Sinemet (Carbidopa-Levodopa)

Last updated Jan. 3, 2022, by Teresa Carvalho, MS

✅ Fact-checked by Ana de Barros, PhD

Sinemet, a therapy developed by Merck, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of symptoms associated with Parkinson’s disease.

The treatment combines two medicines: levodopa (a central nervous system agent) and carbidopa (an agent inhibiting an enzyme called decarboxylase).

Together, these two components increase the level of dopamine in the brain, which normally is low in individuals with Parkinson’s, leading to the motor impairments associated with the disease.

The treatment is an immediate-release oral tablet for which peak levels in the blood are reached in half an hour. A new formulation of Sinemet with a continued release (CR) was approved by the FDA in 2014, but Merck announced it would stop manufacturing it in 2019. The Sinemet CR oral tablet released more slowly than the original formulation, in which the maximum blood level concentration was reached in about two hours, after which the levels started to decline.

In 2019, a generic equivalent of Sinemet, both immediate release and continued release, was approved.

How Sinemet works

The underlying cause for the tremors, stiffness, and slowness of movements associated with Parkinson’s disease is the reduced level of dopamine (a neurotransmitter, or chemical messenger) in the brain. However, the direct administration of dopamine is ineffective in the treatment of Parkinson’s disease 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 or a compound that participates in the chemical reaction that produces dopamine, which is able to cross the blood-brain barrier and reach the brain, where it can be converted to dopamine.

Carbidopa works by preventing the breakdown of levodopa by decarboxylase enzymes. Because it cannot cross the blood-brain barrier, carbidopa ensures the safe delivery of levodopa to the brain, where it becomes exposed to the action of the decarboxylases that generate dopamine.

The combination of carbidopa and levodopa enhances levodopa’s potential of action because it enables the use of much lower doses of levodopa (60–80% less), which helps reduce the drug’s side effects, which include nausea and vomiting.

Sinemet in trials for Parkinson’s

A Phase 3, multicenter, global study (NCT02605434) enrolled adults with fluctuating Parkinson’s disease. The trial’s aim was to determine whether a gastric retention and release system with carbidopa-levodopa (Accordion Pill) was more effective than Sinemet in reducing motor fluctuations in periods when levodopa wears off and symptoms return (“off periods”). A gastric retention and release system enables a controlled release mode that leads to a slow discharge of the medication into the stomach over eight to 12 hours, which could provide a more steady absorption.

While Accordion Pill was previously found to ease motor symptoms in Parkinson’s patients, the results from this trial showed that it did not provide a greater reduction in daily off periods compared with Sinemet.

A Phase 4 (NCT03111485) trial is underway for Parkinson’s patients in Canada to assess whether long-acting treatment with Sinemet CR, taken at night time, improves obstructive sleep apnea.

Other information

Sinemet is commercialized as tablets in three strengths with different concentrations of levodopa and carbidopa. Sinemet 25–100 contains 25 milligrams (mg) of carbidopa and 100 mg of levodopa, Sinemet 10–100 contains 10 mg of carbidopa and 100 mg of levodopa, and Sinemet 25–250 contains 25 mg of carbidopa and 250 mg of levodopa. If necessary, the dosage of 25–250 may be increased by one-half or one tablet every day or every other day to a maximum of eight tablets a day.

Maximum recommended daily dose is 200 mg of carbidopa.

The most common side effects include dyskinesias (uncontrolled, involuntary movements) and nausea.

Patients with serious psychiatric conditions should not be treated with Sinemet as this treatment may cause hallucinations and other psychotic episodes.

The treatment may also cause breathing difficulty and respiratory infections and therefore should be carefully used by those with lung conditions.

Patients with heart conditions should also be cautiously monitored as treatment with Sinemet may cause cardiovascular problems.

Sinemet is contraindicated in patients who are being treated with nonselective monoamine oxidase (MAO) inhibitors. The treatment is also contraindicated in patients with a known adverse reaction to any component of Sinemet and in those with an eye condition called narrow-angle glaucoma.

Moreover, Sinemet should not be used in patients with suspicious, undiagnosed skin lesions or a history of skin cancer (melanoma).

More information can be found on the therapy’s label.


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 other 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.

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