Nomides, 30 mg capsules 10 pcs

PHARMACODINAMICS

Mechanism of action

. Antiviral drug, oseltamivir phosphate 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 respiratory epithelial cells and further spread of the virus in the body. Inhibits influenza virus growth in vitro and suppresses virus replication and pathogenicity in vivo, reduces the release of influenza A and B viruses from the body. Studies of clinical influenza virus isolates have shown that 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 were started on 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 release from the body and a reduction in the area under the “viral titers-time” curve.

The data obtained in 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 adult patients of younger age, but 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.

Treatment of influenza in children

A double-blind, placebo-controlled study was conducted in children aged 1-12 years (mean age 5.3 years) who had fever (˃37.8°C) and one of the respiratory system symptoms (cough or rhinitis) during a period of flu virus circulation in the population. Sixty-seven percent of patients were infected with influenza A virus and 33% of patients were infected with influenza B virus. Oseltamivir (when taken no later than 48 hours after the onset of the first flu infection symptoms) significantly reduced the duration of illness (by 35.8 hours) compared to placebo. The duration of the disease was defined as the time until the cough, nasal congestion, disappearance of fever, and return to normal activity. The incidence of acute otitis media was reduced by 40% in the children treated with oseltamivir compared to the placebo group. Recovery and return to normal activity occurred almost 2 days earlier in children who received oseltamivir compared to the placebo group.

Another study involved children aged 6-12 years with bronchial asthma; 53.6% of patients had influenza infection confirmed serologically and/or in culture. The median duration of illness in the group of patients receiving oseltamivir did not decrease significantly. But by the last 6 days of therapy with oseltamivir, forced expiratory volume in 1 second (FEF1) increased by 10.8% compared with 4.7% in patients receiving placebo (p=0.0148).

The prevention of influenza in adults and adolescents

The preventive efficacy of oseltamivir in natural influenza A and B infection has been proven in 3 separate phase III clinical trials. About 1% of patients became ill with influenza while taking oseltamivir. Oseltamivir also significantly reduced the frequency of virus excretion and prevented transmission from one family member to another.

Adults and adolescents who were in contact with a sick family member started taking oseltamivir within two days of the family member’s flu symptoms and continued it for 7 days, which significantly reduced the incidence of flu in contactees by 92%.

In unvaccinated and generally healthy adults aged 18-65 years, taking oseltamivir during an influenza epidemic significantly reduced the incidence of influenza (by 76%). Patients took the drug for 42 days.

In elderly and seniors in nursing homes, 80% of whom were vaccinated before the season when the study was conducted, oseltamivir significantly reduced the incidence of influenza by 92%. In the same study oseltamivir significantly (86%) reduced the incidence of flu complications: bronchitis, pneumonia, sinusitis. Patients took the drug for 42 days.

Preventing influenza in children

The preventive efficacy of oseltamivir in naturally occurring influenza infection was demonstrated in a study in children from 1 to 12 years after contact with a sick family member or someone in the regular environment. The primary efficacy parameter in this study was the rate of laboratory-confirmed influenza infection. In the study, children who received oseltamivir (oral suspension powder) at a dose of 30 to 75 mg once daily for 10 days and who did not excrete the virus at baseline had a reduced rate of laboratory-confirmed influenza to 4% (2/47) compared with 21% (15/70) in the placebo group.

Influenza prevention in immunocompromised persons

Prevention of influenza in immunocompromised persons

. In immunocompromised individuals with seasonal influenza infection and no viral release at baseline, prophylactic use of oseltamivir resulted in a reduction in the incidence of laboratory-confirmed influenza infection with clinical symptoms to 0.4% (1/232) compared with 3% (7/231) in the placebo group. Laboratory-confirmed influenza infection with clinical symptoms was diagnosed in the presence of oral fever above 37.2 °C, cough and/or acute rhinitis (all reported on the same day while taking the drug/placebo), and a positive reverse-transcriptase polymerase chain reaction for influenza virus RNA.

Resistance

Clinical studies

The risk of influenza viruses with reduced sensitivity or resistance to the drug has been studied in clinical trials. In all patients who were carriers of OC-resistant virus, the carriage was temporary, did not affect the elimination of the virus and did not cause deterioration of the clinical condition.

/table>

*Full genotyping was not performed in any of the studies.

