Sinemet (carbidopa and levodopa) for Parkinson’s disease
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What is Sinemet for Parkinson’s?
Sinemet is an immediate-release formulation of carbidopa and levodopa, approved in the U.S. nearly a half century ago, that’s used to ease disease symptoms in people with Parkinson’s. The combination oral therapy typically reaches peak levels in the blood in about 30 minutes.
The two medications working together enhance the therapy’s effectiveness while helping to reduce potential side effects.
Another formulation of Sinemet, designed to continuously release carbidopa and levodopa over an extended period of time, was later approved in the U.S. and sold under the brand name Sinemet CR. That product, approved almost 40 years after Sinemet, released the compounds more slowly than the original formulation, with maximum blood level concentration of levodopa being reached in about two hours.
However, its developer, Merck, stopped manufacturing Sinemet CR in 2019, citing an inability to secure a reliable supply of the medication.
In June 2021, Merck formed a new spinoff company called Organon Pharma, which now supplies all Sinemet products.
A number of generic equivalents of Sinemet, all immediate-release formulations, also are available.
Therapy snapshot
| Brand Name: | Sinemet |
| Chemical Name: | Carbidopa and levodopa |
| Usage: | Used to ease symptoms of Parkinson’s disease |
| Administration: | Immediate-release oral tablets |
How does Sinemet work?
The underlying cause for the tremors, stiffness, and slowness of movements associated with Parkinson’s disease is a reduced level of dopamine — a neurotransmitter, or chemical messenger — in the brain.
This occurs because dopaminergic neurons, the nerve cells that produce dopamine to communicate with other cells in the brain and spinal cord, are progressively damaged and lost in people with the neurodegenerative disease.
The direct administration of dopamine as a treatment for Parkinson’s is ineffective, however, because it cannot cross the blood-brain barrier and reach the brain. The blood-brain barrier is a semipermeable membrane that protects the brain and spinal cord from the external environment.
Levodopa is a metabolic precursor of dopamine that can directly increase dopamine levels in the brain. The compound is able to cross the blood-brain barrier and enter the brain, where it is converted into dopamine by the action of decarboxylase enzymes.
Carbidopa, in turn, works by preventing the breakdown of levodopa by decarboxylases outside the nervous system. Because it cannot cross the blood-brain barrier, carbidopa ensures the safe delivery of levodopa to the brain, where it can be used to generate dopamine.
The combination of carbidopa and levodopa enhances the therapy’s effects while enabling the use of much lower doses of levodopa, which helps to reduce some side effects, such as nausea and vomiting.
Who with Parkinson’s can take Sinemet?
Sinemet was approved by the U.S. Food and Drug Administration (FDA) in 1975 to treat people with Parkinson’s disease, making it the first carbidopa and levodopa combination therapy to ever be approved in the U.S.
This approval also included other indications, including post-encephalitic parkinsonism, or Parkinson’s-like symptoms that occur after a brain infection, and parkinsonism that may follow carbon monoxide or manganese intoxication.
The extended-release formulation, Sinemet CR, was approved by the FDA in 2014.
Who should not take Sinemet?
Sinemet is not recommended for people who are being treated with a nonselective monoamine oxidase (MAO) inhibitor — an antidepressant medication — or who have taken a MAO inhibitor within the prior two weeks. Using the two medications together may lead to severe orthostatic hypotension, or a severe drop in blood pressure upon standing.
The therapy also is not recommended for patients with a known hypersensitivity to any component of Sinemet or for individuals who also have narrow-angle glaucoma, a disease that can cause vision loss and blindness.
Patients with a major psychotic disorder should generally not receive the therapy due to higher risk of psychosis exacerbation. Also, Sinemet should be administered with caution to patients with severe heart, lung, kidney liver, or endocrine disease.
Individuals taking iron salts or multivitamins that contain iron salts should take Sinemet with caution, as the supplements may reduce the amount of medication available and its ability to control symptoms.
How is Sinemet administered in Parkinson’s?
Sinemet is available as tablets that come in three strengths, each with different concentrations of levodopa and carbidopa:
- Sinemet 25-100 tablets, which contain 25 mg of carbidopa and 100 mg of levodopa, are yellow and oval and imprinted with 650 and a score line on one side.
- Sinemet 10-100 tablets, containing 10 mg of carbidopa and 100 mg of levodopa, are dark dapple-blue and oval, and are imprinted with 647 and a score line on one side.
- Sinemet 25-250 tablets, which contain 25 mg of carbidopa and 250 mg of levodopa, are light dapple-blue and oval, and are plain on one side and imprinted with 654 and a score line on the other.
The initial recommended dose is one tablet of Sinemet 25-100 three times a day, but the optimum daily dosage must be determined by carefully increasing doses in each individual patient until optimal symptom control is achieved.
To avoid nausea and vomiting, at least 70 to 100 mg of carbidopa per day should be provided. If necessary, dosage of 25-100 may be increased by one tablet every day or every other day to a maximum of eight tablets a day, corresponding to the maximum recommended daily dose of 200 mg of carbidopa.
If Sinemet 10-100 tablets are used, dosage may be started with one tablet three or four times a day, which can be increased by one tablet every day or every other day to a maximum of eight tablets a day.
Importantly, for patients who are transitioning from levodopa, the therapy must be discontinued at least 12 hours before treatment with Sinemet is started. A daily dosage of Sinemet should be chosen to provide approximately 25% of the previous levodopa dosage.
Apart from levodopa, standard medications for Parkinson’s disease can be used together with Sinemet, although dosage adjustments may be required.
Sinemet can be taken by patients receiving oral supplements of vitamin B6, as carbidopa does not allow this vitamin to reverse the effects of levodopa. However, changes in diet to foods that are high in protein may delay the absorption of levodopa and may decrease the efficacy of Sinemet.
