Medications

There are many medications available to treat the symptoms of Parkinson’s, although none yet that actually reverse the effects of the disease.

It is common for people with PD to take a variety of these medications – all at different doses and at different times of day - in order to manage the symptoms of the disease.

While keeping track of medications can be a challenging task, understanding your medications and sticking to a schedule will provide the greatest benefit from the drugs and avoid unpleasant “off” periods due to missed doses.

Read below to understand each type of medication, its dosing and side effects.

Find out more about:

• Prescription Medications
• Over-the-Counter Medications

Prescription Medications

Although there are general guidelines that doctors use to choose a treatment regimen, each person with PD 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.

Currently, the types (“classes”) of medications available to treat Parkinson’s on the market include:

• Carbidopa/Levodopa therapy
• Dopamine Agonists
• Anticholinergics
• MAO-B Inhibitors
• COMT Inhibitors
• Other medications

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 people with PD 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 18.75/75/200 mg 31.25/125/200 mg 37.5/150/200 mg 50/200/200 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®), which is also available in an extended release tablet (RequipXL®).  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. In March 2008, UCB Inc., the manufacturer of Neupro® (rotigotine transdermal system), recalled that drug because of concern of a deviation from approved product standards that has apparently reduced the effectiveness of the treatment. Read more about this recall.

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/24hrs 4 mg/24hrs 6 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
Ropinirole extended-release tablets (Requip® XL™)	(All doses taken once a day) 2 mg 4 mg 6 mg 8 mg 10 mg 12 mg 14 mg 16 mg 18 mg 20 mg 22 mg 24 mg	2 mg taken once a day for 1 to 2 weeks, followed by increases of 2 mg/day at 1 week or longer intervals as appropriate	Nausea, dizziness, drowsiness, or sleepiness, headache, sudden uncontrolled movements (dyskinesia), abdominal pain/discomfort, hallucination, constipation and increase or decrease in blood pressure and heart rate. Patients should also tell their doctor if they experience new or increased gambling, sexual, or other intense urges while taking Requip XL. Requip XL may increase the side effects of levodopa.	First course of treatment alone or with levodopa; mimics dopamine to manage major symptoms. 24-hours continuous delivery of the medicine to provide smooth blood levels	Inhibitors (e.g., ciprofloxacin, fluvoxamine) or inducers (e.g., omeprazole or smoking) of CYP1A2 higher doses of estrogen, usually associated with hormone replacement therapy (HRT), dopamine antagonists, such as neuroleptics (e.g., phenothiazines, butyrophenones, thioxanthenes) or metoclopramide.

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 HCI Orally 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®)	0.5mg 1mg	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®)	1.5mg 3mg 4.5mg 6mg 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

* Please note that the side effects listed in the tables that accompany each class of medication are the most commonly experienced. Not all individuals 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.

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.  It 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.