Does treatment with low dose carbidopa/levodopa (Sinemet 12.5/50) 1x1-3, alternatively dosage 2x3,

Fråga: Does treatment with low dose carbidopa/levodopa (Sinemet 12.5/50) 1x1-3, alternatively dosage 2x3, involve an increased risk for cardiac arrhythmias? The questioner works in a rehabilitation unit where this drug is often used.

Sammanfattning: For levodopa alone as well as the combination levodopa/carbidopa cardiac arrhythmias is a known, but with respect to the limited number of reports, relatively rare adverse effect, which seems to arise mainly in patients with existing heart disorders. In one study there was no correlation between dose of levodopa and the risk for arrhythmias, but data on this are scarce.

Svar: Symtoms in connection with parkinsonism are alleviated by levodopa when the substance is decarboxylated to dopamine in the brain. Carbidopa, which does not pass the blood brain barrier, inhibits the extra cerebral decarboxylation of levodopa. This results in more levodopa available for transport to the brain and transformation to dopamine (1).

Levodopa is known to have the capability of causing ventricular arrhythmias in patients with underlying cardiac disorders (2). However, in the files of SADRAC we found only one reported case of palpitations, and no reports of strict arrhythmias connected to the substances in point (3). A search in WHO:s adverse drug reaction database presented 19 reported cases of various heart rate and rhythm disorders during treatment with levodopa and slightly more than 30 cases for the combination carbidopa/levodopa since 1971 (4).

The effects of carbidopa combined with levodopa and levodopa alone on the cardiovascular system of patients with Parkinson´s disease were evaluated in a study where 50 patients, both men and women ages 40 to 80, with Parkinson´s disease participated. Patients with heart disease were included, but patients with uncompensated congestive heart failure or unstable angina and those who were on antiarrhythmic drugs, were excluded. After medical examination, routine electrocardiograms (ECGs) and laboratory studies, 38 of the 50 patients were also able to undergo 24-hour ECG ambulatory monitoring. Three or more isolated ventricular premature contractions (VPRs) per hour, multifocal or repetitive VPRs, or unsustained ventricular tachycardia, were classified as a ventricular arrhythmia. After the 24-hour tape all patients were instructed to remain on their current dose of levodopa and other antiparcinsonian medication for a month, after which they were randomly assigned to one of two treatment modalities: 500mg levdopa or 25mg carbidopa combined with 250mg levodopa. One to three month after initiation of the new regimen all patients underwent a follow-up evaluation, where those patients who had had an arrhythmia underwent a second 24-hour taping. Among the 38 patients who completed the first 24-hour ECG tape, 12 were classified as having had an arrhythmia and 26 did not. Eleven of the 12 patients with an arrhythmia had underlying heart disease, whereas only 8 of the 26 patients without an arrhythmia had heart disease. The incidence of arrhythmias did not correlate with the dose of levodopa. Neither there were any correlation between an arrhythmia and the type of heart disease (5). More recent studies about dose dependency and risk for arrhythmias were not found.