No cases of resistance to the drug were observed in individuals with normal immune system function when oseltamivir was administered for post-exposure prophylaxis (7 days), family contact prophylaxis (10 days), and seasonal prophylaxis (42 days). In the 12-week seasonal prophylaxis study in immunocompromised individuals, there were also no cases of resistance.

Data from individual clinical cases and observational studies

In patients not receiving oseltamivir, naturally occurring mutations of influenza A and B viruses that had reduced sensitivity to oseltamivir were found. In 2008, the H275Y substitution type mutation leading to resistance was found in more than 99% of the 2008 H1N1 virus strains circulating in Europe. The 2009 H1N1 influenza virus (“swine flu”) was sensitive to oseltamivir in most cases. Oseltamivir-resistant strains were found in individuals with normal immune system function and immunocompromised individuals taking oseltamivir. The degree of desensitization to oseltamivir and the frequency of such viruses may vary by season and region. Resistance to oseltamivir was found in patients with pandemic H1N1 influenza who received the drug for both treatment and prevention.

The incidence of resistance may be higher in younger patients and immunocompromised patients. Oseltamivir-resistant laboratory strains of influenza viruses and influenza viruses from patients treated with oseltamivir carry N1 and N2 neuraminidase mutations. The mutations leading to resistance are often specific to the neuraminidase subtype.

When deciding whether to use oseltamivir, the seasonal sensitivity of the influenza virus to the drug should be considered (the latest information can be found on the WHO website).

PHARMACOKINETICS

Pharmacokinetics

Absorption

Oseltamivir phosphate is readily absorbed in the gastrointestinal tract and is highly converted to the active metabolite by hepatic and intestinal esterases. Plasma concentrations of the active metabolite are determined within 30 minutes, time to reach maximum concentrations of 2-3 hours, and are more than 20 times higher than concentrations of prodrug. At least 75% of the dose taken orally enters the systemic bloodstream as an active metabolite, less than 5% as the parent drug. Plasma concentrations of both prodrug and active metabolite are proportional to the dose and independent of food intake.

Distribution

The volume of distribution (Vss) of the active metabolite is 23 liters.

According to animal studies, after oral administration of oseltamivir phosphate, its active metabolite was found in all major foci of infection (lungs, bronchial lavage, nasal mucosa, middle ear and trachea) in concentrations that provide an antiviral effect.

The binding of the active metabolite to plasma proteins is 3%. The binding of prodrug with plasma proteins is 42%, which is not enough to cause significant drug interactions.

Metabolism

Oseltamivir phosphate is highly converted to the active metabolite under the action of esterases, located primarily in the liver. Neither oseltamivir phosphate nor the active metabolite are substrates or inhibitors of cytochrome P450 isoenzymes.

Extracted (>90%) as the active metabolite primarily by the kidneys. Active metabolite does not undergo further transformation and is excreted by the kidneys (>99%) by glomerular filtration and tubular secretion. Renal clearance (18.8 l/h) exceeds glomerular filtration rate (7.5 l/h), indicating that the drug is excreted also by tubular secretion. Less than 20% of the drug taken is excreted through the intestine. The elimination half-life of the active metabolite is 6-10 hours.

Pharmacokinetics in special patient groups

Patients with renal impairment

Pharmacokinetics in special patient groups. When oseltamivir (100 mg twice daily for 5 days) is used in patients with varying degrees of renal impairment, the area under the “concentration of active metabolite in plasma – time” (AUC) curve is inversely proportional to decreased renal function.

The pharmacokinetics of oseltamivir in patients with end-stage renal failure (with creatinine clearance ≤10 mL/min) who are not on dialysis have not been studied.

Patients with liver damage

The data obtained in vitro and in animal studies about the absence of a significant increase in the AUC of oseltamivir or its active metabolite in mild to moderate liver function disorders have also been confirmed in clinical studies (see “Dosing in special cases”). The safety and pharmacokinetics of oseltamivir phosphate in patients with severe hepatic impairment have not been studied.

Elderly and Elderly Patients

In elderly and elderly patients (65-78 years), the exposure of the active metabolite in equilibrium is 25-35% higher than in younger patients when similar doses of oseltamivir are administered. The half-life of the drug in elderly and senile patients was not significantly different from that in younger patients. Given the data on drug exposure and tolerability in elderly and senile patients, no dose adjustments are required in the treatment and prevention of influenza.

