Oseltamivir capsules 75mg, 10pcs

Composition

1 capsule 75 mg contains:

Active ingredient:  oseltamivir phosphate – 98.5 mg (in terms of oseltamivir-30.0 mg).

Auxiliary substances:  pre-gelatinized corn starch, povidone K 30, sodium croscarmellose, talc, sodium stearyl fumarate.

Solid gelatin capsule No. 1:  titanium dioxide, gelatin.

Pharmacological action

An antiviral drug. Oseltamivir is a prodrug, its active metabolite (oseltamivir carboxylate, OK) is an effective and selective inhibitor of neuraminidase of influenza viruses type A and B, an enzyme that catalyzes the release of newly formed viral particles from infected cells, their penetration into uninfected cells of the respiratory epithelium and further spread of the virus in the body. Inhibits the growth of influenza virus in vitro and suppresses the replication of the virus and its pathogenicity in vivo, reduces the release of influenza A and B viruses from the body. The concentration of OK required to inhibit neuraminidase by 50% (IC50) is 0.1-1.3 nM for influenza A virus and 2.6 nM for influenza B. The median IC50 values for influenza B virus are slightly higher and are 8.5 nM.

Clinical efficacy

In the conducted studies, oseltamivir did not affect the formation of anti-influenza antibodies, including the production of antibodies in response to the introduction of inactivated influenza vaccine.

Natural flu infection studies

In clinical trials conducted during seasonal influenza infection, patients started receiving oseltamivir no later than 40 hours after the first symptoms of influenza infection appeared. 97% of patients were infected with the influenza A virus and 3% of patients were infected with the influenza B virus. Oseltamivir significantly reduced the period of clinical manifestations of influenza infection (by 32 hours). In patients with a confirmed diagnosis of influenza who received oseltamivir, the severity of the disease, expressed as the area under the curve for the total symptom index, was 38% less compared to patients who received placebo. Moreover, in young patients without concomitant diseases, oseltamivir reduced by about 50% the incidence of complications of influenza requiring the use of antibiotics (bronchitis, pneumonia, sinusitis, otitis media). There was clear evidence of the drug’s effectiveness in relation to secondary efficacy criteria related to antiviral activity: oseltamivir caused both a shortening of the time of virus release from the body and a decrease in the area under the “viral titers-time”curve.

Data obtained in the study on oseltamivir therapy in elderly and senile patients show that taking oseltamivir at a dose of 75 mg 2 times a day for 5 days was accompanied by a clinically significant decrease 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, patients over 13 years of age with influenza who had concomitant chronic diseases of the cardiovascular and / or respiratory systems received oseltamivir in the same dosage regimen or placebo. There were no differences in the median period before the decrease in clinical manifestations of influenza infection in the oseltamivir and placebo groups, but the period of fever increase when taking oseltamivir was reduced by about 1 day. The proportion of patients who isolated the virus on days 2 and 4 was significantly lower. The safety profile of oseltamivir in patients at risk did not differ from that in the general population of adult patients.

Treatment of flu 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 symptoms of the respiratory system (cough or rhinitis) during the circulation of the influenza virus in the population. 67% of patients were infected with the influenza A virus and 33% of patients were infected with the influenza B virus. Oseltamivir (taken no later than 48 hours after the onset of the first symptoms of influenza infection) significantly reduced the duration of the disease (by 35.8 hours) compared to placebo. The duration of the disease was defined as the time until cough relief, nasal congestion, fever disappearance, and return to normal activity. In the group of children treated with oseltamivir, the incidence of acute otitis media decreased by 40% compared to the placebo group. Recovery and return to normal activity occurred almost 2 days earlier in children treated with oseltamivir compared to the placebo group.

Another study included children aged 6-12 years with bronchial asthma; 53.6% of patients had a serologically and/or culturally confirmed flu infection. The median duration of the disease did not significantly decrease in the group of patients treated with oseltamivir. However, by the last day 6 of oseltamivir therapy, forced expiratory volume per 1 second (FEV 1) increased by 10.8% compared to 4.7% in patients receiving placebo (p = 0.0148).

Prevention of influenza in adults and adolescents

The prophylactic efficacy of oseltamivir in natural influenza infection A and B was demonstrated in 3 separate phase III clinical trials. While taking oseltamivir, about 1% of patients became ill with influenza. Oseltamivir also significantly reduced the frequency of virus isolation and prevented transmission of the virus from one family member to another.