Sinemet in clinical trials
Sinemet’s approval by the FDA was based on several clinical trials. Although specific trial data now are unavailable, key studies — including one at Columbia University in 1969 — contributed to the approval decision.
The Columbia University study examined the combination of levodopa and carbidopa in 28 Parkinson’s patients, finding that carbidopa enhanced levodopa’s brain availability while reducing peripheral side effects. The team of researchers also found that treatment was more effective when levodopa doses were slowly increased over time until an optimal dose was reached.
At the same time, the first placebo-controlled trial reported the efficacy of levodopa on akinesia, which is a lack of movement during regular tasks, as well as on tremor and rigidity. That trial involved 60 patients with Parkinson’s who were treated for periods of time ranging from four to 13 months, or just longer than a year. In the first 4-8 weeks, patients experienced an improvement of about 40% in their symptoms, and those who remained on treatment for up to a year reported average improvements of 59%.
Later, in 1980, one study compared two ratios of carbidopa to levodopa — specifically Sinemet 10-100 and Sinemet 20-100 — with levodopa alone in 29 patients with Parkinson’s disease. Findings from that double-blind study, in which neither researchers nor participants knew which patients were given which treatment, showed that those who received Sinemet 20-100 had significantly more improvements in several measures of motor function than those given the 10-100 combination or levodopa alone.
Common side effects of Sinemet
The most common side effects reported with Sinemet use include:
- uncontrolled, involuntary movements, known as dyskinesia
- nausea.
Other side effects that also have been reported with Sinemet include:
- chest pain
- lack of energy
- cardiac irregularities and palpitations
- low or high blood pressure
- orthostatic hypotension, or a drop in blood pressure upon standing
- gastrointestinal issues, including vomiting, diarrhea, constipation, and dry mouth
- issues with blood, including anemia and low numbers of white blood cells and platelets
- skin-related issues, including rash or itchy skin, increased sweating, and hair loss
- back and shoulder pain
- muscle cramps
- nervous system and psychiatric issues
- on-off phenomenon, when symptoms are not adequately controlled between doses
- upper respiratory infection and shortness of breath
- urinary tract infection and dark urine.
Dyskinesia
Treatment with Sinemet can cause dyskinesia — uncontrolled, involuntary movements common in Parkinson’s disease — which can require a dosage reduction.
Hallucinations, psychosis, and impulse control
Sinemet may cause symptoms such as hallucinations (seeing or hearing things that are not real), psychotic behavior, and impulse control problems, such as urges to gamble and eat or increased sexual urges.
Due to a risk of worsening psychosis, patients with a major psychotic disorder should not be treated with Sinemet. Also, treatment reduction or discontinuation should be considered for patients experiencing impulse control disorders.
Falling asleep during daily activities
There have been reports of people falling asleep during daily activities while on Sinemet alone or in combination with dopaminergic therapies. Before initiating treatment with Sinemet, factors for increased sleepiness, such as sleep disorders and other coprescribed sedating medications, should be assessed by and discussed with prescribing healthcare providers.
Discontinuing treatment should be considered in severe cases of daytime sleepiness or episodes of falling asleep during daily activities. Patients in whom the therapy is not stopped should avoid driving and other activities where falling asleep unexpectedly can be dangerous.
High fever and confusion associated with rapid dose reductions
High fever, stiff muscles, changes in breathing and heartbeat, and confusion have been reported following rapid dose reductions or discontinuation of dopaminergic therapy. As such, patients should be monitored carefully upon sudden discontinuation or rapid dose reduction of Sinemet. When possible, dose reductions or discontinuation should be done at a pace that will prevent such symptoms.
Melanoma
Some studies have shown that Parkinson’s patients have a higher risk of developing melanoma, a type of skin cancer. However, it is not clear whether this increased risk is due to the disease itself or other factors, such as medication. Patients treated with Sinemet should perform periodic skin examinations to monitor for melanoma.
Use in pregnancy and breastfeeding
Sinemet has not been well studied in patients who are pregnant, but based on animal studies, the therapy may cause harm to a developing fetus. Sinemet should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and child.
Traces of levodopa also have been found in human breast milk. As such, caution should be used when administering Sinemet to nursing patients.
Patients who are or plan to become pregnant, and those who are nursing or plan to breastfeed, should discuss this issue with their healthcare providers.
Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Sinemet
The U.S. Food and Drug Administration approved Sinemet in 1975 for the treatment of people with Parkinson’s disease, to ease symptoms of the neurodegenerative disorder. This marked the first approval in the U.S. of a combination therapy containing both levodopa and carbidopa. The regulatory agency also approved the medication for certain kinds of parkinsonism, or conditions with Parkinson’s-like symptoms.
Animal studies suggest that Sinemet may cause harm to a developing fetus. However, the therapy has not been well studied in pregnant women so it should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and child. Patients who become or intend to become pregnant should always talk to their healthcare providers about the potential risks of taking Sinemet.
Some patients on Sinemet have reported somnolence, or sleepiness, and suddenly falling asleep without warning during daily activities. Thus, until patients know exactly how the therapy affects them, those initiating treatment should not drive and should avoid other potentially dangerous activities that might result in harm if they become somnolent.
Sinemet reaches a peak concentration in the blood about half an hour after administration, at which point an easing in Parkinson’s symptoms should already be evident. However, because the initial recommended dose of Sinemet must be carefully determined for each patient, some individuals may require dose adjustments before experiencing the full benefits of the therapy.
There have been some reports of hair loss, known as alopecia, in people taking Sinemet. Weight gain also has been reported with the use of levodopa alone and with various carbidopa and levodopa formulations; this side effect may occur with Sinemet.
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