Wednesday, October 26, 2016

Levodopa/Carbidopa



Class: Dopamine Precursors
VA Class: CN500
CAS Number: 59-92-7
Brands: Lodosyn, Parcopa, Sinemet, Sinemet CR, Stalevo

Introduction

Antiparkinsonian; levodopa is the levorotatory isomer of dihydroxyphenylalanine and the metabolic precursor of dopamine, and carbidopa is a decarboxylase inhibitor that inhibits the peripheral decarboxylation of levodopa to dopamine.104 105 106 107 108


Uses for Levodopa/Carbidopa


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.104 105 106 107 108


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


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


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.101 103 d


Levodopa is used in conjunction with a decarboxylase inhibitor, carbidopa.104 105 106 107 108 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).d 106


Drug-induced Extrapyramidal Effects


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


Levodopa/Carbidopa Dosage and Administration


Administration


Oral Administration


Administer extended-release tablets as whole or half tablets; do not chew or crush.105


Just prior to administration of the orally disintegrating tablet, gently remove the tablet from the bottle with dry hands.104 Place tablet on tongue to dissolve (usually within seconds) and swallow with saliva.104


Administration of orally disintegrating tablet with water is not necessary.104


Do not divide the fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo); administer only one tablet per dosing interval.106


Dosage


Dosage expressed in terms of levodopa and carbidopa.104 105 106 107 108


Available in combination products containing a 1:4 or 1:10 ratio of carbidopa to levodopa.104 105 106 107 Additional carbidopa can be administered separately if a higher carbidopa dosage than is available in the combination preparations is needed.108 The treatment regimen can include levodopa-carbidopa extended-release tablets, conventional tablets, and orally disintegrating tablets and carbidopa tablets based on individual requirements.104 105 107 108 Levodopa no longer is commercially available in the US as a single-entity preparation.d


Also available as a fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo); available in a 1:4 ratio of carbidopa to levodopa.106 Used if optimum maintenance dosage of the 3 drugs corresponds to the dosage in the combination preparation.106 No experience transferring patients receiving levodopa-carbidopa extended-release tablets or levodopa-carbidopa preparations containing the 1:10 ratio.106


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.106


Adjust levodopa-carbidopa dosage carefully according to individual requirements, response, and tolerance.104 105 106 107 108


Dosage adjustment may be needed when other antiparkinsonian drugs are added to or discontinued from the regimen.104 105 106 107 108


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.104 105 107 108 d


Observe patient closely if dosage is reduced abruptly or the drug is discontinued; risk of precipitating a symptom complex resembling neuroleptic malignant syndrome (NMS).104 105 106 107 (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.104 105 106 107 If therapy interrupted, observe for NMS.104 105 106 107 (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.104 107 109


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.104 107 109 d


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.104 107 109 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.104 107 109


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.105 Adjust dosage based on response and tolerance at intervals ≥3 days.105 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.105 Higher dosages (levodopa 2.4 g/carbidopa 600 mg) and shorter intervals (<4 hours) have been used but usually are not recommended.105 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.105


Dosage may be initiated, titrated, and stabilized initially with conventional (immediate-release) tablets.105 107


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.105 (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.108


Prescribing Limits


Adults


Parkinsonian Syndrome

Oral

Experience with carbidopa dosages >200 mg daily limited.104 105 107 108


If fixed-combination preparations containing levodopa 50–150 mg, carbidopa 12.5–37.5 mg, and entacapone 200 mg (Stalevo 50, 75, 100, 125, and 150) are used, maximum of 8 tablets daily.106


If fixed-combination preparation containing levodopa 200 mg, carbidopa 50 mg, and entacapone 200 mg (Stalevo 200) is used, maximum of 6 tablets daily.106


Cautions for Levodopa/Carbidopa


Contraindications



  • Concomitant use with a nonselective MAO inhibitor.104 105 106 107 (See Specific Drugs and Foods under Interactions.)




