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Pronunciation
(lee voe DOE pa & kar bi DOE pa)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes orally-disintegrating tablet
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use
Idiopathic Parkinson's disease; postencephalitic parkinsonism; symptomatic parkinsonism
Use: Unlabeled/Investigational
Restless leg syndrome
Pregnancy Risk Factor
C
Pregnancy Implications
Teratogenic effects were observed with levodopa and carbidopa in animal studies. There are case reports of levodopa crossing the placenta in humans.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to levodopa, carbidopa, or any component of the formulation; narrow-angle glaucoma; use of MAO inhibitors within prior 14 days (however, may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B); history of melanoma or undiagnosed skin lesions
Warnings/Precautions
Concerns related to adverse effects:
• Dyskinesias: May cause or exacerbate dyskinesias.
• Orthostatic hypotension: May cause orthostatic hypotension; Parkinson's disease patients appear to have an impaired capacity to respond to a postural challenge. Use with caution in patients at risk of hypotension (such as those receiving antihypertensive drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Parkinson's patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and should be informed of this risk.
• Somnolence: Patients have reported falling asleep while engaging in activities of daily living; this has been reported to occur without significant warning signs. Monitor for daytime somnolence or pre-existing sleep disorder; caution with concomitant sedating medication; discontinue if significant daytime sleepiness or episodes of falling asleep occur. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive agents. Effects with other sedative drugs or ethanol may be potentiated.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, including a history of myocardial infarction and arrhythmias.
• Endocrine disease: Use with caution when interpreting plasma/urine catecholamine levels; falsely-diagnosed pheochromocytoma has been rarely reported.
• Glaucoma: Use with caution in patients with glaucoma; monitor IOP carefully in patients with wide-angle glaucoma.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Peptic ulcer disease: Use with caution in patients with peptic ulcer disease.
• Psychotic disorders: Use with extreme caution in patients with psychotic disorders; observe patients closely for development of depression with concomitant suicidal tendencies.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease.
Special populations:
• Elderly: Use with caution in the elderly; may be more sensitive to CNS effects of levodopa.
• Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions:
• Dietary protein: Distribute dietary protein throughout the day to avoid fluctuations in levodopa absorption.
• Discontinuation of therapy: Dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on abrupt withdrawal or significant dosage reduction after long-term use.
Adverse Reactions
Frequency not defined.
Cardiovascular: Orthostatic hypotension, arrhythmia, chest pain, hypertension, syncope, palpitation, phlebitis
Central nervous system: Dizziness, anxiety, confusion, nightmares, headache, hallucinations, on-off phenomenon, decreased mental acuity, memory impairment, disorientation, delusions, euphoria, agitation, somnolence, insomnia, gait abnormalities, nervousness, ataxia, EPS, falling, psychosis, peripheral neuropathy, seizure (causal relationship not established)
Dermatologic: Rash, alopecia, malignant melanoma, hypersensitivity (angioedema, urticaria, pruritus, bullous lesions, Henoch-Schönlein purpura)
Endocrine & metabolic: Increased libido
Gastrointestinal: Anorexia, nausea, vomiting, constipation, GI bleeding, duodenal ulcer, diarrhea, dyspepsia, taste alterations, sialorrhea, heartburn
Genitourinary: Discoloration of urine, urinary frequency
Hematologic: Hemolytic anemia, agranulocytosis, thrombocytopenia, leukopenia; decreased hemoglobin and hematocrit; abnormalities in AST and ALT, LDH, bilirubin, BUN, Coombs' test
Neuromuscular & skeletal: Choreiform and involuntary movements, paresthesia, bone pain, shoulder pain, muscle cramps, weakness
Ocular: Blepharospasm, oculogyric crises (may be associated with acute dystonic reactions)
Renal: Difficult urination
Respiratory: Dyspnea, cough
Miscellaneous: Hiccups, discoloration of sweat, diaphoresis (increased)
Drug Interactions
Antacids: Levodopa absorption may be increased; monitor
Anticholinergics: May reduce the efficacy of levodopa, possibly due to reduced gastrointestinal absorption (also see tricyclic antidepressants); limited evidence of clinical significance; monitor
Antipsychotics: May inhibit the antiparkinsonian effects of levodopa via dopamine receptor blockade; use antipsychotics with low dopamine blockade (clozapine, olanzapine, quetiapine)
Benzodiazepines: May inhibit the antiparkinsonian effects of levodopa; monitor for reduced effect
Clonidine: May reduce the efficacy of levodopa; monitor
Dextromethorphan: Toxic reactions have occurred with dextromethorphan
Furazolidone: May increase the effect/toxicity of levodopa; hypertensive episodes have been reported; monitor
Iron salts: Binds levodopa and reduces its bioavailability; separate doses of iron and levodopa
Linezolid: Due to MAO inhibition (see note on MAO inhibitors), this agent is best avoided
MAO inhibitors: Concurrent use of levodopa with nonselective MAO inhibitors may result in hypertensive reactions via an increased storage and release of dopamine, norepinephrine, or both; use with carbidopa to minimize reactions if combination is necessary, otherwise avoid combination.
