Carbidopa

 Risk Factor: CM
 Class: CENTRAL NERVOUS SYSTEM DRUGS / Antiparkinsonian Agents

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

This antiparkinsonian agent has no pharmacologic effect when given alone and is almost always used in conjunction with levodopa (see also Levodopa). Carbidopa (a-methyldopa hydrazine; MK-486) inhibits decarboxylation of extracerebral levodopa. When used in combination with this latter agent, lower doses of levodopa can be administered, resulting in fewer adverse effects, and more levodopa is available for passage to the brain and eventual conversion in that organ to the active metabolite, dopamine.

Combinations of carbidopa and levodopa, as well as levodopa alone, have caused visceral and skeletal malformations in rabbits (1). However, carbidopa, 10 or 100 mg/kg/day given orally to rats from day 1 through day 21 of gestation, did not have a teratogenic effect but did cause a significant dose-related increase in brown fat (interscapular brown adipose tissue) hemorrhage and vasodilation in the newborn pups (2). The hemorrhage, 4.6% and 12.1%, respectively, for the two doses, was thought to be related to dopamine. Combining carbidopa and levodopa resulted in a lower incidence of hemorrhage.

A study published in 1978 examined the effect of carbidopa (20 mg/kg SC every 12 hours for 7 days) and levodopa plus carbidopa (200/20 mg/kg SC every 12 hours for 7 days) on the length of gestation in pregnant rats (3). Only the combination had a statistically significant effect on pregnancy duration, causing a delay in parturition of 12 hours. The results were thought to be consistent with dopamine inhibition of oxytocin release.

In pregnant rats, small amounts of carbidopa cross the placenta and can be detected in amniotic fluid and fetal tissue (4). Carbidopa concentrations were measured at 1, 2, and 4 hours after a 20-mg/kg IV dose administered near the end of gestation (19th day). The highest levels in the maternal plasma, placenta, amniotic fluid, and fetus (time of maximum concentration shown in parentheses) were 9.9 mg/mL (1 hour), 2.35 mg/g (1 hour), 0.32 mg/mL (2 and 4 hours), and 0.65 mg/g (2 hours), respectively.

Human placental transfer of carbidopa, although the amounts were very small, was documented in a study published in 1995 (5). A 34-year-old woman with juvenile Parkinson's disease was treated with carbidopa/levodopa (200/800 mg/day) during two pregnancies (see also Levodopa). Both pregnancies were electively terminated, one at 8 weeks' gestation and the other at 10 weeks. Mean concentrations of carbidopa (expressed as ng/mg protein from 2 fetuses) in the maternal serum, placental tissue (including umbilical cord), fetal peripheral organs (heart, kidney, muscle), and fetal neural tissue (brain and spinal cord) were 2.05, 8.0, 0.14, and <0.15, respectively. The low concentrations of carbidopa in the fetus, compared with those in the mother and placenta, were interpreted as evidence for an effective placental barrier to the transport of carbidopa (5).

Because Parkinson's disease is relatively uncommon in women of childbearing age, only four reports have been located that describe the use of carbidopa, always in combination with levodopa, in human pregnancy (6,7,8 and 9). A woman with at least a 7-year history of parkinsonism conceived while being treated with carbidopa/levodopa (five 25/250-mg tablets/day) and amantadine (100 mg twice/day) (6). She had delivered a normal male infant approximately 6 years earlier, but no medical treatment had been given during that pregnancy. Amantadine was immediately discontinued when the current pregnancy was diagnosed. Other than slight vaginal bleeding in the 1st trimester, there were no maternal or fetal complications. She gave birth to a normal term infant (sex and weight not specified) who was doing well at 1.5 years of age.

