Oseltamivir Group Research Articles

Efficacy and Safety of Oral Oseltamivir for Influenza Prophylaxis in Transplant Recipients

Haematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients are at high risk for severe influenza and its complications, and may not be adequately protected by vaccination. Liver, kidney, or liver-kidney transplant or allogeneic HSCT recipients aged ≥1 year were randomized to oseltamivir (75 mg once daily for those ≥13 years or weight-based dosing for children 1-12 years) or placebo for 12 weeks during periods of local influenza circulation. Patients were assessed for influenza infection via daily diary, every-other-week culture and PCR, and baseline and end-of-treatment serology. A total of 477 subjects were enrolled (239 oseltamivir and 238 placebo); most were adults (96%) and SOT recipients (81%). In the intent-to-treat population, the frequency of laboratory-confirmed clinical influenza (culture positive and/or >4-fold increase in haemagglutinin antibody inhibition [primary end point]) was similar in the oseltamivir and placebo groups (2.1% [5/237] and 2.9% [7/238]). Incidence of laboratory-confirmed influenza was significantly reduced in the oseltamivir group versus placebo when determined by reverse transcriptase-PCR (1.7% [4/237] versus 8.4% [20/238]; 95% CI 2.8, 11.1) or viral culture (<1% [1/237] versus 3.8% [9/238]; 95% CI 0.7, 6.6), giving protective efficacies of 79.9 and 88.8%, respectively. Serious adverse events (oseltamivir 8% and placebo 10%) and adverse events (oseltamivir 55% and placebo 58%) were reported in both arms with a similar frequency. One illness due to oseltamivir-resistant A/H1N1 virus was detected in each group. Oseltamivir prophylaxis is generally well-tolerated and may reduce culture- or PCR-confirmed influenza incidence in transplant recipients.

Comparison of efficacy and safety of oseltamivir and zanamivir in pandemic influenza treatment

Aim:In 2009, a flu pandemic caused panic worldwide. Oseltamivir and zanamivir were widely used in this pandemic. Currently, there are a limited number of studies comparing the efficacy and tolerability of these two drugs. This study aimed to compare the efficacy and tolerability of these two drugs in the treatment of influenza.Materials and Methods:Patients diagnosed with influenza at our infectious disease outpatient clinic during the influenza season between October 1, 2009 and February 1, 2010 were included in the study. Study data were obtained retrospectively from files for consecutive patients. A total of 136 subjects were selected. After exclusion criteria were applied, 56 subjects were discarded. The information for 80 patients in whom oseltamivir or zanamivir therapy was initiated (40 for each therapy) was compiled, and the efficacy and tolerability of the drugs were compared.Results:There was no significant difference in efficacy for the two drugs (P > 0.05). Temperature normalization was significantly faster in patients taking zanamivir (P = 0.0157). Drowsiness was the most frequent adverse event for both drugs (38% for the oseltamivir group, and 22% for the zanamivir group). Respiratory distress was observed in five patients in the zanamivir group, whereas it was not observed in patients in the oseltamivir group (P < 0.05). One patient had to discontinue therapy in the zanamivir group due to respiratory distress.Conclusion:Efficacy (in terms of symptom relief and duration to resumption of work) and adverse events were similar for zanamivir and oseltamivir, but temperature normalization was much more rapid in patients using zanamivir. Patients using zanamivir should be monitored for respiratory distress.

Clinical effectiveness of neuraminidase inhibitors—oseltamivir, zanamivir, laninamivir, and peramivir—for treatment of influenza A(H3N2) and A(H1N1)pdm09 infection: an observational study in the 2010–2011 influenza season in Japan

