Is ranitidine necessary as premedication for regimens containing paclitaxel? A non-inferiority study

Expert Rev Clin Pharmacol. 2023 Jul-Dec;16(9):877-883. doi: 10.1080/17512433.2023.2238596. Epub 2023 Jul 21.

Abstract

Background: Histamine type-2-receptor antagonist drugs (H2-antagonists) have been used as standard treatment to prevent hypersensitivity reactions (HRs) in paclitaxel-containing regimens, however, their use has been strongly questioned. Ranitidine has been the most widely used H2-antagonist. Therefore, especially after its withdrawal from the market, the objective of this study is to determine the impact of its elimination from premedication on HR incidence.

Methods: A cohort, multicenter, observational, prospective, and non-inferiority study, including paclitaxel-naïve cancer patients, designed to determine the incidence of HRs of any grade associated with paclitaxel administration and analyze non-inferiority against the incidence estimated in the literature (20%), with 5% as the maximum difference (Δ). Patients with a solid neoplasm of any type/stage, who initiated treatment with paclitaxel without H2-antagonists in the premedication regimen were enrolled.

Results: A total of 441 patients were included, of whom 50 presented 54 HRs of any grade. The cumulative incidence was 11.3% (95%CI 8.5-14.7), thus fulfilling the hypothesis of non-inferiority. Of the overall HRs detected, 15 were grade ≥ 3 with a cumulative incidence of 3.4% (95%CI 1.9-5.5).

Conclusions: This study demonstrates that the elimination of ranitidine from paclitaxel premedication schedules is non-inferior in the development of HRs of any grade compared to the administration of H2-antagonists.

Keywords: Hypersensitivity reactions; non-inferiority; oncology; paclitaxel; ranitidine.

Publication types

  • Equivalence Trial
  • Multicenter Study
  • Observational Study

MeSH terms

  • Antineoplastic Agents, Phytogenic* / therapeutic use
  • Drug Hypersensitivity* / epidemiology
  • Drug Hypersensitivity* / etiology
  • Drug Hypersensitivity* / prevention & control
  • Histamine H2 Antagonists / adverse effects
  • Humans
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Paclitaxel / adverse effects
  • Premedication
  • Prospective Studies
  • Ranitidine / adverse effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Histamine H2 Antagonists
  • Paclitaxel
  • Ranitidine