Carbidopa is a decarboxylase inhibitor that is used in combination with levodopa for the treatment of Parkinson's disease. The addition of carbidopa allows lower doses of levodopa to be used, allows for more rapid titration of and a smoother response to levodopa treatment, and minimizes certain adverse reactions attributed to levodopa therapy such as nausea and vomiting. Patients with markedly irregular (on-off) responses to levodopa have not been shown to benefit from the addition of carbidopa. The FDA approved carbidopa prior to 1982; however, carbidopa had been available to prescribers only through a compassionate use program. Beginning in December 1999, carbidopa became available to US pharmacies for distribution.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Carbidopa is always administered with levodopa (e.g., Dopar or Laridopa) or with carbidopa-levodopa combination products (e.g., Sinemet).
Carbidopa has not been shown to have any overt pharmacodynamic actions in the recommended doses. No adverse reactions are associated with carbidopa; the adverse reactions reported are those related to combination therapy with levodopa or carbidopa-levodopa combination products (see Carbidopa; Levodopa monograph).
Carbidopa has not been shown to have any overt pharmacodynamic actions in the recommended doses. Other than hypersensitivity to carbidopa there are no contraindications. The only contraindications and precautions reported are those related to combination therapy with levodopa.
There are no adequate and well-controlled studies with carbidopa during pregnancy. In animal studies, carbidopa was not teratogenic and did not impair fertility, but placental transfer occurred. Carbidopa is routinely administered with levodopa, a drug which has caused visceral and skeletal malformations in rabbits. The teratogenic effect of levodopa in rabbits was unchanged by concurrent use of carbidopa. Limited data suggest that carbidopa may be found in higher concentrations in the umbilical cord but in very low concentrations in fetal tissue, indicating that carbidopa crosses the placenta in humans in low concentrations. Levodopa crosses the placenta in humans and reaches levels in the fetus comparable to maternal blood, although pregnancy outcomes have been primarily unremarkable. Two miscarriages were reported in the first trimester during use of carbidopa/levodopa, and one infant exposed to levodopa in utero was reported to have osteomalacia. One case of neonatal seizure occurred after use of bromocriptine plus carbidopa/levodopa/entacapone during pregnancy. Maternal complications reported in 3 pregnancies during use of carbidopa/levodopa included first trimester vaginal bleeding, third trimester nausea and vomiting, depression, and preeclampsia. However, more recent case reports and systematic reviews have demonstrated inconsistent findings. Additionally, recent literature has reported that patients with Parkinson's disease who become pregnant may experience a worsening of motor symptoms as pregnancy progresses, requiring adjustments in their treatment regimen. The mechanism by which these changes occur is unclear, but may be attributed to pregnancy-related pharmacokinetic changes. Because carbidopa is rarely used as monotherapy, the ability to identify risk associated with its use compared to risks of other concomitant medications is difficult. Due to a lack of adequate and well-controlled studies with carbidopa during human pregnancy, carbidopa should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. The effects of carbidopa in labor and delivery are unknown.
According to the manufacturer, because of the potential for serious adverse reactions in the nursing infant, a decision should be made to discontinue breast-feeding or to discontinue carbidopa, taking into account the importance of the drug to the mother. Carbidopa is excreted into maternal rat milk, but the effect in humans is unknown. According to the manufacturer of Sinemet, a combination product containing carbidopa and levodopa, excretion of levodopa into human breast milk has been reported, and caution is advisable in breast-feeding mothers. In one case report of a breast-feeding mother with Parkinson's disease, it was estimated that the nursing infant received an average of 0.3% and 0.5%, respectively, of the maternal weight-adjusted dosage of the sustained release and immediate-release carbidopa/levodopa product (50/200 mg). No adverse effects were observed in her infant, whose development was normal at 2 years of age. It should be noted that interference with proper lactation is possible during use of carbidopa/levodopa combinations since levodopa can inhibit prolactin secretion. If carbidopa/levodopa must be administered during breast-feeding, the infant should be monitored for commonly encountered adverse effects associated with dopaminergic therapy including dyskinesias, insomnia, sedation, nausea, and constipation. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
The use of carbidopa in neonates, infants, children, and adolescents < 18 years of age is not recommended.
