Strong Signs of Increased Number of Intoxications Following Rise in Prescription of Promethazine

Introduction: Promethazine, a first-generation antihistamine, was initially developed for allergies. However, promethazine is today primarily used as a sedative and hypnotic. Promethazine has been approved in Sweden since the 1950s in children over 2 years of age and restricted to prescription only. In recent years, the prescribing of promethazine has increased considerably in Sweden. Promethazine is a phenothiazine derivate and overdose can result in severe intoxication potentially leading to CNS depression, respiratory depression, and even fatalities (1). Objective: We aimed to investigate if the increased use of promethazine was related to increased number of intoxications. Methods: We compared the number of patients per year that were prescribed promethazine with the number of calls to the poison centre concerning promethazine, and with deaths where promethazine was assessed during forensic autopsy as a direct contributor to the death. Prescription data were collected from the Swedish Prescribed Drug Register (SPDR), number of consultative calls about acute poisonings were collected from the Swedish Poison Information Centre (SPIC), and number of deaths were collected from the Swedish National Board of Forensic Medicine. Data were collected between 2016 and 2021. Results: Statistics from the SPDR show that the total prescribing of promethazine increased from 88,568 patients in 2016 to 185,419 in 2021 (109 % increase). This increase can be seen in all age groups except the youngest (0-4 years) and the oldest (85+ years). In 2021, 68 % of those filling prescriptions for promethazine were women. The number of calls to the SPIC increased from 1,133 calls in 2016 to 2,073 calls in 2021 (83 % increase). Most calls concerned intentional overdose. Between 2016 and 2021, promethazine was assessed during forensic autopsy as directly contributing to the death in about 20 cases per year (16, 14, 18, 27, 22, and 22, respectively). Most of the cases (58 %) were considered suicides and 68 % of the deaths occurred in women. Conclusion: The increased number of intoxications as measured by calls to the poison centre seems to be related to the increased prescribing of promethazine. Similarly, deaths confirmed by forensic autopsy show a slight increase during the study period. Calls to the poison centre as well as deaths mainly involved intentional overdose/suicide. When prescribing promethazine it is important to consider the risks of severe intoxication in case of overd