The clinical effectiveness of the newly released neuraminidase inhibitors (NAIs) laninamivir and peramivir has not been sufficiently evaluated in influenza-infected patients in clinical and practical settings. In this study, we analyzed the clinical data of 211 patients infected with influenza A virus subtype H3N2 (A(H3N2)) and 45 patients infected with influenza A virus subtype H1N1pdm (A(H1N1)pdm09) who received the NAIs oseltamivir, zanamivir, laninamivir, or peramivir during the 2010-2011 influenza season. The duration of fever from the first dose of the NAI to fever alleviation to <37.5°C was evaluated as an indicator of the clinical effectiveness of the NAIs in the influenza-infected patients. For the A(H3N2)-infected patients, Kaplan-Meier analysis showed the peramivir treatment group had the fastest time of fever alleviation to <37.5°C (median 17.0h, 95% confidence interval [CI] 7.2-26.8h) of the four treatment groups. No significant difference was found in the time to fever alleviation among the other antivirals, oseltamivir, zanamivir, and laninamivir. Results of multivariate analysis, using a Cox proportional-hazards model (hazard ratio 3.321) adjusted for the factors age, sex, body weight, vaccination status, time from onset to the clinic visit, and body temperature showed significantly faster fever alleviation in the peramivir treatment group compared with the oseltamivir treatment group. For the A(H1N1)pdm09-infected patients, only the oseltamivir and zanamivir treatment groups were compared, and no significant difference in time to alleviation of fever was observed between the two groups. Based on a cycling probe real-time polymerase chain reaction (PCR) assay, none of the A(H1N1)pdm09 strains in this study had the H275Y mutation conferring oseltamivir resistance. Further evaluation of the clinical effectiveness of the newly released NAIs for influenza-infected patients, including those infected with A(H1N1)pdm09, is needed.

Triple-Combination Antiviral Drug for Pandemic H1N1 Influenza Virus Infection in Critically Ill Patients on Mechanical Ventilation

A recent in vitro study showed that the three compounds of antiviral drugs with different mechanisms of action (amantadine, ribavirin, and oseltamivir) could result in synergistic antiviral activity against influenza virus. However, no clinical studies have evaluated the efficacy and safety of combination antiviral therapy in patients with severe influenza illness. A total of 245 adult patients who were critically ill with confirmed pandemic influenza A/H1N1 2009 (pH1N1) virus infection and were admitted to one of the intensive care units of 28 hospitals in Korea were reviewed. Patients who required ventilator support and received either triple-combination antiviral drug (TCAD) therapy or oseltamivir monotherapy were analyzed. A total of 127 patients were included in our analysis. Among them, 24 patients received TCAD therapy, and 103 patients received oseltamivir monotherapy. The 14-day mortality was 17% in the TCAD group and 35% in the oseltamivir group (P = 0.08), and the 90-day mortality was 46% in the TCAD group and 59% in the oseltamivir group (P = 0.23). None of the toxicities attributable to antiviral drugs occurred in either group of our study, including hemolytic anemia and hepatic toxicities related to the use of ribavirin. Logistic regression analysis indicated that the odds ratio for the association of TCAD with 90-day mortality was 0.58 (95% confidence interval, 0.24 to 1.42; P = 0.24). Although this study was retrospective and did not provide virologic outcomes, our results suggest that the treatment outcome of the triple combination of amantadine, ribavirin, and oseltamivir was comparable to that of oseltamivir monotherapy.

Phase III Randomized, Double-Blind Study Comparing Single-Dose Intravenous Peramivir with Oral Oseltamivir in Patients with Seasonal Influenza Virus Infection

