Carbidopa/Levodopa: Side Effects, Dosages, and More

Carbidopa/Levodopa: Answers to Frequently Asked Questions

Loss of neurons in the brain that use dopamine to communicate is one of the hallmark features of Parkinson’s disease (PD), causing slowness, stiffness, tremor, and balance problems. Replacing the brain’s dopamine is therefore one of the key treatment strategies to help improve the motor symptoms of PD. Dopamine itself does not cross the blood-brain barrier and therefore can’t be used to treat PD. Instead, levodopa, a precursor of dopamine, which does cross the blood-brain barrier is used. If levodopa is ingested by itself however, it breaks down in the bloodstream before it crosses into the brain, so levodopa is typically ingested with another medication that stops it from breaking down. In the US, the combination of carbidopa/levodopa is used. When levodopa is taken with carbidopa, much lower doses of levodopa can be consumed and side effects such as nausea are minimized. Carbidopa/levodopa is the mainstay of treatment for PD and is the most effective medication available for PD. APDA research funding played a role in the discovery of levodopa for PD treatment, when we funded the work of Dr. George C. Cotzias back in the 1960s.

Despite its common and widespread use as a treatment for PD, our readers often have questions about carbidopa/levodopa therapy. This week I will address some of these common questions that have been sent to us by readers like you. (If you have questions or a blog topic to suggest, let us know!)

General Questions on Carbidopa/Levodopa

Q: Are there any negatives to consider if I want to postpone starting carbidopa/levodopa? The only symptom that I currently notice is tremor which affects my non-dominant hand and does not affect my daily functioning. I have no problems with my walking or balance, and I exercise every day.

A: In general, there is no downside to postponing levodopa to treat a tremor that is not affecting function. However, there may be subtle other symptoms that are being caused by PD that you are not as aware of. For example, it could be causing you to move slower than you would have. It may therefore be affecting your ability to exercise effectively up to your maximal capabilities. Because exercise may be neuroprotective in PD, if you are not able to exercise maximally when untreated, then you should consider starting medication for that reason.

Q: Does carbidopa/levodopa treat Parkinson’s progression?

A: Carbidopa/levodopa unfortunately does not change the progression of PD as far as we are aware, it just treats the symptoms. It is best at treating the slowness and stiffness of PD, but in many cases, treats the tremor as well.

Q: Does carbidopa/levodopa treat the tremor associated with Parkinson’s?

A: The answer is, sometimes. In many people, carbidopa/levodopa is very effective in controlling the tremor of PD. Yet for some people, carbidopa/levodopa does not seem to help the tremor much. Because tremor is present at rest and often goes away when the person is using the limb, a tremor can be more of a nuisance than a source of disability. For this reason, many movement disorders specialists will focus on whether the carbidopa/levodopa is helping the symptoms that do cause the disability, namely stiffness and slowness. It should also be noted, that for people whose tremor does not improve with medication, deep brain stimulation (DBS) can be considered as a treatment option.

Q: There are so many different versions of carbidopa/levodopa. Can you explain the differences?

A: There are indeed many formulations of carbidopa/levodopa available. This is very beneficial because it gives doctors many treatment options as they try to find the best formulation for each particular patient. Below are the brand names of the different carbidopa/levodopa options available:

• Sinemet – immediate release, the original formulation
• Sinemet CR – a formulation designed to be controlled release (CR) and last longer than a dose of Sinemet
• Stalevo – a combination medication of carbidopa/levodopa and entacapone, designed to last longer than carbidopa/levodopa alone
• Rytary – a formulation designed to be released more slowly from the stomach than regular Sinemet
• Crexont – another formulation designed to be released more slowly from the stomach than regular Sinemet
• Duopa – a gel that is continuously pumped into the small intestine during waking hours
• Parcopa – a formulation that dissolves in the mouth. Although it is absorbed in the gut, the fact that it does not have to be broken down in the stomach means that onset of action of the medication is somewhat quicker than regular Sinemet
• Inbrija – an inhalation formulation (containing only levodopa) designed for quicker onset of action, to be used as a rescue dose if a scheduled dose is not effective enough

Learn more about Parkinson’s medications

Side Effects of Carbidopa/Levodopa

Q: I am newly diagnosed with Parkinson’s disease and just started on carbidopa/levodopa. However, I feel that the medication is making me feel worse than my original symptoms. Can carbidopa/levodopa make PD worse?

