Zanamivir for the Treatment of Influenza A and B Infection in High-Risk Patients

Lalezari, Jacob; Campion, Katrina; Keene, Oliver N.; Silagy, Chris

doi:10.1001/archinte.161.2.212

Cited by 136 publications

(85 citation statements)

References 25 publications

(30 reference statements)

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“…Nevertheless, no other studies were successful in demonstrating such superiority (11,17,23). Moreover, although zanamivir has been shown to shorten the duration of influenza illness among high-risk patients in pooled analyses combining results from several trials (9,15,24,25), a meta-analysis of 6 trials (4) did not yield clear results with regard to oseltamivir (4). Complicating respiratory tract diseases or influenza-associated complications are possible factors underlying the difficulty in showing the efficacy of drugs in shortening the duration of influenza illness among highrisk patients.…”

Section: Discussionmentioning

confidence: 99%

Intravenous Peramivir for Treatment of Influenza A and B Virus Infection in High-Risk Patients

Kohno

Kida

Mizuguchi

et al. 2011

Antimicrob Agents Chemother

110

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Influenza virus infections are known to persist longer in patients with underlying diseases, including respiratory tract diseases, and tend to become complicated by secondary influenza-associated infections, such as pneumonia. To assess the efficacy and safety of the novel anti-influenza virus drug peramivir in high-risk patients, we conducted a clinical trial of patients with diabetes or chronic respiratory tract diseases and patients being treated with drugs that suppress immune function. In this multicenter, uncontrolled, randomized, double-blind study, peramivir was intravenously administered at 300 or 600 mg/day for 1 to 5 days, as needed. Efficacy was investigated in 37 patients (300 mg, n ‫؍‬ 18 patients; 600 mg, n ‫؍‬ 19 patients). The median durations of influenza illness were 68.6 h (90% confidence interval, 41.5 to 113.4 h) overall, 114.4 h (90% confidence interval, 40.2 to 235.3 h) in the 300-mg group, and 42.3 h (90% confidence interval, 30.0 to 82.7 h) in the 600-mg group. The hazard ratio for the 600-mg group compared to the 300-mg group was 0.497 (90% confidence interval, 0.251 to 0.984), and the duration of influenza illness was significantly shorter in the 600-mg group than in the 300-mg group. Among the 42 patients in the safety analysis set, adverse events occurred in 73.8% and adverse drug reactions in 33.3%. No adverse events were particularly problematic clinically, and all patients recovered quickly from all events. The measured blood drug concentrations showed no tendency toward accumulation. Drug accumulation with repeated doses was thus considered to be of little concern. Intravenous peramivir appears to offer a potentially useful treatment for high-risk patients in the future.

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Section: Discussionmentioning

confidence: 99%

Intravenous Peramivir for Treatment of Influenza A and B Virus Infection in High-Risk Patients

Kohno

Kida

Mizuguchi

et al. 2011

Antimicrob Agents Chemother

110

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“…Zanamivir-treated, high-risk patients returned to normal activities signi¢-cantly earlier (3 days) (p 0.022) and had an 11% reduction in their median total symptom scores over days 1^5 of treatment (p 0.039) as compared with placebo. Importantly, zanamivir treatment reduced the incidence of complications requiring antibiotic use by 43% (p 0.045) as compared with placebo (Lalezari et al 2001).…”

Section: Clinical Efficacy Studies (A) Experimental In£uenza Infectionmentioning

confidence: 99%

“…A lower incidence of complications requiring antibiotics and a change in respiratory medication was observed (58% lower) (p 0.064) (Murphy et al 2000). Lalezari et al (2001) published a retrospective pooled analysis of data from high-risk patients (n 321) recruited to randomized, placebo-controlled zanamivir studies that were completed before or during the 1998^1999 in£uenza season. The high-risk population included patients with chronic respiratory disease, cardiovascular disease and the elderly (older than 65 years).…”

Section: Clinical Efficacy Studies (A) Experimental In£uenza Infectionmentioning

confidence: 99%

Zanamivir: from drug design to the clinic

Elliott

2001

Phil. Trans. R. Soc. Lond. B

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The development of the neuraminidase inhibitors has revolutionized the management options for in£u-enza. Zanamivir was the ¢rst such inhibitor to be approved for the treatment of in£uenza in humans. It is delivered by inhalation to the respiratory tract, which is the site of viral replication, in order to ensure immediate antiviral activity. Early treatment with zanamivir in clinical trials rapidly reduced the severity and duration of in£uenza symptoms and associated complications. Furthermore, chemoprophylaxis with zanamivir was shown to be e¡ective in the prevention of in£uenza illness. To date, there is no evidence for the emergence of clinically signi¢cant zanamivir-resistant isolates. In conclusion, zanamivir o¡ers a useful complementary strategy to vaccination in the e¡ective management of in£uenza.

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“…No adverse effect on pulmonary function was noted. A retrospective analysis of high-risk patients (COPD, asthma, cardiovascular disease, age > 65) in several zanamivir, placebo-controlled trials confirmed a 2.5-day reduction in median time to alleviation of clinical symptoms and a 3-day reduction in time to return to normal activities (130). A similar analysis in 10 placebo-controlled studies of oseltamivir has been reported (131).…”

Section: Pathogen-specific Therapymentioning

confidence: 59%

Pathogen-directed Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Martínez

2007

Proceedings of the American Thoracic Society

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Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural history of this chronic lung disorder. These events can be caused by a large number of infectious and noninfectious agents and are associated with an increased local and systemic inflammatory response. Their frequency and severity have been linked to progressive deterioration in lung function and health status. Infectious pathogens ranging from viral to atypical and typical bacteria have been implicated in the majority of episodes. Most therapeutic regimens to date have emphasized broad, nonspecific approaches to bronchoconstriction and pulmonary inflammation. Increasingly, therapy that targets specific etiologic pathogens has been advocated. These include clinical and laboratory-based methods to identify bacterial infections. Further additional investigation has suggested specific pathogens within this broad class. As specific antiviral therapies become available, better diagnostic approaches to identify specific pathogens will be required. Furthermore, prophylactic therapy for at-risk individuals during high-risk times may become a standard therapeutic approach. As such, the future will likely include aggressive diagnostic algorithms based on the combination of clinical syndromes and rapid laboratory modalities to identify specific causative bacteria or viruses.

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Zanamivir for the Treatment of Influenza A and B Infection in High-Risk Patients

Abstract: This pooled analysis shows that zanamivir is an effective and well-tolerated treatment for influenza in patients considered at high-risk of developing influenza-related complications.

Cited by 136 publications

References 25 publications

Intravenous Peramivir for Treatment of Influenza A and B Virus Infection in High-Risk Patients

Intravenous Peramivir for Treatment of Influenza A and B Virus Infection in High-Risk Patients

Zanamivir: from drug design to the clinic

Pathogen-directed Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

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