A 1987 retrospective report described the use of carbidopa/levodopa, starting before conception in five women during seven pregnancies, one of which was electively terminated during the 1st trimester (7). All of the other pregnancies went to term (newborn weights and sexes not specified). Maternal complications in three pregnancies included slight 1st-trimester vaginal bleeding, nausea and vomiting during the 8th and 9th months (the only patient who reported nausea and vomiting after the 1st trimester) and depression that resolved postpartum, and preeclampsia. One infant, whose mother took amantadine and carbidopa/levodopa and whose pregnancy was complicated by preeclampsia, had an inguinal hernia. No adverse effects or congenital anomalies were noted in the other five newborns, and all remained healthy at follow-up (approximately 15 years of age).

A 27-year-old woman with a history of chemotherapy and radiotherapy for non-Hodgkin's lymphoma occurring approximately 4 years earlier had developed a progressive parkinsonism syndrome that was treated with a proprietary preparation of carbidopa/levodopa (co-careldopa; Sinemet Plus; 375 mg/day) (8). She conceived 5 months after treatment began and eventually delivered a healthy, 3540-g male infant at term. Apgar scores were 9 at both 1 and 10 minutes, respectively. Co-careldopa was continued throughout her pregnancy.

A brief case report, published in 1997, described a normal outcome in the third pregnancy of a woman with levodopa-responsive dystonia (Segawa's type) who was treated throughout gestation with 500 mg/day of levodopa alone (9). The male infant weighed 2350 g at birth and was developing normally at the time of the report. Two previous pregnancies had occurred while the woman was being treated with daily doses of levodopa 100 mg and carbidopa 10 mg. Spontaneous abortions had occurred in both pregnancies; one at 6 weeks and the other at 12 weeks. An investigation failed to find any cause for the miscarriages.

In summary, although the number of reports describing the use of carbidopa (in combination with levodopa) during human pregnancy are few, as expected because of the relatively rarity of this condition in women of childbearing age, exposure to this agent during gestation does not appear to present a major risk to the fetus. Limited studies have not found teratogenicity in animals with carbidopa, except when combined with levodopa, and this outcome may be related to the latter drug. The cause of the two miscarriages described above is unknown, but requires further study. Brown fat hemorrhage observed in newborn rats treated during the 1st week of gestation was dose-related, and the toxicity has not been reported in humans. Moreover, the placental passage of carbidopa in animals and humans is limited. Based on the above data and the fact that lower doses of levodopa can be used if carbidopa is added to the mother's regimen, therapy with carbidopa, if indicated, should not be withheld during gestation.

Breast Feeding Summary

No reports describing the use of carbidopa during lactation or measuring the amount of this drug in human milk have been located. In at least two cases, breast feeding did not occur because of concerns with other drug therapy (levodopa or amantadine) that the mother was taking with carbidopa (6,8). Small amounts of carbidopa, probably from nonionic diffusion, were measured in the milk of five rats (15 days postpartum) 2 hours after a 20-mg/kg IV dose (4). The average milk and plasma concentrations were 0.5 mg/mL and 6.1 mg/mL, respectively, representing a milk:plasma ratio of 0.08. The relationship of these amounts to those that might occur in humans is unknown.

References

1. Product information. Sinemet. DuPont Pharma, 2000.
2. Kitchin KT, DiStefano V. L-Dopa and brown fat hemorrhage in the rat pup. Toxicol Appl Pharmacol 1976;38:25163.
3. Seybold VS, Miller JW, Lewis PR. Investigation of a dopaminergic mechanism for regulating oxytocin release. J Pharmacol Exp Ther 1978;207:60510.
4. Vickers S, Stuart EK, Bianchine JR, Hucker HB, Jaffe ME, Rhodes RE, Vandenheuvel WJA. Metabolism of carbidopa [L-(-)-a-hydrazino-3,4-dihydroxy-a-methylhydrocinnamic acid monohydrate], an aromatic amino acid decarboxylase inhibitor, in the rat, dog, rhesus monkey, and man. Drug Metab Dispos 1974;2:922.
5. Merchant CA, Cohen G, Mytilineou C, DiRocco A, Moros D, Molinari S, Yahr MD. Human transplacental transfer of carbidopa/levodopa. J Neural Transm Park Dis Dement Sect 1995;9:23942.
6. Cook DG, Klawans HL. Levodopa during pregnancy. Clin Neuropharmacol 1985;8:935.
7. Golbe LI. Parkinson's disease and pregnancy. Neurology 1987;37:12459.
8. Ball MC, Sagar HJ. Levodopa in pregnancy. Mov Disord 1995;10:115.
9. Nomoto M, Kaseda S, Iwata S, Osame M, Fukuda T. Levodopa in pregnancy. Mov Disord 1997;12:261.
   