Children aged 1 to 8 years and adolescents

The pharmacokinetics of oseltamivir were studied in children aged 1 to 16 years in a single-dose pharmacokinetic study and in a multiple-dose clinical study in a small number of children aged 3-12 years. The weight-adjusted excretion rate of the active metabolite is higher in young children than in adults, resulting in a lower AUC in relation to the specific dose. Administration of the drug in dose of 2 mg/kg and single doses of 30 mg or 45 mg in accordance with the dosage recommendations for children given in section “Dosage and administration” provides the same AUC of oseltamivir carboxylate as is achieved in adults after a single dose of 75 mg capsule (which is equivalent to about 1 mg/kg). The pharmacokinetics of oseltamivir in children over 12 years is the same as in adults.

Extemporally prepared suspension can be used (see “Extemporally prepared suspension”).

You can use the suspension prepared extemporaneously (see “Extemporaneous Suspension Preparation”).

Prevention

The drug should be started at least 2 days after exposure.

Adults and adolescents aged ≥12 years

Please 75 mg (one 75 mg capsule or one 30 mg capsule + one 45 mg capsule) once daily 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 who weigh more than 40 kg or who are 8 to 12 years of age

Children who can swallow the capsules may also receive prophylactic therapy by taking 75 mg (one 75 mg capsule or one 30 mg capsule + one 45 mg capsule) once daily for 10 days.

Children 1 to 8 years of age

The recommended dosing regimen is oseltamivir capsules 30 and 45 mg.

Extemporally prepared suspension can be used (see “Extemporally prepared suspension”).

You can use the suspension prepared extemporaneously (see “Extemporaneous Suspension Preparation”).

Dosage in special cases

Patients with impaired renal function

Treatment

Patients with a creatinine clearance greater than 60 ml/min do not require dose adjustments. In patients with creatinine clearance between 30 and 60 mL/min, the dose of oseltamivir should be reduced to 30 mg twice daily for 5 days.

In patients with a creatinine clearance of 10 to 30 mL/min, the dose of oseltamivir should be reduced to 30 mg once daily for 5 days. In patients on permanent hemodialysis, oseltamivir at the initial dose of 30 mg can be taken before dialysis if influenza symptoms appear within 48 h between dialysis sessions. To maintain plasma concentrations at therapeutic levels, oseltamivir should be taken 30 mg after each dialysis session. Patients on peritoneal dialysis should take oseltamivir at an initial dose of 30 mg before dialysis, then 30 mg every 5 days.

The pharmacokinetics of oseltamivir in patients with end-stage chronic renal failure (with creatinine clearance ≤10 mL/min) who are not on dialysis have not been studied. In this regard, there are no dosing recommendations for this group of patients.

Patients with creatinine clearance greater than 60 mL/min do not require dose adjustment. In patients with creatinine clearance from 30 to 60 ml/min the dose of oseltamivir should be reduced to 30 mg once daily. In patients with a creatinine clearance of 10 to 30 ml/min, it is recommended to reduce the dose of oseltamivir to 30 mg once daily. In patients on permanent hemodialysis, oseltamivir at an initial dose of 30 mg can be taken before dialysis. To maintain plasma concentrations at therapeutic levels, oseltamivir should be taken 30 mg after each subsequent odd-numbered dialysis session. In patients on peritoneal dialysis, oseltamivir should be taken at an initial dose of 30 mg before dialysis, then 30 mg every 7 days. Pharmacokinetics of oseltamivir in patients with end-stage chronic renal failure (with creatinine clearance ≤10 ml/min) who are not on dialysis have not been studied. In this regard, there are no dosing recommendations for this group of patients.

Patients with hepatic impairment

Dose adjustment is not required during treatment and prophylaxis of influenza in patients with mild to moderate hepatic impairment. Safety and pharmacokinetics of oseltamivir in patients with severe hepatic impairment have not been studied.

Elderly and elderly patients

Dose adjustment for prophylaxis or treatment of influenza is not required.

In immunocompromised patients (after transplantation)

For seasonal influenza prophylaxis in immunocompromised patients aged ≥1 year – for 12 weeks, no dose adjustment is necessary.

Children

Oseltamivir in this dosage form should not be administered to children under 1 year of age.

Extemporaneous preparation of Nomides® suspension

In cases in which adults, adolescents and children have trouble swallowing the capsules, or if there are signs of “aging” of the capsules, the capsule should be opened and its contents poured into a small amount (maximum 1 teaspoon) of a suitable sweetened food (see above). (see above) 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.