  • Angle-closure glaucoma.104 105 106 107 d




  • Known hypersensitivity to levodopa, carbidopa, or any ingredient in the formulation.104 105 106 107




  • Malignant melanoma, history of melanoma, or suspicious undiagnosed skin lesions.104 105 106 107



Warnings/Precautions


Warnings


Nervous System and Muscular Effects

Therapy associated with dyskinesias; dosage reduction may be needed.104 105 106 107


Mental disturbances reported.104 105 106 107 d Observe patients for depression with concomitant suicidal tendencies.104 105 106 107 d Use with caution in patients with current or past psychoses.104 105 106 107 d


Bradykinetic Episodes

“On-off” phenomenon: Sudden loss of effectiveness with abrupt onset of akinesia (“off” effect; persists 1–60 minutes) followed by sudden return of effectiveness (“on” effect); may recur many times daily and respond to increased dosing frequency.d


Akinesia Paradoxica (“start hesitation”): Sudden hypotonic freezing (patient falls frequently while attempting to walk); may respond to decreased dosage.d


Cardiovascular Effects

Risk of orthostatic hypotension; usually asymptomatic and tolerance usually develops within a few months.d


Use with care in patients with a history of MI who have residual atrial, nodal, or ventricular arrhythmias; monitor cardiac function in a facility with intensive cardiac care immediately available during the initial dosage adjustment.104 105 106 107 d


Use with caution in patients with severe cardiovascular disease.104 105 106 107 d


Respiratory Effects

Caution in patients with pulmonary disease (e.g., emphysema) or asthma who may require use of sympathomimetics.104 105 106 107 d


GI Effects

Use with caution in patients with a history of peptic ulcers; possibility of upper GI hemorrhage in these patients.d 104 105 106 107


Neuroleptic Malignant Syndrome (NMS)

Symptom complex resembling NMS reported following dosage reduction or abrupt withdrawal of levodopa.104 105 106 107 d


Observe closely when dosage is reduced or the drug discontinued; especially important in patients receiving concomitant therapy with an antipsychotic agent.d 104 105 106 107


General Precautions


Evaluate hepatic, hematopoietic, cardiovascular, and renal function periodically.d 104 105 106 107


Use of Fixed Combinations

When the fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo) is used, observe the usual precautions and contraindications associated with all drugs in the preparation.106


Glaucoma

Can be used with caution in patients with well-controlled open-angle glaucoma; monitor IOP.104 105 106 107 d (See Contraindications under Cautions.)


Endocrine Disorders

Use with caution.104 105 106 107


Closely monitor diabetic patients; levodopa may affect glycemic control.d


Somnolence

Possible somnolence and, very rarely, episodes of sudden onset of sleep, sometimes occurring without the patient’s awareness or without warning during daily activities.105 107


Patients must be informed of this risk; advise patients that they should exercise caution while driving or operating machinery and that they must refrain from such activities if they experience somnolence and/or an episode of sudden sleep onset.105 107


Melanoma

Epidemiologic studies indicate patients with parkinsonian syndrome have a twofold to approximately sixfold higher risk of developing melanoma than the general population.105 106 107 Unclear whether increased risk is due to parkinsonian syndrome or other factors (e.g., drugs used to treat the disease).105 106 107


Monitor for melanoma on a frequent and regular basis.105 106 107 Manufacturer recommends periodic skin examinations performed by appropriately qualified individuals (e.g., dermatologists).105 106 107


Intense Urges

Intense urges (e.g., urge to gamble, increased sexual urges, other intense urges) and inability to control these urges reported in some patients receiving antiparkinsonian agents that increase central dopaminergic tone (including levodopa-carbidopa).105 106 107 Although causal relationship not established, urges stopped in some cases when dosage was reduced or drug was discontinued.105 106 107


Consider reducing dosage or discontinuing levodopa-carbidopa if a patient develops such urges.105 106 107


Phenylketonuria

Levodopa-carbidopa orally disintegrating tablets contain aspartame (NutraSweet), which is metabolized in the GI tract to phenylalanine.104 110 111 112 113 114


Specific Populations


Pregnancy

Category C.104 105 106 107


Lactation

Carbidopa is distributed into milk in rats;106 not known whether carbidopa distributes into human milk.108 Distribution of levodopa into human milk reported in at least one nursing woman.105 107 Caution advised.104 105 106 107


Pediatric Use

Safety and efficacy not established in children <18 years of age.104 105 106 107


Common Adverse Effects


Dyskinesias (choreiform, dystonic, other adventitious movements), nausea.104 105 106 107


Interactions for Levodopa/Carbidopa


Specific Drugs and Foods













































Drug or Food



Interaction



Comments



Anesthetics, general (cyclopropane, halogenated hydrocarbon general anesthetics)



