Description
Nomides Pharmacodynamics
Mechanism of action
Antiviral drug. Oseltamivir is a prodrug, its active metabolite (oseltamivir carboxylate, OC) is an effective and selective inhibitor of influenza virus neuraminidase type A and B – the enzyme that catalyzes the release of newly formed viral particles from infected cells, their penetration into uninfected cells of respiratory epithelium and further spread of the virus in the body. Inhibits the growth of influenza virus in vitro and suppresses viral replication and pathogenicity in vivo, reduces the release of influenza A and B viruses from the body. The concentration of OC needed to inhibit neuraminidase by 50% (IC50) is 0.1-1.3 nM for influenza A virus and 2.6 nM for influenza B virus. The median IC50 value for influenza B virus is slightly higher at 8.5 nM.
Clinical efficacy
In the studies conducted, oseltamivir had no effect on influenza antibody formation, including antibody production in response to administration of inactivated influenza vaccine.
Studies of Natural Influenza Infection
In clinical studies conducted during seasonal influenza infection, patients began receiving oseltamivir no later than 40 h after the first symptoms of influenza infection appeared. 97% of patients were infected with influenza A virus and 3% of patients were infected with influenza B virus. Oseltamivir significantly shortened the period of clinical manifestations of influenza infection (by 32 hours).
In patients with a confirmed diagnosis of influenza who took oseltamivir, the severity of illness, expressed as the area under the curve for the total index of symptoms, was 38% lower compared to patients who received placebo. Moreover, in young patients without comorbidities, oseltamivir reduced by about 50% the incidence of flu complications requiring antibiotics (bronchitis, pneumonia, sinusitis, otitis media). There was clear evidence of efficacy of the drug with respect to secondary efficacy criteria relating to antiviral activity: oseltamivir caused both a shortening of the time of virus excretion from the body and a reduction in the area under the viral titers-time curve.
Data from a study of oseltamivir therapy in elderly and senile patients show that administration of oseltamivir at a dose of 75 mg twice daily for 5 days was accompanied by a clinically significant reduction in the median period of clinical manifestations of influenza infection, similar to that in younger adult patients, but the differences did not reach statistical significance. In another study, influenza patients older than 13 years with concomitant chronic cardiovascular and/or respiratory diseases received oseltamivir in the same dosing regimen or placebo. There were no differences in the median period before reduction of clinical manifestations of influenza infection in the oseltamivir and placebo groups, but the period of fever increase when receiving oseltamivir was about 1 day. The proportion of patients who excreted the virus on days 2 and 4 became significantly less. The safety profile of oseltamivir in at-risk patients did not differ from that in the general adult patient population.
Indications
– Flu treatment for adults and children over 1 year of age.
– Influenza prophylaxis in adults and adolescents over 12 years of age in groups at high risk of infection by the virus (in military units and large industrial teams, in weakened patients).
– Flu prevention for children over 1 year of age.
Contraindications
– Hypersensitivity to oseltamivir phosphate or any component of the drug;
– Terminal stage of renal failure (creatinine clearance ?10 ml/min);
– Severe hepatic insufficiency;
– Childhood under 1 year of age.
Dosage and administration
- Oseltamivir is taken orally, with or without meals. Tolerability may be improved if it is taken with food.
- When used by adults, adolescents, children who cannot swallow the capsule or if there are signs of capsule “aging” (e.g., increased fragility or other physical disorders), open the capsule and pour its contents into a small amount (maximum 1 teaspoon) of a suitable sweetened food (chocolate syrup with normal or no sugar content, honey, light brown sugar or table sugar dissolved in water, sweet dessert, condensed milk with sugar, apple puree or yogurt) in order to mask the bitter taste. The mixture should be thoroughly mixed and given to the patient whole. The mixture should be swallowed immediately after preparation. Detailed recommendations are given in the subsection “Extemporaneous preparation of the suspension”.
- Standard dosing regimen
Treatment
It is necessary to begin taking the drug within 2 days from the date of development of symptoms. - Adults and teenagers aged ? 12 years old.
Recommended daily dose is 150 mg. The drug is prescribed in a dose of 75 mg (one capsule 75 mg or one capsule 30 mg + one capsule 45 mg) 2 times a day orally for 5 days. Increasing the dose over 150 mg/day does not increase the effect. - Children with a body weight of more than 40 kg or between 8 and 12 years of age
- Children who are able to swallow capsules may also be treated by taking 75 mg (one 75 mg capsule or one 30 mg capsule + one 45 mg capsule) 2 times daily for 5 days.
- Children 1 to 8 years of age
Recommended dosing regimen for oseltamivir 30 and 45 mg capsules. - Body weight Recommended dose for 5 days
?15 kg
>15-23 kg
>23-40 kg 30 mg twice daily
45 mg twice a day
60 mg twice a day
It is possible to use extemporally prepared suspension (see subsection “Extemporally prepared suspension”). - Prevention
Administration should begin within 2 days after exposure. - Adults and adolescents aged ? 12 years old.
By 75 mg (one capsule 75 mg or one capsule 30 mg + one capsule 45 mg) 1 time per day orally for at least 10 days after exposure. During seasonal influenza epidemics, 75 mg once daily for 6 weeks. The prophylactic effect lasts as long as the drug intake lasts. - Children with body weight over 40 kg or in age from 8 to 12 years
- Children who are able to swallow the capsules may also receive prophylactic therapy by taking 75 mg (one 75 mg capsule or one 30 mg capsule + one
45 mg) once daily for 10 days. - Children 1 to 8 years of age
Body weight Recommended dosage for 10 days
?15 kg
>15-23 kg
>23-40 kg 30 mg once daily
45 mg once daily
60 mg once daily
