levodopa/carbidopa
antiparkinson agent· Brands: Sinemet, Parcopa, DuodopaPO
Mechanism of action
Levodopa is a prodrug that crosses the blood-brain barrier and is converted to dopamine by aromatic-L-amino-acid decarboxylase in the brain, replenishing dopamine in the striatum. Carbidopa is a peripheral decarboxylase inhibitor that does not cross the blood-brain barrier, so it prevents the metabolism of levodopa to dopamine outside the CNS, reducing peripheral side effects and increasing the amount of levodopa available to the CNS.
Pharmacokinetics
Levodopa is absorbed in the small intestine via active transport, with peak plasma concentrations occurring 1-2 hours after oral administration. Absorption is delayed by food, especially high-protein meals, due to competition for transport. Carbidopa is poorly absorbed and acts locally in the gastrointestinal tract and liver. Levodopa is extensively metabolized in the periphery, primarily by aromatic-L-amino-acid decarboxylase, which is inhibited by carbidopa. The elimination half-life of levodopa is approximately 1.5 hours when given with carbidopa. Excretion is mainly in urine as metabolites.
Indications & dosing
Parkinson's disease
In combination with carbidopa; commonly as 25 mg carbidopa/100 mg levodopa tablets.
- adult · PO: 100 mg levodopa TID · In combination with carbidopa; commonly as 25 mg carbidopa/100 mg levodopa tablets.
Parkinsonism from other causes
Doses are expressed as levodopa content; adjust according to response and formulation.
- adult · PO: 100–200 mg levodopa TID-QID · Doses are expressed as levodopa content; adjust according to response and formulation.
Contraindications & precautions
- Concomitant use of non-selective MAOIs within 14 days · Risk of hypertensive crisis.
- Narrow-angle glaucoma · Levodopa may increase intraocular pressure.
- History of melanoma or suspicious skin lesions · Levodopa can activate melanoma; weigh benefit against risk.
- Severe cardiovascular disease, including arrhythmias · Monitor for dysrhythmias and blood pressure changes.
- Withdraw gradually to reduce the risk of neuroleptic malignant syndrome.
- Take with or shortly after food to minimise nausea, but be aware that high-protein meals may reduce levodopa absorption.
- Monitor for signs of melanoma and advise patients to report any skin changes.
- Use with caution in patients with peptic ulcer, diabetes, or cardiovascular disease.
- Levodopa may cause drowsiness; patients should exercise caution when driving or operating machinery.
Adverse effects
- Dyskinesiasserious
- Nausea and vomiting
- Postural hypotension
- Hallucinations and confusionserious
- Cardiac arrhythmiasserious
- Neuroleptic malignant syndrome on abrupt withdrawalserious
Monitoring, pregnancy & toxicity
- Motor response and dyskinesia · At each clinic visit
- Orthostatic blood pressure · Periodically, especially after dose changes
- Neuropsychiatric symptoms (hallucinations, confusion, depression) · At each clinic visit
- Nausea and vomiting · During dose titration
- Pregnancy: Avoid in pregnancy unless the potential benefit to the mother outweighs the risk to the fetus; there are no adequate and well-controlled studies.
- Toxicity: Severe dyskinesia, dystonia, and involuntary movements · Supportive care; temporarily withhold levodopa/carbidopa and seek specialist advice.
- Toxicity: Agitation, confusion, hallucinations, and psychosis · Supportive care; consider discontinuing other contributing medications; seek specialist advice.
- Toxicity: Cardiac arrhythmias and orthostatic hypotension · Monitor cardiac rhythm and blood pressure; treat hypotension with intravenous fluids and supportive measures.
- Toxicity: Severe nausea and vomiting · Supportive care; consider antiemetic treatment (e.g. domperidone) after specialist advice.
Clinical notes
Levodopa/carbidopa is the most effective symptomatic treatment for Parkinson's disease. It is used to improve motor symptoms such as bradykinesia, rigidity, and tremor, but is not curative. Long-term use can lead to motor fluctuations and dyskinesias. Patients should take the drug on an empty stomach, but if nausea occurs, it may be taken with food, though protein can interfere with absorption. Abrupt withdrawal should be avoided as it can cause neuroleptic malignant syndrome. Concurrent use with non-selective MAO inhibitors is contraindicated because it can lead to hypertensive crisis. The dose should be individualized and adjusted gradually.
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BNF; local formulary