Antiviral medications with activity against influenza viruses are important in controlling influenza. We compared intravenous peramivir, a potent neuraminidase inhibitor, with oseltamivir in patients with seasonal influenza virus infection. In a multinational, multicenter, double-blind, double-dummy randomized controlled study, patients aged ≥ 20 years with influenza A or B virus infection were randomly assigned to receive either a single intravenous infusion of peramivir (300 or 600 mg) or oral administration of oseltamivir (75 mg twice a day [b.i.d.] for 5 days). To demonstrate the noninferiority of peramivir in reducing the time to alleviation of influenza symptoms with hazard model analysis and a noninferiority margin of 0.170, we planned to recruit 1,050 patients in South Korea, Japan, and Taiwan. A total of 1,091 patients (364 receiving 300 mg and 362 receiving 600 mg of peramivir; 365 receiving oseltamivir) were included in the intent-to-treat infected population. The median durations of influenza symptoms were 78.0, 81.0, and 81.8 h in the groups treated with 300 mg of peramivir, 600 mg of peramivir, and oseltamivir, respectively. The hazard ratios of the 300- and 600-mg-peramivir groups compared to the oseltamivir group were 0.946 (97.5% confidence interval [CI], 0.793, 1.129) and 0.970 (97.5% CI, 0.814, 1.157), respectively. Both peramivir groups were noninferior to the oseltamivir group (97.5% CI, <1.170). The overall incidence of adverse drug reactions was significantly lower in the 300-mg-peramivir group, but the incidence of severe reactions in either peramivir group was not different from that in the oseltamivir group. Thus, a single intravenous dose of peramivir may be an alternative to a 5-day oral dose of oseltamivir for patients with seasonal influenza virus infection.

A single intramuscular injection of neuraminidase inhibitor peramivir demonstrates antiviral activity against novel pandemic A/California/04/2009 (H1N1) influenza virus infection in mice

New and emerging influenza virus strains, such as the pandemic influenza A (H1N1) virus require constant vigilance for antiviral drug sensitivity and resistance. Efficacy of intramuscularly (IM) administered neuraminidase (NA) inhibitor, peramivir, was evaluated in mice infected with recently isolated pandemic A/California/04/2009 (H1N1, swine origin, mouse adapted) influenza virus. A single IM injection of peramivir (four dose groups), given 1 h prior to inoculation, significantly reduced weight loss ( p < 0.001) and mortality ( p < 0.05) in mice infected with LD 90 dose of pandemic A/California/04/2009 (H1N1) influenza virus compared to vehicle group. There was 20% survival in the vehicle-treated group, whereas in the peramivir-treated groups, survival increased in a dose-dependent manner with 60, 60, 90 and 100% survivors for the 1, 3, 10, and 30 mg/kg doses, respectively. Weight loss on day 4 in the vehicle-treated group was 3.4 gm, and in the peramivir-treated groups was 2.1, 1.5, 1.8 and 1.8 g for the 1, 3, 10 and 30 mg/kg dose groups, respectively. In the treatment model, peramivir given 24 h after infection as a single IM injection at 50 mg/kg dose, showed significant protection against lethality and weight loss. There was 13% survival in the vehicle-treated group while in the peramivir-treated group at 24, 48, and 72 h post infection, survival was 100, 40, and 50%, respectively. Survival in the oseltamivir groups (10 mg/kg/d twice a day, orally for 5 days) was 90, 30 and 20% at 24, 48 and 72 h, respectively. These data demonstrate efficacy of parenterally administered peramivir against the recently isolated pandemic influenza virus in murine infection models.

The efficacy of ma-huang-tang (maoto) against influenza

In this study, we compared Ma Huang Tang (maoto), a traditional Japanese medicine (Kampo), with antiviral drugs to evaluate their respective and combined effect on the duration of fever and other subjective symptoms of influenza. Forty-five patients enrolled in this randomized control trial had positive type A influenza on rapid influenza antigen test, provided written consent, and sought treatment at Juntendo University Hospital between November 2008 and March 2009. Using a computer-gen- erated list, patients were randomly assigned to one of the four intervention groups: 1): maoto (TJ-27), 9 subjects; 2): Tamiflu (oseltamivir), 13 subjects; 3): Relenza (zanamivir), 6 subjects; and 4): maoto/oseltamivir combination, 9 subjects. Six outcome measures were evaluated, including fever, myalgia, headache, arthralgia, fatigue, and cough. Statistical differences were determined by the Bonferroni-adjusted t-test for multiple comparisons. Our results showed that there were no significant differences among the four groups in the time-course profile of fever and the number of days until fever resolution since treatment was initiated. In addition, no significant intergroup differences were detected in the number of days until resolution of myalgia, headache, fatigue, and cough. However, the maoto group reported a more rapid improvement in joint pain than the oseltamivir group (P = 0.01). In conclusion, maoto showed comparable efficacy as antiviral medications in reducing fever and influenza symptoms. As serious concerns over the indiscriminate use, adverse reactions, and resistance to current antiviral drugs continue to grow, maoto may serve as an elegant option for the treatment of influenza.