A: Carbidopa/levodopa can definitively have an array of side effects such as nausea, fatigue, and dizziness. Your neurologist will try to find a dose that helps your PD symptoms, but does not cause side effects. Carbidopa/levodopa is probably not making your PD worse per se, but it sounds like overall, you are feeling worse on this dose than you did on no medication. You should discuss this problem with your neurologist who may consider changing your medication formulation or dosage.

Q: My husband has had PD for about 10 years. Lately he has been having significant body, arm, and finger movements after a dose of levodopa which improve just before the next dose. Is there any treatment for these abnormal movements?

A: It sounds like these movements may be levodopa-induced dyskinesias, a side effect of the levodopa, which causes extraneous, dance-like movements. The first question to ask is: are the movements bothering your husband or causing him to be more imbalanced? If he is not bothered by the movements and they are not interfering with his function, then it would not be wrong to leave his carbidopa/levodopa dose as is. If he is bothered by the movements, then his neurologist may consider lowering his carbidopa/levodopa, but only if he can tolerate them being lowered. He may need his current dose to achieve mobility. If his carbidopa/levodopa can’t be lowered and dyskinesias are bothersome, there are two medications that can be tried to treat levodopa-induced dyskinesias – amantadine and amantadine CR. Your husband’s neurologist may consider starting one of these medications to help control the movements.

Q: I was advised to take my carbidopa/levodopa at least 30 minutes after a meal. However, this caused a lot of nausea and stomach upset for me, so I now take the medication with meals which is much better for me. Is this OK to do?

A: There is no problem with taking carbidopa/levodopa with meals except for possibly reduced absorption – usually only in the presence of dietary protein and even this is only in a subset of patients. If you find that the medication works well for you when you take it with food, then you can continue doing what you are doing. It is always wise to talk to your doctor about any issues you’re having with your medication and discuss any potential changes in the dosing or timing.

Q: I noticed that I have increased trouble with my symptoms when I eat a meal containing protein. How do I adjust my diet to accommodate this?

A: Dietary protein can interfere with carbidopa/levodopa absorption in some people. This is known as the “protein effect.” The two ways to adjust your diet is to:

• Ingest your daily protein at the end of the day, so that you do not have the protein effect during your active time
• Divide your protein evenly throughout the day – that way, the medication absorption should theoretically be similar throughout the day. This begs the question of how to do that – how to estimate how much protein is in each food that you want to eat in order to spread the protein out evenly. For this, I refer you to one of the APDA webinars discussing nutritional issues related to PD, including the protein effect and how to estimate the protein in different foods. Nutrition issues are covered in the second half of the webinar.

Carbidopa/Levodopa Dosage

Q: I am on carbidopa/levodopa 25/100. What do the numbers 25 and 100 mean?

A: You are taking a combination pill of carbidopa 25 mg and levodopa 100 mg. Without the carbidopa, the levodopa would be broken down in the body before it got a chance to make it into the brain. The carbidopa acts to inhibit the enzyme that breaks down levodopa. There are various formulations of carbidopa/levodopa and your doctor will prescribe the dosage and formulation that is best suited to your particular situation.

Q: What is the maximum dose of carbidopa/levodopa that can be used for PD?

A: The maximum dosage for a particular person is usually the dose at which side effects interfere with the benefits of the medication. Different people therefore will have different maximum dosages tolerated. Some people tolerate and benefit from very large doses of levodopa – greater than 2,000 mg or even higher.

