Carbidopa

Carbidopa
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anusha Vege, M.B.B.S. [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Overview

Carbidopa is an anti-dyskinesia agent and antiparkinson agent that is FDA approved for the treatment of idiopathic Parkinson's disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism. Common adverse reactions include dyskinesia and nausea.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Carbidopa Tablets are indicated for use with carbidopa-levodopa or with levodopa in the treatment of the symptoms of idiopathic Parkinson’s disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism, which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication.

Whether given with carbidopa-levodopa or with levodopa, the optimal daily dose of Carbidopa must be determined by careful titration. Most patients respond to a 1:10 proportion of carbidopa and levodopa, provided the daily dosage of carbidopa is 70 mg or more a day. The maximum daily dosage of carbidopa should not exceed 200 mg, since clinical experience with larger dosages is limited. If the patient is taking carbidopa-levodopa, the amount of carbidopa in carbidopa-levodopa should be considered when calculating the total amount of Carbidopa to be administered each day.

Patients Receiving Carbidopa-Levodopa Who Require Additional Carbidopa

Some patients taking carbidopa-levodopa may not have adequate reduction in nausea and vomiting when the dosage of carbidopa is less than 70 mg a day, and the dosage of levodopa is less than 700 mg a day. When these patients are taking carbidopa-levodopa, 25 mg of Carbidopa may be given with the first dose of carbidopa-levodopa each day. Additional doses of 12.5 mg or 25 mg may be given during the day with each dose of carbidopa-levodopa. Carbidopa may be given with any dose carbidopa-levodopa as required for optimum therapeutic response. The maximum daily dosage of carbidopa, given as Carbidopa and as carbidopa- levodopa), should not exceed 200 mg.

Patients Requiring Individual Titration of Carbidopa and Levodopa Dosage

Although carbidopa-levodopa is the most frequently used of carbidopa and levodopa administration, there may be an occasional patient who requires individually titrated doses of these two drugs. In these patients, carbidopa should be initiated at a dosage of 25 mg three or four times a day. The two drugs should be given at the same time, starting with no more than one-fifth (20%) to one-fourth (25%) of the previous or recommended daily dosage of levodopa when given without Carbidopa. In patients already receiving levodopa therapy, at least twelve hours should elapse between the last dose of levodopa and initiation of therapy with Carbidopa and levodopa. A convenient way to initiate therapy in these patients is in the morning following a night when the patient has not taken levodopa for at least twelve hours. Health care providers who prescribe separate doses of Carbidopa and levodopa should be thoroughly familiar with the directions for use of each drug.

Dosage Adjustment

Dosage of Carbidopa may be adjusted by adding or omitting one-half or one tablet a day. Because both therapeutic and adverse responses occur more rapidly with combined therapy than when only levodopa is given, patients should be monitored closely during the dose adjustment period. Specifically, involuntary movements will occur more rapidly when Carbidopa and levodopa are given concomitantly than when levodopa is given without Carbidopa. The occurrence of involuntary movements may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients.

Current evidence indicates other standard antiparkinsonian drugs may be continued while carbidopa and levodopa are being administered. However, the dosage of such other standard antiparkinsonian drugs may require adjustment.

Interruption of Therapy

Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of carbidopa-levodopa) or carbidopa-levodopa Extended Release. Patients should be observed carefully if abrupt reduction or discontinuation of carbidopa-levodopa or carbidopa-levodopa Extended-Release is required, especially if the patient is receiving neuroleptics.

If general anesthesia is required, therapy may be continued as long as the patient is permitted to take fluids and medication by mouth. When therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS, and the usual daily dosage may be resumed as soon as the patient is able to take medication orally.

Carbidopa is for use with carbidopa-levodopa in patients for whom the dosage of carbidopa-levodopa provides less than adequate daily dosage (usually 70 mg daily) of carbidopa.

Carbidopa is for use with levodopa in the occasional patient whose dosage requirement of carbidopa and levodopa necessitates separate titration of each medication Carbidopa is used with carbidopa-levodopa or with levodopa to permit the administration of lower doses of levodopa with reduced nausea and vomiting, more rapid dosage titration, and with a somewhat smoother response. However, patients with markedly irregular (“on-off”) responses to levodopa have not been shown to benefit from the addition of carbidopa.

