Tamiflu 45 Mg 10 Capsules ingredient Oseltamivir

5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties

Pharmacotherapeutic group: Antiviral ATC code: J05AH02

Oseltamivir phosphate is a prodrug of the active metabolite (oseltamivir carboxylate). The active metabolite is a selective inhibitor of the influenza virus neuraminidase enzymes, which are glycoproteins present on the virion surface. Viral neuraminidase enzyme activity is important both for viral entry into uninfected cells, release of newly formed virus particles from infected cells, and increased spread of the contagious virus in the body.

Oseltamivir carboxylate blocks neuraminidase enzymes of influenza A and B viruses in vitro. Oseltamivir phosphate inhibits influenza virus infection and its replication in vitro. Orally given oseltamivir inhibits influenza A and B virus replication and pathogenicity in vivo in animal models of antiviral influenza infection, and this effect is similar to that obtained in humans with 75 mg twice daily.

Oseltamivirin antiviral activity has been supported for influenza A and B in experimental studies in healthy volunteers.

The oseltamivirin neuroaminidase enzyme IC50 values ​​are between 0.1 nM and 1.3 nM for clinically isolated influenza and 2.6 nM for influenza B, respectively. High IC50 values ​​(mean 8.5 nM) for Influenza B were observed in published studies.

Decreased sensitivity of viral neuraminidase

There is no evidence of drug resistance associated with TAMIFLU use in clinical trials conducted to date after exposure to the disease (7 days), after exposure (10 days), and seasonally (42 days) for influenza No resistance was observed in the 12-week prophylaxis trial in immunocompromised patients.

Oseltamivir has been investigated in clinical trials conducted by Roche with the risk of the emergence of influenza viruses with reduced susceptibility or increased resistance. All patients with oseltamivir-resistant viruses have normally cleared the virus and have not experienced any clinical deterioration.

Resistance may be higher in younger patient groups and in immunocompromised individuals. Oseltamivir-resistant viruses isolated from oseltamivir-treated patients and oseltamivir-resistant laboratory strains of influenza virus include mutations in N1 and N2 neuraminidases. Resistance mutations tend to be specific to the viral subtype (including in H5N1 variants).

Naturally occurring influenza A / H1N1 virus mutations are associated with decreased sensitivity to oseltamivir in vitro and were detected in patients who did not use oseltamivir, based on reported data. The rate of decrease in oseltamivir susceptibility and the prevalence of these viruses varies seasonally and geographically.

Treatment of Influenza infection

Oseltamivir is only effective against diseases caused by influenza virus. For this reason, statistical analysis is presented only for subjects infected with influenza. In the pooled treatment study population (ITT), which included both influenza-positive and influenza-negative subjects, the primary efficacy decreased in proportion to the number of influenza negative persons. In the total treatment population, influenza infection was confirmed in 67% (range, 46% to 74%) of the patients studied. 64% of elderly patients are influenza-positive and 62% of those with chronic cardiac and / or respiratory disease are influenza-positive. In all Phase III treatment trials, patients were taken to work only when the influenza was spread in the local community.

Adults and adolescents aged 13 and over:

Patients were randomly assigned to receive at least one respiratory symptom (cough, nasal symptoms or sore throat) and at least one systemic symptom (myalgia, tremor / sweating, exhaustion, fatigue or headache) with fever> 37.8 ° C ) were selected. All influenza positive participating in treatment trials

75 mg oseltamivir, administered twice daily for five days in a collective analysis of adults and adolescents (N = 2413), reduced the mean duration of influenza illness by one day to 4.2 days (95% GA (confidence interval) 4.0-4.4 days; p <0.0001); in the placebo group this figure was 5.2 days (95% GA 4.9 - 5.5 days).

The proportion of subjects with lower respiratory tract complications (especially bronchitis) treated with antibiotics was 12.7% (135/1063) in the placebo group and 8.6% (116/1350) in the oseltamivir-treated population (p = 0.0012).

Treatment of influenza in high-risk populations:

The mean duration of influenza disease in elderly patients (> 65 years) receiving 75 mg oseltamivir twice daily for five days and in patients with chronic cardiac and / or respiratory disease did not significantly decrease. The total duration of fever decreased by one day in the oseltamivir group. In influenza-positive age, the incidence of lower respiratory tract complications (especially bronchitis) was 19% (52/268) in the placebo group treated with antibiotics, but decreased to 12% (29/250) in the oseltamivir-treated population (p = 0.0156).

In influenza-positive patients with chronic cardiac and / or respiratory disease, the combined incidence of lower respiratory tract complications (especially bronchitis) treated with antibiotics was 17% (22/133) in the placebo group versus 14% (16/118) in the oseltamivir-treated population (p = 0.5976).

Treatment of influenza in children:

In a study of healthy children (65% influenza-positive) aged between 1 and 12 years (mean age 5.3) with fever (> 37.8 ° C) and coughing or fever, 67% of influenza-positive patients were influenza and 33% were influenza B I was infected with. Oseltamivir treatment started within 48 hours after the onset of symptoms and decreased by approximately 1.5 days compared to placebo (95% GA 0.6 - 2.2 days; p <0.0001), with a significant improvement in recovery from disease (return to normal health and activity, fever, cough and remission of fever) . Oseltamivir reduced the incidence of acute otitis media from 26.5% (53/200) in the placebo group to 16% (29/183) in children treated with oseltamivir (p = 0.013).

The second study was completed in 334 asthmatic children aged 6 to 12 years, with 53.6% being influenza-positive. The mean duration of illness in the group treated with oseltamivir did not significantly decrease. From day 6 (the last day of treatment), ZEV1 (forced expiratory volume) increased from 4.7% in the placebo arm to 10.8% in the oseltamivir-treated group (p = 0.0148).

Treatment of Influenza B infection:

In total, 15% of the influenza-positive population was infected with influenza B; the ratios in the studies are between 1 and 33%. The mean duration of disease in patients infected with influenza B did not vary significantly between treatment groups. Data were collected for 504 infected infected individuals with Influenza B from all studies for analysis. Oseltamivir has been shown to reduce the duration of all symptoms by 0.7 days (95% GA 0.1 - 1.6 days; p = 0.022), cough, fever (> 37.8 ° C)