Carbidopa And Levodopa
Carbidopa And Levodopa Prescribing Information
Carbidopa and levodopa extended-release tablets are indicated in the treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.
Carbidopa and levodopa extended-release tablet contains carbidopa and levodopa in a 1:4 ratio as either the 50 mg/200 mg tablet or the 25 mg/100 mg tablet. The daily dosage of carbidopa and levodopa extended-release tablets must be determined by careful titration. Patients should be monitored closely during the dose adjustment period, particularly with regard to appearance or worsening of involuntary movements, dyskinesias or nausea. Carbidopa and levodopa extended-release tablets should not be chewed or crushed.
Standard drugs for Parkinson's disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while carbidopa and levodopa extended-release tablet is being administered, although their dosage may have to be adjusted.
Since carbidopa prevents the reversal of levodopa effects caused by pyridoxine, carbidopa and levodopa extended-release tablets can be given to patients receiving supplemental pyridoxine (vitamin B
6).
Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with carbidopa and levodopa extended-release tablets. These inhibitors must be discontinued at least two weeks prior to initiating therapy with carbidopa and levodopa extended-release tablets. Carbidopa and levodopa extended-release tablets may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl) (see
As with levodopa, periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are recommended during extended therapy.
Patients with chronic wide-angle glaucoma may be treated cautiously with carbidopa and levodopa extended-release tablets provided the intraocular pressure is well-controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.
Levodopa alone, as well as carbidopa and levodopa extended-release tablets, is associated with dyskinesias. The occurrence of dyskinesias may require dosage reduction.
Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In general, hallucinations present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa. Hallucinations may be accompanied by confusion and to a lesser extent sleep disorder (insomnia) and excessive dreaming.
Carbidopa and levodopa extended-release tablets may have similar effects on thinking and behavior. This abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.
Ordinarily, patients with a major psychotic disorder should not be treated with carbidopa and levodopa extended-release tablets, because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson’s disease and may decrease the effectiveness of carbidopa and levodopa extended-release tablets.
Reports of patients taking dopaminergic medications (medications that increase central dopaminergic tone), suggest that patients may experience an intense urge to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or the caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with carbidopa and levodopa extended-release tablets. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa extended-release tablets [see Information for Patients].
Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, is unclear.
For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using carbidopa and levodopa extended-release tablets for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
The patient should be informed that carbidopa and levodopa extended-release tablet is an extended-release formulation of carbidopa levodopa which releases these ingredients over a 4- to 6-hour period. It is important that carbidopa and levodopa extended-release tablets be taken at regular intervals according to the schedule outlined by the physician. The patient should be cautioned not to change the prescribed dosage regimen and not to add any additional antiparkinson medications, including other carbidopa levodopa preparations, without first consulting the physician.
If abnormal involuntary movements appear or get worse during treatment with carbidopa and levodopa extended-release tablets, the physician should be notified, as dosage adjustment may be necessary.
Patients should be advised that sometimes the onset of effect of the first morning dose of carbidopa and levodopa extended-release tablets may be delayed for up to 1 hour compared with the response usually obtained from the first morning dose of carbidopa and levodopa tablets. The physician should be notified if such delayed responses pose a problem in treatment.
Patients should be advised that, occasionally, dark color (red, brown, or black) may appear in saliva, urine, or sweat after ingestion of carbidopa and levodopa extended-release tablets. Although the color appears to be clinically insignificant, garments may become discolored.
The patient should be informed that a change in diet to foods that are high in protein may delay the absorption of levodopa and may reduce the amount taken up in the circulation. Excessive acidity also delays stomach emptying, thus delaying the absorption of levodopa. Iron salts (such as in multivitamin tablets) may also reduce the amount of levodopa available to the body. The above factors may reduce the clinical effectiveness of the levodopa or carbidopa levodopa therapy.
Patients must be advised that the whole or half tablet should be swallowed without chewing or crushing.
Patients should be alerted to the possibility of sudden onset of sleep during daily activities, in some cases without awareness or warning signs, when they are taking dopaminergic agents, including levodopa. Patients should be advised to exercise caution while driving or operating machinery and that if they have experienced somnolence and/or sudden sleep onset, they must refrain from these activities. (See WARNINGS, Falling Asleep During Activities of Daily Living and Somnolence.)
There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease, including carbidopa and levodopa extended-release tablets. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges or other urges while being treated with carbidopa and levodopa extended-release tablets. Patients should inform their physician if they experience new or increased gambling urges, increased sexual urges, or other intense urges while taking carbidopa and levodopa extended-release tablets. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa extended-release tablets. (See PRECAUTIONS, Impulse Control / Compulsive Behaviors).
Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen (BUN) and positive Coombs test have also been reported. Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of carbidopa levodopa preparations than with levodopa.
Carbidopa levodopa preparations, such as carbidopa and levodopa tablets and carbidopa and levodopa extended-release tablets, may cause a false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. This reaction will not be altered by boiling the urine specimen. False-negative tests may result with the use of glucose- oxidase methods of testing for glucosuria.
Cases of falsely diagnosed pheochromocytoma in patients on carbidopa levodopa therapy have been reported very rarely. Caution should be exercised when interpreting the plasma and urine levels of catecholamines and their metabolites in patients on levodopa or carbidopa levodopa therapy.
Symptomatic postural hypotension has occurred when carbidopa levodopa preparations were added to the treatment of patients receiving some antihypertensive drugs. Therefore, when therapy with carbidopa and levodopa extended-release tablets is started, dosage adjustment of the antihypertensive drug may be required.
For patients receiving MAO inhibitors (Type A or B), see CONTRAINDICATIONS. Concomitant therapy with selegiline 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 D2receptor 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 extended-release tablets should be carefully observed for loss of therapeutic response.
Use of carbidopa and levodopa extended-release tablets with dopamine-depleting agents (e.g., reserpine and tetrabenazine) or other drugs known to deplete monoamine stores is not recommended.
Carbidopa and levodopa extended-release tablets 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.
In a two-year bioassay of carbidopa and levodopa tablets, no evidence of carcinogenicity was found in rats receiving doses of approximately two times the maximum daily human dose of carbidopa and four times the maximum daily human dose of levodopa (equivalent to 8 carbidopa and levodopa extended-release tablets).
In reproduction studies with carbidopa and levodopa tablets, no effects on fertility were found in rats receiving doses of approximately two times the maximum daily human dose of carbidopa and four times the maximum daily human dose of levodopa (equivalent to 8 carbidopa and levodopa extended-release tablets).
No teratogenic effects were observed in a study in mice receiving up to 20 times the maximum recommended human dose of carbidopa and levodopa tablets. There was a decrease in the number of live pups delivered by rats receiving approximately two times the maximum recommended human dose of carbidopa and approximately five times the maximum recommended human dose of levodopa during organogenesis. Carbidopa and levodopa tablets caused both visceral and skeletal malformations in rabbits at all doses and ratios of carbidopa/levodopa tested, which ranged from 10 times/5 times the maximum recommended human dose of carbidopa/levodopa to 20 times/10 times the maximum recommended human dose of carbidopa/levodopa.
There are no adequate or well-controlled studies 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. Use of carbidopa and levodopa extended-release tablets in women of childbearing potential requires that the anticipated benefits of the drug be weighed against possible hazards to mother and child.
Levodopa has been detected in human milk. Caution should be exercised when carbidopa and levodopa extended-release tablets are administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established. Use of the drug in patients below the age of 18 is not recommended.
In the clinical efficacy trials for carbidopa and levodopa tablets, almost half of the patients were older than 65, but few were older than 75. No overall meaningful differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals to adverse drug reactions such as hallucinations cannot be ruled out. There is no specific dosing recommendation based upon clinical pharmacology data as carbidopa and levodopa tablets and carbidopa and levodopa extended-release tablets are titrated as tolerated for clinical effect.
As with levodopa, periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are recommended during extended therapy.
Patients with chronic wide-angle glaucoma may be treated cautiously with carbidopa and levodopa extended-release tablets provided the intraocular pressure is well-controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.
Levodopa alone, as well as carbidopa and levodopa extended-release tablets, is associated with dyskinesias. The occurrence of dyskinesias may require dosage reduction.
Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In general, hallucinations present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa. Hallucinations may be accompanied by confusion and to a lesser extent sleep disorder (insomnia) and excessive dreaming.
Carbidopa and levodopa extended-release tablets may have similar effects on thinking and behavior. This abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.
Ordinarily, patients with a major psychotic disorder should not be treated with carbidopa and levodopa extended-release tablets, because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson’s disease and may decrease the effectiveness of carbidopa and levodopa extended-release tablets.
Reports of patients taking dopaminergic medications (medications that increase central dopaminergic tone), suggest that patients may experience an intense urge to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or the caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with carbidopa and levodopa extended-release tablets. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa extended-release tablets [see Information for Patients].
Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, is unclear.