PEPPULES 75 MG

If patients require a dose of 75 MG
, the following instructions should be followed:

1. Holding one 75 mg Nomides®
capsule over a small container, gently open the capsule and pour the powder into the container.

2. Add a small amount (no more than 1 teaspoon) of a suitable sweetened food (to mask the bitter taste) and mix well.

3. Stir the mixture thoroughly and drink it immediately after preparation. If a small amount of mixture remains in the container, you should rinse the container with a small amount of water and drink the remaining mixture.

If patients require doses of 30-60 mg
, the following instructions should be followed for proper dosing:

1. Holding one 75 mg capsule of Nomides®
over a small container, gently open the capsule and pour the powder into the container.

2. add 5 ml of water to the powder with a syringe marked with the amount of liquid taken. Stir thoroughly for 2 minutes.

3. Draw the desired amount of mixture from the container into the syringe according to the chart below:

There is no need to take the undissolved white powder as it is an inactive filler. Pressing the syringe plunger, inject all of its contents into the second reservoir. The unused mixture must be discarded.

4. Add a small amount (max 1 teaspoon) of a suitable sweetened food item to the second cup, to mask the bitter taste, and mix well.

5. Stir the mixture thoroughly and drink it immediately after preparation. If there is a small amount of mixture left in the container, you should rinse the container with a little water and drink the remaining mixture.

This procedure should be repeated before each dose.

30 mg and 45 mg capsules

For proper dosing, you must follow the following instructions:

1. Determine the number of Nomides® capsules required to prepare the mixture:

*Children with a body weight of >40 kg or ages 8 to 12 years and adults may receive Nomides®
using one 45 mg capsule + one 30 mg capsule 2 times daily for treatment or once daily for prevention.

2. Make sure to use the correct dose (according to the table above). Holding one or more Nomides®
capsules over a small container, gently open one or more capsules and pour the powder into the container.

3. add a small amount (no more than 1 teaspoon) of a suitable sweetened food to mask the bitter taste, and mix well.

4. Stir the mixture thoroughly and drink it immediately after preparation. If there is a small amount of mixture left in the container, you should rinse the container with a small amount of water and drink the remaining mixture.

Repeat this process before each dose.

Interaction

Clinically significant drug interactions are unlikely according to pharmacological and pharmacokinetic studies. Oseltamivir phosphate is highly converted to active metabolite under the action of esterases mainly located in the liver. Drug interactions due to competition for binding to active esterase centers are not widely reported in the literature. The low degree of binding of oseltamivir and the active metabolite with plasma proteins does not give reasons to assume the presence of interactions related to displacement of drugs from binding to proteins.

In vitro studies show that neither oseltamivir phosphate nor its active metabolite is a preferred substrate for polyfunctional cytochrome P450 oxidases or for glucuronyltransferases. There is no reason for interaction with oral contraceptives.

Cimetidine, a nonspecific inhibitor of cytochrome P450 system isoenzyme and competes with alkaline and cationic drugs during tubular secretion, does not affect plasma concentrations of oseltamivir and its active metabolite.

It is unlikely that there are clinically significant interdrug interactions involving competition for tubular secretion, given the safety margin for most such drugs, the excretion routes for the active metabolite of oseltamivir (glomerular filtration and anionic tubular secretion), and the excretion capacity of each route.

Probenecid results in an AUC increase of the active metabolite of oseltamivir by approximately 2-fold (due to reduced active renal tubular secretion). However, no dose adjustment is required when concomitant use with probenecid, given the safety margin of the active metabolite.

Concomitant administration with amoxicillin does not affect plasma concentrations of oseltamivir and its components, showing little competition for excretion by anionic tubular secretion.

Concomitant administration with paracetamol has no effect on plasma concentrations of oseltamivir and its active metabolite or paracetamol.

Pharmacokinetic interactions between oseltamivir, its main metabolite were not found when concomitantly taken with paracetamol, acetylsalicylic acid, cimetidine or antacids (magnesium and aluminum hydroxide, calcium carbonate),warfarin, rimantadine or amantadine.

. When using oseltamivir with commonly used drugs such as angiotensin-converting enzyme inhibitors (enalapril, captopril), thiazide diuretics (bendroflumethiazide), antibiotics (penicillin, cephalosporins, azithromycin, erythromycin and doxycycline), H2-histamine receptor blockers (ranitidine, cimetidine), beta-adrenoblockers (propranolol), xanthines (theophylline), sympathomimetics (pseudoephedrine), opiates (codeine), glucocorticosteroids, inhaled bronchodilators and non-narcotic analgesics (acetylsalicylic acid, ibuprofen and paracetamol), no changes in the nature or frequency of adverse events were observed.

