Amantadine: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on May 15, 2024.

1. How it works

• Amantadine may be used to treat Parkinson's disease (PD) or for the prophylaxis and treatment of signs and symptoms of infection caused by various strains of the influenza A virus, although the CDC no longer recommends its use for influenza A.
• Experts aren't sure exactly how amantadine works to treat dyskinesias or "off" episodes in people with PD but it is known that amantadine is a weak antagonist of the NMDA receptor and may have direct and indirect effects on dopamine neurons because it displays dopaminergic-like side effects such as hallucinations and dizziness. It also exhibits anticholinergic-like side effects such as dry mouth, urinary retention, and constipation, even though it has not been shown to possess any direct anticholinergic activity in animal studies.
• Experts are also unclear about the mechanism by which Amantadine exerts its antiviral activity but 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. It may also prevent virus assembly during virus replication.
• Amantadine belongs to the class of medicines known as dopaminergic antiparkinson agents. It may also be called an adamantane antiviral.

2. Upsides

• May be used to treat dyskinesia in people with Parkinson's disease who are already receiving levodopa-based treatment. Dyskinesias are a complication of some Parkinson's disease medications and symptoms include involuntary, erratic, writhing movements of the face, arms, legs, or trunk, which may be fluid, dance-like, or cause rapid jerking or slow and extended muscle spasms.
• May also be used to treat "off" episodes of Parkinson's disease (the times when the person's usual medication stops working) in people already treated with levodopa/carbidopa.
• May be used either with or without dopaminergic medications such as apomorphine, bromocriptine, or cabergoline.
• Can treat and prevent infection caused by various strains of the influenza A virus.
• Consider for the treatment of uncomplicated respiratory tract illness caused by influenza A virus strains especially when administered early in the course of illness.
• When used to treat or prevent influenza A, amantadine does not appear to interfere with the immunogenicity of inactivated influenza A virus vaccine.
• Inhibits the replication of influenza A virus isolates from all subtypes: H1N1, H2N2, and H3N2. Has little or no activity against influenza B virus isolates.
• Individuals who take amantadine for flu are still likely to develop immune responses to natural disease or vaccination and may be protected when later exposed to antigenically related viruses because amantadine does not completely prevent the host immune response to influenza A infection.
• Following vaccination during an influenza A outbreak, amantadine should be considered for the 2- to 4-week time period required to develop an antibody response.
• Taken orally (by mouth).
• Available as immediate-release capsules and tablets which may be taken once or twice a day.
• The usual recommended dosage is 200mg at bedtime for those under 65 and 100mg at bedtime for those over 65.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Nausea, dizziness, and insomnia are the most common side effects reported.
• Visual hallucinations, delusions, illusions, or paranoia may affect up to 25% of all patients. These caused discontinuation of treatment in 8% of patients. Other common side effects include dizziness, dry mouth, peripheral edema, constipation, falls, and orthostatic hypotension. Urinary tract infections, anxiety, and insomnia have also been reported.
• Depression was reported in 6% of people prescribed amantadine and suicidal ideation or suicide attempt was reported in 2%. 3% of people reported confusion and 2% apathy. Consider if the benefits outweigh the risks of treatment in those who develop these effects.
• Intense urges to gamble, spend money, have sex, or binge eat have been reported with medications such as amantadine. Specifically ask patients or their caregivers about new or increased gambling urges, uncontrollable spending, or other urges while being treated with amantadine. Consider dose reduction or discontinuation if these develop.
• Not interchangeable with Gocovri which is an extended-release product.
• The dosage of amantadine needs to be reduced slowly in people who have been taking it for more than four weeks. The manufacturer recommends reducing the dosage by half for the final week of dosing.
• Rapid dose reduction or withdrawal of medications such as amantadine have been associated with a symptom complex resembling neuroleptic malignant syndrome (symptoms include high temperature, muscle rigidity, altered consciousness, and autonomic instability). An increase in the symptoms of PD has also been reported with abrupt discontinuation of amantadine as well as delirium, agitation, delusions, hallucinations, anxiety, depression, and slurred speech.
• Reduce the dosage of amantadine in people with moderate to severe renal impairment. The maximum dosage for severe renal impairment is 68.5mg at bedtime. Avoid amantadine in end-stage renal disease.
• May cause orthostatic hypotension and increase the risk of falls. Warn patients to get up slowly when going from a lying or sitting position to standing. People over the age of 65 years are more at risk.
• May interact with some other medicines including those that cause sedation (including opioids, benzodiazepines, and sedating antihistamines), have anticholinergic properties (such as benztropine), or affect the urinary pH. Alcohol should be avoided.
• May be toxic in overdose, mostly attributable to the anticholinergic effects of amantadine. Cardiac, respiratory, renal, or central nervous system toxicity can occur during an overdose. Deaths have been reported, particularly in those with impaired renal function.
• Drug resistance may develop when used to treat or prevent influenza A in people who have used medications from the same class. This is why the CDC no longer recommends amantadine to treat or prevent influenza A infection.
• Not a substitute for yearly influenza vaccination.
• There are no adequate studies on the use of amantadine during pregnancy but animal studies have shown an increased risk of malformation, reduced body weight, and embryo lethality. Amantadine is excreted into breast milk and may alter breast milk production or secretion. There is no data regarding the effects on the breastfed infant. Animal studies suggest it may impair fertility.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Amantadine may be used to treat dyskinesia or reduce the number of OFF episodes in those with Parkinson's disease (PD) OR in the treatment or prevention of Influenza A viral infection. Nausea, dizziness, insomnia, and hallucinations are common side effects and it may cause a low mood or intense urges to do things such as gamble or spend money in those taking it long-term for PD. When used to prevent or treat influenza A, research shows it prevents 61% of cases and reduces the duration of fever by one day; however, the CDC no longer recommends its use.