Potential for cardiac arrhythmias with these anesthetic agentsd



Use alternative anesthetic agentsd



Anticholinergic agents



Potential for decreased tremor and/or exacerbation of abnormal involuntary movements104 105 106 107 d


Possible delay in levodopa absorption and increase in gastric metabolism of levodopad



Antidepressants, tricyclic



Potential for hypertension and dyskinesia104 105 106 107



Use concomitantly with cautiond



Antipsychotic agents (phenothiazines, butyrophenones, risperidone)



Possible reduction in the therapeutic effects of levodopa104 105 106 107


Possible increased risk of NMS104 105 106 107 (see Neuroleptic Malignant Syndrome under Cautions)



Observe patient for loss of therapeutic effect104 105 106 107



Benzodiazepines



Possible reduction in the therapeutic effects of levodopa with chlordiazepoxide or diazepamd



Use concomitantly with cautiond



Hypotensive agents



Potential for symptomatic postural hypotension104 105 106 107


Potential for toxic CNS effects such as psychosis with methyldopad



Dosage adjustment of the hypotensive agent may be needed104 105 106 107



Iron preparations



Decreased absorption of levodopa and carbidopa104 105 106 107



Clinical importance unknown104 105 106 107



Isoniazid



Possible reduction in the therapeutic effects of levodopa104 105 106 107



Observe patient for loss of therapeutic effect104 105 106 107



MAO inhibitors



Potential for hypertension, headache, hyperexcitability with nonselective MAO inhibitorse


Possible severe orthostatic hypotension with selegiline104 105 106 107



Contraindicated with nonselective MAO inhibitors;104 105 106 107 discontinue nonselective MAO inhibitor at least 2 weeks prior to initiation of levodopa104 105 106 107


May be administered concomitantly with a selective MAO inhibitor (e.g., selegiline) with caution104 105 106 107



Metoclopramide



Possible increase in bioavailability of levodopa104 105 106 107


Possible reduction in the therapeutic effects of levodopa104 105 106 107



Papaverine



Possible reduction in the therapeutic effects of levodopa104 105 106 107



Observe patient for loss of therapeutic effect104 105 106 107



Phenytoin



Possible reduction in the therapeutic effects of levodopa104 105 106 107



Observe patient for loss of therapeutic effect104 105 106 107



Protein



High protein diet may impair absorption104 105 106 107


Levodopa/Carbidopa 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.105


Bioavailability of levodopa from extended-release tablets 70–75% of that from conventional tablets.105


Extended-release tablets result in less fluctuation in plasma concentrations between doses than conventional tablets.105


Levodopa-carbodopa conventional tablets and orally disintegrating tablets begin to release the drugs within 30 minutes of administration.104 107 109 Pharmacokinetic values for orally disintegrating tablet are similar to those for the conventional tablet.109


Food


High protein diet may interfere with absorption of levodopa.104 105 106 107


Extended-release tablets: Food increases bioavailability and peak plasma concentrations of levodopa.105


Distribution


Extent


Widely distributed.d


<1% of levodopa penetrates the CNS;d carbidopa does not cross the blood-brain barrier.104 105 106 107


Plasma Protein Binding


Levodopa: 10–30%.106


Carbidopa: About 36%.106 d


Elimination


Metabolism


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


Carbidopa inhibits peripheral decarboxylation of levodopa, thus increasing availability of levodopa for distribution into the CNS.104 105 106 107


Elimination Route


Levodopa is excreted in urine as metabolites.d


Half-life


Levodopa: 1.5 hours when administered with carbidopa.104 105


Stability


Storage


Oral


Conventional Tablets

25°C (may be exposed to 15–30°C).106 107 108 Protect from light.107


Extended-release Tablets

Tight container; <30°C.105


Orally Disintegrating Tablets

Tight, light-resistant container; 20–25°C (may be exposed to 15–30°C).104


ActionsActions



  • Manifestations of parkinsonian syndrome related to depletion of dopamine in the corpus striatum.104 105 106 107




  • Levodopa relieves symptoms of parkinsonism presumably by increasing dopamine concentrations in the brain.104 105 106 107



Advice to Patients



  • Importance of taking levodopa/carbidopa at regular intervals as scheduled by the clinician.104 105 106 107 Importance of not altering the prescribed dosage regimen or adding other antiparkinsonian drugs.104 105 106 107