L-methionine: May inhibit levodopa's antiparkinsonian effects; monitor for reduced effect
Metoclopramide: May increase the absorption/effect of levodopa; hypertensive episodes have been reported. Levodopa antagonizes metoclopramide's effects on lower esophageal sphincter pressure. Avoid use of metoclopramide for reflux, monitor response to levodopa carefully if used.
Methyldopa: May potentiate the effects of levodopa; levodopa may increase the hypotensive response to methyldopa; monitor
Papaverine: May decrease the efficacy of levodopa; includes other similar agents (ethaverine); monitor
Penicillamine: May increase serum concentrations of levodopa; monitor for increased effect
Phenytoin: May inhibit levodopa's antiparkinsonian effects; monitor for reduced effect
Pyridoxine: May inhibit levodopa's antiparkinsonian effects; monitor for reduced effect (pyridoxine in doses >10-25 mg for levodopa alone, higher doses >200 mg/day may be a problem for levodopa/carbidopa)
Spiramycin: May inhibit levodopa's antiparkinsonian effects; monitor for reduced effect
Tacrine: May inhibit the effects of levodopa via enhanced cholinergic activity; monitor for reduced effect
Tricyclic antidepressants: May decrease the absorption (bioavailability) of levodopa; rare hypertensive episodes have also been attributed to this combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (due to CNS depression).
Food: Avoid high protein diets and high intakes of vitamin B6.
Herb/Nutraceutical: Avoid kava kava (may decrease effects). Pyridoxine in doses >10-25 mg (for levodopa alone) or higher doses >200 mg/day (for levodopa/carbidopa) may decrease efficacy.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from light and moisture.
Mechanism of Action
Parkinson's symptoms are due to a lack of striatal dopamine; levodopa circulates in the plasma to the blood-brain-barrier (BBB), where it crosses, to be converted by striatal enzymes to dopamine; carbidopa inhibits the peripheral plasma breakdown of levodopa by inhibiting its decarboxylation, and thereby increases available levodopa at the BBB
Pharmacodynamics/Kinetics
Duration: Variable, 6-12 hours; longer with sustained release forms
See individual agents.
Dosage
Oral: Adults:
Parkinson's disease:
Immediate release tablet:
Initial: Carbidopa 25 mg/levodopa 100 mg 3 times/day
Dosage adjustment: Alternate tablet strengths may be substituted according to individual carbidopa/levodopa requirements. Increase by 1 tablet every other day as necessary, except when using the carbidopa 25 mg/levodopa 250 mg tablets where increases should be made using 1/2-1 tablet every 1-2 days. Use of more than 1 dosage strength or dosing 4 times/day may be required (maximum: 8 tablets of any strength/day or 200 mg of carbidopa and 2000 mg of levodopa)
Sustained release tablet:
Initial: Carbidopa 50 mg/levodopa 200 mg 2 times/day, at intervals not <6 hours
Dosage adjustment: May adjust every 3 days; intervals should be between 4-8 hours during the waking day (maximum: 8 tablets/day)
Restless leg syndrome (unlabeled use): Carbidopa 25 mg/levodopa 100 mg given 30-60 minutes before bedtime; may repeat dose once
Elderly: Initial: Carbidopa 25 mg/levodopa 100 mg twice daily, increase as necessary
Administration: Oral
Space doses evenly over the waking hours. Give with meals to decrease GI upset. Sustained release product should not be crushed. Orally-disintegrating tablets do not require water; the tablet should disintegrate on the tongue's surface before swallowing.
