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Levodopa / Carbidopa

Pronunciation

Pronunciation: LEE-voe-DOE-puh/CAR-bih-doe-puh
Class: Antiparkinson agent

Trade Names

Parcopa
- Tablets, orally disintegrating 10 mg carbidopa and 100 mg levodopa
- Tablets, orally disintegrating 25 mg carbidopa and 100 mg levodopa
- Tablets, orally disintegrating 25 mg carbidopa and 250 mg levodopa

Sinemet 10/100
- Tablets 10 mg carbidopa and 100 mg levodopa

Sinemet 25/100
- Tablets 25 mg carbidopa and 100 mg levodopa

Sinemet 25/250
- Tablets 25 mg carbidopa and 250 mg levodopa

Sinemet CR
- Tablets, sustained-release 25 mg carbidopa and 100 mg levodopa
- Tablets, sustained-release 50 mg carbidopa and 200 mg levodopa

Apo-Levocarb (Canada)
Apo-Levocarb CR (Canada)

Pharmacology

Levodopa is precursor of dopamine, which is deficient in parkinsonism patients. Carbidopa has no activity of its own but inhibits decarboxylation of levodopa, making it more available to the brain.

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Indications and Usage

Treatment of symptoms of idiopathic Parkinson disease (paralysis agitans), postencephalitic parkinsonism and symptomatic parkinsonism associated with carbon monoxide and manganese poisoning.

Contraindications

Narrow-angle glaucoma; undiagnosed skin lesions or prior history of suspected melanoma; concurrent use of or within 2 wk of MAOIs.

Dosage and Administration

Individualize by careful titration. Combination tablets are available in ratios of carbidopa to levodopa of 1:4 (25 mg/100 mg) and 1:10 (10 mg/100 mg; 25 mg/250 mg). Tablets of the 2 ratios may be administered separately or combined as needed to provide optimum dosage. Provide at least 70 to 100 mg/day of carbidopa to reduce adverse reactions.

Immediate-Release Tablets
Adults

PO Starting dose: 1 tablet of 25 mg carbidopa/100 mg levodopa 3 times daily or 10 mg carbidopa/100 mg levodopa 3 to 4 times daily. Dosage may be increased by 1 tablet once daily or every other day as needed (max, 8 tablets/day).

Sustained-Release Tablets (50 mg carbidopa/200 mg levodopa)
Adults

PO Starting dose: 1 tablet at intervals at least 6 h. Adjust dosage based on response. Usual range is 2 to 8 tablets/day in divided doses 4 to 8 h while awake. Allow at least a 3-day interval between adjustments.

General Advice

  • Discontinue nonselective MAOIs at least 14 days before initiating therapy. Selective MAO type B inhibitor (eg, selegiline) can be used concomitantly as long as manufacturer's recommended dose is not exceeded.
  • If patient is being converted from plain levodopa, discontinue levodopa at least 12 h before initiating therapy with levodopa/carbidopa. Levodopa/carbidopa is generally started at dose providing approximately 25% of previous levodopa dose.
  • Immediate-release tablets can be added to dosage regimen of extended-release tablets in patients with advanced disease who need additional levodopa.
  • Administer prescribed dose without regard to meals. Administer with food if GI upset occurs. Do not administer with high-protein foods because they may reduce absorption and effectiveness.
Immediate-release tablets
  • Tablets of the 2 ratios (1:4 or 1:10) may be given separately or combined to provide optimum dosage.
Extended-release tablets
  • If patient is being converted from immediate-release carbidopa/levodopa to extended-release product, the extended-release carbidopa/levodopa is generally started at a dose that provides approximately 10% more levodopa.
  • Extended-release tablets may be administered as whole or half tablets that should not be crushed or chewed.
Orally disintegrating tablets
  • Contains phenylalanine. Do not administer orally disintegrating tablet to patient with phenylketonuria without first discussing with health care provider.
  • Orally disintegrating tablets of the 2 ratios (1:4 or 1:10) may be given separately or combined to provide optimum dosage.
  • Gently remove tablet from bottle with dry hands. Immediately place tablet on top of tongue and allow to dissolve, then have patient swallow with saliva. Administration with liquids is not necessary.

Storage/Stability

Store at controlled room temperature (59° to 86°F). Protect from light. Protect orally disintegrating tablet from moisture.

Drug Interactions

Antihypertensive drugs

May cause symptomatic orthostatic hypotension.

Butyrophenones, isoniazid, papaverine, phenothiazines, phenytoin, and risperidone

May reduce levodopa efficacy.

Iron salts

May reduce levodopa/carbidopa absorption, decreasing the clinical effects.

MAOIs

May result in hypertensive crisis. Use is contraindicated.

Metoclopramide

May increase levodopa/carbide absorption but, due to dopamine receptor antagonistic properties of metoclopramide, may also interfere with disease control.

Tricyclic antidepressants

Rare cases of hypertension and dyskinesia have occurred.

Laboratory Test Interactions

May cause false-positive reaction for urinary ketone bodies ( Clinitest ) and false-negative test results with glucose-oxidase methods of testing for glucosuria ( Clinistix , Tes-tape ). Pheochromocytoma has been falsely diagnosed in patients. Use caution when interpreting plasma and urine levels of catecholamines and their metabolites.