  • Advise patient not to chew or crush extended-release tablets; however, tablets may be halved.105




  • For patients taking orally disintegrating tablets, advise to gently remove the tablet from the bottle with dry hands just before administering a dose and then placing the tablet on the tongue to dissolve and be swallowed with saliva.104




  • Importance of informing patients with phenylketonuria that the orally disintegrating tablets contain aspartame.104




  • Advise patient to notify clinician if abnormal involuntary movements appear or get worse; dosage adjustment may be needed.104 105 106 107




  • Advise patient of expected onset and duration of effect.104 105 106 107




  • Possibility that dark color (red, brown, black) may appear in saliva, urine, or sweat; garments may be discolored.104 105 106 107




  • Advise patient that a change in diet to food high in protein may delay absorption of levodopa and reduce systemic availability.104 105 106 107 Excess acidity may delay absorption.104 105 106 107




  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.104 105 106 107




  • Risk of somnolence and episodes of sudden sleep onset; importance of exercising caution when driving or operating machinery and of refraining from such activities if somnolence and/or an episode of sudden sleep onset occurs.105 107




  • Importance of asking patients whether they have developed any new or increased gambling urges, sexual urges, or other urges while receiving levodopa-carbidopa and of advising them of the importance of reporting such urges.105 106 107




  • Importance of frequent monitoring for melanoma and periodic dermatologic examinations by a dermatologist.105 106 107




  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.104 105 106 107




  • Importance of advising patients of other important precautionary information.104 105 106 107 (See Cautions.)



Preparations


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.













Carbidopa

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Oral



Tablets



25 mg (of anhydrous carbidopa)



Lodosyn (scored)



Bristol-Myers Squibb


* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name









































































Carbidopa-Levodopa (Co-careldopa)

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Oral



Tablets



Carbidopa 10 mg (of anhydrous carbidopa) and Levodopa 100 mg*



Carbidopa and Levodopa Tablets



Sinemet (scored)



Bristol-Myers Squibb



Carbidopa 25 mg (of anhydours carbidopa) and Levodopa 100 mg*



Carbidopa and Levodopa Tablets



Sinemet (scored)



Bristol-Myers Squibb



Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 250 mg*



Carbidopa and Levodopa Tablets



Sinemet (scored)



Bristol-Myers Squibb



Tablets, extended-release



Carbidopa 50 mg (of anhydrous carbidopa) and Levodopa 200 mg*



Carbidopa and Levodopa Extended-release Tablets



Sinemet CR (scored)



Bristol-Myers Squibb



Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 100 mg*



Carbidopa and Levodopa Extended-release Tablets (scored)



Sinemet CR



Bristol-Myers Squibb



Tablets, orally disintegrating



Carbidopa 10 mg (of anhydrous carbidopa) and Levodopa 100 mg



Parcopa (scored)



Azur



Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 100 mg



Parcopa (scored)



Azur



Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 250 mg



Parcopa (scored)



Azur






































Other Carbidopa Combinations

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Oral



Tablets, film-coated



Carbidopa 12.5 mg (of anhydrous carbidopa) with Entacapone 200 mg and Levodopa 50 mg



Stalevo



Novartis



Carbidopa 18.75 mg (of anhydrous carbidopa) Entacapone 200 mg and Levodopa 75 mg



Stalevo



Novartis



Carbidopa 25 mg (of anhydrous carbidopa) with Entacapone 200 mg and Levodopa 100 mg



Stalevo



Novartis



Carbidopa 31.25 mg (of anhydrous carbidopa) Entacapone 200 mg and Levodopa 125 mg



Stalevo



Novartis



Carbidopa 37.5 mg (of anhydrous carbidopa) with Entacapone 200 mg and Levodopa 150 mg



Stalevo



Novartis



Carbidopa 50 mg (of anhydrous carbidopa) Entacapone 200 mg and Levodopa 200 mg



Stalevo



Novartis


Comparative Pricing


This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.