Monitoring Parameters
Blood pressure, standing and sitting/supine; symptoms of parkinsonism, dyskinesias, mental status
Test Interactions
False-positive reaction for urinary glucose with Clinitest®; false-negative reaction using Clinistix®; false-positive urine ketones with Acetest®, Ketostix®, Labstix®
Dietary Considerations
Levodopa peak serum concentrations may be decreased if taken with food. High protein diets (>2 g/kg) may decrease the efficacy of levodopa via competition with amino acids in crossing the blood-brain barrier.
Parcopa™: Contains phenylalanine 3.4 mg per 10/100 mg and 25/100 mg strengths; phenylalanine 8.4 mg in 25/250 mg strength
Patient Education
Take exactly as directed; do not change dosage or discontinue without consulting prescriber. Do not crush sustained release form. Therapeutic effects may take several weeks or months to achieve and you may need frequent monitoring during first weeks of therapy. Take with meals if GI upset occurs, before meals if dry mouth occurs, after eating if drooling or if nausea occurs. Take at the same time each day. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake; void before taking medication. Do not use alcohol and prescription or OTC sedatives or CNS depressants without consulting prescriber. Urine or perspiration may appear darker. You may experience drowsiness, dizziness, confusion, or vision changes (use caution when driving, climbing stairs, or engaging in tasks requiring alertness until response to drug is known); orthostatic hypotension (use caution when changing position - rising to standing from sitting or lying); increased susceptibility to heat stroke, decreased perspiration (use caution in hot weather - maintain adequate fluids and reduce exercise activity); constipation (increased exercise, fluids, fruit, or fiber may help); dry skin or nasal passages (consult prescriber for appropriate relief); or nausea, vomiting, loss of appetite, or stomach discomfort (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report unresolved constipation or vomiting; chest pain or irregular heartbeat; respiratory difficulty; acute headache or dizziness; CNS changes (hallucination, loss of memory, nervousness, etc); painful or difficult urination; abdominal pain or blood in stool; increased muscle spasticity or rigidity; skin rash; or significant worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
The elderly may be more sensitive to the CNS effects of levodopa.
Additional Information
50-100 mg/day of carbidopa is needed to block the peripheral conversion of levodopa to dopamine. “On-off” (a clinical syndrome characterized by sudden periods of drug activity/inactivity), can be managed by giving smaller, more frequent doses of Sinemet® or adding a dopamine agonist or selegiline; when adding a new agent, doses of Sinemet® can usually be decreased. Protein in the diet should be distributed throughout the day to avoid fluctuations in levodopa absorption. Levodopa is the drug of choice when rigidity is the predominant presenting symptom.
Conversion from levodopa to carbidopa/levodopa: Note: Levodopa must be discontinued at least 12 hours prior to initiation of levodopa/carbidopa:
Initial dose: Levodopa portion of carbidopa/levodopa should be at least 25% of previous levodopa therapy.
