The added value of H2 antagonists in premedication regimens during paclitaxel treatment

Abstract

BACKGROUND: Ranitidine, a histamine 2 blocker, is the standard of care to prevent hypersensitivity reactions (HSRs) caused by paclitaxel infusion. However, the added value of ranitidine in this premedication regimen is controversial. Therefore, we compared the incidence of HSRs during paclitaxel treatment between a standard regimen including ranitidine and a regimen without ranitidine. METHODS: This prospective, pre-post interventional, non-inferiority study compared the standard premedication regimen (N = 183) with dexamethasone, clemastine and ranitidine with a premedication regimen without ranitidine (N = 183). The primary outcome was the incidence of HSR grade ≥3. Non-inferiority was determined by checking whether the upper bound of the twosided 90% confidence interval (CI) for the difference in HSR rates excluded the +6% non-inferiority margin. RESULTS: In both the pre-intervention (with ranitidine) and post-intervention (without ranitidine) group 183 patients were included. The incidence of HSR grade ≥3 was 4.4% (N = 8) in the pre-intervention group and 1.6% (N = 3) in the post-intervention group: difference −2.7% (90% CI: −6.2 to 0.1). CONCLUSIONS: As the upper boundary of the 90% CI does not exceed the predefined non-inferiority margin of +6%, it can be concluded that a premedication regimen without ranitidine is non-inferior to a premedication regimen with ranitidine. CLINICAL TRIAL REGISTRATION: www.trialregister.nl; NL8173.

Histamine‐2 (H2) antagonists can be safely removed from standard paclitaxel premedication regimens

“…This product recall has coincided with the publication of the findings of Cox et al, a pre‐post, interventional, noninferiority study which described the HSR rate in patients treated with paclitaxel using premedication regimens with and without ranitidine. The results of this study demonstrated noninferiority of premedication regimens without ranitidine vs the traditional three‐agent combination 16 …”

“…24,25 Indeed, the results documented by Cox et al demonstrate an increased incidence of HSR grade 3 and above in patient cohorts who received ranitidine vs those that did not (4.4% vs 1.6%, difference À2.7% [90% CI: À6.2 to 0.1]). 16 The authors of that study acknowledge that the low number of HSR events recorded do not allow for meaningful multivariable analysis to demonstrate whether inclusion of ranitidine in premedication regimens is or is not a significant factor in explaining the results obtained. However, it is interesting to note that a similar result was described in earlier work by Greenberger et al in patients receiving radiological contrast media, with both studies suggesting that the inherent HSR risk from ranitidine may provide some explanation for the increased incidence of HSR in patients who received ranitidine as part of a premedication regimen.…”

“…10,26,27 The results presented, alongside those in the RANISTOP study, demonstrate the continued effectiveness of a premedication regimen comprising chlorphenamine and dexamethasone only in reducing the incidence of paclitaxel-induced HSRs. 16 Significant research into the dexamethasone component of premedication has been conducted, providing further evidence of its efficacy across different methods of administration and dosing schedules. [28][29][30] While the components of paclitaxel premedication regimens were originally introduced without This study was the largest of its kind investigating the impact of H 2 antagonists on rates of HSRs as part of premedication regimens in patients receiving paclitaxel, challenging treatments that have been established as standard of care without a rigorous evidence base.…”

“…The results of this study demonstrated noninferiority of premedication regimens without ranitidine vs the traditional three-agent combination. 16 Hospitals in the UK have adopted a range of different response strategies. These can be grouped into three distinct approaches: continuing to use ranitidine (where available), use an alternative H 2 antagonist or cease the use of any H 2 antagonists.…”

H2 blockers in the prevention of paclitaxel-related hypersensitivity reaction

“…In the two study arms with and without ranitidine, the rate of all grades HSR was (20% v. 12%), grade 3 or higher HSR (4.4% v. 1.6%) and grade 1-2 HSR (16% v. 10%). 4 The difference between the two arms was -2.7% (90% CI -6.2% to 0.1%). The present study concluded that ranitidine (H2 blocker) can be safely omitted from the standard paclitaxel pre-medication strategy.…”