SUMMARY
Carbidopa and levodopa tablets USP are a combination of carbidopa and levodopa for the treatment of Parkinsons disease and syndrome.
Carbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water.
Carbidopa and levodopa tablets are indicated in the treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication. This product is indicated in these conditions to permit the administration of lower doses of levodopa with reduced nausea and vomiting, with more rapid dosage titration, with a somewhat smoother response, and with supplemental pyridoxine (vitamin B6).
In some patients a somewhat smoother antiparkinsonian effect results from therapy with carbidopa and levodopa than with levodopa. However, patients with markedly irregular ("on-off") responses to levodopa have not been shown to benefit from carbidopa and levodopa therapy.
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 have improved when carbidopa and levodopa was substituted. This is most likely due to decreased peripheral decarboxylation of levodopa which results from administration of carbidopa rather than to a primary effect of carbidopa on the nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa in parkinsonian syndromes.
In considering whether to give this combination product to patients already on levodopa who have nausea and/or vomiting, the practitioner should be aware that, while many patients may be expected to improve, some do 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, about half of the patients with nausea and/or vomiting on levodopa improved spontaneously despite being retained on the same dose of levodopa during the controlled portion of the trial.
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NEWS HIGHLIGHTS
Published Studies Related to Carbidopa and Levodopa (Carbidopa / Levodopa)
[Management of complications related to intraduodenal infusion of
levodopa/carbidopa in patients with Parkinson's disease]. [Article in Spanish; Abstract available in Spanish from the publisher] [2014] Continuous infusion of intraduodenal levodopa/carbidopa is an effective treatment
that improves the motor complications and the quality of life of patients in the
advanced stages of Parkinson's disease. However, it is not free of complications... The aim of this review is to report on
the management of the complications that can be observed in patients with
advanced Parkinson's disease treated with continuous infusion of intraduodenal
levodopa/carbidopa.
Extended-release carbidopa-levodopa (IPX066) compared with immediate-release
carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a
phase 3 randomised, double-blind trial. [2013] motor fluctuations... INTERPRETATION: Extended-release carbidopa-levodopa might be a useful treatment
Are high doses of carbidopa a concern? A randomized, clinical trial in
Parkinson's disease. [2012] Recommended doses of carbidopa are 75-200 mg/day...
Comparison of orally dissolving carbidopa/levodopa (Parcopa) to conventional oral carbidopa/levodopa: A single-dose, double-blind, double-dummy, placebo-controlled, crossover trial. [2010.12.15] Levodopa use in fluctuating Parkinson's disease (PD) is complicated by an inconsistent and prolonged onset to clinical improvement.This small pilot study did not show significant group differences favoring OD C/L; however, larger studies may be justified, and individual patients may benefit.
Night-time bioavailability of levodopa/carbidopa/entacapone is higher compared to controlled-release levodopa/carbidopa. [2010.11] OBJECTIVE: Controlled-release levodopa/carbidopa (CR-LC) is often used to provide prolonged control of night-time motor symptoms in patients with Parkinson's disease (PD). Levodopa/carbidopa/entacapone (LCE) provides higher bioavailability of levodopa compared with levodopa/carbidopa formulations and has been shown to be effective in PD patients with wearing-off symptoms. The aim of this study was to compare the bioavailability of levodopa after a single evening dose (administered at 10 p.m.) of LCE 200 or CR-LC 200... CONCLUSIONS: The results of this study demonstrate that a single bedtime dose of LCE 200 provides higher bioavailability of levodopa compared to CR-LC 200.
Clinical Trials Related to Carbidopa and Levodopa (Carbidopa / Levodopa)
Augmenting Effects of L-DOPS With Carbidopa and Entacapone [Terminated]
An experimental drug called L-DOPS increases production in the body of a messenger chemical
called norepinephrine. Cells in the brain that make norepinephrine are often gone in
Parkinson disease. The exact consequences of this loss are unknown, but they may be related
to symptoms such as fatigue, depression, or decreased attention that occur commonly in
Parkinson disease. This study will explore effects of L-DOPS in conjunction with carbidopa
and entacapone, which are drugs used to treat Parkinson disease. We wish to find out what
the effects are of increasing norepinephrine production in the brain and whether carbidopa
and entacapone augment those effects.
