| Combination of | |
|---|---|
| Carbidopa | Enzyme inhibitor |
| Levodopa | Agonist |
| Clinical data | |
| Trade names | Atamet, Carbilev, Sinemet, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601068 |
| License data | |
| Pregnancy category | |
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| PubChemCID | |
| ChemSpider |
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| KEGG | |
| CompTox Dashboard(EPA) | |
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Carbidopa/levodopa, also known aslevocarb andco-careldopa, is the combination of the two medicationscarbidopa andlevodopa.[6] It is primarily used to manage the symptoms ofParkinson's disease, but it does not slow down the disease or stop it from getting worse.[6] It is takenby mouth.[6] It can take two to three weeks of treatment before benefits are seen.[7] Each dose then begins working in about ten minutes to two hours with a duration of effect of about five hours.[7][8][9]
Common side effects includemovement problems and nausea.[6] More serious side effects include depression,low blood pressure with standing, sudden onset of sleepiness,psychosis, and increased risk-taking behavior.[6][10] Carbidopa prevents the breakdown of levodopa outside the brain.[10] In the brain, levodopa is broken down intodopamine, its active form.[10] Carbidopa also helps prevent some of the nausea which levodopa causes.[11]
It is on theWorld Health Organization's List of Essential Medicines.[12] It is available as ageneric medication.[10] In 2022, it was the 278th most commonly prescribed medication in the United States, with more than 700,000 prescriptions.[13][14]
It is primarily used to improve the symptoms ofParkinson's disease but does not change the course of the disease.[6] It can take two to three weeks of treatment before benefits are seen.[7] Each dose then begins working in about ten minutes to two hours depending on the formulation, with a duration of effect of about five hours.[7][8][9]
A formulation that can be given in an intra-intestinal pump, known as Duodopa, is being developed.[15][16]
Other uses include fordopamine-responsive dystonia (DRD) andrestless legs syndrome.[10][17][18] Using carbidopa/levodopa may lead to augmentation syndrome, with increasing persistence of restless legs syndrome, and increasing severity.[18]
There is tentative evidence that it is useful inamblyopia when used with other treatments.[19]
Common side effects includedizziness,drowsiness,blurred vision,nausea,vomiting,dry mouth, low appetite,heartburn, diarrhea, constipation, frequent sneezing, nasal congestion,flu-like symptoms, cough, muscle pain, numbness,paresthesia, sleep disturbances, skin rash, itching, or headache.[20]
Less common, but more serious, side effects can include very frequent blinking or twitching of the eyes,fainting, mood changes (e.g.,depression), confusion,hallucinations,delusions, thoughts of suicide,compulsive behavior (e.g.,compulsive gambling),hypersexuality, worsening of involuntary movements orspasms, or othermovement problems.[citation needed]
Levodopa is converted todopamine via the action of a naturally occurringenzyme calledDOPA decarboxylase.[21] This occurs both in the peripheral circulation and in thecentral nervous system after levodopa has crossed theblood–brain barrier. Activation of central dopamine receptors improves the symptoms of Parkinson's disease; however, activation of peripheral dopamine receptors causes nausea and vomiting. For this reason levodopa is usually administered in combination with aDOPA decarboxylase inhibitor (DDCI), in this case carbidopa, which is very polar (and charged at physiologic pH) and cannot cross the blood–brain barrier, however prevents peripheral conversion of levodopa to dopamine and thereby reduces the unwanted peripheral side effects of levodopa. Use of carbidopa also increases the quantity of levodopa in the bloodstream that is available to enter the brain.[citation needed]
In 1960, the Austrian biochemistOleh Hornykiewicz, while at theUniversity of Vienna, examined results of autopsies of patients who had died with Parkinson's disease. He suggested that the disease was associated with, or caused by, a reduction in the levels of dopamine in thebasal ganglia of the brain. Since dopamine itself did not enter the brain, he tried treating twenty patients with aracemic mixture ofdihydroxyphenylalanine (DOPA), which could enter the brain and be converted there to dopamine by the action of DOPA decarboxylase. His results were positive, as were those of another trial in Montreal run byAndré Barbeau. Unfortunately, other investigators were unable to replicate these early results, and the use of DOPA remained in question until 1967, whenGeorge Cotzias at theBrookhaven National Laboratories in Upton, New York, used megadoses of DOPA, up to 16 grams per day. Not long after these results became known, Curt Porter atMerck showed thatL-DOPA was the activestereoisomer, thus reducing the effective dose to half.[22]
WithL-DOPA identified as the active form, Alfred Pletscher and his colleagues atHoffman-LaRoche synthesizedbenserazide, an inhibitor of DOPA decarboxylase, which further reduced the required dose. A drug combiningL-DOPA with benserazide was marketed under the brand name of Madopar. Independent work was carried out by Victor Lotti at Merck in West Point, Pennsylvania. Merck had already synthesized and patented carbidopa, another dopa decarboxylase inhibitor in 1962, and in 1971 Lotti showed that the use of the L-form of carbidopa, further reduced the therapeutic dose ofL-DOPA. The combination ofL-carbidopa andL-DOPA was marketed under the brand name of Sinemet.[22]
It is available as ageneric medication.[10]
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The generic name under theBAN system is Co-careldopa.
It is sold under several brand names, including Sinemet (Merck Sharp & Dohme Limited), Pharmacopa, Atamet, Apo-Levocarb, Duodopa, Kinson, and Pharmacopa, among others.
Extended-release formulations are sold as Rytary and Sinemet-CR. An extended-release enteral solution is sold as Duopa.
In 1991, Merck licensed the rights to the manufacture and sale of Sinemet to a newly created joint venture, DuPont Merck Pharmaceutical Company. That same year, approvals for a sustained release formulation (Sinemet CR) which could be taken less frequently were also obtained.[23]DuPont purchased Merck's share in the joint venture in 1998 and began operating the company as DuPont Pharmaceuticals (DuPont Pharma), but Merck continued to manufacture the drug for DuPont.[24] Starting in late 2009 and continuing into 2011 Merck stopped manufacturing the drug while awaiting regulatory approvals due to a change in the supplier of the active ingredient. This resulted in shortages of the brand name products Sinemet and Sinemet CR, although alternative generic versions were still available.[25]
