Montelukast Prophylaxis Reduces Rituximab Infusion Reactions in Oncology Patients

In this interview with Pharmacy Times at Oncology Pharmacists Connect in Austin, TX, Sian Behrendt-McElroy, PharmD, MS, Medically-Integrated Oncology Pharmacy Resident, Texas Oncology, discusses her poster presentation, Montelukast Prophylaxis for Rituximab Infusion-Related Reactions: A Retrospective Analysis. The study evaluated patients receiving their first rituximab infusion and found that adding montelukast to standard premedications was associated with a 27.4% absolute reduction in infusion-related reactions overall and a 29.4% reduction among patients receiving rituximab for oncology indications. Behrendt-McElroy highlights the practical implications of the findings, noting that the low-cost intervention demonstrated a number needed to treat of just four patients to prevent one infusion reaction. She also discusses ongoing efforts to simplify implementation, including evaluating same-day montelukast administration and the adoption of montelukast as an optional premedication within rituximab-containing treatment regimens across the US Oncology Network to improve patient safety and streamline clinical workflows.

Pharmacy Times: Can you provide an overview of your poster, "Montelukast Prophylaxis for Rituximab Infusion-Related Reactions: A Retrospective Analysis," and the rationale behind evaluating montelukast in this setting?

Sian Behrendt-McLeroy, PharmD, MS: The poster is titled Montelukast Prophylaxis for Rituximab Infusion-Related Reactions: A Retrospective Analysis.

We evaluated all patients who received rituximab infusions across Texas Oncology locations during July 2025 and identified those receiving their first rituximab infusion. These were patients who had not previously received rituximab. Some patients received montelukast prophylaxis in addition to our standard premedication regimen for infusion-related reactions, which consists of acetaminophen and diphenhydramine.

The purpose of the study was to determine whether the addition of montelukast reduced the incidence of infusion-related reactions. The montelukast prophylaxis regimen consisted of 10 mg administered 12 hours before, 30 minutes before, and 30 minutes after the initial rituximab infusion.

We found an absolute risk reduction of 27.4% in infusion-related reactions among patients who received montelukast in addition to standard premedications. We also evaluated patients receiving rituximab for both oncology and nononcology indications. Although we did not achieve statistical significance in the nononcology cohort because of the smaller sample size, we observed a significant benefit in the oncology cohort. In that group, the absolute risk reduction in infusion-related reactions was 29.4% with the addition of montelukast prophylaxis.

Pharmacy Times: Based on your findings, what are the key clinical takeaways for oncology pharmacists, and how do you see montelukast prophylaxis being incorporated into practice moving forward, including any ongoing efforts to optimize its use with rituximab?

Behrendt-McLeroy: The number needed to treat with montelukast prophylaxis was 4, making this a very impactful intervention. We are using a low-cost medication and are able to significantly reduce the incidence of infusion-related reactions.

Pharmacists can play an important role in ensuring that patients receive a montelukast prescription before the day of their rituximab infusion. However, one of the questions that has come up frequently is whether the 12-hour preinfusion dose is truly necessary. From a logistical standpoint, it can be challenging to ensure that patients obtain and take a prescription medication before arriving for their infusion appointment.

Because of this, there has been interest in evaluating a simplified approach using a single dose of montelukast administered on the day of the rituximab infusion. This is something we are currently exploring at Texas Oncology.

I also presented these findings to the US Oncology Collaborative Care Committee. Based on the results, the committee plans to add montelukast as an option within all rituximab-containing regimens that are not maintenance regimens. As a result, for cycle 1, day 1 rituximab administrations, providers will have the option to select montelukast prophylaxis within the treatment plan.

This change should make implementation of the regimen significantly easier and help facilitate broader adoption across the network.