For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using carbidopa and levodopa extended-release tablets for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
The patient should be informed that carbidopa and levodopa extended-release tablet is an extended-release formulation of carbidopa levodopa which releases these ingredients over a 4- to 6-hour period. It is important that carbidopa and levodopa extended-release tablets be taken at regular intervals according to the schedule outlined by the physician. The patient should be cautioned not to change the prescribed dosage regimen and not to add any additional antiparkinson medications, including other carbidopa levodopa preparations, without first consulting the physician.
If abnormal involuntary movements appear or get worse during treatment with carbidopa and levodopa extended-release tablets, the physician should be notified, as dosage adjustment may be necessary.
Patients should be advised that sometimes the onset of effect of the first morning dose of carbidopa and levodopa extended-release tablets may be delayed for up to 1 hour compared with the response usually obtained from the first morning dose of carbidopa and levodopa tablets. The physician should be notified if such delayed responses pose a problem in treatment.
Patients should be advised that, occasionally, dark color (red, brown, or black) may appear in saliva, urine, or sweat after ingestion of carbidopa and levodopa extended-release tablets. Although the color appears to be clinically insignificant, garments may become discolored.
The patient should be informed that a change in diet to foods that are high in protein may delay the absorption of levodopa and may reduce the amount taken up in the circulation. Excessive acidity also delays stomach emptying, thus delaying the absorption of levodopa. Iron salts (such as in multivitamin tablets) may also reduce the amount of levodopa available to the body. The above factors may reduce the clinical effectiveness of the levodopa or carbidopa levodopa therapy.
Patients must be advised that the whole or half tablet should be swallowed without chewing or crushing.
Patients should be alerted to the possibility of sudden onset of sleep during daily activities, in some cases without awareness or warning signs, when they are taking dopaminergic agents, including levodopa. Patients should be advised to exercise caution while driving or operating machinery and that if they have experienced somnolence and/or sudden sleep onset, they must refrain from these activities. (See WARNINGS, Falling Asleep During Activities of Daily Living and Somnolence.)
There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease, including carbidopa and levodopa extended-release tablets. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges or other urges while being treated with carbidopa and levodopa extended-release tablets. Patients should inform their physician if they experience new or increased gambling urges, increased sexual urges, or other intense urges while taking carbidopa and levodopa extended-release tablets. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa extended-release tablets. (See PRECAUTIONS, Impulse Control / Compulsive Behaviors).
Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen (BUN) and positive Coombs test have also been reported. Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of carbidopa levodopa preparations than with levodopa.
Carbidopa levodopa preparations, such as carbidopa and levodopa tablets and carbidopa and levodopa extended-release tablets, may cause a false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. This reaction will not be altered by boiling the urine specimen. False-negative tests may result with the use of glucose- oxidase methods of testing for glucosuria.
Cases of falsely diagnosed pheochromocytoma in patients on carbidopa levodopa therapy have been reported very rarely. Caution should be exercised when interpreting the plasma and urine levels of catecholamines and their metabolites in patients on levodopa or carbidopa levodopa therapy.
Symptomatic postural hypotension has occurred when carbidopa levodopa preparations were added to the treatment of patients receiving some antihypertensive drugs. Therefore, when therapy with carbidopa and levodopa extended-release tablets is started, dosage adjustment of the antihypertensive drug may be required.
For patients receiving MAO inhibitors (Type A or B), see CONTRAINDICATIONS. Concomitant therapy with selegiline 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 D2receptor 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 extended-release tablets should be carefully observed for loss of therapeutic response.
Use of carbidopa and levodopa extended-release tablets with dopamine-depleting agents (e.g., reserpine and tetrabenazine) or other drugs known to deplete monoamine stores is not recommended.
Carbidopa and levodopa extended-release tablets 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.
In a two-year bioassay of carbidopa and levodopa tablets, no evidence of carcinogenicity was found in rats receiving doses of approximately two times the maximum daily human dose of carbidopa and four times the maximum daily human dose of levodopa (equivalent to 8 carbidopa and levodopa extended-release tablets).
In reproduction studies with carbidopa and levodopa tablets, no effects on fertility were found in rats receiving doses of approximately two times the maximum daily human dose of carbidopa and four times the maximum daily human dose of levodopa (equivalent to 8 carbidopa and levodopa extended-release tablets).
