Thursday, November 1, 2007

Medications for Parkinson's


Parkinson’s Medications – An Overview
People with Parkinson’s disease often take a variety of medications in different doses in order to manage the symptoms of the disease. These factors, combined with the frequency with which one must take their medicines, can result in confusion. People with Parkinson’s and their caregivers should become familiar with their medications in order to use them most effectively and avoid possible interactions. Understanding a medication regime and sticking to it will provide the greatest benefit from the drug and avoid unpleasant “off” periods due to missed doses or confusion.
This section of our website contains information about medications for Parkinson’s disease. Included is a table of Parkinson’s drugs, a section on over-the-counter medications, tips for administering drugs and hints to help you save money.
Please note that the side-effects listed in the tables that accompany each class of medication are the most commonly experienced. Not all patients will experience such side-effects. For many people who do experience side-effects, they can often be effectively limited or eliminated with careful adjustments to dosage or the timing of the individual doses. If any side-effects are experienced, speak to the treating physician immediately. For a complete description of each drug and its possible side-effects, please request a “package insert” from your pharmacist for each drug being used. It is recommended that all prescriptions be filled at the same pharmacy to avoid interactions between medications. Interactions can be dangerous and even life-threatening, so make sure the pharmacist knows of all medications and supplements being taken – including over-the-counter medications and supplements.
Although there are general guidelines that doctors use to choose a treatment regimen, each patient must be individually evaluated to determine which drug or combination of drugs is best for them. For some, a “first choice” drug might be one of the levodopa preparations, and for others, an initial prescription may be given for one of the agonists, an MAO inhibitor or an anticholinergic. The choice of drug treatment depends on many variables including symptom presentation, other concurrent health issues (and the medications being used to treat them) and a person’s age. And while the suggested starting dosages (as indicated by the package insert) are listed here, remember that they too can vary greatly depending on a person’s needs and metabolism.
Carbidopa/Levodopa (Sinemet®) Levodopa is a substance that is converted into dopamine by an enzyme in the brain. It is then released by brain cells and activates dopamine receptors allowing for normal function of the movement control centers of the brain. Forty years after its discovery, levodopa remains the most effective medication for Parkinson’s disease. In fact, 70 to 80 percent of treated Parkinson’s patients are on levodopa therapy. Levodopa is the “gold standard” by which all treatments for Parkinson’s are measured.
Levodopa combined with carbidopa (or Sinemet®) represented a significant improvement in the treatment of Parkinson's disease. The addition of carbidopa prevents levodopa from being converted into dopamine in the bloodstream, allowing more of it to get to the brain. Therefore, a smaller dose of levodopa is needed to treat symptoms. In addition, the nausea and vomiting often associated with levodopa treatment is greatly reduced by the presence of carbidopa. Unfortunately, with increased dosing and prolonged use of levodopa, patients experience other side-effects including dyskinesias (spontaneous, involuntary movements) and "on-off" periods when the medication will suddenly and unpredictably start or stop working.
