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Levodopa

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®.

There are many different preparations and strengths of carbidopa/levodopa, including long-acting forms, a combined long and short-acting capsule called Rytary®, a formulation that dissolves in the mouth without water, called Parcopa®, and a combined formulation that includes the COMT inhibitor entacapone, called Stalevo®.

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

Carbidopa/levodopa remains the most effective drug to treat PD. The addition of carbidopa prevents levodopa from being converted into dopamine prematurely in the bloodstream, allowing more of it to get to the brain. Therefore, a smaller dose of levodopa is needed to treat symptoms.

Some people with PD have been reluctant to take it, believing it to be a last resort. But most neurologists agree that delaying treatment too long is unwise and may put a person with PD at risk for falling and decreased optimal, consistent symptom benefit. 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.

Unfortunately, with time, 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. It is unclear whether this is a symptom of starting the medication at an advanced stage of PD or whether it is related to prolonged use of levodopa (although there is some published evidence for the former explanation). 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. The same drugs that interact with carbidopa/levodopa and entacapone interact with Stalevo®.

What are the 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 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. When added, carbidopa enables a much lower dose of levodopa (80 percent less) and helps reduce the side effects of nausea and vomiting. Pills containing both drugs are often labeled “carbidopa-levodopa,” with the active components listed in alphabetical order.
  • 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.
  • Carbidopa-levodopa tablets are available in immediate-release and slow-release forms as well as dissolvable tablets that are placed under the tongue.
  • Carbidopa-levodopa immediate/extended release combination capsules (Rytary™) maintain levodopa concentrations longer than the immediate-release or other available oral levodopa formulations. Following an initial peak at about one hour, plasma levodopa concentrations are maintained for about four to five hours before declining. Clinical trials indicate that patients with motor fluctuations on other oral carbidopa-levodopa products may be able to switch to Rytary™ and experience a reduction in “off” time while requiring fewer medication administrations. Carbidopa/levodopa can be taken with or without food, but high fat meals may delay absorption. Dosages are not interchangeable with dosages other carbidopa-levodopa products. For more information relating to prescribing Rytary™, please see How to Dose Carbidopa and Levodopa Extended-Release Capsules (Rytary), by Dr. Robert A. Hauser of the University of South Florida, a Center of Excellence.
  • Carbidopa/levodopa is also now available via a dopamine intestinal infusion pump (DUOPA™), which provides 16 continuous hours of carbidopa and levodopa for motor symptoms. The small, portable infusion pump delivers carbidopa and levodopa directly into the small intestine. In a clinical trial, the amount of “on” time without troublesome dyskinesia was better in the pump group when compared to the placebo group (4.1 vs. 2.2 hours). One of the major drawbacks to the pump approach is the need for a percutaneous gastrojejunostomy (a small feeding tube). For more information relating to prescribing Duopa™, please see Carbidopa/Levodopa Enteral Suspension (Duopa) by Rajesh Pahwa, MD, and Kelly Lyons, PhD, of the University of Kansas, a Center of Excellence.

Common Side Effects

  • Nausea
  • Vomiting
  • Loss of appetite
  • Lightheadedness
  • Lowered blood pressure
  • Confusion
  • Dyskinesia (if used as a long-term therapy; between three to five years)
    • 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

Eating Proteins with Levodopa/Sinemet*

  • 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.
  • Take the Sinemet® along with non-protein foods.
  • 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 Sinemet because of nausea, upset stomach, you may need to actually take it with food.

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.

 

Medication

Available Doses

Initial Dosing

Side Effects*

Indications

Interactions

Carbidopa/
Levodopa

(Sinemet®)

10/100 mg

25/100 mg

25/100 mg
1/2-1 tablet
2-3X/day

Nausea, vomiting, falling blood pressure upon standing, worsening of glaucoma, dyskinesia, hallucination, psychosis, low blood pressure, confusion, dyskinesia, dry mouth, dizziness

Treatment of motor symptoms in early and advanced PD

Dopamine receptor antagonists — certain psychiatric medications and anti-nausea drugs, nonselective monoamine oxidase inhibitors. Antacids and proteins taken in close proximity to the drug may reduce absorption.