For the treatment of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism, or symptomatic parkinsonism following CNS injury due to carbon monoxide or manganese intoxication:
NOTE: Carbidopa is given in combination with levodopa for all indications. Monitor patients closely during initial carbidopa or levodopa dosage titration and when other antiparkinson medication is added. Maintain carbidopa doses of at least 70 to 100 mg/day; patients receiving less than 70 to 100 mg/day of carbidopa may experience nausea and vomiting. Therapy should be individualized and adjusted based on clinical response.
-for patients already on carbidopa-levodopa combination therapy who need an increase in the carbidopa dosage:
Oral dosage:
Adults: In patients taking 10 mg carbidopa/100 mg levodopa, additional carbidopa 25 mg PO may be given with the first dose of carbidopa/levodopa each day. Additional doses of 12.5 to 25 mg PO may be given during the day with each dose of carbidopa/levodopa as required for optimum therapeutic response. When a patient is taking 25 mg carbidopa/250 mg levodopa or 25 mg carbidopa/100 mg levodopa, then 25 mg carbidopa PO may be given with any dose during the day as required for optimum response. The carbidopa dosage may be adjusted by adding or omitting 12.5 to 25 mg/day PO. Maximum daily dosage: 200 mg/day PO total of carbidopa, taking into account all medications. The addition of other antiparkinson agents may necessitate carbidopa dosage reduction.
-for individual titration of carbidopa and levodopa dosage in the occasional patient who requires individually titrated dosages of these two drugs:
Oral dosage:
Adults: Initially, 25 mg PO given 3 to 4 times per day. Give carbidopa at the same time as the levodopa dose. Reduce levodopa dose to 20% to 25% of the previous daily levodopa dosage when carbidopa is initiated. In patients already receiving levodopa therapy, at least 12 hours should elapse between the last dose of levodopa and the start of combination therapy. The carbidopa dosage may be adjusted by adding or omitting 12.5 to 25 mg/day. Max: 200 mg/day PO total of carbidopa. The addition of other antiparkinson agents may necessitate carbidopa dosage reduction.
Maximum Dosage Limits:
-Adults
200 mg/day PO taking into consideration carbidopa given alone and as part of the combination product.
-Elderly
200 mg/day PO taking into consideration carbidopa given alone and as part of the combination product.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Brentuximab vedotin: (Major) There was a 5% incidence of generalized polyneuropathy during clinical trial evaluation of carbidopa; levodopa enteral suspension (Duopa). The manufacturer recommends an initial evaluation for signs and symptoms of peripheral neuropathy, and periodic monitoring for peripheral neuropathy during treatment with Duopa, particularly in patients receiving other medications that are associated with neuropathy. Peripheral neuropathy has been reported with the use of brentuximab vedotin. Brentuximab vedotin-induced peripheral neuropathy is cumulative.
Droxidopa: (Major) Droxidopa is directly metabolized to norepinephrine by dopa-decarboxylase; therefore, coadministration with dopa-decarboxylase inhibitors (e.g., carbidopa) may prevent the conversion of droxidopa to norepinephrine outside of the central nervous system (CNS). Patients in the clinical trials with droxidopa received concomitant medications used to treat Parkinson's disease. Patients taking droxidopa with levodopa/dopa-decarboxylase inhibitor combinations (e.g., carbidopa; levodopa or carbidopa; levodopa; entacapone) had decreased clearance of droxidopa, an increase in exposure (AUC) to droxidopa of approximately 100%, and an increase in exposure to 3-OM-DOPS of approximately 50%. However, in clinical trials, it was found that the decreased clearance was not associated with a significant need for a different treatment dose or increases in associated adverse events. No dose adjustments are expected to be required. However, the manufacturer states that in some patients, it is possible that dose adjustments for droxidopa will be required.
