title: Extrapyramidal symptoms after exposure to calcium channel blocker-flunarizine or cinnarizine.
abstract: OBJECTIVE
  Flunarizine (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.
  
  
  METHODS
  Patients 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.
  
  
  RESULTS
  Recruited 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).
  
  
  CONCLUSIONS
  Fz 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.
authors.affiliation: Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110, Sec. 1 Jianguo N. Rd., Taichung City, 40201, Taiwan.|Department of Neurology, Lu-Tung Christian Hospital, Changhua, Taiwan.
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Jhang
authors.affiliation: Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110, Sec. 1 Jianguo N. Rd., Taichung City, 40201, Taiwan.
authors.forename: Jing-Yang
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110, Sec. 1 Jianguo N. Rd., Taichung City, 40201, Taiwan.
authors.forename: Oswald Ndi
authors.initials: ON
authors.lastname: Nfor
authors.affiliation: Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Tung
authors.affiliation: Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110, Sec. 1 Jianguo N. Rd., Taichung City, 40201, Taiwan.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Ku
authors.affiliation: Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Te
authors.initials: CT
authors.lastname: Lee
authors.affiliation: Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110, Sec. 1 Jianguo N. Rd., Taichung City, 40201, Taiwan. Liawyp@csmu.edu.tw.|Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan. Liawyp@csmu.edu.tw.
authors.forename: Yung-Po
authors.initials: YP
authors.lastname: Liaw
mesh_terms: D000368:Aged; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D002936:Cinnarizine / Q000009:adverse effects*; D005260:Female; D005444:Flunarizine / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000453:epidemiology / Q000209:etiology*
chemical_list: D002121:Calcium Channel Blockers; D002936:Cinnarizine; D005444:Flunarizine
keywords: Calcium channel blocker; Cinnarizine; Extrapyramidal symptom; Flunarizine; Movement disorder; National Health Insurance Research Database; Taiwan