Adverse Reactions

Cardiovascular

Cardiac irregularities; palpitations; hypertension; phlebitis; orthostatic hypotension; MI; palpitation; syncope.

CNS

Paranoid delusions; psychotic episodes; depression; suicidal ideation; dementia; convulsions; hallucinations; dizziness; choreiform; dystonic and other involuntary movements; fatigue; malaise; asthenia; agitation; bradykinetic episodes (ie, on-off phenomenon); confusion; dream abnormalities (including nightmares); headache; increased libido; insomnia; neuroleptic malignant syndrome; paresthesia.

EENT

Diplopia; blurred vision.

GI

Nausea; anorexia; vomiting; GI distress; epigastric pain; GI bleeding; dry mouth; duodenal ulcer; constipation; altered taste; dark saliva; diarrhea.

Genitourinary

Dark urine; urinary retention; urinary incontinence; priapism; UTI; urinary frequency.

Hematologic

Hemolytic and nonhemolytic anemia; thrombocytopenia; leukopenia; agranulocytosis.

Hepatic

Elevated LFT results; hepatotoxicity.

Hypersensitivity

Angioedema; bullous lesions (including pemphigus-like reactions); Henoch-Schonlein purpura; pruritus; urticaria.

Lab Tests

Positive Coombs' test; decreased hemoglobin and hematocrit; abnormalities in bilirubin, BUN, and lactic dehydrogenase; elevated serum glucose; WBC, bacteria, and blood in urine.

Musculoskeletal

Back pain; muscle cramps; shoulder pain.

Respiratory

Dyspnea; upper respiratory tract infection.

Miscellaneous

Flushing; chest pain; increased sweating; dark sweat; rash.

Precautions

Pregnancy

Category C . Safety and effects unknown.

Lactation

Undetermined.

Special Risk Patients

Use drug with caution in patients with wide-angle glaucoma; severe CV or pulmonary disease; bronchial asthma; renal, hepatic, or endocrine disease; or history of depression or suicidal tendencies.

Abrupt withdrawal

Rapid withdrawal of antiparkinson drugs may produce symptoms of neuroleptic malignant syndrome.

Dose conversion

Patients previously given levodopa alone should discontinue levodopa use at least 12 h before starting carbidopa/levodopa. Eventually substitute combination drug at dosage providing about 25% of previous levodopa dose.

GI hemorrhage

Upper GI hemorrhage has been reported in patients with history of peptic ulcer.

MI

Closely monitor cardiac function in patients with previous history of MI who have residual arrhythmias when initiating drug dosage adjustment in facility with provisions for intensive cardiac care.

Neurologic/Psychiatric effects

Levodopa may cause involuntary movement and mental disturbances. Use drug with caution in patients with psychosis. Dyskinesias may occur at lower doses and sooner than with levodopa alone. Reduce dosages if necessary.

Overdosage

Symptoms

Muscle twitching, blepharospasm, arrhythmias.

Patient Information

  • Advise patient, family, or caregiver that medication is not a cure for Parkinson disease but may help reduce the symptoms of Parkinson disease.
  • Advise patient, family, or caregiver that medication is started at a low dose, gradually increased to achieve maximum benefit, and then may be periodically adjusted during long term therapy to maintain maximum benefit and minimize side effects.
  • Advise patient, family, or caregiver that medication can be taken without regard to meals but to take with food if GI upset occurs. However, caution against taking carbidopa/levodopa with high-protein foods because they may reduce absorption and effectiveness of carbidopa/levodopa.
  • Advise patient, family, or caregiver that medication should not be taken at the same time as iron salts (eg, multivitamins) because the iron can reduce absorption and effectiveness of carbidopa/levodopa.
  • Advise patient, family, and/or caregiver that medication should be taken exactly as prescribed and not to stop taking or change the dose unless advised by health care provider. Emphasize that medication must be taken at regular intervals to obtain max benefit.
  • Advise patient using extended-release tablet to swallow tablet or half tablet (if split) whole and not to crush or chew the tablet.
  • Advise patient using orally disintegrating tablet to gently remove tablet from bottle with dry hands, immediately place tablet on top of tongue, and allow to dissolve, then swallow with saliva. Advise patient that administration with liquids is not necessary.
  • Advise patient, family and/or caregiver that if a dose is missed that it should be taken as soon as remembered unless it is nearing time for the next scheduled dose, in which case, the dose should be skipped and the next dose taken at the regularly scheduled time. Caution patient to never double the dose to catch up or take more than the prescribed total daily dose.
  • Advise patient to continue to take other antiparkinson medications as prescribed by health care provider.
  • Caution patient to avoid sudden position changes to prevent orthostatic hypotension (dizziness or faintness when arising suddenly from a sitting or lying position).
  • Advise patient that drug may cause dizziness or other nervous system disorders and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patient, family, or caregiver that medication may cause a red, brown, or black discoloration of saliva, urine, or sweat that is not harmful but may discolor clothing or bedding.
  • Advise patient, family, or caregiver to report any of the following to health care provider: worsening of Parkinson symptoms before next dose (wearing off effect); frequent or persistent nausea or vomiting; involuntary body or facial movements; mood or mental changes; hallucinations; any unexplained symptom or problem.

Copyright © 2009 Wolters Kluwer Health.

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