Carbidopa and Levodopa (Page 3 of 5)

Drug Interactions

Caution should be exercised when the following drugs are administered concomitantly with carbidopa and levodopa extended-release tablets.

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 monoamine oxidase (MAO) inhibitors (Type A or B), see CONTRAINDICATIONS. Concomitant therapy with selegiline and carbidopa-levodopa may be associated with severe orthostatic hypotention 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 extended-release tablets should be carefully observed for loss of therapeutic response.

Iron salts may reduce the bioavailability of levodopa and carbidopa. The clinical relevance is unclear.

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a two-year bioassay of carbidopa-levodopa, 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-levodopa, no effects on fertility were found in rats receiving doses 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).


Pregnancy Category C

No teratogenic effects were observed in a study in mice receiving up to 20 times the maximum recommended human dose of carbidopa-levodopa. 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-levodopa 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.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when carbidopa and levodopa extended-release tablets are administered to a nursing woman.

Pediatric Use

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 controlled clinical trials, patients predominantly with moderate to severe motor fluctuations while on carbidopa-levodopa 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 the carbidopa and levodopa tablets, as shown in Table I.

Table I. Clinical Adverse Experiences Occurring in 1% or Greater of Patients
Adverse Experience Carbidopa/Levodopa Extended-Release Tablets n=491 % Carbidopa and Levodopa Tablets n=524 %
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:

Body as a Whole : Asthenia, fatigue, abdominal pain, orthostatic effects.

Cardiovascular : Palpitation, hypertension, hypotension, myocardial infarction.

Gastrointestinal : Gastrointestinal pain, dysphagia, heartburn.

Metabolic : Weight loss.

Musculoskeletal : Leg pain.

Nervous System/Psychiatric : Chorea, somnolence, falling, anxiety, disorientation, decreased mental acuity, gait abnormalities, extrapyramidal disorder, agitation, nervousness, sleep disorders, memory impairment.

Respiratory : Cough, pharyngeal pain, common cold.

Skin : Rash.

Special Senses : Blurred vision.

Urogenital : Urinary incontinence.

Laboratory Tests : Decreased white blood cell count and serum potassium; increased BUN, serum creatinine and serum LDH; protein and glucose in urine.

The following adverse experiences have been reported in post-marketing experience with carbidopa and levodopa extended-release tablets.

Cardiovascular : Cardiac irregularities, syncope.

Gastrointestinal : Taste alterations, dark saliva.

Hypersensitivity : Angioedema, urticaria, pruritus, bullous lesions (including pemphigus-like reactions).

Nervous System/Psychiatric : Neuroleptic malignant syndrome (see WARNINGS), increased tremor, peripheral neuropathy, psychotic episodes including delusions and paranoid ideation, increased libido.

Skin : Alopecia, flushing, dark sweat.

Urogenital : 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:

Cardiovascular : Phlebitis.

Gastrointestinal : Gastrointestinal bleeding, development of duodenal ulcer, sialorrhea, bruxism, hiccups, flatulence, burning sensation of tongue.

Hematologic : Hemolytic and nonhemolytic anemia, thrombocytopenia, leukopenia, agranulocytosis.

Hypersensitivity : Henoch-Schonlein purpura.

Metabolic : Weight gain, edema.

Nervous System/Psychiatric : 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.

Skin : Malignant melanoma (see also CONTRAINDICATIONS), increased sweating.

Special Senses : Oculogyric crises, mydriasis, diplopia.

Urogenital : Urinary retention, priapism.

Miscellaneous : Faintness, hoarseness, malaise, hot flashes, sense of stimulation, bizarre breathing patterns.

Laboratory Tests : Abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), bilirubin, Coombs test, uric acid.

All resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2023. All Rights Reserved.