Check with a doctor before taking any of the following to avoid possible interactions: antacids, anti-seizure drugs, anti-hypertensives, anti-depressants and high protein food.
Stalevo® (carbidopa, levodopa and entacapone) is a combination tablet for patients who experience end-of-dose "wearing-off." The tablet combines carbidopa/levodopa with entacapone. While carbidopa reduces the side effects of levodopa, entacapone extends the time levodopa is active in the brain (up to 10 percent longer). The same drugs that interact with carbidopa/levodopa and entacapone interact with Stalevo®.
Medication
Available Doses
Initial Dosing
Side Effects
Indications
Interactions
Carbidopa/
Levodopa
(Sinemet®)
10/100 mg
25/100 mg
50/200 mg
25/100 mg 2-3X/day
Low blood pressure, nausea, confusion, dyskinesia, dry mouth, dizziness
First course of treatment; converts to dopamine to manage major symptoms
Antacids, anti-seizure drugs, anti-hypertensives, anti-depressants, high protein food
Carbidopa/
Levodopa
controlled release
(Sinemet CR®)
10/100 mg
25/100 mg
50/200 mg
50/200 mg 2X/day
Low blood pressure, nausea, confusion, dyskinesia, dry mouth, dizziness
First course of treatment; converts to dopamine to manage major symptoms and may prolong effectiveness
Antacids, anti-seizure drugs, anti-hypertensives, anti-depressants, high protein food
Carbidopa/
Levodopa/
Entacapone
(Stalevo®)
12.5/50/200 mg
25/100/200 mg
37.5/150/200 mg
12.5/50/200 mg
Dyskinesia, nausea, diarrhea, hyperkinesia, abdominal pain, dizziness, harmless discoloration of urine, saliva and/or sweat
Secondary course of treatment; combines entacapone with levodopa/carbidopa to block COMT enzyme and prolong levodopa’s effectiveness
Same as levodopa/carbidopa, MAO inhibitors, Comtan, Sinemet, high doses (10 mg or more) of selegiline
Carbidopa/
Levodopa
Orally disintegrating tablet
(Parcopa®)
10/100 mg
25/100 mg
25/250 mg
25/100 mg 2-3X/day
Low blood pressure, nausea, confusion, dyskinesia, dry mouth, dizziness
First course of treatment; converts to dopamine to manage major symptoms; also for patients with swallowing difficulties
Antacids, anti-seizure drugs, anti-hypertensives, anti-depressants, high protein food
Dopamine agonists are drugs that stimulate the parts of the human brain that receive dopamine. In effect, the brain "thinks" it is receiving dopamine, so these drugs help satisfy the brain's need for dopamine. Dopamine agonists can be taken alone or in combination with medications containing levodopa. Agonists available in the United States include bromocriptine (Parlodel®), pramipexole (Mirapex®) and ropinirole (Requip®). In March 2007, the dopamine agonist pergolide (Permax) was pulled from the market by the US Food and Drug Administration in response to reports of heart valve damage.
Consult a doctor before taking any of the following to avoid possible interactions: alcohol, anti-psychotics, medications that lower blood pressure, Navane® (thiothixene), Taractan® (chlorprothixene), Haldol® (haloperidol), Reglan® (metoclopramide), phenothiazines, thiozanthenes, cimetidine, phenothiazines, butyrophenones, Cipro® and benzodiazepines.
Medication
Available Doses
Initial Dosing
Side Effects
Indications
Interactions
APOKYN™ injection (apomorphine hydrochloride)
.02 mL –
.06 mL
.02 mL during “off” periods
Nausea, vomiting, low blood pressure, sleepiness, dyskinesias, hallucinations, chest pain
Adjunct levodopa therapy to treat “off” periods
5HT3 agonists (for example, Zofran®, Kytril®) antihypertensives (for example Norvasc® and Zestril®)
Bromocriptine
(Parlodel®)
2.5 mg
5 mg
2.5 mg 3X/day

