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Uses

Parkinsonian Syndrome

Symptomatic treatment of idiopathic Parkinson’s disease (paralysis agitans), parkinsonian syndrome (postencephalitic parkinsonism), and symptomatic parkinsonism resulting from carbon monoxide intoxication and/or manganese intoxication.

Levodopa is the most effective drug for relieving the symptoms of parkinsonian syndrome.

Levodopa provides symptomatic relief (e.g., akinesia, rigidity, tremor); does not alter the disease course.

Drug of choice in the management of idiopathic parkinsonian syndrome, especially in patients >70 years of age, those with cognitive impairment, and those with severe disease.

Levodopa is used in conjunction with a decarboxylase inhibitor, carbidopa. Levodopa-carbidopa can be used alone or in conjunction with other antiparkinsonian drugs (e.g. ergot- and nonergot-derivative dopamine receptor agonists, catechol-O-methyltransferase [COMT] inhibitor, and/or selegiline).

Drug-induced Extrapyramidal Effects

Not effective in the management of extrapyramidal effects† induced by antipsychotic agents (e.g., phenothiazines).

Dosage and Administration

Administration

Oral Administration

Administer extended-release tablets as whole or half tablets; do not chew or crush.

Just prior to administration of the orally disintegrating tablet, gently remove the tablet from the bottle with dry hands. Place tablet on tongue to dissolve (usually within seconds) and swallow with saliva.

Administration of orally disintegrating tablet with water is not necessary.

Do not divide the fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo^®); administer only one tablet per dosing interval.

Dosage

Dosage expressed in terms of levodopa and carbidopa.

Available in combination products containing a 1:4 or 1:10 ratio of carbidopa to levodopa. Additional carbidopa can be administered separately if a higher carbidopa dosage than is available in the combination preparations is needed. The treatment regimen can include levodopa-carbidopa extended-release tablets, conventional tablets, and orally disintegrating tablets and carbidopa tablets based on individual requirements. Levodopa no longer is commercially available in the US as a single-entity preparation.

Also available as a fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo^®); available in a 1:4 ratio of carbidopa to levodopa. Used if optimum maintenance dosage of the 3 drugs corresponds to the dosage in the combination preparation. No experience transferring patients receiving levodopa-carbidopa extended-release tablets or levodopa-carbidopa preparations containing the 1:10 ratio.

For some patients (maintenance levodopa dosage ≤600 mg daily, no dyskinesias), the fixed combination containing levodopa, carbidopa, and entacapone (Stalevo^®) can be used when initiating entacapone therapy if optimum maintenance dosage of levodopa-carbidopa corresponds to dosage in the combination preparation.

Adjust levodopa-carbidopa dosage carefully according to individual requirements, response, and tolerance.

Dosage adjustment may be needed when other antiparkinsonian drugs are added to or discontinued from the regimen.

Daily dosage of carbidopa should be at least 70–100 mg daily; patients receiving <70–100 mg daily are likely to experience nausea and vomiting.

Observe patient closely if dosage is reduced abruptly or the drug is discontinued; risk of precipitating a symptom complex resembling neuroleptic malignant syndrome (NMS). (See Neuroleptic Malignant Syndrome under Cautions.)

If general anesthesia required, continue therapy as long as patient permitted to take oral medications; resume as soon as patient is able to take oral medication. If therapy interrupted, observe for NMS. (See Neuroleptic Malignant Syndrome under Cautions.)

Adults

Parkinsonian Syndrome

Levodopa-Carbidopa Conventional Tablets or Orally Disintegrating Tablets

Oral

Initially, levodopa 100 mg/carbidopa 25 mg (as 1 tablet) 3 times daily.

Increase dosage by levodopa 100 mg/carbidopa 25 mg (1 tablet) daily or every other day until a daily dosage of levodopa 800 mg/carbidopa 200 mg is reached or adverse effects prevent further increases or necessitate discontinuance.

Alternatively, initiate with levodopa 100 mg/carbidopa 10 mg (as 1 tablet) 3 or 4 times daily; this dosage will not provide an adequate dose of carbidopa for most patients. Increase dosage by levodopa 100 mg/carbidopa 10 mg (1 tablet) daily or every other day until a daily dosage of levodopa 800 mg/carbidopa 80 mg is reached.

Levodopa-Carbidopa Extended-release Tablets

Oral

Initially, levodopa 200 mg/carbidopa 50 mg (as 1 extended-release tablet) twice daily; initial dosage should not be given at intervals <6 hours. Adjust dosage based on response and tolerance at intervals ≥3 days. Most patients are treated adequately with levodopa 400 mg to 1.6 g daily and carbidopa 100–400 mg daily, administered in divided doses at intervals ranging from 4–8 hours while awake. Higher dosages (levodopa 2.4 g/carbidopa 600 mg) and shorter intervals (<4 hours) have been used but usually are not recommended. If the dosing interval is <4 hours and/or the divided doses are not equal, the smaller doses can be given at the end of the day.

Dosage may be initiated, titrated, and stabilized initially with conventional (immediate-release) tablets.

Transfer to extended-release tablets: initial dosage should provide 10% more levodopa daily than dosage previously received as conventional tablets; levodopa dosage may need to be increased up to 30% more daily, depending on response. (See Bioavailability under Pharmacokinetics.)

Carbidopa

Carbidopa: 25 mg with first dose of levodopa/carbidopa each day for patients who need additional carbidopa; additional 12.5- or 25-mg doses may given during the day with each dose of levodopa/carbidopa.

Prescribing Limits

Adults

Parkinsonian Syndrome

Oral

Experience with carbidopa dosages >200 mg daily limited.