LODOSYN (Carbidopa) has no antiparkinsonian effect when given alone. It is indicated for use with SINEMET (Carbidopa-Levodopa) or levodopa. LODOSYN (Carbidopa) does not decrease adverse reactions due to central effects of levodopa.

When LODOSYN (Carbidopa) is to be given to carbidopa-naive patients who are being treated with levodopa alone, the two drugs should be given at the same time. At least twelve hours should elapse between the last dose of levodopa and initiation of therapy with LODOSYN (Carbidopa) and levodopa in combination. Start with no more than one-fifth (20%) to one-fourth (25%) of the previous daily dosage of levodopa when given without LODOSYN (Carbidopa). See the DOSAGE AND ADMINISTRATION section before initiating therapy.

As with levodopa, concomitant administration of LODOSYN (carbidopa) and levodopa may cause involuntary movements and mental disturbances. These reactions are thought to be due to increased brain dopamine following administration of levodopa. All patients should be observed carefully for the development of depression with concomitant suicidal tendencies. Patients with past or current psychoses should be treated with caution. Because LODOSYN (Carbidopa) permits more levodopa to reach the brain and, thus, more dopamine to be formed, dyskinesias may occur at lower levodopa dosages and sooner with concomitant use of LODOSYN (Carbidopa) and levodopa or carbidopa-levodopa combination products than with levodopa alone. The occurrence of dyskinesias may require levodopa dosage reduction.

Levodopa, with or without LODOSYN (carbidopa) , should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic, or endocrine disease.

Care should be exercised in administering levodopa, with or without LODOSYN (carbidopa) , to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. In such patients, cardiac function should be monitored with particular care during the period of initial dosage adjustment, in a facility with provisions for intensive cardiac care.

As with levodopa alone there is a possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.

Neuroleptic Malignant Syndrome (NMS): Sporadic cases of a symptom complex resembling NMS have been reported in association with dose reductions or withdrawal of certain antiparkinsonian agents such as levodopa, SINEMET (Carbidopa-Levodopa), or SINEMET CR (Carbidopa-Levodopa) Sustained-Release. Therefore, patients should be observed carefully when the dosage of levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.

NMS is an uncommon but life-threatening syndrome characterized by fever or hyperthermia. Neurological findings, including muscle rigidity, involuntary movements, altered consciousness, mental status changes; other disturbances, such as autonomic dysfunction, tachycardia, tachypnea, sweating, hyper- or hypotension; laboratory findings, such as creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin, have been reported.

The early diagnosis of this condition is important for the appropriate management of these patients. Considering NMS as a possible diagnosis and ruling out other acute illnesses (e.g., pneumonia, systemic infection, etc.) is essential. This may be especially complex if the clinical presentation includes both serious medical illness and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology.

The management of NMS should include: 1) intensive symptomatic treatment and medical monitoring and 2) treatment of any concomitant serious medical problems for which specific treatments are available. Dopamine agonists, such as bromocriptine, and muscle relaxants, such as dantrolene, are often used in the treatment of NMS; however, their effectiveness has not been demonstrated in controlled studies.

General

As with levodopa alone, periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are recommended during extended concomitant therapy with LODOSYN and levodopa, or with LODOSYN and SINEMET (Carbidopa-Levodopa), or any combination of these drugs.

Patients with chronic wide-angle glaucoma may be treated cautiously with LODOSYN (carbidopa) and levodopa or SINEMET, or any combination of these drugs, just as with levodopa alone, provided the intraocular pressure is well controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.

Laboratory Tests

Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase, and bilirubin. Abnormalities in blood urea nitrogen and positive Coombs test have also been reported. Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during concomitant administration of carbidopa and levodopa than with levodopa alone.

Levodopa and carbidopa-levodopa combination products 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

There were no significant differences between treated and control rats with respect to mortality or neoplasia in a 96-week study of carbidopa at oral doses of 25, 45, or 135 mg/kg/day.

Combinations of carbidopa and levodopa (10-20, 10-50, 10-100 mg/kg/day) were given orally to rats for 106 weeks. No effect on mortality or incidence and type of neoplasia was seen when compared to concurrent controls.

Mutagenesis

Mutagenicity studies have not been performed with either carbidopa or the combination of carbidopa and levodopa.

Fertility

Carbidopa had no effect on the mating performance, fertility, or survival of the young when administered orally to rats at doses of 30, 60, or 120 mg/kg/day. The highest dose caused a moderate decrease in body weight gain in males.

The administration of carbidopa-levodopa at dose levels of 10-20, 10-50, or 10-100 mg/kg/day did not adversely affect the fertility of male or female rats, their reproductive performance, or the growth and survival of the young.

Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies with LODOSYN (carbidopa) 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. LODOSYN (carbidopa) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Carbidopa, at doses as high as 120 mg/kg/day, was without teratogenic effects in the mouse or rabbit. In the rabbit, but not in the mouse, carbidopa-levodopa produced visceral anomalies, similar to those seen with levodopa alone, at approximately 7 times the maximum recommended human dose. The teratogenic effect of levodopa in rabbits was unchanged by the concomitant administration of carbidopa.

Nursing Mothers

It is not known whether carbidopa is excreted in human milk. Because many drugs are excreted in human milk, and because of their potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established, and use of the drug in patients below the age of 18 is not recommended.

Last reviewed on RxList: 10/3/2008
This monograph has been modified to include the generic and brand name in many instances.