Study backs oseltamivir as first option in flu

[tetano]

(Reuters) - Swiss drugmaker Roche's Tamiflu relieves flu symptoms more effectively than a combination of it and GlaxoSmithKline's Relenza, and should be first choice for flu patients, scientists said.

French researchers writing in the Public Library of Science (PLoS) Medicine journal said a study of antiviral drugs during the 2008-09 flu season found doctors should be wary of combining the two antivirals and should use Tamiflu as the first treatment option.

Tamiflu, or oseltamivir, which comes as a pill made by Roche under license from Gilead Sciences, is the drug of choice to fight flu, but some scientists have worried its overuse may prompt flu viruses to develop resistance, and so had suggested a drug combination might reduce this risk.

Relenza is an inhaled drug that works in a similar manner to Tamiflu and is known generically as zanamivir.

Scientists know flu is highly prone to mutation and most strains of the virus have evolved resistance against two older flu drugs, amantadine and rimantadine.

"When we started the trial in 2008, we felt at the time that a flu pandemic might come and there would be wide use of antivirals for influenza," said Catherine Leport from the University of Paris, France, who led the study.

"It is a common knowledge in infectious disease that when you have wide use of a single or a limited number of drugs, you may promote the emergence of resistant viruses. So a combination could be useful instead," she said in an interview.

But in results of their study, which involved 541 patients given either Tamiflu alone, Relenza alone, or a combination, Leport's team found the combination was less effective at fighting flu.

They also found that the clinical effects of the oseltamivir-zanamivir combination on the time it took for symptoms to subside was "not significantly different" from that of using Relenza alone.

"This suggests that, at the least, we should be careful about using this combination," Leport said.

Tamiflu was widely used all over the world during the H1N1 flu pandemic, which began in early 2009 and was declared over by World Health Organization (WHO) in August this year.

http://in.reuters.com/article/idINTRE6A15UD20101102

 

[tetano]

Re: Study backs Roche's Tamiflu as first option in flu

Re: Study backs Roche's Tamiflu as first option in flu

Plos Medicine

Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial

Xavier Duval1,2,3, Sylvie van der Werf4,5,6, Thierry Blanchon7,8, Anne Mosnier9, Maude Bouscambert-Duchamp10,11, Annick Tibi12,13, Vincent Enouf4, Cécile Charlois-Ou14, Corine Vincent2,3,15, Laurent Andreoletti16,17, Florence Tubach2,3,18, Bruno Lina10,11, France Mentré2,3,15, Catherine Leport14,19*, and the Bivir Study Group¶

1 Inserm CIC 007, APHP, Hôpital Bichat, Paris, France, 2 Inserm U738, Paris, France, 3 Université Paris Diderot, Paris 7, UFR de Médecine, site Bichat, Paris, France, 4 Institut Pasteur, Centre National de Référence des virus influenzae (Région-Nord), Unité de Génétique Moléculaire des Virus à ARN, Paris, France, 5 CNRS URA3015, Paris, France, 6 Université Paris Diderot, Paris 7, UFR Sciences du Vivant, Paris, France, 7 Inserm UPMC UMR-S 707, Faculté de médecine Pierre et Marie Curie, Paris, France, 8 Université Pierre et Marie Curie, Paris 6, UFR de Médecine, U707, Paris, France, 9 Réseau des Groupes Régionaux d'Observation de la Grippe (GROG), Coordination nationale, Paris, France, 10 Hospices Civils de Lyon, Centre National de Référence des virus influenzae (Région-Sud), GHE, Bron, France, 11 Université Lyon 1, VirPatH, CNRS FRE 3011, Lyon, France, 12 APHP- Agence Générale des Equipements et Produits de Santé, Unité Essais Cliniques, Paris, France, 13 Université Paris Descartes, Paris 5, Faculté de Pharmacie, Paris, France, 14 Université Paris Diderot, Paris 7, UFR de Médecine, site Bichat, Laboratoire de Recherche en Pathologie Infectieuse, Paris, France, 15 APHP, Hôpital Bichat, Unité de Biostatistiques, Paris, France, 16 Hôpital Robert Debré, Unité de Virologie médicale, Reims, France, 17 Unité de Virologie Médicale et Moléculaire Faculté de Médecine Université Champagne-Ardenne IFR53/EA-4303, Reims, France, 18 APHP Hôpital Bichat, Département d'Epidémiologie, Biostatistiques et Recherche Clinique, Paris, France, 19 APHP, Unité de Coordination des Risques Epidémiques et Biologiques, Paris, France

Background

Neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo.
Methods and Findings

We conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008–2009 seasonal influenza epidemic. Patients, general practitioners, and outcome assessors were all blinded to treatment assignment. Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z). Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14. Overall 541 patients (of the 900 planned) were included (OZ, n = 192; O, n = 176; Z, n = 173), 49% male, mean age 39 years. In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n = 157), O (n = 141), and Z (n = 149) arms had RT-PCR<200 cgeq/µl (−13.0%, 95% confidence interval [CI] −23.1 to −2.9, p = 0.025; +12.3%, 95% CI 2.39–22.2, p = 0.028 for OZ/O and OZ/Z comparisons). Mean day 0 to day 2 viral load decrease was 2.14, 2.49, and 1.68 log10 cgeq/µl (p = 0.060, p = 0.016 for OZ/O and OZ/Z). Median time to alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0–4.0, p = 0.018; +0.0, 95% CI −3.0 to 3.0, p = 0.960 for OZ/O and OZ/Z). Four severe adverse events were observed. Nausea and/or vomiting tended to be more frequent in the combination arm (OZ, n = 13; O, n = 4; and Z, n = 5 patients, respectively).
Conclusions

In adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy. Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice.

http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000362