5. Tips

• May be taken with or without food.
• Do not drink alcohol while taking amantadine.
• May cause drowsiness and affect your ability to drive, operate machinery, or perform hazardous tasks. In addition, other treatments for Parkinson's Disease may increase your risk of falling asleep suddenly without warning, while doing normal daily tasks, such as housework, gardening, conversations, eating, or driving a motor vehicle. Other medications that you take may increase this risk further. If you develop daytime sleepiness or fall asleep during daily activities, tell your doctor immediately because amantadine​ may not be suitable for you. If your doctor decides to continue amantadine, then you should not drive and you should avoid other potentially dangerous activities.
• Amantadine may increase your risk of depression. Tell your doctor if you are feeling low or depressed, or if you begin having thoughts about suicide. Ask friends and family to monitor you for this as well as gambling or spending urges, psychotic behavior, or hallucinations.
• Do not stand up suddenly from a sitting or lying position as amantadine can cause a sudden drop in blood pressure (this is called orthostatic hypotension), which may increase your risk of falling. Tell your doctor if you experience dizziness on standing or fall frequently.
• Do not stop amantadine suddenly. If you need to stop amantadine because you are not tolerating it or for some other reason, talk to your doctor who will advise you on how to reduce the dosage of amantadine slowly.
• If you miss a dose of amantadine, take the dose as soon as you remember. If it is the next day, then just take the next dose as scheduled, do not double up on dosages.
• Tell your doctor if you have any mental health issues or medical conditions, such as kidney disease, that may affect the dosing of amantadine.
• Tell your doctor if you are pregnant, intending to become pregnant, or breastfeeding because amantadine may not be suitable for you.
• Amantadine can interact with some other medications. Talk to your doctor or pharmacist before taking any other medications, including those brought from a drug store or supermarket.

6. Response and effectiveness

• It takes around 48 hours for amantadine to start working for PD.
• The Unified Dyskinesia Rating Scale (UDysRS) measures factors associated with dyskinesias, such as patient perceptions, time factors, anatomical distribution, objective impairment, severity, and disability. In two studies, a significant change in UDysRS from a baseline of -15.9 to -20.7 was reported in patients taking amantadine compared to only -6.3 to -8.0 in those taking a placebo (an inactive pill) after 12 weeks. In addition, there was a significant decrease in ON-time without dyskinesias and a significant decrease in OFF-time between baseline and week 12.
• Most people with PD are 65 and older and in amantadine for PD studies, only 46% were less than 65 years of age, 39% were 65 to 74 years of age, and 15% were aged 75 years or older.
• A Cochrane review found amantadine prevented 25% of influenza-like illness cases and 61% of influenza A cases. It reduced the duration of fever by one day. Gastrointestinal and central nervous system side effects were significant. Amantadine did not affect the rate of viral shedding from the nose or the course of asymptomatic influenza.

7. Interactions

Medicines that interact with amantadine may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with amantadine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with amantadine include:

• anti-anxiety medications such as lorazepam or diazepam
• anticholinergics, such as atropine, belladonna, benztropine
• antidepressants, such as amitriptyline, imipramine, nortriptyline, fluoxetine, or sertraline
• antipsychotics, such as aripiprazole or olanzapine
• antihistamines that cause sedation, such as diphenhydramine
• bupropion
• chlorothiazide or hydrochlorothiazide
• cyclizine
• duloxetine
• flibanserin
• ginkgo
• ketamine
• live vaccines, such as influenza, MMR, varicella, and rotavirus (may interfere with the efficacy of these)
• metoclopramide
• polyethylene glycol
• muscle relaxants such as cyclobenzaprine
• sleeping pills, such as zolpidem
• tramadol
• ziprasidone.

Alcohol may worsen the side effects of amantadine such as confusion, drowsiness, dizziness, and orthostatic hypotension.

The excretion rate of amantadine can be influenced by the pH of the urine. Urinary pH can be altered by diet, drugs (eg, sodium bicarbonate, carbonic anhydrase inhibitors), and other medical conditions such as urinary tract infections or renal tubular acidosis. Alterations towards acidic urine rapidly increase the excretion of amantadine, whereas alterations towards an alkaline pH may lead to an accumulation of Gocovir and possibly an increase in side effects.

Note that this list is not all-inclusive and includes only common medications that may interact with amantadine. You should refer to the prescribing information for amantadine for a complete list of interactions.

References

• Amantadine. Updated 04/2024. Strides Pharma Science Limited. https://www.drugs.com/pro/amantadine.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use amantadine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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