Adults and adolescents who were in contact with a sick family member started oseltamivir within two days after the onset of flu symptoms in family members and continued it for 7 days, which significantly reduced the frequency of flu cases in those who were in contact 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.

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

Prevention of flu in children

The prophylactic efficacy of oseltamivir in natural influenza infection has been demonstrated in children aged 1 to 12 years after contact with a sick family member or with someone from a permanent environment. The main parameter of effectiveness was the frequency of laboratory-confirmed influenza infection. In children who received oseltamivir as an oral suspension powder at a dose of 30 to 75 mg once daily for 10 days and did not isolate the virus at baseline, the incidence of laboratory-confirmed influenza decreased to 4% (2/47) compared to 21% (15/70) in the placebo group.

Flu prevention in immunocompromised individuals

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 to 3% (7/231) in the placebo group. Laboratory-confirmed influenza infection, accompanied by clinical symptoms, was diagnosed in the presence of an oral temperature above 37.2 °C, cough and/or acute rhinitis (all registered on the same day while taking the drug / placebo), as well as a positive result of a reverse transcriptase polymerase chain reaction to influenza virus RNA.

Resistance

Clinical trials

In all patients who were carriers of the OK-resistant virus, the carriage was temporary, did not affect the elimination of the virus and did not cause a deterioration in the clinical condition.

Patient population	Patients with mutations leading to resistance
	Phenotyping*	Geno-and phenotyping*
Adults and adolescents	4/1245 (0.32%)	5/1245 (0,4%)
Children (1-12 years old)	19/464 (4,1%)	25/464 (5,4%)

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

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

Data from individual clinical cases and observational studies

Patients who did not receive oseltamivir were found to have naturally occurring mutations of influenza A and B viruses that had reduced sensitivity to oseltamivir. In 2008, an H275Y substitution mutation leading to resistance was detected in more than 99% of the 2008 H1N1 virus strains circulating in Europe. The 2009 H1N1 influenza virus (“swine flu”) was susceptible to oseltamivir in most cases.Oseltamivir-resistant strains were found in individuals with normal immune system function and immunocompromised individuals treated with oseltamivir. The degree of decreased sensitivity to oseltamivir and the frequency of occurrence of such viruses may vary depending on the season and region. Resistance to oseltamivir was found in patients with H1N1 pandemic influenza treated with the drug for both treatment and prevention.

The incidence of resistance may be higher in younger and immunocompromised patients. Laboratory strains of influenza viruses resistant to oseltamivir and influenza viruses from patients treated with oseltamivir carry N1 and N2 neuraminidase mutations. 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 taken into account (up-to-date information can be found on the WHO website).

Preclinical data

Preclinical data obtained on the basis of standard studies on pharmacological safety, genotoxicity and chronic toxicity did not reveal a particular danger to humans.

Carcinogenicity: results of 3 studies to identify carcinogenic potential (two 2-year studies in rats and mice for oseltamivir and one 6-month study in transgenic Tg mice:AC for the active metabolite) were negative.

Mutagenicity: Standard genotoxic tests for oseltamivir and the active metabolite were negative.

Effect on fertility: oseltamivir at a dose of 1500 mg / kg / day did not affect the generative function of male and female rats.

Teratogenicity: in studies on the teratogenicity of oseltamivir at a dose of up to 1500 mg/kg/day (in rats) and up to 500 mg/kg/day (in rabbits), no effect on embryo-fetal development was found. In studies on the antenatal and postnatal periods of development in rats, an increase in the delivery period was observed when oseltamivir was administered at a dose of 1500 mg/kg/day: the safety limit between human exposure and the maximum non-effecting dose in rats (500 mg / kg / day) It is 480 – fold higher for oseltamivir, and 44-fold higher for its active metabolite. Fetal exposure was 15-20% of that of the mother.

Other: oseltamivir and its active metabolite are excreted in the milk of lactating rats. Limited data indicate that oseltamivir and its active metabolite are excreted in human breast milk. According to the results of extrapolation of data obtained in animal studies, their amount in breast milk can be 0.01 mg / day and 0.3 mg / day, respectively.

Approximately 50% of the guinea pigs tested showed skin sensitisation in the form of erythema when the maximum doses of the Active ingredient oseltamivir were administered. Reversible eye irritation was also detected in rabbits.