   

Questions and Answers

does anyone know if and what side effectcs are to suddenly stop taking tramadol and carbidopa?, these are both pain meds that I have been on for quite some time.1 and 2 yrs. 1 dose is 3 x a dayand the other is 1/2 @ night. I am ttc. (6 mo.) I feel this may be stopping me from that. thanks.

Why do you have to stop suddendly? it is usually not dangerous to do so, but you can feel bad.Why not get off slower -like 0.5 tablets every 3-4 days.You will enventually get there anyway.
All the best

marya

is it ok to take vitamin B complex when you are on SINEMET (Levodopa-Carbidopa) therapy?, because ive read that vit B6 in the B complex breaks down the levodopa in the blood but there are also reports that with the combination of levo and carbidopa,it would prevent that effect.anybody care to enilghten me more about this?its for my mom coz she take the drug becoz of parkinson's symptoms.thanks!

Found this to share, "If you are taking levodopa alone, you shouldn't take more than 5 mg per day of vitamin B 6 or it might impair the effectiveness of the drug. But if you use levodopa/carbidopa combinations that provide a total daily dose of at least 75 mg of carbidopa, this issue is not a concern."

So it sounds like if you are taking a dose of Sinemet that contains more than 75mg of Carbidopa, you should be fine. The worse that would happen is the Sinemet won't work as well. My doctor didn't mention anything to me about B vitamins - he did tell me that if I eat a meal with a lot of protein in it, to wait at least an hour before taking the Sinemet.

Is anyone taking 4a risperidone/Risperdal, 4b fluoxetine/Prozac, or 4c levodopa & carbidopa/Sinemet or ANY OT, I would like to know when, why and if it worked? Also, if there any side effects?

Thank you all.

i am taking prozac,lithium,topomax,and should be on a benzaprine, all of mine work beautifully. i am bi-polar, and have severe migraines, and am being treated for anxiety. lithum gives you diahrea, benziprenes are addictive, prozac-no sides affects, topomax makes you sleepy

can you overdose on sinemet (levodopa/carbidopa) ?, My father takes sinemet for his parkinson's disease. He also suffers badly from depression, especially since his wife (my mother) died. He gets loads of sinemet every week from the doctor. I'm worried about the danger of him overdosing on it. Can it kill you in overdose ?.

Well yes, you can overdose, but if he is taking the recommended doseage as prescribed he should be fine.

If you are worried about a possible overdose, I would recommend getting one of those pill boxes with the days of the week on. You can fill one up for him week at a time and you can visually keep track of the pills he is taking.

I have found the below for you:

Overdosing on Sinemet CR: An Introduction
Sinemet® CR (carbidopa-levodopa CR) is a prescription drug usually used to treat Parkinson's disease. As with any medication, it is possible to take too much Sinemet CR. The specific effects of a Sinemet CR overdose may vary, depending on a number of factors, including the dosage and whether it was taken with any other medications or substances.

Symptoms of a Sinemet CR Overdose
In cases of an overdose with levodopa (one of the components of Sinemet CR), the following symptoms were reported:


* Involuntary body movements
* Nausea and vomiting
* Rapid heart rate (tachycardia)
* Confusion or agitation
* Insomnia and restlessness
* Low blood pressure (hypotension) or high blood pressure (hypertension).


It is expected that Sinemet CR will cause similar overdose symptoms, compared to just levodopa.