Since carbidopa prevents the reversal of levodopa effects caused by pyridoxine, supplemental pyridoxine (vitamin B6), can be given to patients when they are receiving carbidopa and levodopa concomitantly or as carbidopa-levodopa.

Although the administration of Carbidopa permits control of parkinsonism and Parkinson’s disease with much lower doses of levodopa, there is no conclusive evidence at present that this is beneficial other than in reducing nausea and vomiting, permitting more rapid titration, and providing a somewhat smoother response to levodopa.

Certain patients who responded poorly to levodopa alone have improved when carbidopa and levodopa were given concurrently. This was most likely due to decreased peripheral decarboxylation of levodopa rather than to a primary effect of carbidopa on the peripheral nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa.

In deciding whether to give Carbidopa with carbidopa-levodopa or with levodopa to patients who have nausea and/or vomiting, the physician should be aware that, while many patients may be expected to improve, some may not. Since one cannot predict which patients are likely to improve, this can only be determined by a trial of therapy. It should be further noted that in controlled trials comparing carbidopa and levodopa with levodopa alone, about half the patients with nausea and/or vomiting on levodopa alone improved spontaneously despite being retained on the same dose of levodopa during the controlled portion of the trial.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Carbidopa in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Carbidopa in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and effectiveness in pediatric patients have not been established, and use of the drug in patients below the age of 18 is not recommended.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Carbidopa in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Carbidopa in pediatric patients.

Contraindications

• Carbidopa is contraindicated in patients with known hypersensitivity to any component of this drug.

• Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with levodopa or carbidopa-levodopa combination products with or without Carbidopa. These inhibitors must be discontinued at least two weeks prior to initiating therapy with levodopa. Carbidopa-levodopa or levodopa may be administered concomitantly with the manufacturer’s recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl).

• Levodopa or carbidopa-levodopa products, with or without Carbidopa, are contraindicated in patients with narrow-angle glaucoma.

Warnings

Carbidopa has no antiparkinsonian effect when given alone. It is indicated for use with carbidopa-levodopa or levodopa. Carbidopa does not decrease adverse reactions due to central effects of levodopa.

When Carbidopa is to be given to carbidopa-naive patients who are being treated with levodopa alone, the two drugs should be given at the same time. At least twelve hours should elapse between the last dose of levodopa and initiation of therapy with Carbidopa and levodopa in combination. Start with no more than one-fifth (20%) to one-fourth (25%) of the previous daily dosage of levodopa when given without Carbidopa. See the DOSAGE AND ADMINISTRATION section before initiating therapy.

The addition of Carbidopa with levodopa or carbidopa-levodopa reduces the peripheral effects (nausea, vomiting) due to decarboxylation of levodopa; however, Carbidopa does not decrease the adverse reactions due to the central effects of levodopa. Because Carbidopa permits more levodopa to reach the brain and more dopamine to be formed, certain adverse central nervous system (CNS) effects, e.g., dyskinesias (involuntary movements), may occur at lower dosages and sooner with levodopa in combination with Carbidopa than with levodopa alone.

Falling Asleep During Activities of Daily Living and Somnolence

Adverse Reactions

Clinical Trials Experience

Carbidopa has not been demonstrated to have any overt pharmacodynamic actions in the recommended doses. The only adverse reactions that have been observed have been with concomitant use of carbidopa with other drugs such as levodopa, and with carbidopalevodopa combination products. When LODOSYN is administered concomitantly with levodopa or carbidopa-levodopa combination products, the most common adverse reactions have included dyskinesias such as choreiform, dystonic, and other involuntary movements, and nausea. Other adverse reactions reported with LODOSYN when administered concomitantly with levodopa alone or carbidopa-levodopa combination products were psychotic episodes including delusions, hallucinations, and paranoid ideation, depression with or without development of suicidal tendencies, and dementia. Convulsions also have occurred; however, a causal relationship with concomitant use of LODOSYN and levodopa has not been established. The following other adverse reactions have been reported with levodopa and carbidopa-levodopa combination products. These same adverse reactions may also occur when LODOSYN is administered with these products.

