The Great Influenza
Rae-Ellen W. Kavey, Allison B. Kavey in Viral Pandemics, 2020
There are currently six licensed prescription influenza antiviral agents available in the United States: three are neuraminidase inhibitors that block the release of viral progeny in influenza A and B: the best known is oral oseltamivir phosphate, sold as Tamiflu; zanamivir is an inhaled drug marketed as Relenza; and intravenous peramivir is marketed as Rapivab. The fourth recommended drug is oral baloxavir marboxil marketed as Xofluza – it is an endonuclease inhibitor that interferes with viral RNA transcription and blocks virus replication. The majority of currently circulating influenza viruses are susceptible to the neuraminidase inhibitor antiviral medications, oseltamivir (Tamiflu), zanamivir and peramivir. A second category of antiviral drugs is a class of medications known as adamantanes, which target the M2 ion channel protein of influenza A viruses: amantadine and rimantadine are only active against influenza A. There are high levels of resistance in the circulating influenza A virus population to the adamantanes so they are not currently recommended for treatment of influenza.
Influenza in solid organ transplant recipients: epidemiology, management, and outcomes
Published in Expert Review of Anti-infective Therapy, 2020
Matteo Mombelli, Eleftheria Kampouri, Oriol Manuel
More recently developed antivirals include laninamivir and baloxavir marboxil (Table 1). Laninamivir is a long acting inhaled neuraminidase inhibitor approved for treatment and prophylaxis of influenza in Japan [45]. A single dose of laninamivir has been demonstrated to be non-inferior compared to oseltamivir in adults with influenza and effective in preventing influenza after exposure. However, no data are available on the use of laninamivir in SOT recipients [45,46]. Baloxavir marboxil is a recently approved antiviral drug with a novel mechanism of action relying on the selective inhibition of the influenza cap-endonuclease [47]. In a large study including healthy individuals mainly infected with H3N2 influenza strain, time to symptom alleviation was reduced by 1 day with a single dose of baloxavir when compared to placebo, but not to oseltamivir. Interestingly, the viral shedding duration was 48 h shorter with baloxavir compared to oseltamivir [47]. The low genetic barrier of baloxavir may be of concern: under treatment with baloxavir the I38T/M amino acid substitution emerged in 9.7% of the patients and resulted in prolonged viral shedding, transient rise in infectious virus titers, and prolonged duration of symptoms [48]. Although the impact of the mutation on the viral fitness is not completely elucidated, human-to-human transmission of an H3N2 strain harboring the I38T mutations has recently been reported [49]. No data exist on the use of baloxavir in SOT recipients.
Investigational antiviral therapies for the treatment of influenza
Published in Expert Opinion on Investigational Drugs, 2019
Jie Yang, Yingna Huang, Shuwen Liu
Another cap-dependent endonuclease inhibitor which revolutionized our understanding of influenza virus biology is Baloxavir marboxil (Baloxavir). The chemical structure of baloxavir marboxil is shown in Figure 2 [64]. Baloxavir (formerly S-033188; BXM) is a prodrug of baloxavir acid (formerly S-033447; BXA). In 2018, the drug was licensed in Japan for the treatment of both adult and pediatric patients infected with influenza virus. It is also approved for use in children older than 12 age with acute uncomplicated influenza [65]. For pediatric influenza-infected patients from birth to under 1 year, the safety, efficacy, and pharmacokinetics of baloxavir are under-investigated. A summary of clinical trials of baloxavir was shown in Table 2.A single dose of baloxavir was found to reduce viral load in a dose-dependent manner and significantly improve the survival of mice compared to oseltamivir group in a mouse infection model. Moreover, baloxavir has remarkable antiviral effect for mice exposed to lethal doses, even administration of the agents beyond 24–96 h after viral infection [66]. Furthermore, the results of clinical trials shown single-dose baloxavir were generally safe and well tolerated. Importantly, baloxavir could significantly reduce time to alleviation of symptoms and viral shedding, compared with oseltamivir or placebo [67–70].
Antiviral drugs for coronavirus disease 2019 (COVID-19): a systematic review with network meta-analysis
Published in Expert Review of Anti-infective Therapy, 2022
George N. Okoli, Rasheda Rabbani, Amenah Al-Juboori, Leslie Copstein, Nicole Askin, Ahmed M. Abou-Setta
Ten different interventions involving 1,884 patients were included in the intervention network plot for nausea (Figure 3). These included two different treatment durations (10-day and 5-day treatment) for the same dose of remdesivir (100 mg). The forest plots for the direct comparisons between the antiviral drugs and placebo/no treatment are shown in Appendix Figure 8, and the league table of all the comparisons is presented in Appendix Figure 9. Lopinavir (400 mg) with ritonavir (100 mg) significantly increased nausea compared with placebo/no treatment [RR 2.92; 95% Crl 1.20 to 6.39]. Remdesivir (100 mg – 10 days) significantly increased nausea compared with placebo/no treatment [RR 2.27; 95% Crl 1.29 to 3.81]. Remdesivir (100 mg – 5 days) significantly increased nausea compared with placebo/no treatment [RR 2.47; 95% Crl 1.37 to 4.22] and compared with ribavirin (400 mg) with interferon-β-1b (8million-IU) [RR 2.47; 95% Crl 1.07 to 4.88]. Baloxavir marboxil (80 mg) ranked best in terms of the likelihood of decreased nausea, while lopinavir (400 mg) with ritonavir (100 mg) ranked worst (Appendix Figure 10).
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