Levodopa medicines for Parkinson's disease

Examples

Generic Name	Brand Name
levodopa/carbidopa	Sinemet, Sinemet CR [controlled-release]
levodopa/benserazide	Prolopa

How It Works

Levodopa is a medicine that the brain converts to dopamine.

Carbidopa is a medicine (called a decarboxylase inhibitor) that, when taken with levodopa, helps prevent the levodopa from converting to dopamine outside the brain. The combination of carbidopa and levodopa has several benefits:

• It allows more levodopa to get to the brain and thus increases the supply of dopamine in the brain.
• It decreases side effects caused by increased dopamine levels outside the brain by reducing the supply of “free” dopamine outside the brain. (Increased dopamine levels outside the brain can result in side effects such as nausea, vomiting, and low blood pressure.)
• It enhances the effect of levodopa, so that less levodopa is needed to control symptoms.

Why It Is Used

Levodopa is a medicine used to control symptoms of Parkinson's disease and may be used at all stages of the disease. Although in the past levodopa was often the first drug used to treat people who were newly diagnosed with Parkinson's disease, more experts are recommending that initial treatment begin with a dopamine agonist. Levodopa can then be added when the dopamine agonist no longer controls symptoms adequately. Treatment with levodopa (or any medicine) should be started only when symptoms start to significantly affect a person's work or daily activities.¹

Close monitoring is required for people with certain medical conditions who are taking levodopa. These medical conditions include:

• Heart and blood vessel disease.
• Hormone problems.
• Mental illness.
• Kidney or liver disease.
• Glaucoma.
• Open sores in the stomach lining (stomach ulcer).
• Skin cancer (melanoma) or undiagnosed skin sores.

Levodopa/carbidopa may interfere with certain medicines that are used to treat depression.

How Well It Works

Levodopa is the most effective medicine for relieving symptoms of Parkinson's disease. It helps reduce tremor, stiffness, and slowness and helps improve muscle control, balance, and walking. It does not affect freezing, dementia, or problems with involuntary (autonomic) functions, such as constipation, urinary problems, impotence, or pain.²

Levodopa does not slow the disease process, but it improves muscle movement and delays severe disability. The use of levodopa allows people with Parkinson's disease to remain independent and able to function for longer periods of time. However, the majority of people taking levodopa develop complications caused by long-term levodopa therapy within 5 to 10 years. Movement problems (motor fluctuations) are the most common and troublesome complication.²

Side Effects

Levodopa can cause many side effects, including:

• Sudden, jerky, uncontrollable movements (dyskinesias).
• Loss of appetite.
• Nausea and vomiting with or without stomach pain. Levodopa can be taken after meals at first to reduce nausea, but as your body adjusts to the medicine and nausea stops, it is most effective when it is taken 30 minutes before meals or 2 hours after meals (on an empty stomach).
• Drooling and difficulty swallowing.
• Increased hand tremor.
• Headache, dizziness, or fainting.
• Numbness or weakness.
• Grinding of teeth.
• Confusion, hallucinations (seeing or hearing things that aren't really there), delusions, and nightmares. These are more common in older adults.
• Insomnia, agitation, anxiety, malaise, fatigue, and euphoria.
• Decreased blood pressure when rising from a seated position (orthostatic hypotension).

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Experts recommend the use of a dopamine agonist instead of levodopa for most people who have been recently diagnosed with Parkinson's disease. Although dopamine agonists are less effective than levodopa, they often control symptoms of early Parkinson's disease adequately, delaying the need for levodopa and the development of levodopa-related motor fluctuations.

As motor fluctuations become more severe, it may be necessary to add another type of medicine to the person's levodopa treatment. Options include:

• A dopamine agonist (such as bromocriptine, pramipexole, or ropinirole), which may be used in combination with levodopa to reduce the amount of levodopa needed and reduce side effects and motor fluctuations.
• A catechol O-methyltransferase (COMT) inhibitor (such as entacapone), which may be used if adding a dopamine agonist to levodopa treatment does not control symptoms and reduce motor fluctuations. Sometimes a COMT inhibitor may be used from the outset of treatment with levodopa, rather than waiting until motor fluctuations develop.
• A monoamine oxidase (MAO) inhibitor (such as rasagiline or selegiline), that prolongs the effects of dopamine in the brain by preventing its breakdown. Selegiline may be prescribed in some cases, but it is not commonly used.

Treating Parkinson's disease with a combination of the medicines listed above, rather than just increasing the levodopa dose, may produce a more consistent, longer-lasting effect on symptoms and may result in fewer motor fluctuations. A neurologist who is experienced in treating Parkinson's disease is usually best qualified to make these medicine adjustments.

Using carbidopa or benserazide with levodopa reduces side effects such as nausea, decreased appetite, and decreased blood pressure. The controlled-release form of levodopa (Sinemet CR) also may cause less nausea. Different people will respond to levodopa/carbidopa or levodopa/benserazide for different lengths of time. However, some people begin to develop side effects that limit the medicine's effectiveness. The effect of levodopa depends in part on how much food is in the stomach and the amount of time between taking the medicine and eating a meal.

Tremor may be less responsive to levodopa, but it often improves to some degree.

Because of occasional serious side effects, people taking levodopa/carbidopa should have regular medical evaluations of their liver, blood, kidneys, and heart. Abruptly stopping levodopa can cause serious problems and should be avoided.

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Author:	Douglas Dana Monica Rhodes	Last Updated: February 12, 2007
Medical Review:	Anne C. Poinier, MD - Internal Medicine E. Gregory Thompson, MD - Internal Medicine Colin Chalk, MD, CM, FRCPC - Neurology
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