Tamiflu
[A multicenter study of efficacy and safety of oseltamivir in the treatment of suspected influenza patients.]

[Article in Chinese]

Deng WW, Li QY, Zhong NS; On Behalf of "Oseltamivir in the treatment of suspected influenza patients" Study Group.

Department of Respiratory Disease, Shanghai Ruijin Hospital, Shanghai 200025, China.

OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of suspected influenza patients. METHODS: A randomized, open, control and multiple center trial was conducted among 1176 individuals with suspected influenza. They were randomized either to oseltamivir group (oseltamivir 75 mg, twice daily for 5 days) or control group who were given symptom relief medicine. RESULTS: No difference was found between two groups in influenza symptoms of the patients (P > 0.05) before the treatment. (1) Oseltamivir treatment significantly reduced the duration of fever about 25 hours post treatment. (2) The AUC score of other symptoms was decreased by 160.21 (about 30.21%), and the duration was shorten by 20 hours. (3) The ratio and duration of antibiotic use in oseltamivir group were less than that of control group (P < 0.0001 and P < 0.05). (4) The incident rate of second generation influenza in oseltamivir group was also less than that of control group (P < 0.0001). (5) Secondary complications such as bronchitis, sinusitis and pneumonia occurred 3.23% in Oseltamivir group and 4.16% in the control group (chi(2) = 1.209, P = 0.272). (6) Digestive symptom such as light nausea were occur in patients who took oseltamivir, there was no difference of side effects rate between two groups (5.18% and 4.16%, chi(2) = 0.680, P = 0.410). (7) 75.68% (28) were confirmed with positive result of virus test in 37suspected influenza patients. CONCLUSION: Our data suggests that Oseltamivir is effective and well tolerated in suspected influenza patients. It can reduces the duration and severity of influenza symptom and fever, decrease the incidence of suspected influenza in the contacted population, antibiotic using, and with light side-effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15730636&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Economic evaluation of oseltamivir phosphate for postexposure prophylaxis of influenza in long-term care facilities.

Risebrough NA, Bowles SK, Simor AE, McGeer A, Oh PI.

Health Outcomes and PharmacoEconomics Research Center, Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada.

Objectives: To compare the cost-effectiveness of oseltamivir postexposure prophylaxis during influenza A outbreaks with that of amantadine postexposure prophylaxis or no postexposure prophylaxis in long-term care facilities (LTCFs). Design: Cost-effectiveness analysis based on decision analytic model from a government-payer perspective. Setting: A Canadian LTCF, with high staff vaccination, at the beginning of influenza season. Participants: Elderly, influenza-vaccinated patients living in a Canadian LTCF. Measurements: Incremental costs (or savings) per influenza-like illness case avoided compared with usual care. Results: From a government-payer perspective, this analysis showed that oseltamivir was a dominant strategy because it was associated with the fewest influenza-like illness cases, with cost savings of $1,249 per 100 patients in 2001 Canadian dollars compared with amantadine and $3,357 per 100 patients compared with no prophylaxis. Costs for amantadine dose calculation and hospitalization for adverse events contributed to amantadine being a more-expensive prophylaxis strategy than oseltamivir. Both prophylaxis strategies were more cost-effective than no prophylaxis. Conclusion: Despite high influenza vaccination rates, influenza outbreaks continue to emerge in LTCFs, necessitating cost-effective measures to further limit the spread of influenza and related complications. Although amantadine has a lower acquisition cost than oseltamivir, it is associated with more adverse events, lower efficacy, and individualized dosing requirements, leading to higher overall costs and more influenza-like illness cases than oseltamivir. Therefore the use of oseltamivir postexposure prophylaxis is more cost-effective than the current standard of care with amantadine prophylaxis or no prophylaxis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15743287&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Oral Oseltamivir Improves Pulmonary Function and Reduces Exacerbation Frequency for Influenza-Infected Children With Asthma.

Johnston SL, Ferrero F, Garcia ML, Dutkowski R.

