Flunarizine related movement disorders: a nationwide population-based study

Flunarizine (fz) causes side effects such as movement disorders (MDs). We investigated risk factors associated with fz-related MDs. Participants were recruited from the longitudinal health insurance databases and included patients who took fz for more than 1 month. Patients with one of the underlying diseases, or with concomitant drug use (antipsychotics, metoclopramide or reserpine), and those diagnosed with MDs before fz use were excluded. Fz-related MD was defined as a new diagnosis of parkinsonism or hyperkinetic syndrome including dyskinesia or secondary dystonia during fz use or within 3 months after drug discontinuation. After exposure, 288 individuals had fz-related MDs (parkinsonism, n = 240; hyperkinesia, n = 48). Risk factors associated with these disorders were higher-dose exposure (cumulative defined daily dose [cDDD] ≥87.75, odds ratio [OR]: 3.80; 95% CI: 2.61-5.52), older age (OR: 1.07; 95% CI: 1.06-1.09), history of essential tremor (OR: 6.39; 95% CI: 2.29-17.78) and cardiovascular disease (CVD) (OR: 1.47; 95% CI: 1.14-1.9). The optimal value of cDDD to predict MDs was 58.5 (sensitivity: 0.67, specificity: 0.60), indicating an overall exposure of 585 mg. Higher exposure dose and duration, older age, history of essential tremor, and CVD were associated with fz-associated MDs. Clinicians ought to watch for extrapyramidal side effects when prescribing fz.