Safinamide 100mg tablets

INTRODUCTION: Parkinson's disease (PD) involves the progressive loss of dopaminergic neurons, leading to motor and non-motor symptoms that significantly impact patients' quality of life. Safinamide modulates dopaminergic and glutamatergic systems, offering a promising treatment approach. METHODS: This meta-analysis evaluated the efficacy of safinamide as an add-on therapy to levodopa for PD patients with motor fluctuations. Following PRISMA guidelines, literature searches were conducted in PubMed and Embase (2014-2022). Inclusion criteria were studies on adult PD patients receiving safinamide with levodopa. Outcomes included on-time without troublesome dyskinesia, off-time, UPDRS Part III motor scores, UPDRS Part II activities of daily living scores, PDQ-39 emotional well-being, and GRID-HAMD scores. RESULTS: Among thirteen eligible studies, safinamide significantly improved on-time without troublesome dyskinesia at 100 mg/day (mean difference [MD]: -0.90; 95% CI: -1.12 to -0.67; p < 0.00001) and 50 mg/day (MD: -0.77; 95% CI: -1.21 to -0.34; p = 0.0005) compared to placebo. It also reduced off-time (100 mg/day: MD: -0.94; 95% CI: -1.19 to -0.70; p < 0.00001; 50 mg/day: MD: -0.72; 95% CI: -1.03 to -0.41; p < 0.00001) and improved UPDRS-III motor scores (100 mg/day: MD: -3.01; 95% CI: -4.15 to -1.86; p < 0.00001; 50 mg/day: MD: -2.93; 95% CI: -5.14 to -0.71; p = 0.001). Mood improvements were noted in PDQ-39 emotional well-being scores (MD: -5.22; 95% CI: -6.90 to -3.54) and GRID-HAMD scores (MD: -0.60; 95% CI: -0.95 to -0.25; p = 0.0009). Safinamide also positively affected pain (RR: 1.10; 95% CI: 1.03 to 1.18). CONCLUSION: Compared to placebo, safinamide significantly benefits motor and non-motor symptoms in PD patients, but further research is necessary to fully explore its therapeutic potential.

