Amantadine Parkinson’s Side Effects

How Do Dopamine Agonists Work

Dopamine agonists are a class of drugs used to treat the symptoms of Parkinson’s disease. They mimic the action of naturally occurring dopamine.

The direct cause of Parkinson’s disease or Parkinsonian-like syndrome is the deficiency of the neurotransmitter dopamine in the brain. Antiparkinson medicines aim to prolong the action of dopamine in the brain by:

Replacing dopamine

Sensitizing dopamine receptors to stimulate dopamine release

Dopamine agonists bind to the dopamine receptors to release more dopamine in the brain.

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

Benjamin L. Walter M.D., Jerrold L. Vitek M.D., Ph.D., in, 2006

Can Amantadine Cause Problems

Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the common ones associated with amantadine. You will find a full list in the manufacturer’s information leaflet supplied with your medicine. The unwanted effects often improve as your body adjusts to the new medicine, but speak with your doctor or pharmacist if any of the following continue or become troublesome.

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What Drugs Interact With Symmetrel

• Careful observation is required when Symmetrel 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 resulted in a higher plasma amantadine concentration in a 61-year-old man receiving Symmetrel 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 concurrent use of Symmetrel with live attenuated influenza vaccine intranasal has not been evaluated. However, because of the potential for interference between these products, LAIV should not be administered within 2 weeks before or 48 hours after administration of Symmetrel , unless medically indicated.
• The concern about possible interference arises from the potential for antiviral drugs to inhibit replication of live vaccine virus. Trivalent inactivated influenza vaccine can be administered at any time relative to use of Symmetrel .

For People With Parkinson’s Disease

• Try to keep your regular appointments with your doctor. This is so your doctor can check on your progress. During the first few weeks of treatment in particular, your dose may require adjusting.
• Stay as active as possible and exercise regularly as much as you are able. You may walk more slowly than before but a daily walk is good exercise and may help to loosen up stiff muscles.
• If you are a driver you should tell the DVLA and your insurance company that you have Parkinson’s disease. Depending on the severity of symptoms and the medicines that you are taking, you may still be allowed to drive following a medical assessment.
• Treatment with medicines for Parkinson’s disease can sometimes cause problems with impulsive types of behaviour. If you notice any changes in your behaviour, such as an increased desire to gamble, binge eat, or spend excessively, or an increased sex drive, you must let your doctor know as soon as possible.
• Continue to take amantadine regularly. Stopping treatment suddenly can cause serious problems. Your doctor will probably want you to reduce your dose gradually if this becomes necessary.

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Randomization And Treatment Interventions

Patients were judged eligible by neurologists at the participating hospitals and were consented for enrollment peripheral blood was sampled at each hospital, and creatinine clearance was calculated at the coordination center. Eligible participants were provided unique subject identification numbers according to study criteria and were assigned to Arm 1 or Arm 2 by a research technician , according to a computer-generated, randomization plan, which included stratification by severity of dyskinesia . Study medications were sent to each hospital from the coordinating center, according to the schedule. A list of subject identification numbers and corresponding treatment assignments was restricted to K.H. and were concealed from other study personnel.

Arm 1 intervention consisted of an observation period , amantadine hydrochloride treatment period , washout period , and placebo treatment period . Arm 2 intervention consisted of an observation period, placebo period, a washout period, and an amantadine treatment period . Amantadine was increased in a step-by-step manner , followed by a decreased treatment regimen . Placebo was also administered in a similar manner. The subjects were interviewed every 7th day, and adverse effects were monitored. Trial drugs were not increased if the patients did not desire the increase or if adverse effects were detected.

What If I Miss Giving My Pet The Medication

Its entirely okay. If you fail to give medicine at the scheduled time, give it as soon as you can. However, offer it at the next scheduled dose if it is almost time for his next intake. After this, you can continue with the normal medication program.

Just dont give two drugs, 8 hours apart. Additionally, avoid giving your dog teo different types of medication simultaneously.

While the research is not extensive, experts recommend their use for chronic pain management in dogs. Your dog will be able to adequately manage chronic pain, provided the administration, dosage, frequency, and treatment duration are accurate.

Follow the guidelines and orders correctly as instructed by your veterinarian.

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Kidney Or Liver Disease

The kidneys primarily excrete amantadine via the urine. In people with impaired kidney function, the drug can build up in the body. The doctor will lower the dose of amantadine, as a result.

Amantadine can also increase liver enzyme numbers. Anyone with a history of liver disease should take amantadine with caution.

Amantadine For Dyskinesias In Parkinson’s Disease: A Randomized Controlled Trial

• Affiliation Clinical Research Center, Utano National Hospital, Kyoto City, Japan

• Affiliation Clinical Research Center, Utano National Hospital, Kyoto City, Japan

• Affiliation National Center for Neurological and Psychiatric Disorders, Kodaira, Japan

• Affiliation Department of Therapeutic Medicine, School of Medicine, Ehime University, Toon, Japan

• Affiliation Clinical Research Center, Utano National Hospital, Kyoto City, Japan

• Affiliation Department of Neurology, Kagawa Prefectural Central Hospital, Takamatsu, Japan

• Affiliation Department of Neurology, Miyagi National Hospital, Watari-gun, Japan

• Affiliation Student Health Center, Kyoto University, Kyoto City, Japan

• ¶Membership of the Amantadine Study Group is provided in the Acknowledgments.