Long‐Acting Neuraminidase Inhibitor Laninamivir Octanoate versus Oseltamivir for Treatment of Influenza: A Double‐Blind, Randomized, Noninferiority Clinical Trial

A single administration of laninamivir octanoate, a long-acting neuraminidase inhibitor, against influenza infection has been proven effective in nonclinical studies. This study evaluated the clinical efficacy of laninamivir octanoate for the treatment of adult influenza patients. A double-blind, randomized controlled trial examined whether laninamivir octanoate was noninferior to oseltamivir. A total of 1003 patients aged ≥ 20 years with febrile influenza symptoms for no more than 36 h were randomized to receive either 40 mg of laninamivir octanoate, 20 mg of laninamivir octanoate, or oseltamivir. Laninamivir octanoate was inhaled once on day 1, and oseltamivir (75 mg) was administered orally twice daily for 5 days. The primary end point was the time to illness alleviation. A total of 996 patients were included in the primary analysis (40-mg laninamivir octanoate, n = 334; 20-mg laninamivir octanoate, n = 326; and oseltamivir, n = 336). The median time to illness alleviation in the 40-mg laninamivir octanoate, 20-mg laninamivir octanoate, and oseltamivir groups was 73.0, 85.8, and 73.6 h, respectively. The difference between laninamivir octanoate and oseltamivir was -0.6 h (95% confidence interval, -9.9 to 6.9 h) for the 40-mg group and 12.2 h (95% confidence interval, -1.5 to 17.2 h) for the 20-mg group. The upper limits of the 95% confidence intervals were less than the prespecified noninferiority margin (18 h). The proportion of patients shedding virus at day 3 was significantly lower in the 40-mg laninamivir octanoate group than in the oseltamivir group (P = .006). A single inhalation of laninamivir octanoate is effective for the treatment of seasonal influenza, including that caused by oseltamivir-resistant virus, in adults. NCT00803595.

Isolation and molecular characterization of a H5N1 virus isolated from a Jungle crow (Corvus macrohynchos) in India

In 2008, India experienced widespread outbreaks of H5N1 virus in West Bengal, Tripura, and Assam. The virus was detected in Kamrup district of Assam in November 2008 and subsequently spread to eight more districts. Two Jungle or Large billed crows (Corvus macrohynchos) were found dead in a hospital campus at about 8 km from the foci of initial detection of the virus in the same district. One of the crows was positive for H5N1 avian influenza virus by virus isolation, real time RT-PCR, and RT-PCR tests. Full length sequencing of all the eight segments of the virus was carried out. The phylogenetic analysis indicated that all the eight genes grouped with clade 2.2 viruses and were closely related to the human isolate of Bangladesh and avian isolates from India, Bangladesh, Kuwait, Germany, and Saudi Arabia. The molecular analysis indicated avian receptor (alpha 2,3 sialic acid) specificity, susceptibility to oseltamivir and amantadine group of antivirals and lower pathogenicity to mice.

Long-Acting Neuraminidase Inhibitor Laninamivir Octanoate (CS-8958) versus Oseltamivir as Treatment for Children with Influenza Virus Infection

We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness.

