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Carbidopa/levodopa, also known as levocarb and co-careldopa, is the combination of the two medications carbidopa and levodopa. It is primarily used to manage the symptoms of Parkinson's disease, although it does not slow down the disease or slow down progression. Carbidopa/levodopa is taken orally.
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It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 310th most commonly prescribed medication in the United States, with more than 200,000 prescriptions.
Medical uses
thumb|upright|Bottle of prescription carbidopa (25 mg) / levodopa (100 mg) in Australia
Parkinson's disease
It is primarily used to improve the symptoms of Parkinson's disease but does not change the course of the disease.
Other
Other uses include for dopamine-responsive dystonia (DRD) and restless legs syndrome. Using carbidopa/levodopa may lead to augmentation syndrome, with increasing persistence of restless legs syndrome, and increasing severity.
Side effects
Common side effects include dizziness, 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.
Less common, but more serious, side effects can include very frequent blinking or twitching of the eyes and other forms of levodopa-induced dyskinesia (LID), fainting, mood changes (e.g., depression), confusion, hallucinations, delusions, thoughts of suicide, compulsive behavior (e.g., compulsive gambling), hypersexuality, worsening of involuntary movements or spasms, or other movement problems.
Mechanism of action
Levodopa is converted to dopamine via the action of a naturally occurring enzyme called DOPA decarboxylase. This occurs both in the peripheral circulation and in the central nervous system after levodopa has crossed the blood–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 a DOPA decarboxylase inhibitor (DDCI), in this case carbidopa, which cannot cross the blood–brain barrier (due to it being polar and charged at physiologic pH). This prevents peripheral conversion of levodopa to dopamine, thereby reducing the unwanted peripheral side effects. This also functions to increase the quantity of levodopa that is available to enter the brain.
Society and culture
Economics
It is available as a generic medication.
Extended-release formulations are sold as Sinemet-CR, Rytary and Crexont. An extended-release enteral solution is sold as Duopa.
Shortages
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. 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. 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.