warnings
WARNINGS When patients are receiving levodopa without a decarboxylase inhibitor, levodopa must be discontinued at least twelve hours before carbidopa and levodopa extended release tablets are started. In order to reduce adverse reactions, it is necessary to individualize therapy. Carbidopa and levodopa extended release tablets should be substituted at a dosage that will provide approximately 25 percent of the previous levodopa dosage (see DOSAGE AND ADMINISTRATION ). Carbidopa does not decrease adverse reactions due to central effects of levodopa. By permitting more levodopa to reach the brain, particularly when nausea and vomiting is not a dose-limiting factor, certain adverse CNS effects, e.g., dyskinesias, will occur at lower dosages and sooner during therapy with carbidopa and levodopa extended release tablets than with levodopa alone. Patients receiving carbidopa and levodopa extended release tablets may develop increased dyskinesias compared to carbidopa and levodopa tablets. Dyskinesias are a common side effect of carbidopa and levodopa treatment. The occurrence of dyskinesias may require dosage reduction. As with levodopa, carbidopa and levodopa extended release tablets may cause 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. Carbidopa and levodopa extended release tablets should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease. As with levodopa, care should be exercised in administering carbidopa and levodopa extended release tablets 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, treatment with carbidopa and levodopa extended release tablets may increase the 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 carbidopa and levodopa tablets and carbidopa and levodopa extended release tablets. Therefore, patients should be observed carefully when the dosage of carbidopa and levodopa extended release tablets 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.