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Search Methods For Identification Of Studies

1. The review was based on the search strategy of the Movement Disorders Group. In general the search crossreferenced amantadine and its proprietary names with Parkinson’s disease and its derivations, all as MeSH headings and as text words. The following databases were searched:

• Clinical trial databases: The Cochrane Controlled Trials Register , Clinicaltrials.gov , metaRegister of Controlled Trials , NIDRR and NRR .
• General biomedical and science databases: MEDLINE , EMBASE , SCISEARCH , BIOSIS , GEROLIT and OLDMEDLINE .
• English language databases of foreign language research and third world publications: LILACS , MedCarib , PASCAL , JICSTEPLUS , RUSSMED .

2. The reference lists of located trials and review articles were searched.

3. Hand searching of appropriate journals was performed.

4. The following grey literature was searched: DISSERTATION ABSTRACTS , SIGLE , ISIISTP , Aslib Index to Theses , Abstracts of the International Congress of Movement Disorders and Abstracts of the XIII International Congress on Parkinson’s Disease .

Further details on this search strategy are available in the Group’s module within the Cochrane library . This includes explanations of the acronyms, sources and web sites.

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.

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How To Take Amantadine

• Before you start the treatment, read the manufacturer’s printed information leaflet from inside the pack and any additional information your doctor has given to you. These will give you more information about amantadine and will provide you with a full list of the side-effects which you may experience from taking it.
• Take amantadine exactly as your doctor tells you to.
• If you have been prescribed amantadine for Parkinson’s disease symptoms it is usual to take 100 mg daily for the first week, and then for the dose to increase to twice a day. Some people may require doses of up to 400 mg daily.
• If you have been prescribed amantadine to prevent a shingles rash and nerve pain the dose is 100 mg twice a day for 14 days. If you are still in pain after 14 days a further course of treatment may be prescribed.
• Your doctor or pharmacist will tell you what dose to take each day, and the directions will also be printed on the label of the pack to remind you about what the doctor said to you.
• Try to take your doses of amantadine at the same time each day, as this will help you remember to take it regularly.
• If you forget to take a dose, take it as soon as you remember. Try to take the correct number of doses each day but do not take two doses together to make up for a missed dose.

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 .

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Dosage For Parkinsons Disease

Generic: Amantadine

• Strength: 68.5 mg, 137 mg

Immediate-release capsule

Adult dosage

• Typical starting dosage: 100 mg, taken twice per day, when not used with other drugs for Parkinsons disease.
• In some cases: Some people may need to start with 100 mg, taken once per day, if they have certain serious medical illnesses or are taking high doses of other drugs to treat Parkinsons disease.
• Maximum dosage: 200 mg, taken twice per day.

Child dosage

It has not been confirmed that amantadine is safe and effective for use in people younger than 18 years.

Senior dosage

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, a higher amount of a drug stays in your body for a longer time. This increases your risk of side effects.

Extended-release capsule

Adult dosage

• Typical starting dosage: 137 mg, taken once a day at bedtime.
• Dosage increases: After one week, your doctor will likely increase your dosage to 274 mg once a day at bedtime.

Child dosage

It has not been confirmed that amantadine is safe and effective for use in people younger than 18 years.

Senior dosage

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, a higher amount of a drug stays in your body for a longer time. This increases your risk of side effects, such as falls and hallucinations.

When To Call The Doctor

• You should call your doctor if your Parkinsons disease gets worse, if your movement disorder gets worse, or if your flu symptoms become more severe.
• If any of these things occur, your doctor may need to change your dosage or prescribe a different medication.

All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

• how severe your condition is
• other medical conditions you have
• how you react to the first dose

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Study Design And Organization

This trial was registered in the UMIN Clinical Trial Registry on July 30, 2007 .

This multi-center, placebo-controlled, double-blinded, randomized, cross-over trial was organized by a study group comprising 13 sites in 11 prefectures in Japan. Amantadine hydrochloride was donated by Novartis Pharma Corporation, Tokyo, Japan. The study was conducted by a coordination center at Utano National Hospital and was approved by the Bioethics Committee of Utano National Hospital, the Ethica of National Center for Neurological and Psychiatric Disorders, Ehime University Hospital IRB, the Ethics Committee of Miyagi National Hospital, the Ethics Committee of Mie University Hospital, the Ethics Committee at Sagamihara National Hospital, the Ethical Committee of Research Institute for Brain and Blood Vessels Akita, the Ethical Review Committee of National Defense Medical College, the Ethics Committee of Nishitaga National Hospital, Bioethics Committee of Jichi Medical University, the Ethics Committee of Saigata National Hospital, and the Institutional Review Board of Kagawa Prefectural Central Hospital. All subjects were informed of study protocols and study relevance, and the subjects provided written consent. Safety was monitored with attention paid to adverse effects.

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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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.

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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