms of increased rigidity, confusion, urinary retention, or bulbar palsy.
Amantadine is classified as a pregnancy category C drug. No complete or well-controlled studies have been done. Use during pregnancy should be avoided unless the potential benefits outweigh the possible risks to the fetus.
DRUG INTERACTIONS: Ethanol should not be used with amantadine because of the possible increase of CNS effects such as dizziness, confusion, lightheadedness, fainting, or orthostatic hypotension.
Amantadine should be used with caution with anticholinergics, tricyclic antidepressants, antihistamines, or phenothiazines because of the possible increase of anticholinergic effects, especially hallucinations, nightmares, or confusion. Reductions in the dosage of both drugs may be necessary before using them together.
Amantadine can produce undesirable reactions if opiate agonists are used concomitantly in large doses. Usual therapeutic doses should not produce any interaction.
Amantadine can increase the efficiency of levodopa by its action on central nerve terminals. Patients who exhibit psychoses should avoid this combination because of the possibility of an increased psychotic effect.
Amantadine used concomitantly with CNS stimulants can result in increased stimulant effects, such as nervousness, irritability, or insomnia, and can lead to seizures or cardiac arrhythmias. Close monitoring of the patient is recommended.
Concurrent use with hydrochlorothiazide or triamterene can reduce renal clearance of amantadine, with subsequent increase in plasma amantadine and possible toxicity.
Mental status changes have been reported after co-trimoxazole was administered to a patient taking amantadine. Although it is not clear which drug in co-trimoxazole may be responsible, trimethoprim and amantadine both undergo tubular secretion. As a result, each drug can interfere with the renal clearance of the other. Trimethoprim should be used cautiously in patients receiving therapy with amantadine.
ADVERSE REACTIONS: Adverse reactions reported with amantadine therapy are primarily associated with the central nervous system (CNS). Those CNS reactions occurring in > 5% of patients receiving amantadine include dizziness, anxiety, impaired coordination, insomnia, and nervousness. Effects can appear after a few hours or several days of therapy, or after an increase in dosage. Although effects are generally mild, they can be worse or more disconcerting for elderly patients. Other CNS effects in 1-5% of patients include headache, irritability, nightmares, depression, ataxia, confusion, somnolence/drowsiness, agitation, fatigue, and hallucinations and in ' 1% include psychosis, abnormal thinking, weakness, amnesia, slurred speech, and hyperkinesia. In addition to the above adverse reactions, amantadine has been reported to cause other more serious effects including increased frequency of seizures, suicidal ideation, and neuroleptic malignant syndrome (NMS).
Orthostatic hypotension and possible congestive heart failure can occur during chronic therapy with amantadine. Lightheadedness occurred in > 5% of patients receiving amantadine. Patients presenting with symptoms should be monitored carefully; dose reduction may be necessary.
Nausea/vomiting is observed in 5-10% of patients receiving amantadine. Other GI effects (1-5% of patients) include diarrhea, constipation, anorexia, and xerostomia. Some of these problems may be due to anticholinergic effects and will respond to dose reduction. Anticholinergic-like effects from amantadine use are more likely to occur in patients with who may have increased plasma concentrations of the drug such as those with renal dysfunction or in the elderly. They also can include blurred vision and urinary retention. These adverse effects are reversible.
Livedo reticularis is a frequent (up to 5% of patients) adverse reaction of amantadine in parkinsonian patients. It can appear 1 month to 1 year from initiation of therapy, and it can be an exacerbation of a preexistant condition. Livedo reticularis is believed to be caused by abnormal capillary permeability associated with peripheral vasoconstriction which results in decreased skin temperature and peripheral blood flow. Patients with peripheral edema should be closely monitored since the edema may be indicative of livedo reticularis. Dosage reduction or drug discontinuation may be necessary.
Diffuse, white, subendothelial corneal opacification has been reported with amantadine. After discontinuation of amantidine the opacities will usually resolve within a few weeks. Other ophthalmic adverse reactions include corneal edema, light sensitivity, and optic nerve palsy.
Adverse effects reported with amantadine therapy at a frequency of ' 1% include hypertension, urinary retention, decreased libido, dyspnea, and rash. Leukopenia, neutropenia, eczematoid dermatitis, photosensitization, increased urinary frequency, oculogyric crisis, and reversible elevated hepatic enzymes have all been reported rarely.
PATIENT INFORMATION:
What do amantadine capsules do?
AMANTADINE (SymmetrelTM ) is an antiviral agent. Amantadine prevents or treats certain influenza (flu) infections. It is not an effective treatment for colds or other viruses. Amantadine can also improve muscle control and reduce muscle stiffness in patients with Parkinson's disease (shaking palsy) or similar movement disorders. Generic amantadine capsules are available.
What should my doctor, dentist, or pharmacist know before I take amantadine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take amantadine capsules by mouth. Follow the directions on the prescription label. Swallow whole with a full glass of water. If it upsets your stomach you can take amantadine with food. Take your doses at regular intervals. Do not take your medicine more often than directed. Finish the full course prescribed by your doctor even if you think your condition is better. Do not stop taking except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children under 1 year old.
Elderly patients over 65 years old may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with amantadine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking amantadine?
Serious side effects with amantadine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with amantadine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take amantadine?
Let your doctor know if your symptoms do not improve in a few days.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how amantadine affects you. To reduce the risk of dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Alcohol can make you more drowsy and dizzy, increase confusion and lightheadedness. Avoid alcoholic drinks.
If you are taking amantadine for a movement disorder, do not suddenly stop taking it. You may get muscle stiffness, paralysis, confusion, or find it difficult to pass urine.
If you are taking amantadine for Parkinson's disease, be careful not to overdo physical activity as your condition improves. Gradually increase activity so that your body has time to adjust.
Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water will help. Brush and floss teeth regularly and carefully to avoid problems with the mouth and gums.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Keep container tightly closed. Throw away any unused medicine after the expiration date.
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