The use of oseltamivir in combination with drugs with a narrow therapeutic scope (e.g., chlorpropamide, methotrexate, butadione) should be used with caution.

Special Instructions

Extemporaneous preparation of Nomides^® suspension from capsules

. In cases where adults, adolescents and children have trouble swallowing the capsules or where there are signs of “aging” of the capsules, you should 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) 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.

Capsules 75 mg

If patients require a dose of 75 mg, the following instructions should be followed:

1. Holding one 75 mg capsule of Nomides^® over a small container, gently open the capsule and pour the powder into the container.

2. Add a small amount (no more than 1 teaspoon) of a suitable sweetened food (to mask the bitter taste) and mix well.

3. Stir the mixture thoroughly and drink it immediately after preparation. If a small amount of mixture remains in the container, you should rinse the container with a small amount of water and drink the remaining mixture.

If patients require doses of 30-60 mg, the following instructions should be followed for proper dosing:

1. Holding one 75 mg capsule of Nomides^® over a small container, gently open the capsule and pour the powder into the container.

2. add 5 ml of water to the powder, using a syringe marked with the amount of liquid taken. Stir thoroughly for 2 minutes.

3. Draw the desired amount of mixture from the container into the syringe according to the following table.

There is no need to take the undissolved white powder because it is an inactive filler. Pressing the syringe plunger, inject all of its contents into the second reservoir. The unused mixture must be discarded.

4. Add a small amount (max 1 teaspoon) of a suitable sweetened food item to the second cup, to mask the bitter taste, and mix well.

5. Stir the mixture thoroughly and drink it immediately after preparation. If there is a small amount of mixture left in the container, you should rinse the container with a little water and drink the remaining mixture.

This process needs to be repeated before each dose.

Contraindications

• Hypersensitivity to oseltamivir phosphate or any component of the drug;

• End-stage renal failure (creatinine clearance ≤10 mL/min);

• Severe hepatic failure;

• Children under 1 year.

With caution

Pregnancy, period of breastfeeding.

Side effects

In studies of influenza treatment in adult/adolescent patients, the most common adverse reactions (HP) were nausea, vomiting, and headache. Most HP occurred on the first or second day of treatment and resolved on their own within 1-2 days. In studies of flu prevention in adults and adolescents, the most frequent HP were nausea, vomiting, headache, and pain. In children, vomiting was most common. The HPs described did not require drug withdrawal in most cases.

Treatment and prevention of influenza in adults and adolescents

. Table 1 shows the HP that occurred most frequently (≥1%) when taking the recommended dose of oseltamivir in influenza prevention and treatment studies in adults and adolescents (75 mg 2 times daily for 5 days for treatment and 75 mg once daily up to 6 weeks for prevention) and that had at least a 1% higher incidence compared with placebo. The influenza treatment studies included adults/adolescents without concomitant pathology and patients in risk groups, i.e., patients at high risk of developing influenza complications (elderly and elderly patients, patients with chronic heart or respiratory diseases). In general, the safety profile of at-risk patients was consistent with that of adult/adolescent patients without concomitant pathology.

In influenza prevention trials, the safety profile in patients receiving the recommended dose of the drug (75 mg once daily up to 6 weeks) did not differ from that in influenza treatment trials, despite longer administration of the drug.

Table 1. Percentage of adults/adolescents with HP occurring at ≥1% in the oseltamivir group in influenza infection treatment and prevention trials (difference from placebo ≥1%).

a Frequency category is provided for the oseltamivir group only. The following frequency categories are used to estimate the frequency of HP: very frequent (≥1/10); frequent (≥1/100, < 1/10).

The following are adverse events that occurred with a frequency of ≥1% in adults and adolescents who received oseltamivir as therapy and prophylaxis for influenza infection. These adverse events either occurred more frequently in patients receiving placebo, or the difference in frequency between the oseltamivir and placebo groups was less than 1%.

Gastrointestinal disorders (oseltamivir versus placebo):

Treatment – diarrhea (6% vs. 7%), abdominal pain (including upper abdominal pain, 2% vs. 3%);

Prevention – diarrhea (3% vs. 4%), upper abdominal pain (2% vs. 2%), dyspepsia (1% vs. 1%).

