Associations Of Outcome With Amantadine Exposure
Risk Factors for COVID-19 Infection
Older age and history of contact with COVID case were each associated with increased odds of COVID-19 in multivariable-adjusted models as follows: , , respectively .
Table 5. Odds ratio and its 95% confidence limits of COVID-19 predictors using forced entry multiple logistic regression model.
Amantadine was associated with a significantly reduced risk of COVID-19 disease infection after adjustment for several covariates, including age, sex, and other risk factors . Similarly, taking precautions was associated with a significantly reduced risk of COVID-19 disease .
Amantadine May Interact With Other Medications
Amantadine oral capsule can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.
To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs youre taking. To find out how this drug might interact with something else youre taking, talk to your doctor or pharmacist.
Examples of drugs that can cause interactions with amantadine are listed below.
Warnings For Other Groups
For pregnant women: Amantadine is a category C pregnancy drug. That means two things:
Talk to your doctor if youre pregnant or planning to become pregnant. This drug should be used only if the potential benefit justifies the potential risk to your pregnancy.
If you become pregnant while taking this drug, call your doctor right away.
For women who are breastfeeding: Amantadine passes into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this drug.
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Why Is This Medication Prescribed
Amantadine is used to treat the symptoms of Parkinson’s disease and other similar conditions. It is also used to control movement problems that are a side effect of certain medications used to treat Parkinson’s disease. Amantadine extended-release capsules are used along with the combination of levodopa and carbidopa to treat ”off” episodes in people with Parkinson’s disease. It also is used to prevent symptoms of influenza A virus infection and for treatment of respiratory infections caused by influenza A virus. Amantadine is in a class of medications called adamantanes. It is thought to work to control movement problems by increasing the amount of dopamine in certain parts of the body. It works against influenza A virus by stopping the spread of the virus in the body.
What You Need To Know About Amantadine For Parkinson Disease
This guide includes everything you need to know about amantadine for the treatment of Parkinson disease and drug-induced extrapyramidal reactions in adults.
In February 2018, the FDA approved amantadine for the treatment of Parkinson disease and drug-induced extrapyramidal reactions in adults.1
Parkinson disease is a neurological disorder where patients have a lack of dopaminergic neurons in the substantia nigra. The affected population is estimated to extend toward 10 million worldwide.2 Drug-induced extrapyramidal reactions, mainly caused by antipsychotics, has led to many problematic symptoms such as dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia. Anticholinergics, such as amantadine have been used to treat extrapyramidal symptoms caused by antipsychotics for many years now.3
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Criteria For Considering Studies For This Review
Types of studies
All randomised controlled trials comparing monotherapy and adjuvant oral amantadine therapy with placebo were considered for inclusion in the study.
Types of participants
Patients with a clinical diagnosis of idiopathic Parkinson’s disease as defined by the authors of the trial reports. All ages were included.
Types of interventions
Oral amantadine or placebo. Any trial duration was accepted.
Types of outcome measures
Outcomes were recorded where they were available in the trial reports:a. Quality of life and health economics assessments. b. Parkinson’s disease activities of daily living rating scales. c. Parkinson’s disease motor impairment rating scales. d. Tests of individual motor impairments. e. Patient selfevaluation rating scales. f. Reduction in levodopa dose g. Adverse event frequency. h. Number of withdrawals as a result of lack of efficacy and/or sideeffects.
Mechanisms Of Action: Antiviral
The mechanism by which amantadine hydrochloride exerts its antiviral activity is not clearly understood. 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. In certain cases, amantadine hydrochloride is also known to prevent virus assembly during virus replication. It does not appear to interfere with the immunogenicity of inactivated influenza A virus vaccine.
Antiviral Activity
Amantadine hydrochloride inhibits the replication of influenza A virus isolates from each of the subtypes, i.e., H1N1, H2N2 and H3N2. It has very little or no activity against influenza B virus isolates. A quantitative relationship between the in vitro susceptibility of influenza A virus to amantadine hydrochloride and the clinical response to therapy has not been established in man. Sensitivity test results, expressed as the concentration of amantadine hydrochloride required to inhibit by 50% the growth of virus in tissue culture vary greatly depending upon the assay protocol used, size of virus inoculum, isolates of influenza A virus strains tested, and the cell type used. Host cells in tissue culture readily tolerated amantadine hydrochloride up to a concentration of 100 µg/mL.
Drug Resistance
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Data Collection And Analysis
The identified trials were assessed by NC and KD. Disagreements about inclusions were resolved by discussion. The methodological quality of the studies was evaluated in a qualitative fashion by assessing the methods of randomisation and concealment of allocation, whether studies were blinded, whether an intentiontotreat evaluation was presented and the number of patients lost to follow up.
Eligible data was abstracted onto standardised forms by the authors independently, checked for accuracy and amalgamated.
