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

• Published in: European journal of clinical pharmacology Vol. 73; no. 7; pp. 911 - 916
• Main Authors: Jhang, Kai-Ming, Huang, Jing-Yang, Nfor, Oswald Ndi, Tung, Yu-Chun, Ku, Wen-Yuan, Lee, Chun-Te, Liaw, Yung-Po
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2017; Springer Nature B.V
• Subjects: Aged; Basal ganglia; Biomedical and Life Sciences; Biomedicine; Brain diseases; Calcium; Calcium Channel Blockers - adverse effects; Central nervous system diseases; Cinnarizine - adverse effects; Dyskinesia; Dystonia; Exposure; Extrapyramidal system; Female; Flunarizine - adverse effects; Humans; Incidence; Male; Middle Aged; Movement disorders; Movement Disorders - epidemiology; Movement Disorders - etiology; Pharmacoepidemiology and Prescription; Pharmacology/Toxicology; Prescription drugs; Side effects; Cinnarizine; National Health Insurance Research Database; Calcium channel blocker; Movement disorder; Taiwan; Flunarizine; Extrapyramidal symptom
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-017-2247-x

Purpose 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. Method 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.