Infections and invasions (oseltamivir vs placebo):

Treatment – bronchitis (3% vs. 4%), sinusitis (1% vs. 1%), herpes simplex (1% vs. 1%);

Prevention – nasopharyngitis (4% vs. 4%), upper respiratory infections (3% vs. 3%), influenza infection (2% vs. 3%).

General disorders (oseltamivir vs placebo):

Treatment – dizziness (including vertigo, 2% vs. 3%);

Prevention – fatigue (7% vs. 7%), pyrexia (2% vs. 2%), flu-like illness (1% vs. 2%), dizziness (1% vs. 1%), limb pain (1% vs. 1%).

Nervous system disorders (oseltamivir vs placebo):

Treatment – insomnia (1% vs. 1%);

Prevention – insomnia (1% vs. 1%).

Respiratory, thoracic, and mediastinal disorders (oseltamivir vs. placebo):

Treatment – cough (2% vs. 2%), nasal congestion (1% vs. 1%);

Prevention – nasal congestion (7% vs. 7%), sore throat (5% vs. 5%), cough (5% vs. 6%), rhinorrhea (1% vs. 1%).

Muscular and connective tissue disorders (oseltamivir vs placebo):

Preventive – back pain (2% vs. 3%), arthralgia (1% vs. 2%), myalgia (1% vs. 1%).

Renital and breast disorders (oseltamivir vs placebo):

Preventive dysmenorrhea (3% vs. 3%).

The treatment and prevention of influenza infection in the elderly and elderly

The safety profile in 942 elderly and elderly patients who received oseltamivir or placebo was not clinically different from that in younger individuals (under 65 years).

The prevention of influenza infection in immunocompromised patients

In a 12-week influenza prevention study involving 475 immunocompromised patients (including 18 children aged 1 to 12 years), patients taking oseltamivir (n = 238) had a safety profile consistent with that previously described in influenza prevention studies.

The treatment and prevention of influenza infection in children without comorbidities aged 1 to 12 years and patients with bronchial asthma

In studies of the treatment of natural influenza infection in children aged 1 to 12 years, HP vomiting was noted at ≥1% and at least 1% more frequently when using oseltamivir (n = 858) compared with placebo (n = 622). Vomiting was most common in children who received the recommended dose of the drug once daily as post-exposure prophylaxis at home (8% in the oseltamivir group versus 2% in the non-preventive treatment group). Oseltamivir was well tolerated, the reported adverse events were consistent with those previously described in the treatment of influenza in children. Adverse events reported in children with an incidence of ≥1% in influenza treatment trials (n = 858) or with an incidence of ≥5% in influenza prevention trials (n = 148) are presented below. These adverse events were more frequent in the placebo/no prophylaxis group; the difference between the oseltamivir and placebo/no prophylaxis groups was less than 1%.

Gastrointestinal disorders (oseltamivir versus placebo):

Treatment – diarrhea (9% vs. 9%), nausea (4% vs. 4%), abdominal pain (including upper abdominal pain, 3% vs. 3%).

Infections and invasions (oseltamivir vs placebo):

The treatments were otitis media (5% vs. 8%), bronchitis (2% vs. 3%), pneumonia (1% vs. 3%), and sinusitis (1% vs. 2%).

Respiratory, thoracic, and mediastinal disorders (oseltamivir vs. placebo):

Treatment – asthma (including exacerbation, 3% vs. 4%), nasal bleeding (2% vs. 2%);

Prevention – cough (12% vs. 26%), nasal congestion (11% vs. 20%).

Skin and subcutaneous tissue disorders (oseltamivir vs placebo):

The treatment was dermatitis (including allergic and atopic dermatitis, 1% vs. 2%).

Hearing and labyrinth disorders (oseltamivir vs placebo):

The treatment was ear pain (1% vs. 1%).

Visual organ disorders (oseltamivir vs placebo):

treatment – conjunctivitis (including eye redness, ocular discharge, and eye pain, 1% vs < 1%).

Additional adverse events noted with flu treatment in children that did not meet the criteria described above.

Disorders of the blood and lymphatic system (oseltamivir vs. placebo):

The treatment was lymphoadenopathy (< 1% vs.)

Hearing and labyrinth disorders (oseltamivir vs placebo):

Treatment – Damage to the eardrum (< 1% vs.)