Impact of oseltamivir treatment on the incidence and course of acute otitis media in children with influenza

Objective Acute otitis media (AOM) is the most common complication of pediatric influenza, and imposes a substantial health care burden. We examined the influence of oseltamivir treatment on the incidence and course of AOM in children with influenza. Methods In the original study, 695 children 1–12 years who presented within 48 h of the onset of influenza-like symptoms were randomized to oseltamivir (2 mg/kg) or placebo given twice daily for 5 days. AOM was assessed at enrollment and days 3, 6 (±1), 10 (±2) and 28 (±7). AOM was clinically diagnosed by the participating primary care provider, supported by tympanometry when possible. We performed a retrospective analysis of those participants with laboratory-confirmed influenza (LCI). Assessments included the incidence and clinical course of new AOM cases. Results In all, 452 children had LCI; 217 received oseltamivir and 235 placebo. AOM was diagnosed on or after study day 3 at a significantly lower frequency in the oseltamivir versus placebo group (12.4% versus 21.7%; relative risk [RR]: 0.57 [95% CI: 0.37, 0.88], respectively). Treatment effects were greatest for children 1–2 years (RR = 0.42 [95% CI: 0.20, 0.89]) and 3–5 years (RR = 0.45 [95% CI: 0.19, 1.04]), in whom the incidence of AOM was highest. Conclusions Oseltamivir treatment significantly reduces the emergence of new AOM infections in children with LCI; effects are most pronounced in those <5 years. Clinical trial number: WV15758.

A Single Intramuscular Injection of Peramivir Demonstrates Anti-influenza Activity Against Recently Isolated Pandemic Flu Virus H1N1 (A/CA/04/2009)

Background: Peramivir is a potent and selective inhibitor of influenza neuraminidase. Here we demonstrate the efficacy of a single intramuscular (IM) injection of peramivir in mice infected with recently isolated pandemic flu virus H1N1 A/CA/04/09 (swine origin). Methods: In the treatment model peramivir was administered as a single IM injection at 50 mg/kg dose and oseltamivir was given orally at 10 mg/kg/d bid for 5 days. In the prophylaxis model, peramivir was given as a single IM injection. Each infected, drug treated group contained 9-10 mice and the saline treated groups contained 10-15 mice. Results: Peramivir potently inhibits the neuraminidase enzyme N1 from H1N1 (A/CA/04/09) in vitro with an IC50 of 0.43 + 0.07 nM (n=2). A single IM injection of peramivir, given 1 hr prior to infection (prophylaxis model), significantly reduced weight loss and mortality in mice infected with pandemic Influenza A/H1N1 virus (Table). In the therapeutic treatment model, peramivir given 24, 48 and 72 hrs after infection as a single IM injection at 50 mg/kg dose, showed significant protection against lethality. There was 13% survival in the vehicle treated group whereas in the peramivir treated group at 24, 48, and 72 hrs, the survival was 100, 40, and 50%, respectively, Survival in the oseltamivir groups at 24, 48 and 72 hrs was 90, 30 and 20%, respectively. Conclusion: These data demonstrate efficacy of parenterally administered peramivir against the recently isolated pandemic flu virus.

Boost of mucosal secretory immunoglobulin A response by clarithromycin in paediatric influenza

The antiviral neuraminidase inhibitor oseltamivir (OSV) is used to treat influenza. The macrolide clarithromycin (CAM) is used to treat bacterial infections and has anti-inflammatory and immunomodulatory activities. This retrospective study investigated the immunomodulatory effects of CAM in children presenting with influenza A. The study recruited 40 children with acute influenza, and grouped them according to the treatment received: 5-day treatment with OSV (n = 14), CAM (n = 8), OSV + CAM (n = 12) and untreated (n = 6). The before and after treatment comparisons were made of the level of secretory IgA (sIgA) against influenza A virus (H3N2) and (H1N1), total sIgA, viral RNA copy numbers in nasopharyngeal aspirates and disease symptoms. Infection induced anti-viral mucosal sIgA in the nasopharyngeal aspirates of most patients of all treatment groups. Particularly prominent increases in the levels were found in the CAM and OSV + CAM groups. Low induction of anti-viral sIgA was observed in the OSV group, but the addition of CAM to OSV augmented sIgA production and restored local mucosal sIgA levels. The frequency of residual cough in the OSV + CAM group was significantly lower than in the other groups including the group treated with OSV. CAM boosted the nasopharyngeal mucosal immune response in children presenting with influenza A, even in those treated with OSV who had low production of mucosal anti-viral sIgA, and alleviated the symptoms of influenza.