No teratogenic effects were observed in a study in mice receiving up to 20 times the maximum recommended human dose of carbidopa and levodopa tablets. There was a decrease in the number of live pups delivered by rats receiving approximately two times the maximum recommended human dose of carbidopa and approximately five times the maximum recommended human dose of levodopa during organogenesis. Carbidopa and levodopa tablets caused both visceral and skeletal malformations in rabbits at all doses and ratios of carbidopa/levodopa tested, which ranged from 10 times/5 times the maximum recommended human dose of carbidopa/levodopa to 20 times/10 times the maximum recommended human dose of carbidopa/levodopa.
There are no adequate or well-controlled studies 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. Use of carbidopa and levodopa extended-release tablets in women of childbearing potential requires that the anticipated benefits of the drug be weighed against possible hazards to mother and child.
Levodopa has been detected in human milk. Caution should be exercised when carbidopa and levodopa extended-release tablets are administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established. Use of the drug in patients below the age of 18 is not recommended.
In the clinical efficacy trials for carbidopa and levodopa tablets, almost half of the patients were older than 65, but few were older than 75. No overall meaningful differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals to adverse drug reactions such as hallucinations cannot be ruled out. There is no specific dosing recommendation based upon clinical pharmacology data as carbidopa and levodopa tablets and carbidopa and levodopa extended-release tablets are titrated as tolerated for clinical effect.
carbidopa and levodopa extended-release tablets are contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma.
In controlled clinical trials, patients predominantly with moderate to severe motor fluctuations while on carbidopa and levodopa tablets were randomized to therapy with either carbidopa and levodopa tablets or carbidopa and levodopa extended-release tablets. The adverse experience frequency profile of carbidopa and levodopa extended-release tablets did not differ substantially from that of carbidopa and levodopa extended-release tablets, as shown in Table 1.
Carbidopa and levodopa extended-release tablets | Carbidopa and levodopa tablets | |
n=491 | n=524 | |
Adverse Experience | % | % |
Dyskinesia | 16.5 | 12.2 |
Nausea | 5.5 | 5.7 |
Hallucinations | 3.9 | 3.2 |
Confusion | 3.7 | 2.3 |
Dizziness | 2.9 | 2.3 |
Depression | 2.2 | 1.3 |
Urinary tract infection | 2.2 | 2.3 |
Headache | 2.0 | 1.9 |
Dream abnormalities | 1.8 | 0.8 |
Dystonia | 1.8 | 0.8 |
Vomiting | 1.8 | 1.9 |
Upper respiratory infection | 1.8 | 1.0 |
Dyspnea | 1.6 | 0.4 |
‘On-Off’ phenomena | 1.6 | 1.1 |
Back pain | 1.6 | 0.6 |
Dry mouth | 1.4 | 1.1 |
Anorexia | 1.2 | 1.1 |
Diarrhea | 1.2 | 0.6 |
Insomnia | 1.2 | 1.0 |
Orthostatic hypotension | 1.0 | 1.1 |
Shoulder pain | 1.0 | 0.6 |
Chest pain | 1.0 | 0.8 |
Muscle cramps | 0.8 | 1.0 |
Paresthesia | 0.8 | 1.1 |
Urinary frequency | 0.8 | 1.1 |
Dyspepsia | 0.6 | 1.1 |
Constipation | 0.2 | 1.5 |
Abnormal laboratory findings occurring at a frequency of 1% or greater in approximately 443 patients who received carbidopa and levodopa extended-release tablets and 475 who received carbidopa and levodopa tablets during controlled clinical trials included: decreased hemoglobin and hematocrit; elevated serum glucose; white blood cells, bacteria and blood in the urine.
The adverse experiences observed in patients in uncontrolled studies were similar to those seen in controlled clinical studies.
Other adverse experiences reported overall in clinical trials in 748 patients treated with carbidopa and levodopa extended-release tablets, listed by body system in order of decreasing frequency, include:
Asthenia, fatigue, abdominal pain, orthostatic effects.
Palpitation, hypertension, hypotension, myocardial infarction.
Gastrointestinal pain, dysphagia, heartburn.
Weight loss.
Leg pain.
Chorea, somnolence, falling, anxiety, disorientation, decreased mental acuity, gait abnormalities, extrapyramidal disorder, agitation, nervousness, sleep disorders, memory impairment.
Cough, pharyngeal pain, common cold.
Rash.
Blurred vision.
Urinary incontinence.
Decreased white blood cell count and serum potassium; increased BUN, serum creatinine and serum LDH; protein and glucose in the urine.
The following adverse experiences have been reported in postmarketing experience with carbidopa and levodopa extended-release tablets:
Cardiac irregularities, syncope.
Taste alterations, dark saliva.
Angioedema, urticaria, pruritus, bullous lesions (including pemphigus-like reactions).