In order to determine the right dose for you (which means how much medication to take in one dose, how many doses to take a day and how much time should be between each dose), you and your physician should discuss:

• what (if any) positive effects that carbidopa/levodopa has on your symptoms
• how long it takes for a dose to take effect
• how long the effects of a dose last for you
• the side effects that the medication is causing (which includes but is not limited to: nausea, low blood pressure, hallucinations, fatigue, and carbidopa/levodopa-induced dyskinesias.) Remember, each potential side effect only occurs in a subset of people on the medication

Based on the answers to these questions, your dose can be adjusted.

Q: For how many years can levodopa be effective?

A: Levodopa is typically effective for as long as a person has PD. However, over time, people with PD tend to need to take more levodopa. The reason for this is that as progression of PD takes place, there are fewer dopaminergic neurons in the brain that can produce their own dopamine. A person with PD tends to need more medication containing dopamine over time to compensate for these changes. Therefore, needing more carbidopa/levodopa over time does not mean that the medication is no longer working, it means that the disease is changing.

In addition, as PD progresses, a person may start to develop more symptoms that are not responsive to carbidopa/levodopa. Carbidopa/levodopa best treats the motor symptoms of PD – mostly slowness, stiffness, and tremor. Some motor symptoms, such as balance problems, do not respond as well to carbidopa/levodopa. Non-motor symptoms including fatigue, depression, sleep problems, cognitive difficulties, variations in blood pressure, urinary problems, and constipation, also do not respond to carbidopa/levodopa and may cause more disability over time than motor problems. The perception may be that over time, carbidopa/levodopa is not effective, when in fact new symptoms developed that carbidopa/levodopa can’t treat.

Q: I have had PD for about 10 years. Over the years, the length of time that a particular dose of carbidopa/levodopa works has gotten shorter. One dose used to last five hours, but recently, it lasts closer to three hours. In addition, sometimes my dose does not work at all. What is going on?

A: This shifting response to medication is known as motor fluctuations and can be a very significant challenge in the treatment of PD as the disease progresses. There are many strategies that your doctor can use to try to lengthen a dose of medication and even out your response to medication throughout the day. These strategies include changing the timing or strength of a dose, using different formulations of carbidopa/levodopa, or adding other medications. All of these strategies are summarized in an APDA publication on enhancing communication about OFF periods.

Q: How long does it take for a dose of carbidopa/levodopa to take effect?

A: This is variable between people, but typically it takes 30 minutes to one hour for a dose to start working. For some people, the amount of time that it takes for a dose to work is variable from dose to dose and they may wait a short period for some doses and a very long period for others. At times, there can even be dose failures when a dose never kicks in.

Q: How should you space your doses of carbidopa/levodopa?

A: For carbidopa/levodopa immediate release (Sinemet), this typically depends on how advanced the disease state is. For those in early stages, one dose can last six hours or even more. As the disease advances, this amount of time tends to get shorter and some people require medication every two hours.

There are other formulations of carbidopa/levodopa, for example carbidopa/levodopa extended release capsules (Rytary). This formulation is meant to last longer than the immediate release version. Again, the amount of time the dose lasts varies from person to person.

Q: What happens if you miss a dose of carbidopa/levodopa?

A: This depends on the person. For some people, a missed dose is not a problem and when the person remembers to take the dose, he/she can resume without an issue. For others, a missed dose will cause an OFF period in which the motor symptoms of PD return. The person should therefore take the dose as soon as he/she remembers so that the PD symptoms resolve.

Q: What happens if you take levodopa and you don’t have Parkinson’s?

A: There should be no adverse effects if you take levodopa and don’t have PD.

Tips and Takeaways

• Carbidopa/levodopa remains the most effective medication for treatment of the motor symptoms of PD, yet despite its widespread use, people have many questions. Never hesitate to ask your doctor about your medication.
• Be sure to mention all your symptoms to your neurologist as some may be side effects of carbidopa/levodopa. Adjusting medication dosage and timing can help reduce many side effects.
• There are many different formulations of carbidopa/levodopa. Your doctor will work with you to select the best one for your symptoms.

Adjusting your diet may help with improved