Promethazine Adverse Events after Implementation of a Medication Shortage Interchange

Abstract

BACKGROUND: Prochlorperazine and droperidol were commonly used antiemetics at the University of Pittsburgh Medical Center– Presbyterian Hospital until a shortage of prochlorperazine occurred and a black box warning was added to droperidol prescribing information. Subsequently, promethazine was selected as the approved intravenous antiemetic for therapeutic interchange in December 2001. Promethazine use and adverse drug events (ADEs) were investigated following review of a serious ADE that identified promethazine use as a probable contributing factor. OBJECTIVE: To illustrate ADEs associated with promethazine and characterize high-risk patients. METHODS: An ADE database analysis identified promethazine ADEs reported from 2000 to 2003. Promethazine utilization and ADEs were compared with those of other antiemetics during the pre- and post-interchange periods. RESULTS: Promethazine utilization increased significantly during the post-interchange period compared with all other antiemetics (p < 0.001). Promethazine ADEs increased from one event during the pre-interchange period to 13 events during the post-interchange period. Causality assessment using the Naranjo algorithm ranged from possible to probable. The promethazine ADE rate per 10 000 doses was significantly higher than the combined ADE rate for all other antiemetics (p < 0.001; incident rate ratio [IRR] 4.32). Elderly patients (aged ≥65 y) experienced more promethazine ADEs than younger patients (p = 0.005; IRR 4.68). Concurrent use of opioids and/or sedating drugs contributed to promethazine ADEs in 11 of 14 (78.6%) patients. CONCLUSIONS: Geriatric status is a significant risk factor for promethazine ADEs. Concomitant use of sedating drugs may further increase the risk for ADEs. Therapeutic interchange programs should be monitored for both ADEs and utilization.