Author: Payton Winghart, PharmD.
With the frequency of seasonal influenza outbreaks, it is easy to forget that the flu can often be associated with severe morbidity and mortality, especially in certain populations, like pediatrics.1 Children, in particular, those that are less than 5 years of age or those with underlying medical conditions such as asthma, sickle cell disease, epilepsy, or metabolic disorders are at high risk for severe influenza complications. 1In pharmacy, we understand that primary prevention is the most effective way of combating the flu. A primary role of a pharmacist is to promote influenza vaccinations and educate parents and caregivers on the benefits of receiving the vaccine to those who are eligible (i.e. children 6 months old and older).1 However, vaccination rates are not as high as one would like. Thus,secondary treatment measures are often utilized. One of the newest agents used to combat the flu is baloxavir (Xofluza).2
Baloxavir was FDA approved on October 24, 2018 for the treatment of acute, uncomplicated influenza for patients ages 12 years old and older.3 Baloxavir works by inhibiting the endonuclease within the polymerase acidic protein sub-unit of the viral polymerase. 3 In targeting a particular site on the virus than other antivirals currently on the market, baloxavir has the added advantage of aiming to inhibit a different part of the viral replication process. Therefore, it can be used in oseltamivir-resistant strains of influenza. It should be administered within 48 hours of symptom onset and is given as a single 40 mg dose if the patient is between 40 and 80 kg or 80 mg dose if the patient is greater than 80 kg.4 The cost of the dose of this medication is approximately $150.3 Some of the common adverse effects associated with baloxavir are diarrhea, nose and throat irritation, headache, and upset stomach, similar to oseltamivir and the other neuraminidase inhibitors.4 The Institute for Safe Medication Practices has issued an alert regarding life-threatening hypersensitivity reactions associated with baloxavir after a single dose. As for administration,it should not be taken concomitantly with calcium or calcium containing products.4 Baloxavir is the first and only FDA-approved treatment specifically indicated for those at high risk of flu complications.5
The CAPSTONE-2 Trial was one of the trials that was conducted to evaluate the efficacy of a single, oral dose of baloxavir compared with placebo.6 The main outcome measure was time to improvement of influenza symptoms from day 1 up to day 14. This was a randomized, parallel, double blind, placebo-controlled trial with a total of 2,184 participants. Results showed that baloxavir was well-tolerated and associated with faster recovery in high risk influenza patients compared to placebo, ultimately leading to FDA approval.6 Another trial known as the MINISTONE-2 trial evaluated the safety and efficacy of baloxavir in children ages 1-12 compared to the safety and efficacy of oseltamivir in this population. The primary endpoint of the study was the proportion of patients with adverse events at day 29. The study results demonstrated that baloxavir successfully reduced the length of viral shedding by one day when compared to oseltamivir. Baloxavir also had a favorable tolerability profile in terms of adverse effects, and was similar to those of oseltamivir.7
There are certain advantages and disadvantages to using baloxavir in clinical practice. As far as benefits are concerned, the one-time dose allows for ease of administration and encourages adherence.
3 It also provides coverage for patients who may be infected with oseltamivir-resistant influenza strains.3 There is also evidence that it may reduce time to symptom alleviation by one day in comparison to oseltamivir.6 In terms of detriments of baloxavir therapy, the cost of the one-time therapy is higher than that of a full course of oseltamivir.6 Baloxavir has also been shown to be less effective against influenza B strains, which is particularly an issue this season, as most of the outbreaks have been caused by influenza B.7 The use of baloxavir has also not been studied in as many populations as oseltamivir, so safety in the very young and very old is still to be determined.7 In conclusion, despite the limitations associated with baloxavir therapy, influenza infection remains a healthcare burden in our society, and the development of new medications such as baloxavir are our next best step secondary to promoting vaccination.
1. People at High Risk for Flu Complications. Centers for Disease Control and Prevention. 2018; https://www.cdc.gov/flu/highrisk/index.htm
2. Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018;379(10):913-923.
3. Mushtaq A. Baloxavir: game-changer or much ado about nothing? Lancet Respir Med. 2018;6(12):903-904.
4. Ng KE. Xofluza (Baloxavir Marboxil) for the Treatment Of Acute Uncomplicated Influenza. P T. 2019;44(1):9-11.
5. Takashita E, Morita H, Ogawa R, et al. Susceptibility of Influenza Viruses to the Novel Cap-Dependent Endonuclease Inhibitor Baloxavir Marboxil. Front Microbiol. 2018;9:3026.
6. Ison M, Portsmouth S, Uehara T, et al. Phase 3 Trial of Baloxavir Marboxil in High-Risk Influenza Patients (CAPSTONE-2 Study. Open Forum Infectious Diseases. 2018;5:S764-S765.
7. Koshimichi H, Tsuda Y, Ishibashi T, Wajima T. Population Pharmacokinetic and Exposure-Response Analyses of Baloxavir Marboxil in Adults and Adolescents Including Patients With Influenza. J Pharm Sci. 2019;108(5):1896-1904.