• Body as a Whole: abdominal pain and distress, asthenia, chest pain, fatigue.
• Cardiovascular: cardiac irregularities, hypertension, myocardial infarction, hypotension including orthostatic hypotension, palpitation, phlebitis, syncope.
• Gastrointestinal: anorexia, bruxism, burning sensation of the tongue, constipation, dark saliva, development of duodenal ulcer, diarrhea, dry mouth, dyspepsia, dysphagia, flatulence, gastrointestinal bleeding, gastrointestinal pain, heartburn, hiccups, sialorrhea, taste alterations, vomiting.
• Hematologic: hemolytic and non-hemolytic anemia, leukopenia, thrombocytopenia, agranulocytosis.
• Hypersensitivity: angioedema, urticaria, pruritus, Henoch-Schonlein purpura, bullous lesions (including pemphigus-like reactions).
• Metabolic: edema, weight gain, weight loss.
• Musculoskeletal: back pain, leg pain, muscle cramps, shoulder pain.
• Nervous System/Psychiatric: Psychotic episodes including delusions, hallucinations and paranoid ideation,neuroleptic malignant syndrome (NMS, see WARNINGS), bradykinetic episodes (“on-off”phenomenon),confusion, agitation, dizziness, somnolence, dream abnormalities including nightmares,insomnia, paresthesia, headache, depression with or without development of suicidal tendencies, dementia, pathological gambling, increased libido including hypersexuality, impulse control symptoms. Convulsions also have occurred; however, a causal relationship with LODOSYN and levodopa, has not been established.
• Skin: flushing, increased sweating, malignant melanoma (see also CONTRAINDICATIONS ), rash, alopecia, dark sweat.
• Special Senses: oculogyric crises, diplopia, blurred vision, dilated pupils.
• Urogenital: dark urine, priapism, urinary frequency, urinary incontinence, urinary retention, urinary tract infection.
• Laboratory Tests: abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase, bilirubin, blood urea nitrogen (BUN), Coombs test; elevated serum glucose; decreased hemoglobin and hematocrit; decreased white blood cell count and serum potassium; increased serum creatinine and uric acid; white blood cells, bacteria and blood in the urine; protein and glucose in the urine.
• Miscellaneous: bizarre breathing patterns, faintness, hoarseness, hot flashes, malaise, neuroleptic malignant syndrome, sense of stimulation.

Postmarketing Experience

There is limited information regarding Carbidopa Postmarketing Experience in the drug label.

Drug Interactions

Caution should be exercised when the following drugs are administered concomitantly with Carbidopa given with levodopa or carbidopa-levodopa fixed-dose combination products.

Symptomatic postural hypotension has occurred when Carbidopa, given with levodopa or carbidopa-levodopa combination products, was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with Carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

For patients receiving monoamine oxidase inhibitors (Type A or B), see CONTRAINDICATIONS. Concomitant therapy with selegiline and rasigiline and carbidopa and carbidopa-levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa-levodopa alone (see CONTRAINDICATIONS).

There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and carbidopa-levodopa preparations.

Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the therapeutic effects of levodopa. In addition, the beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with Carbidopa and levodopa or carbidopa-levodopa combination products should be carefully observed for loss of therapeutic response.

Carbidopa and iron salts or multivitamins containing iron salts should be coadministered with caution. Iron salts can form chelates with levodopa and carbidopa and consequently reduce the bioavailability of carbidopa and levodopa.

Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also adversely affect disease control by its dopamine receptor antagonistic properties.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C There are no adequate and well-controlled studies with Carbidopa in pregnant women. It has been reported from individual cases that levodopa crosses the human placental barrier, enters the fetus, and is metabolized. Carbidopa concentrations in fetal tissue appeared to be minimal. Carbidopa should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Carbidopa, at doses as high as 120 mg/kg/day, was without teratogenic effects in the mouse or rabbit. In the rabbit, but not in the mouse, carbidopa-levodopa produced visceral anomalies, similar to those seen with levodopa alone, at approximately 7 times the maximum recommended human dose. The teratogenic effect of levodopa in rabbits was unchanged by the concomitant administration of carbidopa.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Carbidopa in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Carbidopa during labor and delivery.