Isoniazid, INH: (Major) There was a 5% incidence of generalized polyneuropathy during clinical trial evaluation of carbidopa; levodopa enteral suspension (Duopa). The manufacturer recommends an initial evaluation for signs and symptoms of peripheral neuropathy, and periodic monitoring for peripheral neuropathy during treatment with Duopa, particularly in patients receiving other medications that are associated with neuropathy. Isoniazid, INH can cause peripheral neuropathy due to pyridoxine antagonism or increased excretion of pyridoxine. In addition, concomitant use of carbidopa; levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity, such as isoniazid, INH, can result in hypertensive crisis or unstable blood pressure changes. Simultaneous use of these agents or combination products containing isoniazid (e.g., isoniazid, INH; pyrazinamide, PZA; rifampin or isoniazid, INH; rifampin) should be avoided if possible.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) There was a 5% incidence of generalized polyneuropathy during clinical trial evaluation of carbidopa; levodopa enteral suspension (Duopa). The manufacturer recommends an initial evaluation for signs and symptoms of peripheral neuropathy, and periodic monitoring for peripheral neuropathy during treatment with Duopa, particularly in patients receiving other medications that are associated with neuropathy. Isoniazid, INH can cause peripheral neuropathy due to pyridoxine antagonism or increased excretion of pyridoxine. In addition, concomitant use of carbidopa; levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity, such as isoniazid, INH, can result in hypertensive crisis or unstable blood pressure changes. Simultaneous use of these agents or combination products containing isoniazid (e.g., isoniazid, INH; pyrazinamide, PZA; rifampin or isoniazid, INH; rifampin) should be avoided if possible.
Isoniazid, INH; Rifampin: (Major) There was a 5% incidence of generalized polyneuropathy during clinical trial evaluation of carbidopa; levodopa enteral suspension (Duopa). The manufacturer recommends an initial evaluation for signs and symptoms of peripheral neuropathy, and periodic monitoring for peripheral neuropathy during treatment with Duopa, particularly in patients receiving other medications that are associated with neuropathy. Isoniazid, INH can cause peripheral neuropathy due to pyridoxine antagonism or increased excretion of pyridoxine. In addition, concomitant use of carbidopa; levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity, such as isoniazid, INH, can result in hypertensive crisis or unstable blood pressure changes. Simultaneous use of these agents or combination products containing isoniazid (e.g., isoniazid, INH; pyrazinamide, PZA; rifampin or isoniazid, INH; rifampin) should be avoided if possible.
Carbidopa is a noncompetitive decarboxylase inhibitor that, when administered with levodopa, inhibits the peripheral conversion of levodopa to dopamine by aromatic L-amino acid decarboxylase. This results in increased amount of levodopa available for transport to the CNS. Because carbidopa does not cross the blood-brain barrier, carbidopa does not affect the metabolism of levodopa within the CNS. Carbidopa also increases the bioavailability of levodopa by inhibiting the metabolism of levodopa in the GI tract. Less than 1% of levodopa would reach the CNS if given without carbidopa. Carbidopa reduces the dosage of levodopa required to produce a given effect by about 75%. When administered with levodopa, carbidopa increases both plasma levels and the plasma half-life of levodopa and decreases levels of dopamine and homavanillic acid in the plasma and urine. In clinical studies, simultaneous administration of separate carbidopa and levodopa tablets produced greater urinary excretion of levodopa in proportion to the excretion of dopamine when compared to the two drugs given at separate times. Carbidopa also inhibits the peripheral decarboxylation of oxitriptan to serotonin by aromatic L-amino acid decarboxylase. Thus, more oxitriptan is available for transport into the CNS. At recommended doses, carbidopa has no overt pharmacodynamic effects.
Carbidopa is administered orally. Carbidopa does not cross the blood-brain barrier; however, it is widely distributed to other tissues, crosses the placenta, and is distributed into breast milk. The plasma half-life of carbidopa is 1-2 hours. Carbidopa is not extensively metabolized and is renally eliminated.
-Route-Specific Pharmacokinetics
Oral Route
Approximately 40-70% of an oral dose is absorbed. Approximately 30% of an oral dose of carbidopa is excreted unchanged in the urine within 24 hours.
-Special Populations
Hepatic Impairment
No dosage adjustments are required for patients with hepatic impairment.
Renal Impairment
No dosage adjustments are required for patients with renal impairment.