Volunteers for this study must be at least 18 years of age and able to give consent to
participate in the study. To participate in the study, volunteers must discontinue use of
alcohol, tobacco, and certain herbal medicines or dietary supplements, and must also taper
or discontinue certain kinds of medications that might interfere with the results of the
study. Candidates will be screened with a medical history and physical exam.
Participants will be admitted to the National Institutes of Health Clinical Center for two
weeks of testing. The study will have three testing phases in a randomly chosen order for
each participant:
- Single dose of L-DOPS
- Single dose of L-DOPS in conjunction with carbidopa
- Single dose of L-DOPS in conjunction with entacapone
Each phase will last two days, with a washout day between each phase in which no drugs
will be given and no testing will be performed. In each phase, participants will undergo a
series of tests and measurements, including blood pressure and electrocardiogram tests.
Participants who are healthy volunteers will also have blood drawn and will undergo a lumbar
puncture (also known as a spinal tap) to obtain spinal fluid for chemical tests.
Study To Assess The Clinical Benefit Of Droxidopa And Droxidopa/Carbidopa In Subjects With Fibromyalgia [Completed]
A correlation between increased norepinephrine concentration in the central nervous system
(CNS) and a decrease in fibromyalgia pain has been suggested in clinical studies.
Therefore, as a pro-drug of norepinephrine, droxidopa could potentially benefit fibromyalgia
patients by reducing pain as a result of increasing CNS levels of norepinephrine.
As this benefit is presumed to be a central effect, the addition of carbidopa, a peripheral
DOPA decarboxylase (DDC) inhibitor, may favorably impact the drug's treatment profile.
Carbidopa is utilized as a blocker of peripheral DDC, an enzyme required for the conversion
of droxidopa into norepinephrine. Therefore, inhibition of peripheral DDC should result in a
reduction of any side effects resulting from the peripheral production of norepinephrine,
whilst allowing for increased central levels, and hence, increased centrally mediated
benefits.
The purpose of the study is the obtain information regarding the proper dosing,
effectiveness and safety of droxidopa and combination droxidopa/carbidopa treatments in
patients with fibromyalgia.
Carbidopa for the Treatment of Nausea and Vomiting in Familial Dysautonomia [Completed]
This is a pilot clinical trial of carbidopa to treat disabling attacks of nausea and
vomiting in patients with familial dysautonomia (FD, also known as Riley Day syndrome or
hereditary sensory and autonomic neuropathy type III). FD is a rare autosomal recessive
disease in which the growth and development of selective nerves is impaired. Patients with
FD suffer recurrent uncontrollable nausea and vomiting crises accompanied by skin flushing,
tachycardia and arterial hypertension. Current treatments of nausea are ineffective or have
intolerable side sides. Our long-term goal is to treat nausea effectively and without side
effects, a therapeutic intervention that would markedly improve the quality of life of
patients with FD.
The investigators have recently found that resting plasma dopamine levels are high in
patients with FD and increase up to 40-fold during nausea and vomiting attacks. This led us
to postulate that stimulation of dopamine receptors in the chemoreceptor trigger zone of the
brainstem is the likely mechanism of vomiting.
Carbidopa is a reversible competitive inhibitor of aromatic L-amino acid decarboxylase (also
known as dopa-decarboxylase) that cannot cross the blood brain barrier. It has been used
successfully for many years to block the extracerebral synthesis of dopamine and avoid
nausea and vomiting in patients with Parkinson's disease taking levodopa. The investigators
reasoned that carbidopa could have a similar antiemetic effect in patients with FD.
