Caution should be exercised when the following drugs are administered concomitantly with levodopa + carbidopa: Anticholinergics: May affect the absorption of levodopa and thus, the patient's response.
Antihypertensive agents: Concomitant use may be associated with symptomatic postural hypotension. Dosage adjustment of the antihypertensive agent may be required.
Tricyclic Antidepressants: Hypertension and dyskinesia have been reported with concomitant use.
Selegiline: Concomitant use may be associated with severe orthostatic hypotension not attributable to levodopa + carbidopa alone (see Contraindications).
Dopamine D2 receptor antagonists (e.g., phenothiazine, butyrophenones, risperidone) and isoniazid: May reduce the therapeutic effects of levodopa.
Dopamine-depleting agents (e.g., reserpine and tetrabenazone) and other drugs depleting monoamine stores: Concomitant use is not recommended.
Phenytoin and papaverine: The beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine, requiring close observation for possible loss of therapeutic response.
Metoclopramide: 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.
Iron salts: Reduced bioavailability of levodopa and/or carbidopa when it is ingested with ferrous sulfate or ferrous gluconate.
Other interactions: The absorption of levodopa + carbidopa may be impaired in some patients on a high protein diet since levodopa competes with certain amino acids.
Levodopa + carbidopa may be given to patients with Parkinson's disease and syndrome who are taking vitamin preparations that contain pyridoxine hydrochloride (Vitamin B6). While pyridoxine hydrochloride is known to accelerate the peripheral metabolism of levodopa to dopamine, carbidopa prevents this action.
The effect of simultaneous administration of antacids with levodopa + carbidopa on the bioavailability of levodopa has not been studied.
Laboratory Test Alterations: Elevation of liver function tests such as alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen (BUN) and positive Coombs test have also been reported. Commonly, levels of BUN, creatinine, and uric acid are lower during administration of levodopa + carbidopa than with levodopa.
Levodopa + carbidopa may cause a false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. False-negative tests may result with the use of glucose-oxidase methods for testing for glucosuria.
Exercise caution when interpreting the plasma and urine levels of catecholamines and their metabolites in patients on levodopa or levodopa + carbidopa therapy. Cases of falsely diagnosed pheochromocytoma in patients on levodopa + carbidopa therapy have been reported very rarely.