Levodopa

woman taking pills

The most potent medication for Parkinson’s disease (PD) is levodopa. Its development in the late 1960s represents one of the most important breakthroughs in the history of medicine. Plain levodopa produces nausea and vomiting. It is combined with carbidopa to prevent this side effect. The well-known combined carbidopa/levodopa name brand formulation is called Sinemet®. Carbidopa/levodopa remains the most effective drug to treat PD. In addition to helping prevent nausea, carbidopa prevents levodopa from being converted into dopamine prematurely in the bloodstream, allowing more of it to get to the brain.

Forms of Levodopa

It is important that people with PD are aware which carbidopa/levodopa preparation they are taking because there are so many different pill sizes, strengths and manufacturers. Be careful when renewing prescriptions at the pharmacy or when receiving medications in the hospital because the accidental substitute of a different formulation may lead to an overdose or underdose.

Carbidopa/levodopa Immediate Release Tablets (Sinemet)

Available Doses: 10/100 mg, 25/100 mg, 25/250 mg
Typical Treatment Regimen: 150–1000 mg of levodopa total/day (divided 3-4 times)
Common Side Effects: Low blood pressure, nausea, confusion, dyskinesia
Indications for Usage: Monotherapy or combination therapy for slowness, stiffness and tremor

Carbidopa/levodopa Controlled Release Tablets (Sinemet CR*)

*Sinemet CR is no longer being produced, but the generic forms continue to be available

Available Doses: 25/100 mg, 50/200 mg
Typical Treatment Regimen: 400-1600 mg of levodopa in divided doses, depending on daily need
Common Side Effects: Low blood pressure, nausea, confusion, dyskinesia
Indications for Usage: Monotherapy or combination therapy for slowness, stiffness and tremor

Carbidopa/levodopa orally disintegrating tablets (Parcopa)

Available Doses: 10/100 mg, 25/100 mg, 25/250 mg
Typical Treatment Regimen: 150–1000 mg of levodopa total/day (divided 3-4 times)
Common Side Effects: Low blood pressure, nausea, confusion, dyskinesia
Indications for Usage: Monotherapy or combination therapy for slowness, stiffness and tremor, plus need for dissolvable medication in mouth especially if swallowing is impaired

Carbidopa/levodopa enteral Suspension (Duopa)

This form of Carbidopa/levodopa is delivered through a surgically implanted tube in small intestine rather than in pill form. This increases “on” time without troublesome dyskinesia, but is not available until surgery is performed.

Available Doses: 4.86/20 per ml.
Typical Treatment Regimen: Up to 2000 mg of levodopa over 16 hours
Common Side Effects: Low blood pressure, nausea, confusion, dyskinesia
Indications for Usage: For the treatment of motor fluctuations in patients with advanced Parkinson’s disease

Carbidopa/levodopa Extended Release capsules (Rytary)

This form of Carbidopa/levodopa contains beads of both medications that dissolve and are absorbed at different rates. This can improve “on” time while requiring fewer medication doses. Dosages of carbidopa/levodopa ER capsules are not interchangeable with dosages of other carbidopa/levodopa products.

Available Doses: 23.75/95 mg, 36.25/145 mg, 48.75/195 mg, 61.25/245 mg
Typical Treatment Regimen: 855-2340 mg of levodopa total daily dose
Common Side Effects: Low blood pressure, nausea, confusion, dyskinesia
Indications for Usage: Monotherapy or adjunct therapy for slowness, stiffness and tremor.

Carbidopa/levodopa/entacapone tablets (Stalevo)

This is a combination drug which includes entacapone and levodopa in one pill. It is more convenient compared with carbidopa/levodopa + entacapone taken separately.