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There has been a steadily growing armamentarium of drugs for the symptomatic treatment of Parkinson's disease (PD). Consequently, as various various pharmaceutical agents are used, it has become more difficult to perform and compare clinical trials with different medication regimens. Given that levodopa remains the gold standard treatment, conversion factors have been proposed to calculate l-dopa equivalent doses (LEDs) for each drug to facilitate comparison of medication regimens. Adding up LEDs of each drug leads to a daily total LED that is artificial but feasible and—if used as a standard scheme—comparable internationally. Since the last widely accepted proposal of LEDs for PD drugs by Tomlinson et al.,1 there has been no update. We hereby propose LED conversion factors for opicapone and safinamide, which are currently missing, but urgently needed, in ongoing clinical trials and observational studies. Opicapone is a new peripheral catechol-O-methyl transferase (COMT) inhibitor. Tomlinson et al. have proposed a conversion ratio, rather than a conversion factor, for inhibitors of COMT activity, by considering the mode of action of these drugs in terms of prolongation of the duration of the coadministered l-dopa treatment. The suggested ratio for entacapone is 0.33 × LD (coadministered l-dopa dose); the suggested ratio for tolcapone is LD × 0.5, respectively.1 For opicapone, we suggest a ratio higher than for entacapone, given that our literature search (see Supporting Information S1) and clinical experience suggest that opicapone is slightly more efficacious than entacapone.2 However, there are no intriguing data suggesting that opicapone might be more efficient than tolcapone3; we therefore propose using the same ratio for calculating the LED of opicapone as is used for tolcapone (LD × 0.5). Safinamide is mainly a reversible monoamine oxidase-B (MAO-B) inhibitor. Other proposed mechanisms likely play no relevant additional role concerning l-dopa equivalence. For safinamide, we propose an LED of 100 mg, independently of the actual administered dose, given that full reversible inhibition of MAO-B activity is already reached in the lowest commercially available preparations of safinamide.4 In the previous scheme,1 this would make safinamide equivalent to 1 mg of rasagiline and 10 mg of oral selegiline. All existing LED proposals (including our current additions) are based on clinical experience and empirical approaches. They pooled together studies by individual researchers, which provided sparse and inconsistent data. Consequently, these proposals are neither objective nor inherently scientific. To the best of our knowledge, there has not been a thorough evaluation so far. There needs to be a critical retrospective discussion on whether calculating LED reflects what we ought to measure and whether conclusions drawn from these calculations are valid. This pseudo-validity remains the major limitation of calculating LEDs. In conclusion, we believe that our proposed conversions fit reasonably well into the previous scheme of conversion factors (Table 1) and still sufficiently reflect the potential of both drugs. However, they follow the same limitations as the previous proposals.1 Prospectively, the LED conversion factor scheme needs a global reassessment with an attempt to use more objective measurements (using validated rating scales, adjusting for placebo, etc.) and thereby allowing the inclusion of new agents. We thank Anne-Marie Williams for language editing and formatting the manuscript. We thank Joaquim Ferreira for his valuable input and for reviewing an earlier version of the manuscript (including detailed results and conclusions of our literature search). (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Manuscript: A. Writing of the First Draft, B. Review and Critique. S.S.: 1A, 1B, 1C, 2A, 2B B.M.: 1C, 2B C.T.: 1A, 2B Ethical Compliance Statement: The authors confirm that the approval of an institutional review board or patient consent was not required for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest. Financial Disclosures for previous 12 months: S.S. has received salaries from the EU Horizon 2020 research and innovation program under grant agreement No. 634821 and from the Deutsche Forschungsgemeinschaft (DFG) under grant agreement No. MO 2088/5-1. B.M. has received honoraria for consultancy from Roche, Biogen, UCB, and Sun Pharma Advanced Research Company. B.M. is a member of the executive steering committee of the Parkinson Progression Marker Initiative and PI of the Systemic Synuclein Sampling Study of the Michael J. Fox Foundation for Parkinson's Research and has received research funding from the Deutsche Forschungsgemeinschaft (DFG), EU (Horizon2020), Parkinson Fonds Deutschland, Deutsche Parkinson Vereinigung, and the Michael J. Fox Foundation for Parkinson's Research. C.T. has received honoraria for consultancy from Britannia and Roche and for educational lectures from UCB. She has received research grants from the Michael J. Fox Foundation for Parkinson's Research and the EU (Horizon2020). She holds patents for the treatment of dyskinesia in PD with oxycodone/naloxone and the PDSS-2 Scale as well as publishing royalties for a book for PD patients published in Schattauer Verlag, Germany, 2015. Supporting Information Material S1. Methods, results, and references for literature search. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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Safinamide is a monoamine oxidase B inhibitor that was approved in Europe in February 2015 to complement a stable dose of levodopa in monotherapy or in combination with other antiparkinsonian agents in adults affected by mid-stage or advanced Parkinson disease (PD) with fluctuations. It is characterized by a dual mechanism of action (dopaminergic and non-dopaminergic), thus enabling an innovative approach in the management of motor and non-motor symptoms. The safety and efficacy profile of safinamide was previously shown in placebo-controlled randomized clinical trials, which demonstrated that ON time could be increased without the onset of dyskinesia and that OFF time could be decreased, with an improvement in PD. However, the strict inclusion and exclusion criteria in these studies meant that not all patients seen in daily clinical practice were represented, hence the importance of observational studies that evaluate the drug in these situations. The objective of the present article was to collect and review reports from Spanish authors presented at national and international conferences on the use of safinamide in patients with PD. We reviewed a total of 36 reports covering around 2000 patients with PD. The reports confirm the safety and efficacy results obtained in clinical trials, showing a significant improvement in motor and non-motor fluctuations and enabling the dose of levodopa to be reduced, thus decreasing the likelihood of motor complications.

