Adverse Drug Reactions to Selegiline[colon] A Review of the French Pharmacovigilance Database

Abstract

The present pharmacoepidemiologic study was performed to characterize the profile of adverse drug reactions (ADRs) reported with selegiline, a monoamine oxidase B (MAO-B) inhibitor used in the treatment of Parkinson's disease and previously reported to induce an excess of mortality. The analysis was performed with use of the French Pharmacovigilance Database between 1989 and 1997. This database includes all ADRs reported by French practitioners (and especially "serious" and "unexpected" ADRs). Three different analyses were performed: identification of ADRs reported with selegiline, comparison with the ADR profile observed with other antiparkinsonian drugs, and a case/non-case study investigating the occurrence of cardiovascular ADRs with selegiline in comparison with other drugs in general and other antiparkinsonian drugs (e.g., levodopa [L-Dopa], dopamine agonists) in particular. The most often reported ADRs with selegiline were psychiatric (delirium, hallucinations, agitations), cardiovascular (orthostatic hypotension, arterial hypertension, etc.) and neurologic (sedation, abnormal movements, etc.). Psychiatric and cardiovascular ADRs were more frequently reported with selegiline than with L-Dopa or dopamine agonists. The case/ non-case study found an increased risk of cardiovascular ADRs (OR = 1.72; 95% Cl = 1.16-2.55)when selegiline was associated with L-Dopa. These data show that the profile of selegiline-induced ADRs differs from that of other antiparkinsonian drugs (L-Dopa, dopamine agonists) with more psychiatric and cardiovascular ADRs. We suggest that the higher frequency of cardiovascular ADRs could explain, at least partially, the previously reported increase in mortality rate.

Changes in vascular alpha1‐ and alpha2‐adrenoceptor responsiveness by selegiline treatment

“…The same group confirmed these findings in a longitudinal study on the effects of selegiline withdrawal [9]. Finally, in a pharmacoepidemiological study performed for 1989 to 1997, using the French Pharmacovigilance Database, we found an excess risk of cardiovascular adverse drug reactions (dysautonomia, cardiac arrhythmias or rise in blood pressure) when selegiline was associated with levodopa [27]. Recently, Lefebvre [28] reported that, in a group of 29 parkinsonian patients receiving selegiline, the drug increased plasma and urinary noradrenaline levels.…”

Clinical Pharmacology of Rasagiline: A Novel, Second‐Generation Propargylamine for the Treatment of Parkinson Disease

“…A concern exists for psychiatric and vasoreactive side effects (eg, hallucinations and orthostatic hypotension) associated with some propargylamine MAO‐B inhibitors. Long‐term postmarketing data have revealed that these types of side effects are frequently reported during selegiline treatment, especially when combined with levodopa 50 . These effects may be due to the amphetamine metabolites of selegiline or augmentation of dopaminergic activity.…”

Orthostatic hypotension, balance and falls in Parkinson's disease

“…OH in PD is related to impaired baroreflex‐cardiovagal functions, sympathetic cardiac and also partially extracardiac denervation, and baroreflex‐sympathoneural failure 6. Furthermore, medications used to treat PD, including L‐DOPA , selegiline, and dopamine agonists, may result in or contribute to OH 7–12…”