Effects of generic exchange of levodopa: a pharmacy practice and biopharmaceutical approach

• At: PPR SIG 2021 (2021)
• Type: Digital
• By: WEITZEL, Johanna (WWU Münster, Germany, Germany)
• Co-author(s): Johanna Weitzel PhD Student, Prof. Dr. Klaus Langer1 , Dr. Olaf Rose, Pharm.D.2 1. Department of Pharmaceutical Technology and Biopharmaceutics, WWU Muenster, Germany, 2. Department of Pharmacotherapy & Translational Research, College of Pharmacy, University of Florida, Gainesville, FL
  
• Abstract:

  Introduction

  Combination of levodopa with decarboxylase or catecholamine-o-methyltransferase inhibitors are a frequently prescribed medication in Parkinson`s disease (PD). Due to the direct effects on motor symptoms, levodopa was chosen as a model to study patient-oriented outcomes of generic exchange.

  Objectives

  The project aims to identify outcomes related to a generic switch of levodopa medication and it’s effect on patient´s symptoms by a questionnaire as well as dissolution characteristics.

  Methods

  The questionnaire was provided to all members of the national PD support group in April 2020 by mail. Analysis was performed using Chi-square-tests with Monte-Carlo-simulation and McNemar test. Dissolution testing was performed in simulated gastric fluid, tap water and whole milk to simulate a meal. Evaluation was conducted with a reversed-phase high-performance liquid chromatographic (RP HPLC) with diode array detection (DAD). Significant differences in dissolution behaviour were calculated using ANOVA.

  Results

  Inclusion criteria were met by 410. More than 55% of the patients were confused by any switch of medication, with women more likely than men (p=0.036)). Patients who switched their medication (n=206) experienced more difficulties in swallowing compared to non-switchers (n=204) (p=0.004). Side effects were reported by 29,5% of switchers, while 21,5% switched back to the previous product. Patients stated, that a switch worsened symptoms (p=<0.001). Our present finding suggest differences regarding the dissolution profiles in drugs containing levodopa/ carbidopa/ benserazide or entacapone in different dissolution media. Decarboxylase inhibitors were extremely prone to oxidation and rapid degradation.

  Conclusion

  PD patients are affected by a generic switch of their levodopa containing medication and experienced confusion and a worsening of symptoms. Problems with swallowing are prevalent after a switch. Large discrepancies in dissolution were detected between different brands, also depending on dissolution media.