Treatment for a Sinemet CR Overdose
The treatment for a Sinemet CR overdose may also vary, and there is no known antidote. If the overdose was recent, a healthcare provider may "pump the stomach" or administer certain medications to induce vomiting. Treatment may also involve supportive care, which consists of treating the symptoms that occur as a result of the overdose. For example, supportive treatment options for a Sinemet CR overdose may include:


* Careful monitoring of the heart, blood pressure, and breathing
* Fluids through an intravenous line (IV)
* Other treatments based on the complications that occur.


It is important that you seek medical attention immediately if you believe that you may have overdosed on Sinemet CR.

why carbidopa is given with levodopa?,

Levodopa is metabolized in the blood stream to dopamine. Dopamine cannot cross the blood-brain barrier so in the past, doctors had to give huge amounts of levodopa to achieve any benefit. This led to major side effects (low blood pressure and nausea/vomiting) that made it intolerable to many patients. Carbidopa was then found to block the enzyme in the bloodstream responsible for converting levodopa to dopamine allowing doctors to give much lower doses of levodopa and therefore causing fewer side effects.

As an aside, the trade name of carbidopa-levodopa is Sinemet which is derived from Greek meaning "without vomiting".

extraction method for carbidopa in plasma by lc-ms/ms?, carbidopa+levodopa

Dosage:

Your doctor will tailor your individual dosage carefully, depending on your response to previous therapy and symptoms.

ADULTS

For patients with mild to moderate symptoms, the initial recommended dose is 1 tablet of Carbidopa taken 2 times a day.

Starting doses should be spaced out every 4 to 8 hours and then adjusted to each patient's individual response.

The usual long-term dose is 2 to 8 tablets per day, taken in divided doses every 4 to 8 hours during the waking day.

Higher doses (12 or more tablets per day) and shorter intervals (less than 4 hours) have been used, but are not usually recommended.

When doses of Carbidopa are given at intervals of less than 4 hours, and/or if the divided doses are not equal, it is recommended that the smaller doses be given at the end of the day.

An interval of at least 3 days between dosage adjustments is recommended.

Dosage adjustment of Carbidopa may be necessary if your doctor prescribes additional medications.

CHILDREN

Use of Carbidopa in children under 18 is not recommended.

What are dangers for using carbidopa monohydrate 5 yrs and how to stop taking them as lady at the age of 50?, Medicine used is CARBILEV 25/250 & is S4 rated. Tablet contains Carbidopa Monohydrate equivalent to 25mg anhydrous carbidopa and 250mg levodopa. Medicine was prescribed for restless leg syndrome 5years ago but condition worsened and addictive conditions have set in already. An attuned Usui & Tibetan Reiki Master was asked to treat the ailment as no positive results were obtained. Tree tablets per day are presently consumed and bring on restless sleeping paterns due to the worsening 'restless leg syndrome' and adictivity. Would there be any natural remedies available besides natural healthy eating paterns?

u need to consult a psychiatrist or a rehab specialist in this regard.one way of stopping is to withdraw the drug very slowly like tapering it over weeks before stopping them
all the best

Cerebral palsy-looking information?, Hi
My cousin is born with Cereberal palsy .CP is discovered after 30 days of his birth .he is premature and now he is 8 year old.He is under gone for many surgeries and physio therapy .Surgery was mainly near to the hip to loose the rigid muscles.Still he does not walk and mentally he is a perfect kid.
Recently one of the doctor suggested to give Levodopa and carbidopa medicines..
No idea will this cure..Is CP patient can walk after certain age?

you can know more about CP at this medical blog
http://teensandhealth.blogspot.com/

Parkinsons disease?, How does the drug carbidopa prevent levodopa from breaking down before it reaches the brain?

Carbidopa supports the action of levodopa. It is a drug that increases the availability of L-dopa to the brain and is administered with it in the treatment of Parkinson's disease. Usually dopamines cannot cross the blood brain barrier, but this has been especially designed to cross and produce the requried lock and key effect in the receptors.