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

Aims: We conducted a cohort study utilizing a nationwide health insurance database to assess the European Medicines Agency's restrictions on using metoclopramide and its association with the risk of parkinsonism. Methods: New oral metoclopramide users aged ≥20 years, and age‐ and gender‐matched non‐users were recruited between 2001 and 2011. Users were divided into high‐exposure (dose >30 mg day–1 and/or duration >5 days) and standard‐exposure (dose ≤30 mg day–1 and duration ≤5 days) groups. The adjusted hazard ratio (aHR) with 95% confidence interval (CI) estimated the risk of parkinsonism. Results: During a 1‐year period, 122 of 218 931 (0.06%) users of metoclopramide vs. 56 of 218 931 (0.03%) non‐users developed parkinsonism (P < 0.001). Among the 122 cases of parkinsonism in users, 64 (0.04%) were from 168 566 standard‐exposure users and 58 (0.12%) from 50 365 high‐exposure users. Compared with non‐users, the risk of parkinsonism was higher in users (aHR 2.16; 95% CI 1.54, 3.02), including standard‐exposure (aHR 1.73; 95% CI 1.11, 2.70), and high‐exposure (aHR 3.15; 95% CI 1.78, 5.57) users. High‐exposure users had a higher risk of parkinsonism than standard‐exposure users (aHR 1.83; 95% CI 1.28, 2.63). Within the high‐exposure group, 45 233 of 50 365 (89.81%) users and 55 of 58 (94.83%) parkinsonism were from long‐duration exposure; 5 132 of 50 365 (10.19%) users and 3 of 58 (5.17%) parkinsonism were from high‐dose exposure and long‐duration + high‐dose exposure. Conclusions: The risk of parkinsonism in metoclopramide users, although extremely low (0.06%), is 2.16‐fold greater than in non‐users. High‐exposure users have a 1.83‐fold higher risk than standard‐exposure users. As users in high‐exposure group had a higher risk of parkinsonism than in standard‐exposure group, and the majority of users and parkinsonism in high‐exposure group were from long‐duration exposure; thus, physician are advised to avoid prescribing metoclopramide for >5 days, even if the daily dose is ≤30 mg. [ABSTRACT FROM AUTHOR]