Overnight switch from rasagiline to safinamide in Parkinson's disease patients with motor fluctuations: a tolerability and safety study

Abstract

Background and purpose: When switching between monoamine oxidase type B (MAO-B) inhibitors, a 15-day suspension period is a precautionary measure to avoid a serotonin syndrome and hypertensive crisis. However, this indication results in a major inconvenience for parkinsonian patients because of the worsening of their clinical condition. In routine clinical practice, neurologists often perform a substitution of these two drugs without solution of continuity (i.e. overnight), to avoid worsening of fluctuations and prolonged OFF periods. Therefore, a safety open label study was performed to investigate the possible risks of switching overnight from rasagiline to safinamide. Methods: The study population included 20 advanced patients with Parkinson's disease on stable treatment with rasagiline and levodopa (alone or in combination with other anti-parkinsonian medication). The possible occurrence of serotonin syndrome and hypertension was monitored through a strict clinical observation and a 24-h Holter recording (ABPM) performed twice, whilst subjects were on rasagiline and immediately after switching to safinamide. Results: No cases of serotonin syndrome or hypertensive crisis occurred during the study. Changes that were not significant occurred in the primary endpoint: 24-h mean blood pressure (BP) had a mild +4.4% increase in the ABPM2 versus ABPM1 (P = 0.17), 24-h systolic and diastolic BP values were slightly higher at ABPM2 compared to ABPM1 (respectively +3.3%, P = 0.13; and 5.4%, P = 0.08) and 24-h systolic BP variability was unchanged between the two ABPM evaluations (from 8.6 AE 2.9 to 8.9 AE 1.8; P = 0.27). Conclusion: The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients.

Safinamide improves sleep and daytime sleepiness in Parkinson’s disease: results from the SAFINONMOTOR study

“…In line with this, we found that the improvement in the global NMS burden (NMSS total score) observed in 50 PD patients from the SAFINONMOTOR study 6 months after starting with safinamide with a mean dose of 99 mg/day did not significantly differ of the improvement observed at 1 month with a mean dose of 55 mg/day [ 10 ]. Furthermore, it is not clear whether the dopaminergic action of safinamide could be more potent than that of other MAO-B inhibitors such as rasagiline or if benefits could be related to its effect involving the glutamatergic system, or both [ 11 , 18 , 19 ]. A recent study [ 11 ] observed an improvement of nocturnal sleep, diurnal sleepiness, and daytime dysfunction in fluctuating PD patients treated with safinamide ( N = 46), as assessed by sleep questionnaires, but not with rasagiline ( N = 15).…”

Safinamide in the treatment pathway of Parkinson’s Disease: a European Delphi Consensus

“…The consensus on a likely lack of positive effects of safinamide on orthostatic hypotension was expected : even though the use of safinamide has been associated to a slight, non-significant raise in blood pressure values in pivotal trials 18 , 19 , the enhancements of the vasodilating action of dopaminergic drugs may explain the lack of tolerability observed in patients with OH. It has to be noted though that in a post-marketing study performed to evaluate the safety of the immediate switch from rasagiline to safinamide, blood pressure variability in systolic and diastolic values was unchanged between baseline and end of study 24-hour ambulatory blood pressure monitoring recordings 41 .…”

Collective Expert Perspectives on the Use of Safinamide as Adjunctive Therapy for Parkinson’s Disease: Online-Based Delphi Survey

“…Based on these results, the authors consider that safinamide may have a negligible influence on blood pressure variability and a low risk of orthostatic hypotension. In Japan, when switching from MAO-B inhibitors, a wash-out period is required, and concomitant use of multiple MAO-B inhibitors is contraindicated, although an overnight switch from rasagiline to safinamide was reported as safe [24].…”