Abstract 2375: Oseltamivir Treatment Reduces the Risk of Stroke Following Influenza Infection

Background: Influenza infection is known to trigger the incidence of heart attack and ischemic stroke. Seasonal influenza epidemics are associated with an increased risk of cardiovascular diseases, including ischemic stroke. Influenza vaccine has been shown to reduce the risk of myocardial infarction and stroke. The antiviral drug oseltamivir has been shown to reduce the severity and duration of influenza symptoms and the risk of hospitalization in patients diagnosed with influenza. We conducted a retrospective cohort study to examine the impact of oseltamivir treatment on the risk of stroke and transient ischemic attack (TIA) following influenza in adults. Methods: Anonymous, patient-level medical and pharmaceutical claims data from May 2000 to September 2006 were obtained from a managed care database. We selected patients diagnosed with influenza who were prescribed oseltamivir within 1 day before or 2 days after influenza diagnosis (oseltamivir group) and compared them to patients who were not prescribed any antiviral treatment for influenza (control group). The incidence of stroke or TIA in the 6 months following influenza diagnosis in the two groups was compared using multivariate analyses adjusted for factors including age, gender, and history of risk factors for stroke, and differences expressed as hazard ratios (HR) with 95% confidence intervals (CI). Results: There were 151,930 eligible patients aged ≥18 years: 49,238 patients in the oseltamivir group, and 102,692 patients in the control group. Treatment with oseltamivir was associated with a significant 29% reduction in the risk of stroke or TIA at 6 months following an influenza diagnosis (HR=0.71; 95% CI 0.61– 0.81). Significant reductions in risk were also observed at 1 and 3 months. The effect of oseltamivir on the risk of stroke or TIA was more pronounced in patients aged ≥40 years: significant risk reductions were observed at months 1 (HR=0.50; 95% CI 0.37– 0.68), 3 (HR=0.62; 95% CI 0.51– 0.75), and 6 (HR=0.73; 95% CI 0.63– 0.84). In those aged &lt;40, HR at 6 months was 0.56 (95% CI: 0.37– 0.86). Conclusions: Prescription of oseltamivir after influenza is associated with a reduced risk of stroke or TIA. Our results, once confirmed by randomized studies, offer a novel approach to prevent stroke and TIA.

Oseltamivir and the risk of influenza-related complications and hospitalizations in patients with diabetes

Objective: This subgroup analysis of a retrospective cohort study examined, from a managed care perspective, the risk of influenza-related complications and hospitalizations in patients with diabetes who were prescribed oseltamivir for the treatment of influenza and those who were not prescribed antiviral treatment. Methods: Health insurance claims data from the Thomson Healthcare MarketScan Research Database for 6 influenza seasons (October 1-March 31) between 2000 and 2006 were used to identify patients aged ≥18 years with influenza and diabetes. Patients who received a prescription for oseltamivir within 1 day of a diagnosis of influenza were compared with those who received no antiviral treatment. Outcomes included the frequency of pneumonia, respiratory diagnoses, and otitis media and its complications, and rates of hospitalization within 14 days of the diagnosis of influenza. Cox proportional hazards regression was used to determine the relative risk (RR) of influenza-related complications and hospitalizations. Results: A total of 9090 patients with diabetes and a diagnosis of influenza were identified who met all study criteria. Of these, 2919 (32%) received a prescription for oseltamivir and 6171 (68%) received no antiviral treatment. Patients receiving oseltamivir had a significant 17% reduction in the risk of respiratory illnesses (RR = 0.83; 95% CI, 0.73-0.93) and a 30% reduction in the risk of hospitalization for any reason (RR = 0.70; 95% CI, 0.52-0.94). There were no significant differences between the oseltamivir and control groups in terms of the risks for pneumonia (RR = 0.87; 95% CI, 0.64-1.18), otitis media and its complications (RR = 0.96; 95% CI, 0.48-1.91), or hospitalization for pneumonia (RR = 0.81; 95% CI, 0.41-1.58). Conclusion: In this retrospective study, the risk of influenza-associated respiratory illnesses and the number of hospitalizations for any reason were reduced in patients with diabetes who were prescribed oseltamivir compared with an unmatched group that was not prescribed antiviral therapy.