While very high oral single doses (657 mg / kg and higher) of oseltamivir had no effect on adult rats, these doses had toxic effects on immature 7-day-old baby rats, including leading to the death of animals. No adverse effects were observed with chronic use at a dose of 500 mg / kg / day from 7 to 21 days of the postnatal period.

Indications

Treatment of influenza in adults and children over the age of 1 year.

Prevention of influenza in adults and adolescents over the age of 12 years who are at high risk of infection with the virus (in military units and large industrial groups, in weakened patients).

Prevention of influenza in children older than 1 year.

Contraindications

Hypersensitivity to oseltamivir or any component of the drug. End-stage renal failure (creatinine clearance < 10 ml / min). Children under 1 year of age.

Severe liver failure.

With caution

Pregnancy, breast-feeding period.

Side effects

Clinical trials

In studies on the treatment of influenza in adults/adolescents, the most common adverse reactions (HP) were nausea, vomiting, and headache.

Most HPV occurred on the first or second day of treatment and resolved independently within 1-2 days. In studies on flu prevention in adults and adolescents, the most common HPV symptoms were nausea, vomiting, headache, and pain. Vomiting was most common in children. The described HP in most cases did not require discontinuation of the drug.

Treatment and prevention of influenza in adults and adolescents

Table 1 shows HP that occurred most frequently (≥1%) when taking the recommended dose of oseltamivir in studies on the prevention and treatment of influenza in adults and adolescents (75 mg 2 times a day for 5 days for treatment and 75 mg 1 time a day for up to 6 weeks for prevention), and the frequency of which is at least 1% higher compared to placebo. Studies on the treatment of influenza included adults/adolescents without comorbidities and at-risk patients, i. e. patients with a high risk of developing complications of influenza (elderly and senile patients, patients with chronic heart or respiratory diseases). In general, the safety profile in patients at risk was similar to that in adults/adolescents without concomitant pathology.

In influenza prevention studies, the safety profile of patients who received the recommended dose of oseltamivir (75 mg once daily for up to 6 weeks) did not differ from that in influenza treatment studies, despite longer use of the drug.

Table 1. Percentage of adults/adolescents with HP occurring with a frequency of ≥ 1% in the oseltamivir group in studies on the treatment and prevention of influenza infection (difference with placebo ≥ 1%).

Systemic organ class Adverse reaction	Treatment		Prevention		Frequency categorya
	Oseltamivir (75 mg twice daily) N = 2647	Placebo N=1977	Oseltamivir (75 mg 1 time / day) N = 1945	Placebo N = 1588
Disorders of the gastrointestinal tract
Nausea	10%	6%	8%	4%	very common
Vomiting	8%	3%	2%	1%	often
Nervous system disorders
Headache	2%	1%	17%	16%	very common
Common disorders
Pain	<1%	<1%	4%	3%	often

a The frequency category is presented only for the oseltamivir group. The following frequency categories were used to estimate the HP frequency: very frequent (>1/10): frequent (>1/100, >>

The following are adverse events that occurred with a frequency of ≥ 1% in adults and adolescents treated with oseltamivir as therapy and prevention of influenza infection. These adverse events were either more common in patients treated with placebo, or the difference in frequency between the oseltamivir and placebo groups was less than 1%.

Gastrointestinal disorders (oseltamivir vs. 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 infestations (oseltamivir vs. placebo):

treatment bronchitis (3% vs 4%), sinusitis (1% vs 1%), herpes simplex (1% vs 1%);

prevention nasopharyngitis (4% vs 4%), infections of the upper respiratory tract infection(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%), pain in the extremity (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%).

Musculoskeletal and connective tissue disorders (oseltamivir vs. placebo):

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

Genital and breast disorders (oseltamivir vs. placebo):

prevention-dysmenorrhea (3% vs. 3%).

Treatment and prevention of influenza infection in elderly and senile patients

The safety profile of 942 elderly and senile patients treated with oseltamivir or placebo did not differ clinically from that of younger patients (up to 65 years).

Prevention of influenza infection in immunocompromised patients

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

Treatment and prevention of influenza infection in children without concomitant diseases aged 1-12 years and patients with bronchial asthma

In studies on the treatment of natural influenza infection in children aged 1 to 12 years, HP with oseltamivir (n = 858) was observed with a frequency of ≥ 1% and at least 1% more often than placebo (n = 622).

