Saskia Müller-Rebstein1,2, Claudia Trenkwalder1, Jens Ebentheuer1, Wolfgang H Oertel3, Carsten Culmsee4, Günter U Höglinger5,6. 1. Department of Neurosurgery, Paracelsus-Elena Klinik Kassel, University Medical Center, Goettingen, Germany. 2. Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, 81677, Munich, Germany. 3. Department of Neurology, Philipps Universität, Marburg, Germany. 4. Department of Pharmacy, Philipps Universität, Marburg, Germany. 5. Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, 81677, Munich, Germany. guenter.hoeglinger@dzne.de. 6. Department of Neurology, Technische Universität München, Munich, Germany. guenter.hoeglinger@dzne.de.
Abstract
BACKGROUND: Polypharmacy is common in geriatric Parkinson's disease (PD) patients in advanced disease stages with multiple comorbidities, bearing multiple risks for drug safety in theory. OBJECTIVE: The aim of this study was to empirically identify the most frequent and relevant contraindications and drug interactions actually occurring and compromising drug safety in PD in real life. METHODS: We conducted a prospective observational study in a multimorbid cohort of PD patients with polypharmacy admitted to a specialized hospital. Inclusion criteria were the presence of at least one comorbidity requiring pharmacotherapy and at least five different drugs in the discharge prescription. Hoehn and Yahr stage during the 'on' state, therapeutic problems related to motor and non-motor PD symptoms, comorbidities, and drug regimens on admission and discharge were analyzed for contraindications and interactions. RESULTS: Overall, 127 patients were included (medium Hoehn and Yahr stage = IV, range II-V). Interactions with the anti-PD medication were mainly caused by other central nervous system (CNS)-active substances, cytochrome P450-metabolized substances, and QT-time prolonging substances. Contraindications against the anti-PD medication mainly occurred from internal, haematopoietic, neurologic and psychiatric diseases, and QT-time prolonging drugs. The highest frequency of interactions and contraindications were identified with levodopa (n = 119 at admission/n = 126 at discharge), entacapone (n = 46/42), pramipexole (n = 44/24), and amantadine (n = 32/30). CONCLUSIONS: Several medically relevant risk factors (interactions and contraindications) frequently occurred in advanced PD patients. These findings provide a basis for developing programmes for awareness, education, monitoring, and preventive interventions to avoid adverse incidents. Future studies will need to evaluate preventive efficacy of structured drug safety programmes.
BACKGROUND: Polypharmacy is common in geriatric Parkinson's disease (PD) patients in advanced disease stages with multiple comorbidities, bearing multiple risks for drug safety in theory. OBJECTIVE: The aim of this study was to empirically identify the most frequent and relevant contraindications and drug interactions actually occurring and compromising drug safety in PD in real life. METHODS: We conducted a prospective observational study in a multimorbid cohort of PDpatients with polypharmacy admitted to a specialized hospital. Inclusion criteria were the presence of at least one comorbidity requiring pharmacotherapy and at least five different drugs in the discharge prescription. Hoehn and Yahr stage during the 'on' state, therapeutic problems related to motor and non-motor PD symptoms, comorbidities, and drug regimens on admission and discharge were analyzed for contraindications and interactions. RESULTS: Overall, 127 patients were included (medium Hoehn and Yahr stage = IV, range II-V). Interactions with the anti-PD medication were mainly caused by other central nervous system (CNS)-active substances, cytochrome P450-metabolized substances, and QT-time prolonging substances. Contraindications against the anti-PD medication mainly occurred from internal, haematopoietic, neurologic and psychiatric diseases, and QT-time prolonging drugs. The highest frequency of interactions and contraindications were identified with levodopa (n = 119 at admission/n = 126 at discharge), entacapone (n = 46/42), pramipexole (n = 44/24), and amantadine (n = 32/30). CONCLUSIONS: Several medically relevant risk factors (interactions and contraindications) frequently occurred in advanced PDpatients. These findings provide a basis for developing programmes for awareness, education, monitoring, and preventive interventions to avoid adverse incidents. Future studies will need to evaluate preventive efficacy of structured drug safety programmes.
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