What is the effect of Carbidopa (CD) and Levodopa (L-DOPA)?

From the Guidelines

Carbidopa-levodopa is a medication used primarily to treat Parkinson's disease and its symptoms, but it may cause metabolic effects, weight loss, and hyperhomocysteinemia, and its use should be carefully monitored and managed to minimize these risks. The combination of levodopa and carbidopa helps manage symptoms like tremors, stiffness, slow movement, and poor balance by increasing dopamine levels in the brain. Typical starting doses are 25/100 mg (carbidopa/levodopa) taken three times daily, with adjustments made based on individual response 1.

Key Considerations

• The medication should be taken consistently, sometimes with food to reduce nausea, and at least 30 minutes before meals to maximize levodopa absorption and efficacy 1.
• Common side effects include nausea, dizziness, and headache, while long-term use may lead to dyskinesias (involuntary movements) and "on-off" fluctuations in symptom control.
• Patients should not abruptly stop taking this medication and should inform their doctor about all other medications they're taking to avoid interactions.
• Regular follow-up appointments are important to monitor effectiveness and adjust dosing as needed.
• Patients on levodopa may require supplementation with vitamins B6, B12, and folate to maintain normal homocysteine levels and prevent hyperhomocysteinemia 1.
• A protein-redistribution dietary regimen may be recommended to maximize levodopa absorption and efficacy in patients experiencing motor fluctuations 1.

Monitoring and Management

• Patients should undergo active monitoring of their weight, nutritional status, and vitamin levels to minimize the risks associated with carbidopa-levodopa use.
• The use of levodopa may be associated with impaired nutritional status and risk for malnutrition, and patients should be monitored for these risks 1.
• The medication should be adjusted as needed to minimize side effects and maximize efficacy, and patients should be educated on how to manage their condition and recognize potential complications.

From the FDA Drug Label

Carbidopa and levodopa tablets are indicated in the treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication. Carbidopa allows patients treated for Parkinson's disease to use much lower doses of levodopa. Some patients who responded poorly to levodopa have improved on carbidopa and levodopa tablets. This is most likely due to decreased peripheral decarboxylation of levodopa caused by administration of carbidopa rather than by a primary effect of carbidopa on the nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa. Carbidopa may also reduce nausea and vomiting and permit more rapid titration of levodopa.

The effect of Carbidopa (CD) and Levodopa (L-DOPA) is to treat Parkinson's disease by:

• Allowing patients to use lower doses of levodopa
• Improving response in patients who responded poorly to levodopa alone
• Reducing nausea and vomiting associated with levodopa therapy
• Increasing the availability of levodopa in the brain, thereby forming more dopamine 2

From the Research

Effects of Carbidopa and Levodopa

• The combination of Carbidopa (CD) and Levodopa (L-DOPA) is used to treat Parkinson's disease, with Carbidopa inhibiting the peripheral conversion of Levodopa to dopamine, reducing nausea and increasing central bioavailability 3, 4.
• Increasing the dosage of Carbidopa in patients receiving low doses of Levodopa can produce a moderate decrease in the severity of parkinsonism and a marked decrease in peripheral adverse reactions, without a significant increase in central adverse effects of Levodopa 3.
• Individualized Levodopa/Carbidopa dosing using microtablets can improve treatment effects for some patients, with good usability and high adherence 5.

Motor Complications and Dyskinesias

• The chronic use of Levodopa is associated with the development of motor complications, including wearing off, motor fluctuations, and dyskinesias 4.
• Adding a COMT inhibitor, such as Entacapone, to the combination of Levodopa and Carbidopa can extend the Levodopa peripheral half-life and increase central bioavailability, reducing motor fluctuations and dyskinesias 4, 6.
• However, Entacapone can cause drowsiness, and cases of cholestatic hepatitis have been reported, with risks of liver toxicity, rhabdomyolysis, and neuroleptic malignant syndrome remaining to be determined 6.

Treatment Guidelines

• Levodopa combined with Carbidopa is still the most effective treatment for symptoms of Parkinson's disease, with dopamine agonists being the next most effective class of drugs 7.
• Addition of a peripherally-acting COMT inhibitor or an MAO-B inhibitor to Levodopa can reduce motor fluctuations in patients with advanced disease, and Amantadine may have mild symptomatic benefit and decrease Levodopa-induced dyskinesias 7.