Nursing Mothers

t is not known whether carbidopa is excreted in human milk. Because many drugs are excreted in human milk, and because of their potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established, and use of the drug in patients below the age of 18 is not recommended.

Geriatic Use

Clinical studies of Carbidopa did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease and other drug therapy.

Gender

There is no FDA guidance on the use of Carbidopa with respect to specific gender populations.

Race

There is no FDA guidance on the use of Carbidopa with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Carbidopa in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Carbidopa in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Carbidopa in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Carbidopa in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Carbidopa Administration in the drug label.

Monitoring

There is limited information regarding Carbidopa Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Carbidopa and IV administrations.

Overdosage

There is limited information regarding Carbidopa overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Carbidopa Pharmacology in the drug label.

Mechanism of Action

Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson's disease apparently because it does not cross the blood-brain barrier. However, levodopa, the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves symptoms of Parkinson's disease.

Structure

There is limited information regarding Carbidopa Structure in the drug label.

Pharmacodynamics

When levodopa is administered orally it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. For this reason, large doses of levodopa are required for adequate therapeutic effect and these may often be accompanied by nausea and other adverse reactions, some of which are attributable to dopamine formed in extracerebral tissues.

The incidence of levodopa-induced nausea and vomiting is less when Carbidopa is used with levodopa than when levodopa is used without Carbidopa. In many patients this reduction in nausea and vomiting will permit more rapid dosage titration.

Carbidopa inhibits decarboxylation of peripheral levodopa. Carbidopa has not been demonstrated to have any overt pharmacodynamic actions in the recommended doses. It does not appear to cross the blood-brain barrier readily and does not affect the metabolism of levodopa within the central nervous system at doses of carbidopa that are recommended for maximum effective inhibition of peripheral decarboxylation of levodopa.

Since its decarboxylase-inhibiting activity is limited primarily to extracerebral tissues, administration of carbidopa with levodopa makes more levodopa available for transport to the brain. However, since levodopa and carbidopa compete with certain amino acids for transport across the gut wall, the absorption of levodopa and carbidopa may be impaired in some patients on a high protein diet.

Pharmacokinetics

Carbidopa reduces the amount of levodopa required to produce a given response by about 75% and, when administered with levodopa, increases both plasma levels and the plasma half-life of levodopa, and decreases plasma and urinary dopamine and homovanillic acid.

In clinical pharmacologic studies, simultaneous administration of separate tablets of carbidopa and levodopa produced greater urinary excretion of levodopa in proportion to the excretion of dopamine when compared to the two drugs administered at separate times.

Supplemental pyridoxine (vitamin B6) can be given to patients when they are receiving carbidopa and levodopa concomitantly or the fixed combination carbidopa-levodopa or carbidopa-levodopa extended release. Previous reports in the medical literature cautioned that high doses of vitamin B6 should not be taken by patients on levodopa therapy alone because exogenously administered pyridoxine would enhance the metabolism of levodopa to dopamine. The introduction of carbidopa to levodopa therapy, which inhibits the peripheral decarboxylation of levodopa to dopamine, counteracts the metabolic-enhancing effect of pyridoxine.

Carbidopa is combined with levodopa in carbidopa-levodopa and carbidopa-levodopa extended release tablets.

Nonclinical Toxicology

There is limited information regarding Carbidopa Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Carbidopa Clinical Studies in the drug label.

How Supplied

carbidopa Tablets, 25 mg, are orange, round, compressed tablets that are scored and coded 711 on one side and LODOSYN on the other.

They are supplied as follows:

NDC 68682-200-25 bottles of 100.

Storage

Store at 25°C (77°F), excursions permitted to 15–30°C (59–86°F).

Images

Drug Images

{{#ask: Page Name::Carbidopa |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Carbidopa |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Carbidopa Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Carbidopa interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Carbidopa Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Carbidopa Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.