Impact of oseltamivir on the incidence of secondary complications of influenza in adolescent and adult patients: results from a retrospective population-based study

ABSTRACTObjective: To assess the effectiveness of oseltamivir in reducing the risks of influenza-related secondary complications in otherwise healthy adolescent and adult patients aged ≥ 13 years.Research design and methods: Retrospective cohort analysis utilizing health insurance claims data in the USA (Thomson MarketScan Research Database) from six influenza seasons (October–March) between 2000 and 2006 to identify adults and adolescents (≥ 13 years) with influenza. Patients who received a prescription for oseltamivir within ±1 day of diagnosis were compared with a propensity-matched control group receiving no antiviral treatment. The first claim evidence of influenza was used to establish the study index date. Differences in outcomes were determined using Cox proportional hazards regression and expressed in terms of hazard ratios (HR) with 95% confidence intervals (CI).Main outcome measures: Diagnosis of pneumonia, any respiratory condition, otitis media and its complications, hospitalizations due to pneumonia, and hospitalization for any reason within 14 days of the index date. Healthcare expenditure within 30 days of the index date was also analyzed.Results: The oseltamivir and untreated control groups each included 36 751 eligible patients. Oseltamivir use reduced the risks of otitis media and its complications by 23% (HR=0.77; 95% CI: 0.65, 0.93), any respiratory disease by 18% (HR 0.82; 95% CI: 0.79, 0.86), and hospitalization for any reason by 22% (HR 0.78; 95% CI: 0.67, 0.91). There were no differences in any other clinical outcomes, including hospitalization for respiratory disease. Healthcare expenditure did not differ between the two groups.Limitations: The retrospective nature of the study meant that the findings may be susceptible to missing or lost data. The results obtained here represent individuals enrolled in private healthcare plans and may not, therefore, be representative of the entire US population. The lack of a virologic diagnosis of influenza, and an index date based on the first diagnosis of influenza rather than first exposure or symptom onset, may have resulted in a conservative estimate of treatment effect.Conclusions: Secondary complications of influenza, such as respiratory disease and otitis media, were reduced in patients treated with oseltamivir. The risk of hospitalization for respiratory diseases was not reduced, although there was a reduction in the risk of hospitalization for any reason. Clinical benefits observed with oseltamivir were not associated with a change in healthcare costs.

Antipyretic effect of Mao-to, a Japanese herbal medicine, for treatment of type A influenza infection in children

Mao-to is a Japanese traditional herbal medicine which has been used since ancient times for the treatment of influenza-like illness. This study was conducted to evaluate the effect of oral Mao-to administration in children with type A influenza, in comparison to Oseltamivir. We performed a controlled trial of 60 children, from 5 months through 13 years of age, with fever and influenza-like symptom of up to 48 h duration. Diagnosis of influenza type A was performed by virus isolation or detection of a viral gene by RT-PCR. Patients assigned into the following 3 groups: oral Mao-to powder (TJ-27) 0.06 g/kg body wt./dose three times daily (n=17), Oseltamivir 2 mg/kg body wt./dose twice daily (n=18) or both oral Mao-to plus Oseltamivir (n=14). The median duration of fever after treatment was significantly shorter in the Mao-to and Mao-to plus Oseltamivir groups, compared with the Oseltamivir only group (15 h [95%CI 13.2-22.1] p<0.01; 18 h[15.2-27.7] p<0.05; 24 h[23.5-43.0], respectively). Oral Mao-to administration was effective in the control of fever due to type A influenza infection in children.