Carbidopa/
Levodopa

Orally disintegrating tablet

(Parcopa®)

10/100 mg

25/100 mg

25/250 mg

25/100 mg
2-3X/day

Nausea, vomiting, falling blood pressure upon standing, worsening of glaucoma, dyskinesia, hallucination, psychosis, low blood pressure, confusion, dyskinesia, dry mouth, dizziness

Treatment of motor symptoms in early and advanced PD

Dopamine receptor antagonists — certain psychiatric medications and anti-nausea drugs, nonselective monoamine oxidase inhibitors. Antacids and proteins taken in close proximity to the drug may reduce absorption.

Carbidopa/
Levodopa

Controlled release

(Sinemet CR®)

25/100 mg

50/200 mg

25/10.0 mg 2X/day

50/200 mg 2X/day

Nausea, vomiting, falling blood pressure upon standing, worsening of glaucoma, dyskinesia, hallucination, psychosis, low blood pressure, confusion, dyskinesia, dry mouth, dizziness

Treatment of motor symptoms in early and advanced PD

Dopamine receptor antagonists — certain psychiatric medications and anti-nausea drugs, nonselective monoamine oxidase inhibitors. Antacids and proteins taken in close proximity to the drug may reduce absorption.

Carbidopa/
Levodopa/
Entacapone

(Stalevo®)

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

 

12.5/50/200 mg

Nausea, vomiting, falling blood pressure upon standing, worsening of glaucoma, dyskinesia, hallucination, psychosis, dyskinesia, 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

Dopamine receptor antagonists — certain psychiatric medications and anti-nausea drugs, nonselective monoamine oxidase inhibitors. Antacids and proteins taken in close proximity to the drug may reduce absorption.

Carbidopa/
Levodopa

Extended-release capsules

(Rytary™)

23.75 mg / 95 mg

36.25 mg / 145 mg

48.75 mg / 195 mg

61.25 mg / 245 mg

For those first starting carbidopa/
levodopa, 36.25mg/145 mg 3 times daily; for those converting from another form of carbidopa/
levodopa, calculation based on prior therapeutic dose.

Nausea, vomiting, falling blood pressure upon standing, worsening of glaucoma, dyskinesia, hallucination, psychosis, dizziness, headache, insomnia, abnormal dreams, dry mouth, dyskinesia, anxiety, constipation, vomiting, and orthostatic hypotension Cardiovascular events possible in people with history of cardiovascular disease; hallucinations or psychosis: dyskinesia. May cause falling asleep during activities of daily living.

Secondary course of treatment for people with Parkinson’s disease who are experiencing disabling wearing-off periods.

Dopamine receptor antagonists — certain psychiatric medications and anti-nausea drugs, nonselective monoamine oxidase inhibitors. Antacids and proteins taken in close proximity to the drug may reduce absorption.

Carbidopa/
Levodopa

Enteral Suspension

(Duopa™)

(This is a gel formulation of the drug that requires a surgically-placed tube. Learn more here)

Carbidopa/
Levodopa 4.63/20 mg per mL of suspension (about 25/100 mg per teaspoon).

Dosing depends on conversion from the prior dose of carbidopa/
levodopa tablets to an equivalent daily dose of the suspension which is then delivered to the small intestine using a surgically inserted tube and a pump. The medication is pumped continuously over 16 hours each day.

Nausea, vomiting, falling blood pressure upon standing, worsening of glaucoma, dyskinesia, hallucination, psychosis. Complications of the device or surgery (movement or dislocation of the tube, infection, redness at the insertion point, pancreatitis, bleeding into the intestines, air or infection in the abdominal cavity, failure of the pump,) ankle swelling, high blood pressure, upper respiratory tract infection, mouth or throat pain, lung problems. May cause falling asleep during daily activities dyskinesias. hallucinations/
psychosis/
confusion; depression and suicidality; and damage to peripheral nerves.

For the treatment of motor fluctuations in advanced Parkinson's disease.

Duopa is contraindicated for individuals taking nonselective monoamine oxidase (MAO) inhibitors. If taken with selective MAO-B inhibitors, it may cause orthostatic hypotension. If taken with antihypertensive drugs, it may cause symptomatic postural hypotension. Dopamine D2 receptor antagonists, isoniazid, iron salts, and high-protein diet may reduce drug effectiveness of Duopa.

* 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.

Page reviewed by Dr. Chauncey Spears, Movement Disorders Fellow at the University of Florida, a Parkinson’s Foundation Center of Excellence.

 

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