Post-marketing follow-up

The following are the adverse events with oseltamivir that were observed during the post-marketing follow-up period. The frequency of these adverse events and/or the causal relationship to the use of the drug cannot be determined because the true population size is not known due to the voluntary nature of the reports.

Skin and subcutaneous tissue disorders: hypersensitivity reactions – dermatitis, skin rash, eczema, urticaria, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, allergy, anaphylactic and anaphylactoid reactions, Quincke’s edema.

Hepatic and biliary tract disorders: hepatitis, increased “liver” enzyme activity in patients with flu-like symptoms receiving oseltamivir; fulminant hepatitis (including fatal), liver failure, jaundice.

Nervous mental disorders

Influenza infection can be associated with a variety of neurological symptoms and behavioral changes, including symptoms such as hallucinations, delusions, and abnormal behavior. In some cases they can be fatal. These phenomena may occur against the background of encephalopathy or encephalitis, or without the manifestation of these diseases.

Convulsions and delirium (including symptoms such as impaired consciousness, disorientation in time and space, abnormal behavior, delirium, hallucinations, agitation, anxiety, nightmares) have been reported in patients (mostly children and adolescents) who took oseltamivir for flu treatment. These cases were rarely accompanied by life-threatening acts. The role of oseltamivir in the development of these phenomena is unknown. Similar neuropsychiatric disorders have also been reported in influenza patients who did not receive oseltamivir.

Gastrointestinal disorders: gastrointestinal bleeding after taking oseltamivir (in particular, the connection between hemorrhagic colitis and taking oseltamivir cannot be excluded, since these phenomena disappeared both after the patient recovered from the flu and after discontinuation of the drug).

Visual disorders: visual impairment.

Cardiac disorders: arrhythmia.

Overdose

In most cases, overdose during clinical trials and during post-marketing use of oseltamivir was not accompanied by any adverse events. In other cases, the symptoms of overdose corresponded to the adverse events presented in the section “Adverse effects”.

Pregnancy use

There have been no controlled studies in pregnant women. However, results of post-marketing and observational studies have demonstrated the benefit of the proposed standard dosing regimen for this patient population. Results of the pharmacokinetic analysis showed lower exposure of the active metabolite (approximately 30% across all trimesters of pregnancy) in pregnant women compared to nonpregnant women. Nevertheless, the estimated exposure value remains above inhibitory concentrations (IC95 value) and therapeutic values for many strains of influenza virus. Changing the dosing regimen in pregnant women during therapy or prophylaxis is not recommended. No direct or indirect adverse effects of the drug on pregnancy, embryo-fetal or postnatal development have been found (see “Preclinical data”). When prescribing oseltamivir to pregnant women, both safety data and the course of pregnancy and pathogenicity of the circulating strain of influenza virus should be considered.

In preclinical studies, oseltamivir and the active metabolite penetrated the milk of lactating rats. There are limited data on the excretion of oseltamivir with breast milk in humans and the use of oseltamivir in lactating women. Oseltamivir and its active metabolite penetrate into breast milk in small amounts (see “Preclinical data”), producing subtherapeutic concentrations in the blood of the infant. When prescribing oseltamivir to breastfeeding women, the concomitant disease and pathogenicity of the circulating strain of influenza virus should also be considered.

In pregnancy and during breastfeeding, oseltamivir is used only if the estimated benefit to the mother outweighs the potential risk to the fetus and child.

Psychiatric disorders

Convulsions and delirium-like neuropsychiatric disorders have been reported in patients (mostly children and adolescents) who have taken oseltamivir for influenza treatment. These cases were rarely accompanied by life-threatening actions. The role of oseltamivir in the development of these phenomena is unknown. Similar neuropsychiatric disorders have also been reported in influenza patients who did not receive oseltamivir. The risk of neuropsychiatric disorders in patients treated with oseltamivir is not greater than in influenza patients who do not receive antiviral medications.

Careful monitoring of the condition and behavior of patients, especially children and adolescents, is recommended to detect signs of abnormal behavior and to assess the risk of continuing the drug if these phenomena develop.

There are no data on the effectiveness of oseltamivir in any disease caused by pathogens other than influenza A and B viruses.

Oseltamivir is not a substitute for vaccination.

The prophylactic administration of the drug is possible under epidemiological indications. For recommendations on dose adjustment in patients with kidney disease, see Dosing in Special Cases.

Similarities

Tamiflu, Nomides, Oseltamivir