Clinical Features Associated With Anti
Of the 30 participants who completed the study, 20 patients responded to amantadine. The demographical and clinical features were included for analysis using multivariate logistic regression models. Results showed that patients with a higher age of Parkinson’s disease onset /10 years) and higher doses of dopamine agonists /100mg LDED) were more likely to respond to amantadine.
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Impulsive And Compulsive Behaviours
Behaviours may involve gambling, becoming a shopaholic, binge eating or focusing on sexual feelings and thoughts. This can have a huge impact on peoples lives including family and friends.
Not everyone who takes Parkinsons medication will experience impulsive and compulsive behaviours, so these side effects should not put you off taking your medication to control your symptoms.
Comparisons With The Literature
Our study has several important strengths. The patient’s exposure to medication was not only based on issued prescriptions but was confirmed by asking the patient about actual use, not the one prescribed. Importantly, PCR’s results were retrieved blindly by an author without access to patients’ questionnaires. The long duration of compliance on medication besides retrieval of one-year data is remarkable to strengths as well.
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Chemistry Mechanism Of Action Spectrum And Resistance
Amantadine and rimantadine are symmetric tricyclic amines with cagelike structures that are closely related structurally to one another. Amantadine was the first antiviral agent to be licensed for systemic use in the U.S. The activity of amantadine and rimantadine is limited to influenza A viruses. Rimantadine is 4- to 10-fold more active than amantadine.268 The target of the inhibitory action for both amantadine and rimantadine is the influenza A virus M2 protein. Resistance to amantadine and rimantadine results from a point mutation in the RNA sequence encoding for the M2 protein transmembrane domain.269 Resistance typically appears in the treated subject and his or her close contacts within 2 to 3 days of the initiation of therapy as many as one-third of treated adults and children shed resistant strains of influenza by the fifth day of treatment.270
Howard S. Smith, … Christine N. Sang, in, 2009
How Should This Medicine Be Used
Amantadine comes as a capsule, extended-release capsule , tablet, extended-release tablet , and liquid to take by mouth. The capsules, tablets, and liquid medications are usually taken once or twice a day. The extended-release capsules are usually taken once a day at bedtime. The extended-release tablets are usually taken once a day in the morning. Take amantadine at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take amantadine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the extended-release capsules and extended-release tablets whole do not split, chew, or crush them. If you have difficulty swallowing the extended-release capsule, you may open the capsule and sprinkle the entire contents on a teaspoonful of soft food, like applesauce. Eat the mixture right away and swallow without chewing.
If you are taking amantadine for Parkinson’s disease, your doctor may start you on a low dose of amantadine and gradually increase your dose.
Do not stop taking amantadine without talking to your doctor. If you suddenly stop taking amantadine, you may experience fever, confusion, changes in mental state, or severe muscle stiffness. Your doctor will probably decrease your dose gradually.
Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient.
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Topiramate As An Adjunct To Amantadine In The Treatment Of Dyskinesia In Parkinson’s Disease
Objective/Rationale: Dyskinesia is a term used to describe involuntary movements that develop as side effects of dopamine drugs used to treat Parkinson’s disease. Dyskinesias are frequent and disabling to many patients. They can interrupt smooth coordinated movements, affect communication and disrupt activities of daily living. Currently, among medications to treat dyskinesia, only amantadine is effective and readily available. A recent laboratory study documented that a readily available drug, topiramate, provided additional improvement with amantadine in parkinsonian pre-clinical models with dyskinesia. In fact, the benefit of the combination of topiramate and amantadine proved to be better than the benefits from either one alone even if the individual effects were added. This study will build on the laboratory information to test topiramate in Parkinsons disease patients with dyskinesia who are already taking daily amantadine.
Anticipated Outcome:The anticipated outcomes are that i) topiramate treatment will be safe and well-tolerated in patients and ii) those patients receiving both topiramate and amantadine will have reduced dyskinesia in comparison to those patients receiving only amantadine and placebo tablets.
How Should I Take Amantadine
Take amantadine exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.
If you take amantadine to treat influenza A, start taking the medicine within 24 to 48 hours after flu symptoms begin. Keep taking this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared.
You may take amantadine with or without food. You may need to take this medicine only at bedtime. Follow your doctor’s instructions.
Measure liquid oral solution carefully. Use the dosing syringe provided, or use a medicine dose-measuring device .
Swallow the capsule or tablet whole and do not crush, chew, or break it.
If you cannot swallow a capsule whole, open it and sprinkle the medicine into a spoonful of applesauce. Swallow the mixture right away without chewing. Do not save it for later use.
Call your doctor if your symptoms do not improve, or if you have a fever with a headache, cough, skin rash, or other new symptoms.
If you take amantadine for Parkinson symptoms: You should not stop using amantadine suddenly or your condition may become worse. Stopping suddenly may also cause unpleasant withdrawal symptoms. Ask your doctor how to safely stop using this medicine.
Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.
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Drug Interactions And Contraindications
Other drugs that have anticholinergic effects can worsen the anticholinergic adverse effects of amantadine. Doses may need to be reduced if anticholinergic AEs occur .4
Amantadine has an excretion rate related to the acidity of the urine. Any drug, change in diet, or patient state that influences urine pH may alter the elimination or accumulation of amantadine and will need to be monitored.
Alcohol increases sedation and orthostatic hypotension and should not be taken with amantadine. Live influenza vaccines are also not recommended as amantadine may interfere with the efficacy of the vaccine.
Amantadine is contraindicated in patients with end-stage renal disease .
Summary Of Key Results
In our hospital-based retrospective study, we assessed risk factors for COVID-19 among a cohort of patients known to have PD or MS and its relation to the use of amantadine.
Consistent with existing evidence, individuals who have a history of contact with COVID-19 cases had a higher risk of being diagnosed with SARS-CoV-2 . In addition, older people have a higher COVID-19 risk . Amantadine prescriptions were associated with a reduced risk of COVID-19 PCR positive cases adjusted for a wide area of demographic factors, potential comorbidities, and other medication. We found a shred of evidence that pre-exposure use of amantadine was associated with a lower risk of COVID-19 infection.
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What Other Information Should I Know
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your response to amantadine.
If you are taking the extended-release tablets , you may notice something that looks like a tablet in your stool. This is just the empty tablet shell, and does not mean that you did not get your complete dose of medication.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
What Is Amantadine Used For
Amantadine is used to treat involuntary body movements associated with
- Parkinsons disease – involuntary tremors and dyskinesia while on levodopa based medicines
- extrapyramidal symptoms which are side effects from medication that block dopamine receptors including muscle spasm, tremor and irregular, jerky movements
- Chorea due to Huntington disease
Amantadine brand names available in the US are Gocovri and Osmolex. They do not have the same labeled indications and are not interchangeable.
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Enhancing Healthcare Team Outcomes
Amantadine was once widely prescribed for Parkinson disease and even influenza. However, there are many more effective drugs on the market, and the use of amantadine has declined. Nevertheless, nurse practitioners, physician assistants, or primary care providers who prescribe this agent should closely monitor the patient for adverse effects. Also, the patient’s renal function and mental status require monitoring. Amantadine can increase the risk of depression and lower the threshold for seizures, so nurses should explicitly query and search for this information on patient intake. Irreversible changes in the liver can occur, and hence liver enzymes require monitoring at the same time. Pharmacists should examine the patient’s medical record, look for drug interactions, verify dosing, and express any concerns to the prescriber. With an interprofessional team approach to healthcare, amantadine therapy can be most effective in those cases where it is still useful, and other agents can substitute for it with a collaborative assessment of the patient’s needs and regimen.
Data Source And Study Population
We conducted a retrospective cohort study using electronic health record data from hospital care practices focusing on patients with the diagnosis of PD and MS who were compliant on their usual medications for at least 6 months before enrollment, with information on age, sex, and medications. Institutional Review Board approval was obtained from our hospital and the ministry of health .
All are 16 years old or above.
Patients
We selected participants from Parkinson’s disease and multiple sclerosis patients who attended the outpatient clinic. Patients on amantadine acted as a case group and non-amantadine users as a control group.
Exclusion Criteria
– Patients who were not regularly on amantadine in the last 6 months before enrollment in the study.
– Recent change in his medications .
– Patients outside Kuwait during the COVID-19 pandemic period results).
– MS patients who recently received glucocorticoids that may increase the risk of contracting infections , including COVID-19 .
We divided patients according to their current treatment into two groups amantadine-user group and a sample of patients with randomly selected diagnoses matched non-amantadine users group II, with the proportion of 1:2.
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What Other Drugs Will Affect Amantadine
Using amantadine with other drugs that make you drowsy can worsen this effect. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures.
Tell your doctor about all your other medicines, especially:
-
glaucoma medication or
-
medicine that contains sodium bicarbonate .
This list is not complete. Other drugs may interact with amantadine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.
Warnings For People With Certain Health Conditions
For people with epilepsy or seizures: Taking amantadine can increase the severity and number of seizures you have.
For people with kidney disease: Deaths have been reported in people with kidney disease who took more than the recommended dosage of amantadine. This can happen with doses as low as 1 g and can cause heart failure, breathing failure, kidney failure, and central nervous system failure.
For people with heart disease: People with a history of congestive heart failure or peripheral edema are at increased risk of heart failure when they take amantadine.
For people with glaucoma: People with certain types of glaucoma should not use amantadine because it can cause the pupils to dilate.
For people with recurring eczema-type rash: Taking amantadine can increase the severity of the rash or number of rashes you get.
For people with psychiatric disorders: Taking amantadine can make your disorder become more severe. You may also have increased suicidal thoughts or behaviors.
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