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Introduction: Randomized clinical trials should be complemented with data from real-world studies. We report our long-term experience with safinamide in a movement disorders unit. Methods: This retrospective study included patients with Parkinson’s disease (PD) treated with safinamide in our unit from February 2016 to May 2022 under routine clinical practice. Assessments included the Hoehn and Yahr (HY) stage, unified Parkinson’s disease rating scale (UPDRS) part III score, levodopa equivalent daily dose (LEDD), LEDD for dopamine agonists, and safinamide treatment discontinuation. Results: We included 180 patients with a median age of 74 years (IQR 11), and the majority (90.6%) had an HY stage of ≤2. After a median follow-up of 40 months (IQR 34), 14 patients discontinued treatment with safinamide (7.8%, 95% CI 4.7 to 12.6). Among the 166 patients who remained on safinamide, the UPDRS III score was stable (10 (IQR 9) vs. 9 (IQR 13), p = 0.455). The LEDD significantly increased from a median of 300 mg to 500 mg (p &lt; 0.001), whereas the LEDD for dopamine agonists did not significantly increase. A subgroup of 89 patients who did not require dopamine agonists during follow-up showed stable UPDRS III score (10 (IQR 7) vs. 9 (IQR 14); p = 0.923), with a significant LEDD increase (300 mg to 400 mg, p &lt; 0.001). Conclusions: Our results support the long-term effectiveness and tolerability of safinamide in patients with PD in clinical practice.

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Safinamide is a selective, reversible monoamine oxidase type B inhibitor (MAO-B inhibitor) used as an adjunct to oral levodopa in patients with Parkinson’s disease (PD) experiencing motor fluctuations. Unlike other MAO-B inhibitors, safinamide possesses a dual mechanism of action, combining dopaminergic enhancement through MAO-B inhibition with modulation of abnormal glutamatergic transmission. In clinical practice, safinamide is primarily recognized for its ability to reduce motor fluctuations. However, its pharmacological profile suggests a broader therapeutic potential beyond dopaminergic modulation alone. Randomized controlled trials have shown that safinamide increases daily ON time without worsening troublesome dyskinesia. Nevertheless, reported effects on dyskinesia have generally been modest and inconsistent across studies. Clinical observations from longer-term follow-up and real-world studies suggest that improvements in dyskinesia and certain non-motor symptoms may emerge more gradually than the early motor benefits. Based on this observed pattern, it can be hypothesized that safinamide may exhibit a dual timeline of clinical effects, with early dopaminergic improvements in motor ON time followed by later modulation of dyskinesia and selected non-motor symptoms potentially mediated through glutamatergic mechanisms. On the basis of these pharmacological characteristics and clinical observations, a phenotype-oriented approach to patient selection for safinamide therapy may be considered. In addition, recognizing the potential for a dual timeline of therapeutic effects may help clinicians guide patients’ expectations of treatment and interpret treatment response, as well as optimizing follow-up strategies in routine clinical practice.

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Parkinson’s disease (PD) imposes a large burden on Asian countries and threatens to grow rapidly as Asian populations age. PD phenotypes in Asian patients differ from those reported in the West, yet management generally follows a similar approach. Levodopa (l- dopa) is a mainstay of therapy and is typically followed by the addition of a catechol- O -methyltransferase inhibitor or a monoamine oxidase-B (MAO-B) inhibitor to address the wearing-off effect. There is little guidance on switching between MAO-B inhibitors or other adjunct therapies that consider the newer evidence for safinamide as an add-on PD therapy in Asian patients. Therefore, a group of PD experts in Asia evaluated the evidence supporting safinamide for the treatment of PD with a focus on integrating this treatment option into local clinical practice. A narrative review was conducted to identify supportive evidence for the formulation of summary statements on key topics. The efficacy and safety of safinamide added to l -dopa in Asian patients with PD are supported by both clinical trials and observational data, including two randomized trials enrolling exclusively Asian patients ( n = 406; n = 307) and an Asian subpopulation analysis from another randomized trial ( n = 173). Safinamide reduces wear-off duration and has beneficial effects on motor symptoms of PD, with good tolerability outcomes. Safinamide may also have beneficial effects on non-motor symptoms of PD such as urinary symptoms, apathy and sleep disturbances, and it is a suitable treatment for older patients. Overall, safinamide is an effective and well-tolerated treatment for the wear-off effect of l -dopa in Asian patients and, during long-term treatment, might reduce the risk of dyskinesia in patients without pre-existing dyskinesia. Additional research is needed to better understand the role of safinamide for patients with fluctuating pain, the dose–effect relationship of safinamide in Asian patients and the efficacy of safinamide in Asian patients with early-onset PD.

