Sedating antihistamine treatment with promethazine in patients with severe COPD with and without asthma: death and severe exacerbations in a nationwide register study

Barbara Bonnesen, Valdemar Rømer, Sidse Graff Jensen, Jon Torgny Wilcke, Julie Janner, Jens Bak, Sofie Johansson, Christian B Laursen, Lars Pedersen, Josefin Eklof, Pradeesh Sivapalan, Jens-Ulrik Stæhr Jensen*

*Corresponding author for this work

Abstract

BACKGROUND: Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome.

METHODS: Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma.

RESULTS: In our registry of 56,523 patients with COPD, 5,661 collected promethazine (n = 3,723) or melatonin (n = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis.Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27-1.58, p < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32-1.77, p < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine (p = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94-2.38, p<0.0001).

CONCLUSIONS: Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin.

Original languageEnglish
Article number2250604
JournalEuropean Clinical Respiratory Journal
Volume10
Issue number1
Pages (from-to)2250604
ISSN2001-8525
DOIs
Publication statusPublished - 2023

Keywords

  • admission
  • asthma
  • COPD
  • exacerbation
  • melatonin
  • mortality
  • promethazine

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