From the *Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom; daggerHospital de Ninos Pedro de Elizalde, Docencia e Investigacion, Buenos Aires, Argentina; double daggerHospital Severo Ochoa, Neumologia Infantil, Madrid, Spain; and section signF. Hoffmann-La Roche, Nutley, NJ.

BACKGROUND:: Among asthmatic children, influenza is associated with increased hospitalizations. Although vaccination is safe and effective among asthmatic children, its protective efficacy varies and uptake rates can be low. In comparison, oseltamivir (Tamiflu) is effective against all influenza strains and can reduce the severity and duration of influenza among adults and children. This study determined the effects of oseltamivir among influenza-infected children with asthma. METHODS:: Asthmatic children (6-12 years of age) were randomized to receive oseltamivir (2 mg/kg) or placebo twice daily, as a syrup. The primary efficacy endpoint was the time to freedom from illness. Secondary endpoints included the area under the symptom score-hour curve, the proportion of patients with asthma exacerbations and changes in forced expiratory volume at 1 second during the dosing period. Analysis was performed for both the intent-to-treat infected (n = 179) and per protocol (n = 162) populations. RESULTS:: The primary endpoint for this study was not met. Oseltamivir tended to reduce the time to freedom from illness in the intent-to-treat infected population (10.4 hours, 8%; P = 0.5420), the per protocol population (24.3 hours, 17%; P = 0.1607) and patients who started treatment <24 hours after symptom onset (39.8 hours, 25%; P = 0.0780). However, an improvement in pulmonary function was observed. The improvement in forced expiratory volume at 1 second was significantly greater among oseltamivir-treated patients (10.8% versus 4.7%; P = 0.0148). Oseltamivir-treated patients also experienced fewer asthma exacerbations up to day 7 (68% versus 51%; P = 0.031). Oseltamivir was safe and well-tolerated. CONCLUSIONS:: Oseltamivir is safe and well-tolerated among asthmatic children, may reduce symptom duration and helps improve lung function and reduce asthma exacerbations during influenza infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15750458&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Development of a high-performance liquid chromatographic-mass spectrometric assay for the specific and sensitive quantification of Ro 64-0802, an anti-influenza drug, and its pro-drug, oseltamivir, in human and animal plasma and urine.

Wiltshire H, Wiltshire B, Citron A, Clarke T, Serpe C, Gray D, Herron W.

Roche Discovery Welwyn, Welwyn Garden City, Herts, UK.

Oseltamivir phosphate (Ro 64-0796/002) is a pro-drug of the anti-influenza neuraminidase inhibitor, Ro 64-0802, and as Tamiflu, has been developed for the treatment of both A and B strains of the disease. This paper describes an HPLC-MS-MS assay for both compounds in plasma and urine which fulfils all of the criteria for a good analytical method. It is sensitive with limits of quantification of 1 and 10 ng/ml for the pro-drug and active neuraminidase inhibitor, respectively. It is both accurate and precise with typical coefficients of variation from some 5,000 quality control samples of approximately +/-3 and +/-6%, respectively. Extensive stability studies have demonstrated the absence of significant problems associated with the decomposition of either compound, although ex vivo hydrolysis of Ro 64-0796 to Ro 64-0802 in rodent plasma has to be prevented by the use of the esterase inhibitor, dichlorvos.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11043756&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Synthesis of 6-acetamido-5-amino- and -5-guanidino-3, 4-dehydro-N-(2-ethylbutyryl)- 3-piperidinecarboxylic acids related to zanamivir and oseltamivir, inhibitors of influenza virus neuraminidases.

Shitara E, Nishimura Y, Nerome K, Hiramoto Y, Takeuchi T.

Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

[reaction: see text] 6-Acetamido-5-amino- and -5-guanidino-3, 4-dehydro-N-(2-ethylbutyryl)-3-piperidinecarboxylic acids (8 and 9) have been synthesized starting from natural siastatin B, a bacterial neuraminidase inhibitor isolated from Streptomyces culture in a stereospecific fashion. These compounds are related to zanamivir and oseltamivir, inhibitors of influenza virus neuraminidases.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11101432&dopt=Abstract oseltamivir Tamiflu