Low blood pressure, nausea, edema, confusion, dry mouth, depression, headaches
First course of treatment alone or with levodopa;
mimics dopamine to manage major symptoms
Alcohol, anti-psychotics, blood pressure lowering medications
Rotigotine Transdermal System (Neupro®)
2mg/24hrs4 mg/24hrs6 mg/24hrs
One 2 mg patch a day
Nausea, application site reactions, somnolence, dizziness, headache, vomiting, sleep attacks, insomnia.
First course of treatment alone or with levodopa in early-stage idiopathic Parkinson’s disease; mimics dopamine to manage major symptoms
May cause allergic-type reactions including anaphylactic symptoms especially in people sensitive to sulfites, including those with asthma.
Pramipexole
(Mirapex®)
.125 mg
.25 mg
.5 mg
1 mg
1.5 mg
.125 mg 3X/day
Arthritis, chest pain, nausea, low blood pressure, sleep disturbances, sedation
First course of treatment alone or with levodopa;
mimics dopamine to manage major symptoms
Sedatives and tranquilizers; metocipramide, thiozanthenes, cimetidine, phenothiazines, butyrophenones

Ropinirole
(Requip®)
.25 mg
.5 mg
1 mg
2 mg
3 mg
4 mg
5mg

.25 mg 2X/day
Abdominal pain, sleep disturbances, nausea, low blood pressure, sedation
First course of treatment alone or with levodopa;
mimics dopamine to manage major symptoms
Alcohol, anti-depressants, Cipro®, anti-psychotics, benzodiazipines
Anticholinergics (trihexyphenidyl, benztropine mesylate, procyclidine, etc.) do not act directly on the dopaminergic system. Instead they decrease the activity of another neurotransmitter that controls movement, called acetylcholine, to balance out the production of dopamine and acetylcholine. In general, mild PD that consists of tremor at rest can often be treated initially with anticholinergic agents. Adverse effects of these drugs include blurred vision, dry mouth and urinary retention. Anticholinergics may be contraindicated in older patients because they can cause confusion and hallucination.
Check with a doctor before using anticholinergics with anti-histamines, Haldol®, Thorazine®, Symmetrel®, Clozaril® and alcohol.
Medication
Available Doses
Initial Dosing
Side Effects
Indications
Interactions
Benzotropine mesylate
(Cogentin®)
.5 mg
.5 mg 2X/day
Confusion, hallucinations, nausea, blurred vision, dry mouth, urinary retention, nervousness; not used long-term due to side effects
Secondary medication; tremor; attempts to restore balance by inhibiting other enzymes and nerve cells that may attack dopamine
Anti-histamines, Propulside®, Haldol®, Thorazine®, Symmetrel®, Clozaril®, alcohol
Trihexyphenidyl HCL
(Artane®)
1 mg
2 mg
1-2 mg 2X/day
Confusion, hallucinations, nausea, blurred vision, dry mouth, urinary retention, nervousness; not used long-term due to side effects
Secondary medication; tremor; attempts to restore balance by inhibiting other enzymes and nerve cells that may attack dopamine
Anti-histamines
MAO-B inhibitors such as selegiline or deprenyl (Eldepryl®) are used to block an enzyme in the brain that breaks down levodopa. They have been shown to delay the need for Sinemet® when prescribed in the earliest stage of Parkinson’s, and have also been approved for use in later stages of the disease to boost the effects of Sinemet®. Eldepryl® may interact with anti-depressants, narcotic pain killers and decongestants. Check with a doctor before taking any new medications.
Medication
Available Doses
Initial Dosing
Side Effects
Indications
Interactions
Selegiline
(Eldepryl®, Carbex®)
5 mg
5 mg 2X/day
(max dose)
Agitation, insomnia, hallucinations
Tertiary medication; controls brain’s metabolism of dopamine
Anti-depressants, narcotic painkillers, decongestants
Selegiline HCIOrally disintegrating tablet(Zelapar®)
1.25mg
1.25mg 1X daily
Dizziness, nausea, pain, headache, insomnia, rhinitis, dyskinesias, back pain, stomatitis, dyspepsia
Adjunct to levodopa in patients with significant "off" periods
Anti-depressants, narcotic painkillers, decongestants
Rasagiline (Azilect®)
0.5mg1mg
0.5mg 1X daily
Increased dyskinesias, postural hypotension, headaches, joint pain, indigestion
Signs and symptoms of PD as initial monotherapy and adjunct to levodopa
High tyramine content foods (for example, draft beer, red wine, aged cheeses, soy sauce and other products), narcotic painkillers, anti-depressants, decongestants

COMT inhibitors such as entacapone (Comtan®) represent a different class of Parkinson's medications and they must be taken with levodopa. COMT inhibitors prolong symptom relief by blocking the action of an enzyme which breaks down levodopa, allowing a larger amount of levodopa to reach the brain, which raises the dopamine level. This helps provide a more stable, constant supply of levodopa.
Medication
Available Doses
Initial Dosing
Side Effects
Indications
Interactions
Entacapone
(Comtan®)
200 mg
200 mg with levodopa; max 8 per day
Abdominal pain, back pain, constipation, nausea, diarrhea, blood in urine
Secondary medication; delays wearing off by prolonging effectiveness of levodopa
MAO inhibitors
Tolcapone
(Tasmar®)
100 mg
200 mg
100 mg 3X/day
Abdominal pain, back pain, constipation, nausea, diarrhea, blood in urine, liver failure
Tertiary medication for motor fluctuations; limited in use to those who have exhausted other treatment options
MAO inhibitors
Other medications
Medication
Available Doses
Initial Dosing
Side Effects
Indications
Interactions
Amantadine
(Symmetrel®)
100 mg
100 mg 2-3 X/day
Dizziness, weakness, dry mouth, constipation, skin blotches
Secondary medication for tremor and muscle rigidity
Cogentin® (benztropine), Disipal® (orphenadrine), Sinemet® (levodopa), Artane® (trihexyphenidyl), amphetamines, alcohol
Rivastigmine tartrate
(Exelon®)
1.5mg3mg4.5mg6mg Patch 10 (9.5 mg/24 hrs) Patch 20 (17.4 mg/24 hrs)
1.5mg 2X per day
Nausea, vomiting, loss of appetite, weight loss
Dementia associated with PD
No known drug-drug interactions