Carbidopa-Levodopa 10-100MG Tablets (TEVA PHARMACEUTICALS USA): 90/$34.99 or 180/$65.97


Carbidopa-Levodopa 25-100MG Tablets (ACTAVIS ELIZABETH): 90/$39.98 or 270/$101.98


Carbidopa-Levodopa 25-250MG Tablets (TEVA PHARMACEUTICALS USA): 60/$33.99 or 180/$82.98


Carbidopa-Levodopa CR 25-100MG Controlled-release Tablets (MYLAN): 60/$40.99 or 180/$116.98


Carbidopa-Levodopa CR 50-200MG Controlled-release Tablets (MYLAN): 60/$80.99 or 180/$221.98


Parcopa 25-100MG Dispersible Tablets (AZUR PHARMA): 30/$97.64 or 90/$234.33


Sinemet 10-100MG Tablets (MERCK SHARP &amp; DOHME): 90/$91.16 or 270/$256.57


Sinemet 25-100MG Tablets (MERCK SHARP &amp; DOHME): 90/$113.41 or 270/$305.96


Sinemet 25-250MG Tablets (MERCK SHARP &amp; DOHME): 60/$88.99 or 180/$255.97


Sinemet CR 25-100MG Controlled-release Tablets (MERCK SHARP &amp; DOHME): 60/$78.99 or 180/$225.96


Sinemet CR 50-200MG Controlled-release Tablets (MERCK SHARP &amp; DOHME): 60/$145.5 or 180/$417.26


Stalevo 100 25-100-200MG Tablets (NOVARTIS): 90/$318 or 270/$898.92


Stalevo 150 37.5-150-200MG Tablets (NOVARTIS): 30/$113.99 or 90/$334.97


Stalevo 200 50-200-200MG Tablets (NOVARTIS): 100/$363.99 or 300/$1043.97


Stalevo 50 12.5-50-200MG Tablets (NOVARTIS): 30/$110.98 or 90/$317.97



Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.


The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 01, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.


† Use is not currently included in the labeling approved by the US Food and Drug Administration.




References


Only references cited for selected revisions after 1984 are available electronically.



101. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001; 56:S1-S88.



102. Chong BS, Mersfelder TL. Entacapone. Ann Pharmacother. 2000; 34:1056-65. [IDIS 452302] [PubMed 10981253]



103. Anon. Initial treatment of Parkinson’s disease: wait just a minute. Med Lett Drugs Ther. 2001; 43:59-60. [PubMed 11445778]



104. Azur Pharma. Parcopa (carbidopa-levodopa) orally disintegrating tablets prescribing information. Philadelphia, PA; 2009 Sep.



105. Bristol-Myers Squibb. Sinemet CR (carbidopa-levodopa) sustained-release tablets prescribing information. Princeton, NJ; 2009 Jan.



106. Novartis. Stalevo 50, Stalevo 75, Stalevo 100, Stalevo 125, Stalevo 150, Stalevo 200 (carbidopa, levodopa and entacapone) tablets prescribing information. East Hanover, NJ; 2009 Mar.



107. Bristol-Myers Squibb. Sinemet (carbidopa-levodopa) tablets prescribing information. Princeton, NJ; 2009 Jan.



108. Bristol-Myers Squibb. Lodosyn (carbidopa) tablets prescribing information. Princeton, NJ; 2006 Sep.



109. Anon. Parcopa: a rapidly dissolving formulation of carbidopa/levodopa. Med Lett Drugs Ther. 2005; 47:12.



110. American Medical Association Council on Scientific Affairs. Aspartame: review of safety issues. JAMA. 1985; 254:400 2. [IDIS 202002] [PubMed 2861297]



111. Gossel TA. A review of aspartame: characteristics, safety and uses. US Pharm. 1984; 9:26,28 30.



112. Food and Drug Administration. Aspartame as an inactive ingredient in human drug products; labeling requirements. Proposed rule. [21 CFR Part 201] Fed Regist. 1983; 48:54993 5. (lDIS 178728)



113. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; aspartame. Final rule. [21 CFR Part 172] Fed Regist. 1983; 48:31376 82. (IDIS 172957)



114. Anon. Aspartame and other sweeteners. Med Lett Drugs Ther. 1982; 24:1 2. [PubMed 7054648]



d. AHFS drug information 2004. McEvoy GK, ed. Levodopa/carbidopa. Bethesda, MD: American Society of Health-System Pharmacists; 2005:2485-90.



e. AHFS drug information 2004. McEvoy GK, ed. Monoamine Oxidase Inhibitors General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2005:2174-80.



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