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Drug Notebook

Generic Name: levodopa

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Larodopa, Dopar
a dopaminergic antiparkinsonism agent
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Interactions

Specific Drugs and Foods

Drug or Food Interaction Comments
Anesthetics, general (cyclopropane, halogenated hydrocarbon general anesthetics) Potential for cardiac arrhythmias with these anesthetic agents Use alternative anesthetic agents
Anticholinergic agents

Potential for decreased tremor and/or exacerbation of abnormal involuntary movements

Possible delay in levodopa absorption and increase in gastric metabolism of levodopa
Antidepressants, tricyclic Potential for hypertension and dyskinesia Use concomitantly with caution
Antipsychotic agents (phenothiazines, butyrophenones, risperidone)

Possible reduction in the therapeutic effects of levodopa

Possible increased risk of NMS (see Neuroleptic Malignant Syndrome under Cautions)

 Observe patient for loss of therapeutic effect
Benzodiazepines Possible reduction in the therapeutic effects of levodopa with chlordiazepoxide or diazepam Use concomitantly with caution
Hypotensive agents

Potential for symptomatic postural hypotension

Potential for toxic CNS effects such as psychosis with methyldopa

 Dosage adjustment of the hypotensive agent may be needed
Iron preparations Decreased absorption of levodopa and carbidopa Clinical importance unknown
Isoniazid Possible reduction in the therapeutic effects of levodopa Observe patient for loss of therapeutic effect
MAO inhibitors

Potential for hypertension, headache, hyperexcitability with nonselective MAO inhibitors

Possible severe orthostatic hypotension with selegiline

Contraindicated with nonselective MAO inhibitors; discontinue nonselective MAO inhibitor at least 2 weeks prior to initiation of levodopa

May be administered concomitantly with a selective MAO inhibitor (e.g., selegiline) with caution

Metoclopramide

Possible increase in bioavailability of levodopa

Possible reduction in the therapeutic effects of levodopa
Papaverine Possible reduction in the therapeutic effects of levodopa Observe patient for loss of therapeutic effect
Phenytoin Possible reduction in the therapeutic effects of levodopa Observe patient for loss of therapeutic effect
Protein High protein diet may impair absorption

Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract; peak plasma levodopa concentrations achieved within 0.5 or 2 hours following administration of conventional tablets or extended-release tablets, respectively.

Bioavailability of levodopa from extended-release tablets 70–75% of that from conventional tablets.

Extended-release tablets result in less fluctuation in plasma concentrations between doses than conventional tablets.

Levodopa-carbodopa conventional tablets and orally disintegrating tablets begin to release the drugs within 30 minutes of administration. Pharmacokinetic values for orally disintegrating tablet are similar to those for the conventional tablet.

Food

High protein diet may interfere with absorption of levodopa.

Extended-release tablets: Food increases bioavailability and peak plasma concentrations of levodopa.

Distribution

Extent

Widely distributed.

<1% of levodopa penetrates the CNS; carbidopa does not cross the blood-brain barrier.

Plasma Protein Binding

Levodopa: 10–30%.

Carbidopa: About 36%.

Elimination

Metabolism

Levodopa is metabolized in the stomach and intestine and on first pass through the liver; absorbed levodopa decarboxylated to dopamine.

Carbidopa inhibits peripheral decarboxylation of levodopa, thus increasing availability of levodopa for distribution into the CNS.

Elimination Route

Levodopa is excreted in urine as metabolites.

Half-life

Levodopa: 1.5 hours when administered with carbidopa.

Stability

Storage

Oral

Conventional Tablets

Protect from light.

Extended-release Tablets

Tight container; avoid temperatures >30°C.

Orally Disintegrating Tablets

Tight, light-resistant container; 20–25°C (may be exposed to 15–30°C).

Actions

  • Manifestations of parkinsonian syndrome related to depletion of dopamine in the corpus striatum.
  • Levodopa relieves symptoms of parkinsonism presumably by increasing dopamine concentrations in the brain.


Last Updated: May 01, 2008
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Uses Dosage and Administration Cautions Interactions Pharmacokinetics Stability Actions Advice to Patients Preparations
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