Extrapyramidal symptoms after exposure to calcium channel blocker-flunarizine or cinnarizine

Abstract

PurposeFlunarizine (fz) and cinnarizine (cz) have well-known extrapyramidal side effects (EPSEs). The aim of this study was to evaluate the incidence and occurrence time of cz- and fz-related EPSEs.MethodPatients who took fz or cz for more than 1 month were identified from the longitudinal health insurance database 2005 and 2010. Excluded were patients with any of the underlying diseases that may cause parkinsonism. Drug-induced EPSEs were defined as the new diagnosis of parkinsonism, dyskinesia, or secondary dystonia during drug use or within 3 months after discontinuing the medication. Age- and sex-matched controls were included in this study.ResultsRecruited for analysis were individuals who took fz (n = 26,133) and cz (n = 7186). The incidence rates of fz- and cz-induced EPSEs were 21.03 and 10.3 per 10,000 person-months, respectively. The hazard ratios (HRs) of EPSEs among fz and cz subjects were 8.03 (95% CI 6.55–9.84) and 3.41 (95% CI 2.50–4.63) when compared with the control individuals. Both fz and cz patients had a higher cumulative incidence of EPSEs than their control individuals (p < 0.001). Among subjects who took fz, the incidence of EPSEs was higher in the second than first year of drug exposure (45.59 vs 21.03 per 10,000 person-months).ConclusionsFz and cz significantly increased the risk of parkinsonism, dyskinesia, and dystonia. Potential benefits and risks should be weighed when considering long-term use of these drugs especially fz.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-017-2247-x) contains supplementary material, which is available to authorized users.

Identifying Therapeutic Agents for Amelioration of Mitochondrial Clearance Disorder in Neurons of Familial Parkinson Disease

“…Flunarizine is effective in treating migraine but has side effects, such as depression and weight gain ( Sørensen et al., 1991 ). CCBs can induce parkinsonism ( Jhang et al., 2017 ), but some reports suggested that CCBs lower the risk of PD ( Jhang et al., 2017 , Simon et al., 2010 , Swart and Hurley, 2016 ). The ergot-derived dopamine agonists were commonly used as a treatment for PD, but lots of adverse events, such as valvar heart disease, retroperitoneal fibrosis, pleurisy, and pericarditis have been reported ( Horvath et al., 2004 , Schade et al., 2007 ).…”

Trimetazidine Use and the Risk of Parkinsonism: A Nationwide Population-Based Study

“…Both in vitro and in vivo studies have demonstrated blockade of D 2 receptors by certain drugs with the piperazine structure, such as chlorpromazine, cinnarizine, and TMZ [ 21 , 22 ]. Since the affinity for D 2 receptors is dependent on the chemical structure of piperazine ligands [ 22 , 23 ] and may contribute to developing parkinsonism [ 24 ], further investigation into the affinities of receptors for TMZ and its metabolites is necessary.…”

High exposure compared with standard exposure to metoclopramide associated with a higher risk of parkinsonism: a nationwide population‐based cohort study

“…The endpoint event was defined as during a 1‐year follow‐up, participants were diagnosed with parkinsonism in either an outpatient visit or a hospital admission that allowed a temporary prescription of at least one of the APDs. We used the ICD‐9‐CM codes and pharmacy data to identify and distinguish cases of parkinsonism and IPD . The ICD‐9‐CM diagnostic codes that could incorporate all possible parkinsonian features, including 332 (PD), 332.0 (paralysis agitans), 332.1 (secondary parkinsonism) and 333 (other extrapyramidal diseases and abnormal movement disorders), were used to indicate the diagnosis of parkinsonism .…”

“…We used the ICD‐9‐CM codes and pharmacy data to identify and distinguish cases of parkinsonism and IPD . The ICD‐9‐CM diagnostic codes that could incorporate all possible parkinsonian features, including 332 (PD), 332.0 (paralysis agitans), 332.1 (secondary parkinsonism) and 333 (other extrapyramidal diseases and abnormal movement disorders), were used to indicate the diagnosis of parkinsonism . A temporary prescription of at least one of the APDs for a total duration of ≤4 weeks during a 1‐year follow‐up was allowed further to support the assertion that identified parkinsonism cases were DIP and make the diagnosis of IPD unlikely .…”

“…As one of the largest databanks of medical information in the world, NHIRD provides a unique opportunity to assess the risk factors for various diseases. The application of NHIRD in risk factor evaluation for Parkinson's disease (PD) has been validated in a number of previous studies [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34].…”