Increased tremor, peripheral neuropathy, psychotic episodes including delusions and paranoid ideation, pathological gambling, increased libido including hypersexuality, impulse control symptoms.
Alopecia, flushing, dark sweat.
Dark urine.
Other adverse reactions that have been reported with levodopa alone and with various carbidopa levodopa formulations and may occur with carbidopa and levodopa extended-release tablets are:
Phlebitis.
Gastrointestinal bleeding, development of duodenal ulcer, sialorrhea, bruxism, hiccups, flatulence, burning sensation of tongue.
Hemolytic and non-hemolytic anemia, thrombocytopenia, leukopenia, agranulocytosis.
Henoch-Schönlein purpura.
Weight gain, edema.
Ataxia, depression with suicidal tendencies, dementia, euphoria, convulsions (however, a causal relationship has not been established); bradykinetic episodes, numbness, muscle twitching, blepharospasm (which may be taken as an early sign of excess dosage; consideration of dosage reduction may be made at this time), trismus, activation of latent Horner's syndrome, nightmares.
Malignant melanoma (see also
Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with carbidopa and levodopa extended-release tablets. These inhibitors must be discontinued at least two weeks prior to initiating therapy with carbidopa and levodopa extended-release tablets. Carbidopa and levodopa extended-release tablets may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl) (see PRECAUTIONS,
carbidopa and levodopa extended-release tablets are contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma.
Oculogyric crises, mydriasis, diplopia.
Urinary retention, priapism.
Faintness, hoarseness, malaise, hot flashes, sense of stimulation, bizarre breathing patterns.
Abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), bilirubin, Coombs test, uric acid.
Carbidopa and Levodopa extended-release tablets, USP are extended-release oral dosage form and are combination of carbidopa and levodopa for the treatment of Parkinson's disease and syndrome.
Carbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.3. It is designated chemically as (-)-L-α-hydrazino- α -methyl-β-(3,4-dihydroxybenzene) propanoic acid monohydrate. Its empirical formula is C
10H
14N
2O
4•H
2O, and its structural formula is:
Tablet content is expressed in terms of anhydrous carbidopa, which has a molecular weight of 226.3.
Levodopa, an aromatic amino acid, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 197.2. It is designated chemically as (-)-L- α -amino- β -(3,4-dihydroxybenzene) propanoic acid. Its empirical formula is C
9H
11NO
4, and its structural formula is:
Carbidopa and levodopa extended-release tablets, USP are supplied as extended-release tablets containing either 50 mg of carbidopa and 200 mg of levodopa, or 25 mg of carbidopa and 100 mg of levodopa. Inactive ingredients are hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, magnesium stearate, and colloidal silicon dioxide. Carbidopa and levodopa extended-release tablets, USP 25 mg/100 mg and 50 mg/ 200 mg also contain FD&C red 40 Alu lake and FD&C blue 2 Alu lake.
The 25 mg/100 mg tablet is supplied as light purple to purple, dappled, oval, uncoated tablets, debossed with “Λ50” on one side and plain on other. The 50 mg/200 mg tablet is supplied as light purple to purple, dappled, oval, uncoated tablets, debossed with “Λ51” on one side and plain on other. Carbidopa and levodopa extended-release tablets are polymeric-based drug delivery system that controls the release of carbidopa and levodopa as it slowly erodes. Carbidopa and levodopa extended-release tablets 25 mg/100 mg are available to facilitate titration when 100 mg steps are required.
FDA approved dissolution test specifications differ from USP.
Carbidopa and levodopa extended-release tablets, USP 25 mg/100 mg are light purple to purple, dappled, oval, uncoated tablets, debossed with “Λ50” on one side and plain on other. They are supplied as follows:
NDC 72888-155-30, bottles of 30.
NDC 72888-155-01, bottles of 100.
NDC 72888-155-05, bottles of 500.
NDC 72888-155-00, bottles of 1000.
Carbidopa and levodopa extended-release tablets, USP 50 mg/200 mg are light purple to purple, dappled, oval, uncoated tablets, debossed with “Λ51” on one side and plain on other. They are supplied as follows:
NDC 72888-156-30, bottles of 30.
NDC 72888-156-01, bottles of 100.
NDC 72888-156-05, bottles of 500.
NDC 72888-156-00, bottles of 1000.
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Store in a tightly closed container, protected from light and moisture.
Dispense in a tightly closed, light-resistant container.
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Rubicon Research Limited
Thane 421506, India
Advagen Pharma Ltd.,
East Windsor, NJ 08520, USA
Revision: 12/2025