The investigators propose to conduct a pilot trial to assess the safety, tolerability and
efficacy of carbidopa for the treatment of nausea in patients with FD. The pilot trial will
recruit 25 patients with FD who complain of severe nausea that affects their quality of
life. The trial will be divided into two consecutive, but independent parts. Part 1, will
address the safety and tolerability of carbidopa in patients with FD using an open-label
dose titration phase followed by 4-weeks of open-label treatment. Part 2, will address the
efficacy of carbidopa for the treatment of nausea in patients with FD using a randomized,
placebo controlled, double blind, 4-week cross over design.
The investigators hope to demonstrate that carbidopa is a safe, well-tolerated drug that
blocks the peripheral formation of dopamine and thus prevents dopamine-induced nausea and
vomiting attacks in patients with FD.
Study on Tolerability of Levodopa/Carbidopa in Children With Angelman Syndrome [Completed]
This study is designed to determine the highest dose of levodopa/carbidopa that can be
tolerated without any serious side effects by children with Angelman syndrome.
It has been hypothesized that levodopa may lead to an improvement in the neurodevelopment
and abnormal movements (e. g. tremors) in children with Angelman syndrome.
Data from this study will be used to design a phase II trial to determine the efficacy of
levodopa in treating children with Angelman syndrome.
High and Low Dose Carbidopa Treatment of Parkinson's Disease [Completed]
Hypothesis: We hypothesize that carbidopa in daily doses of 450mg will enter the central
nervous system and partially inhibit AAAD, thereby reducing the decarboxylation of exogenous
levodopa to dopamine, and thereby blunt the therapeutic effects of levodopa in PD subjects.
The purpose of this study is to see how low dose vs. high dose of the study drug, carbidopa
effect movement in subjects with Parkinson's disease. The low dose of the study drug is 75
mg and the high dose is 450mg.
Subjects will be recruited from the investigators clinic when they are seen for treatment
for Parkinson's disease. Subjects will also be recruited through flyers hung at OHSU and at
the VA.
Subjects will take part in 2 screening visits one week apart to determine eligibility.
Subjects will be randomly chosen to start either high or low dose carbidopa and take it for
4 weeks. Subjects will be called 2, 4, and 6 or 7 days after this visit to ask how they are
doing after starting this dose of study drug. We will leave them a message if we cannot
reach them. If there are any problems, we will schedule them to come to the clinic within
the next 2 days.
Subjects will have an outpatient visit 2 weeks after screening and a hospital admission 2
weeks after that. At the hospital, subjects will stay for 3 days. They will have blood
drawn and their Parkinson's disease assessed by a finger tapping exercise, timing their
walking, and looking at their uncontrolled movements.
The subject will then receive the opposite dose of carbidopa for 4 weeks. Subjects will be
called 2, 4, and 6 or 7 days after this visit to ask how they are doing after starting this
dose of study drug. We will leave them a message if we cannot reach them. If there are any
problems, we will schedule them to come to the clinic within the next 2 days.
The outpatient visit and hospital admission will repeat again. At the end of the second
hospital admission, treatment on the study is over and subjects will go back to their
original Parkinson's disease medications. The study will end with a follow up phone call or
clinic visit 2 - 4 weeks after the final hospital admission.
Subjects will fill out a daily diary that asks about their movement throughout the day for 3
days before they come to the Oregon Clinical and Translational Research Institute.
Carbidopa is used for the treatment of Parkinson's disease with levodopa. This protocol is
using a high dose of 450mg of carbidopa. This study is also using IV levodopa, which is a
different route than is normally given.
Finger tapping rates will be compared between high and low dose study drug use to see if one
group has slower rates than the other.
Reports of Suspected Carbidopa and Levodopa (Carbidopa / Levodopa) Side Effects
Dyskinesia (16),
Hallucination, Visual (12),
Tremor (10),
Agitation (9),
Confusional State (9),
Fall (9),
Gait Disturbance (9),
Respiratory Disorder (6),
Muscle Rigidity (6),
Delirium (6), more >>
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Page last updated: 2015-08-10
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