Over-the-Counter Medications
Although there is little conclusive scientific information on natural supplements, researchers are examining several substances to evaluate their effectiveness on slowing Parkinson's disease progression and managing its symptoms. Nutritional supplements are not regulated with the same approval method for prescription drugs, and people with Parkinson's should discuss any medications (prescription or over-the-counter) with a doctor before taking them to avoid potentially dangerous interactions.
Since there is evidence relating oxidative damage of nerve cells to PD, some researchers are studying antioxidants. A 2002 study focused on the potential antioxidant Coenzyme Q10 (CoQ10), which is believed to play an important role in mitochondria health. Mitochondria are the "powerhouses" of a cell, and some scientists think that abnormalities of mitochondrial function may play a role in Parkinson's. A recent clinical trial found that high doses of CoQ10 (up to 1200 mg) showed a possible slowing of disease progression in a small number of subjects. These results are promising but researchers have not studied CoQ10 extensively enough to recommend it to Parkinson's patients.
Scientists have also examined Vitamin E, Vitamin C and health foods to evaluate their oxidative properties. Vitamin E can fight damage in the brain caused by free radicals, and has been suggested to lower the risk of PD. However, researchers conducted an extensive and thorough study over 10 years ago ( the DATATOP trial) and failed to find any evidence that Vitamin E slows the progression of Parkinson's or manages symptoms. Since Vitamin E has very few side-effects, many Parkinson's patients continue to take it in high doses of 400 IU or more. Researchers are also examining health foods, such as fermented papaya and blueberries, to determine their role in slowing nerve cell death. Scientists are optimistic about the research but do not have enough conclusive data to recommend these supplements to treat Parkinson's disease.
Creatine is another compound of scientific interest that increases levels of phosphocreatine (an energy source in muscle and the brain). The National Institute of Neurological Disorders and Stroke (NINDS) is conducting a multi-center clinical trial to determine if creatine protects against nerve cell damage. Researchers have also studied a compound called glutathione to determine its effect on nerve cell metabolism and its power as an antioxidant. Both compounds show promise, but the appropriate dosing is unclear, as are the most effective method of administration, side-effects and long-term dosing risks.
Although nutritional supplements have shown some promising results in preliminary studies, it is important to remember that there is not sufficient scientific data to recommend them for Parkinson's disease. Over-the-counter medications can and do have side-effects and interactions with other drugs. They tend to be expensive and they vary with different manufacturers. Before taking any over-the-counter medication, it is very important that a person with Parkinson's discuss the addition of these supplements with their doctor.

Managing Your Medications
Taking medications for Parkinson's disease is straightforward for most people during the first several years of treatment. The effect of each dose usually lasts well into the period after the next dose, and delaying a dose even by an hour does not disrupt the effective coverage of symptoms.
The situation is different for many people who have been taking Parkinson's medications for several years (usually five years or more). In these stages of the disease, effective relief from symptoms can depend on carefully following a regular schedule of medication doses. There are several ways for Parkinson's patients to achieve the greatest possible benefit from their medications. Since in the more advanced stages of Parkinson's disease the symptoms are often unpredictable and can fluctuate daily, it is important to take an active role in finding a routine that is tailor-made and makes the most of the medicine. A person should ask themselves how long it takes for a pill to work and how long its positive effects remain. Note if the pills should be taken with food, between meals or on an empty stomach and how it feels when medication starts to wear off. The answers to these questions can help explain how the pill works and possibly increase "on" time.
People with Parkinson's must know what medications they are taking, when and why. This can be achieved by working with one pharmacist. A pharmacist will note all of the medications a person is taking in a computer, which safeguards them from any interactions. Another way to obtain this information is by constructing a medication chart (to download a sample chart, click here). The chart should include information such as the medication's name, the strength and a time schedule of when it should be taken. This chart can help the patient and/or caregiver easily recognize the medication and decreases the chance of a missed dose. People with Parkinson's can also share this chart with a neurologist to make sure both parties are clear on what is being taken and why.
Organization is a key factor in getting the most from Parkinson's medications. Since several medications will probably be taken at different times of the day, a timing device can be crucial in avoiding missed doses. Talking systems, beeping watches and multi-alarm timers are widely available. These systems can be both discreet and loud, with vibrating and sound features. In addition, pill dispensers organize pills by day and time to eliminate carrying several large prescription bottles.
These tips can help people with Parkinson's manage their medications and develop a personal routine to suit their lifestyles and needs.

Saving on Medications
The substantial cost of Parkinson's medications is often a burden for many people. Several pharmaceutical companies feature programs to help eligible applicants reduce their medication costs. These programs are usually limited to the company's brand-name medications, and will most likely have specific requirements including age and income. Visit drug makers' websites or call the company's toll-free hotline for more information on money-saving assistance programs. These programs are often best accessed with the help of your doctor and healthcare team.
Researching the various drug assistance programs can be a great deal of work. An organization called The Partnership for Prescription Assistance (PPRA) may be able to help navigate these systems to find the best options. PPRA brings together America's pharmaceutical companies, doctors, other health care providers, patient advocacy organizations and community groups to help qualifying patients who lack prescription coverage get the medicines they need through public or private programs. PPRA's website, http://www.pparx.org/, provides access to more than 275 public and private patient assistance programs, including more than 150 programs offered by pharmaceutical companies. PPRA can also be contacted by calling (888) 477-2669.

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