Levodopa <1500 mg/day: Sinemet® or Parcopa™ (levodopa 25 mg/carbidopa 100 mg) 3-4 times/day
Levodopa ?1500 mg/day: Sinemet® or Parcopa™ (levodopa 25 mg/carbidopa 250 mg) 3-4 times/day
Conversion from immediate release carbidopa/levodopa (Sinemet® or Parcopa™) to Sinemet® CR (50/200):
Sinemet® or Parcopa™ [total daily dose of levodopa]/Sinemet® CR:
Sinemet® or Parcopa™ (levodopa 300-400 mg/day): Sinemet® CR (50/200) 1 tablet twice daily
Sinemet® or Parcopa™ (levodopa 500-600 mg/day): Sinemet® CR (50/200) 1 1/2 tablets twice daily or 1 tablet 3 times/day
Sinemet® or Parcopa™ (levodopa 700-800 mg/day): Sinemet® CR (50/200) 4 tablets in 3 or more divided doses
Sinemet® or Parcopa™ (levodopa 900-1000 mg/day): Sinemet® CR (50/200) 5 tablets in 3 or more divided doses
Intervals between doses of Sinemet® CR should be 4-8 hours while awake; when divided doses are not equal, smaller doses should be given toward the end of the day,
Anesthesia and Critical Care Concerns/Other Considerations
Consider use of alternative therapies before attempting to use levodopa containing products.
50-100 mg/day of carbidopa is needed to block the peripheral conversion of levodopa to dopamine. “On-off” (a clinical syndrome characterized by sudden periods of drug activity/inactivity), can be managed by giving smaller, more frequent doses of Sinemet® or adding a dopamine agonist or selegiline; when adding a new agent, doses of Sinemet® can usually be decreased. Protein in the diet should be distributed throughout the day to avoid fluctuations in levodopa absorption. Levodopa is the drug of choice when rigidity is the predominant presenting symptom.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) and taste alterations. Dopaminergic therapy in Parkinson's disease (ie, treatment with levodopa and carbidopa combination) is associated with orthostatic hypotension. Patients medicated with this drug combination should be carefully assisted from the chair and observed for signs of orthostatic hypotension.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Monitor therapeutic effectiveness and adverse reactions (including levodopa toxicity) at beginning of therapy and periodically throughout therapy. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet immediate release (Sinemet®):
10/100: Carbidopa 10 mg and levodopa 100 mg
25/100: Carbidopa 25 mg and levodopa 100 mg
25/250: Carbidopa 25 mg and levodopa 250 mg
Tablet, immediate release, orally disintegrating (Parcopa™):
10/100: Carbidopa 10 mg and levodopa 100 mg [contains phenylalanine 3.4 mg/tablet; mint flavor]
25/100: Carbidopa 25 mg and levodopa 100 mg [contains phenylalanine 3.4 mg/tablet; mint flavor]
25/250: Carbidopa 25 mg and levodopa 250 mg [contains phenylalanine 8.4 mg/tablet; mint flavor]
Tablet, sustained release (Sinemet® CR):
Carbidopa 25 mg and levodopa 100 mg
Carbidopa 50 mg and levodopa 200 mg
Pricing: U.S. (www.drugstore.com)
Tablet, controlled release (Carbidopa-Levodopa CR)
25-100 mg (60): $40.99
50-200 mg (60): $80.99
Tablet, controlled release (Sinemet CR)
25-100 mg (60): $72.53
50-200 mg (60): $131.86
Tablet, orally-disintegrating (Parcopa)
10-100 mg (30): $28.11
25-100 mg (30): $36.99
25-250 mg (30): $41.09
Tablets (Carbidopa-Levodopa)
10-100 mg (90): $34.99
25-100 mg (90): $39.99
25-250 mg (60): $33.99
Tablets (Sinemet)
10-100 mg (90): $85.19
25-100 mg (90): $94.50
25-250 mg (60): $82.77
References
Olanow CW, Watts RL, and Koller WC, “An Algorithm (Decision Tree) for the Management of Parkinson's Disease (2001): Treatment Guidelines,” Neurology, 2001, 56(11 Suppl 5):1-88.
Restless Leg Syndrome Foundation, Inc, 2001 Medical Bulletin, revised April 2001. Available at: http://www.rls.org/frames/home_frame.htm. Accessed May 1, 2002.
Stern MB, “Contemporary Approaches to the Pharmacotherapeutic Management of Parkinson's Disease: An Overview,” Neurology, 1997, 49(1 Suppl 1):2-9.
Walker SW, Fina A, and Kryger MH, “L-Dopa/Carbidopa for Nocturnal Movement Disorders in Uremia,” Sleep, 1996, 19(3):214-8.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2008
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