Available Doses: 12.5/50/200 mg, 18.75/75/200 mg, 25/100/200 mg, 31.25/125/200 mg, 37.5/150/200 mg, 50/200/200 mg
Typical Treatment Regimen: 150-1600 mg of levodopa total daily dose, depending on daily need. Max 8 tab/day
Common Side Effects: Low blood pressure, nausea, confusion, dyskinesia, diarrhea and discolored urine
Indications for Usage: Replacement for carbidopa/ levodopa, for motor fluctuations (benefit of entacapone)

Common Side Effects for levodopa

  • Nausea
  • Vomiting
  • Loss of appetite
  • Lightheadedness
  • Lowered blood pressure
  • Confusion
  • Dyskinesia

Such side effects can be minimized with a low starting dose when initiating treatment with any antiparkinsonian drug and increasing the dose slowly to a satisfactory level. This is particularly helpful in elderly people with PD whose tolerance for medications is often less than in younger persons. Taking drugs with meals can also reduce the frequency and intensity of gastrointestinal side effects. For those patients who have persistent nausea or vomiting, adding extra carbidopa (Lodosyn) to each dose of carbidopa/levodopa can help.

Understanding Dyskinesias
People who use levodopa long term may experience dyskinesia at some point, usually three to five years after starting the medication.

The term dyskinesia describes involuntary, erratic, writhing movements of the face, arms, legs, and/or trunk, which usually occur one to two hours after a dose of levodopa has been absorbed into the bloodstream and is having its peak clinical effect.

Uncommon Side Effects

  • Sleepiness, sudden onset sleep

Special Considerations 

Nutrition and Levodopa/Sinemet

Most people have no problem taking medications with meals, but some experience less benefit if they take carbidopa/levodopa with a stomach full of protein (including meats, cheeses and other dairy products. When this occurs, it is recommended to only take carbidopa/levodopa along with non-protein foods.

With more advanced PD, it is best to take Sinemet® 30 to 60 minutes before eating a meal. This allows for quick absorption before food can interfere.

Managing Nausea caused by Levodopa/Sinemet

Ginger tea is a good choice for many people, because it often “settles the stomach”.

A graham or soda cracker along with ginger tea may help and are low in protein so should not interfere with the absorption of Sinemet®.

If you cannot tolerate carbidopa/levodopa because of nausea, upset stomach, you may need to take it with food.

Delaying Use of Carbidopa/levodopa

Some people with PD have been reluctant to rely on carbidopa/levodopa, believing it to be a last resort. But most neurologists agree that delaying treatment too long is unwise, and expert practitioners in the Parkinson’s Foundation’s Parkinson’s Outcomes Project report utilizing levodopa more than any other drug for Parkinson’s therapy. There is no reliable data that levodopa speeds disease progression or produces damage to brain cells.  Levodopa is extremely beneficial to the people with PD and can dramatically improve quality of life.

The decision about when to start carbidopa/levodopa is different for every person with PD and requires consideration of potential benefits, risks and the availability of alternatives.

An important thing to consider is that, with time, patients can experience dyskinesias, which are spontaneous, involuntary movements, from extended years of carbidopa/levodopa use. Additionally, "on-off" periods are common in patients who have been on carbidopa/levodopa for many years. “On-off” periods are when the medication will suddenly and unpredictably start or stop working.

Quick Facts

  • The drug levodopa is synthesized in the brain into dopamine. It is the most important first-line drug for the management of Parkinson's.
  • Levodopa in pill form is absorbed in the blood from the small intestine and travels through the blood to the brain, where it is converted into dopamine, needed by the body for movement.
  • Levodopa is almost always given in combination with the drug carbidopa, which prevents the nausea that can be caused by levodopa alone. Carbidopa is also a levodopa enhancer.
  • Carbidopa-levodopa is delivered in many forms, including immediate-release and slow-release pills or capsules as well as in gel form and through an inhaler.

Disclaimers:

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.

Speak to the treating physician immediately if any side effects are experienced. For a complete description of each drug and its possible side effects, please request a “package insert” from your pharmacist for each drug 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.

Caution: PD medications may have interactions with certain foods, other medications, vitamins, herbal supplements, over the counter cold pills and other remedies. Anyone taking a PD medication should talk to their doctor and pharmacist about potential drug interactions.

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