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Abstract A novel, highly sensitive and eco-friendly micellar-mediated spectrofluorimetric method was developed and validated for the determination of the novel antiparkinsonian drug safinamide mesylate in the presence of its related precursor impurity, 4-hydroxybenzaldehyde. The proposed approach relies on increasing the inherent fluorescence emission at 296 nm of safinamide, by forming hydrogen bonds between the mentioned drug and sodium dodecyl sulfate in the micellar system using 0.1 N HCl as a solvent, following excitation at 226 nm. A thorough investigation was conducted into the experimental factors affecting spectrofluorimetric behavior of the studied drug. A linearity plot of safinamide over the concentration range of 10.0–1000.0 ng/mL against the relative fluorescence intensities was established. The proposed method demonstrated excellent sensitivity down to the nano-gram level with detection and quantitation limits of 1.91 and 5.79 ng/mL, respectively. The studied drug was effectively determined in Parkimedine ® Tablets. Furthermore, the proposed method allows for ultrasensitive quantification of safinamide in spiked human plasma, with satisfactory percentage recovery (98.97–102.28%). Additionally, the greenness assessment using the advanced green certificate classification approach, the complementary green analytical procedure index (Complex-GAPI), and the analytical GREEness metric approach (AGREE), along with the practicality check using the Blue Applicability Grade Index in addition to the all-inclusive overall whiteness evaluation using the RGB-12 model were carried out. The outcomes demonstrated the effectiveness and whiteness of the proposed technique. Clearly, the suggested approach has the advantages of being simple, requiring no pretreatment steps, and relying solely on direct measuring procedures.

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BACKGROUND: Safinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice. METHODS: This multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment. RESULTS: In total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change -7.0 [p = 0.012], -2.4 [p = 0.007] and - 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild. CONCLUSION: Safinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns. STUDY REGISTRATION: University Hospital Medical Information Network in Japan; study ID: UMIN000044341.

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Abstract Parkinson's disease (PD) emerges as a notable health concern among the elderly population. Safinamide mesylate (SAF) is a novel and emerging add-on therapy in PD treatment. The stability of innovative drug formulations and the development of appropriate stability-indicating methods are of great importance to modern pharmaceutical analysis. The current work has established novel comprehensive stability-indicating chromatographic approaches, HPTLC coupled with densitometric quantification and HPLC–DAD, for the selective assay of SAF in pharmaceutical formulation along with its synthetic precursor impurity; 4-hydroxy benzaldehyde (4-HBD) in presence of its stress induced degradation products. The stability of SAF was investigated under different stress conditions. It was found that SAF is likely to undergo acid, base hydrolysis, and oxidative degradation. Using mass spectrometry and infrared spectroscopy, the structures of the forced degradation products were confirmed and elucidated. The dissolution behavior of Parkimedine ® Tablets was also monitored in the FDA suitable medium. Multiple assessment tools were used to evaluate the environmental sustainability of the proposed methods and the reported one. The greenness tools included Complex-GAPI and AGREE metrics. In addition, the innovative concepts of "blueness" and "whiteness" evaluation were incorporated through the newly introduced BAGI and RGB12 algorithms, respectively.

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