Rimantadine and Oseltamivir Demonstrate Synergistic Combination Effect in an Experimental Infection with Type a (H3N2) Influenza Virus in Mice

We studied the combination effect of rimantadine hydrochloride and oseltamivir phosphate on mice infected with influenza A/Aichi/2/68 (H3N2) virus. Compounds were simultaneously administered in a 5-day-treatment course, starting 4 h before intranasal infection with 10 or 20 viral 50% mouse lethal doses. Initially, we tested combinations of oseltamivir (0.05, 0.1 and 0.2 mg/kg/day) and rimantadine (2.5, 5.0 and 7.5 mg/kg/day). Significant differences were recorded between combination-treated groups, and groups with separately applied compounds and the placebo group, such as: protection index of oseltamivir with 5.0 or 7.5 mg/kg rimantadine varied between 34-41% and 43-87%, respectively, whereas the individual effects of oseltamivir, 5 mg/kg of rimantadine and 7.5 mg/kg of rimantadine were 0-10%, 0% and 18.7-29.6%, respectively; mean survival time in combination-treated groups was lengthened by 3.1-6.9 days, in oseltamivir groups by 0-1.9 days, and in rimantadine groups by 0.8-1.3 days at 5 mg/kg and 2.6-3.2 days at 7.5 mg/kg. The three-dimensional method of Prichard and Shipman characterized the combination effect as synergistic. Further, we studied the activity of 0.05 mg/kg/day of oseltamivir combined with 5 mg/kg of rimantadine. Lung virus titre in Madin Darby canine kidney cells, lung index and consolidation score proved the high effectiveness of the combination. When compared with the placebo group, a 2.8 log10 lower titre of 50% cell culture infectious dose (CCID50) was recorded in the combination-treated group at 48-60 h post-infection (the peak of lung virus growth). This is in contrast to the 0.1-1.0 log10 and 1.1-1.4 log10 reduction in CCID50 titre observed in the oseltamivir and rimantadine groups, respectively. These data emphasize the high anti-influenza A potential of the combination.

Duration of isolation of children with influenza A treated with oseltamivir

The duration of fervescence (24 hours in children or 30 hours in adults) was shorter in the oseltamivir group than in the placebo group. According to a Japanese law enacted before oseltamivir therapy became available, schoolchildren with influenza must be isolated 48 hours after defervescence. Our data suggest isolation should be at least 84 hours for children with influenza A treated with oseltamivir and 108 hours for preschool children.

A multicentre, randomized, controlled trial of oseltamivir in the treatment of influenza in a high-risk Chinese population

ABSTRACTObjective: To evaluate the efficacy and safety of oseltamivir treatment in a population at high risk for influenza.Research design and methods: This was a randomized, open-label, controlled trial involving Chinese patients with chronic respiratory diseases (chronic bronchitis, obstructive emphysema, bronchial asthma or bronchiectasis) or chronic cardiac disease. Patients showing symptoms of influenza were randomly assigned to receive oral oseltamivir 75 mg twice daily for 5 days (oseltamivir group), or symptomatic treatment (control group) within 48 h after symptom onset.Main outcome measures: The main outcome measures were duration and severity of illness in influenza-infected patients. Other outcome measures included incidence of complications, antibiotic use, hospitalization and total medical cost.Results: Of the 118 recruited patients, 56 were identified as influenza-infected through laboratory tests (oseltamivir, N = 27; control, N = 29). Relative to symptomatic treatment, oseltamivir significantly reduced the duration of influenza symptoms by 36.8% ( p = 0.0479), and the severity by 43.1% ( p = 0.0002). In addition, oseltamivir significantly reduced the duration of fever by 45.2% ( p = 0.0051), and the time to return to baseline health status by 5 days ( p = 0.0011). The incidence of complications (11% vs. 45%, p = 0.0053) and antibiotic use (37% vs. 69%, p = 0.0167) were also significantly lower in the oseltamivir group compared with the control group. The cost of treating influenza and its complications was comparable between the two groups ( p = 0.2462).Conclusions: Oseltamivir is effective and well tolerated in high-risk patients with chronic respiratory or cardiac diseases. It can reduce the duration and severity of influenza symptoms and decrease the incidence of secondary complications and antibiotic use, without increasing the total medical cost.