Children who received the recommended dose of oseltamivir once a day as a post-exposure prophylaxis at home were most likely to experience vomiting(8% in the oseltamivir group versus 2% in the group that did not receive preventive treatment). Oseltamivir was well tolerated, and the reported adverse events were consistent with those previously described in the treatment of influenza in children.

The following adverse events were reported in children with a frequency of ≥ 1% in influenza treatment studies (n = 858) or with a frequency of ≥ 5% in influenza prevention studies (n = 148). These adverse events were more frequently observed in the placebo/no-prophylaxis group, and the difference between the oseltamivir and placebo/no-prophylaxis groups was less than 1%.

Gastrointestinal disorders (oseltamivir vs. placebo): treatment – diarrhea (9% vs. 9%), nausea (4% vs. 4%), abdominal pain (including upper abdominal pain,3% vs. 3%).

Infections and infestations (oseltamivir vs. placebo):

treatment – otitis media (5% vs. 8%), bronchitis (2% vs. 3%), pneumonia (1% vs. 3%), sinusitis (1% vs. 2%).

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

treatment – asthma (including exacerbation,3% vs 4%), nosebleeds (2% vs 2%);

prevention-cough (12% vs. 26%), nasal congestion (11% vs. 20%). Skin and subcutaneous tissue disorders (oseltamivir vs. placebo): treatment – dermatitis (including allergic and atopic dermatitis,1% vs. 2%). Hearing disorders and labyrinth disorders (oseltamivir vs. placebo):

treatment – ear pain (1% vs. 1%).

Visual disturbances (oseltamivir vs. placebo):

treatment-conjunctivitis (including redness of the eyes, discharge from the eye and pain in the eyes,1% vs

Additional adverse events reported during the treatment of influenza in children that did not meet the criteria described above.

Blood and lymphatic system disorders (oseltamivir vs. placebo): treatment-lymphadenopathy (

Hearing disorders and labyrinth disorders (oseltamivir vs. placebo):

treatment – damage to the eardrum (

Post-marketing surveillance

The following are some of the adverse events associated with oseltamivir that were observed during the post-marketing follow-up period. The frequency of these adverse events and / or a causal relationship with the use of oseltamivir cannot be established, as the true population size is unknown 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, allergies, anaphylactic and anaphylactoid reactions, Quincke’s edema.

Liver and biliary tract disorders: hepatitis, increased activity of “liver” enzymes in patients with flu-like symptoms treated with oseltamivir; fulminant hepatitis (including fatal outcome), liver failure, jaundice.

Neuropsychiatric disorders

Flu 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. Such phenomena can occur both against the background of the development of encephalopathy or encephalitis, and without the manifestation of these diseases. Seizures and delirium (including symptoms such as impaired consciousness, disorientation in time and space, abnormal behavior, delusions, hallucinations, agitation, anxiety, and nightmares) have been reported in patients (mainly children and adolescents) taking oseltamivir for the treatment of influenza. These cases were rarely accompanied by life-threatening actions. The role of oseltamivir in the development of these phenomena is unknown. Similar neuropsychiatric disorders were also reported in patients with influenza who did not receive oseltamivir.

Gastrointestinal disorders: gastrointestinal bleeding after taking oseltamivir (in particular, a link between the phenomena of 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.

Interaction

Clinically significant drug interactions are unlikely according to pharmacological and pharmacokinetic studies.

Oseltamivir is extensively converted to the active metabolite by esterases mainly located in the liver. Drug interactions caused by competition for binding to the active sites of esterases are not widely represented in the literature. The low degree of binding of oseltamivir and the active metabolite to plasma proteins does not suggest the presence of interactions associated with the displacement of drugs from protein binding.

In vitro studies show that neither oseltamivir nor its active metabolite is the preferred substrate for polyfunctional cytochrome P450 oxidases or for glucuronyltransferases (see section “Pharmacokinetics”). There are no grounds for interaction with oral contraceptives.

Cimetidine, a non-specific inhibitor of cytochrome P450 isoenzymes and competing in the process of tubular secretion with alkaline-type drugs and cations, does not affect the plasma concentrations of oseltamivir and its active metabolite. Clinically significant drug-drug interactions associated with competition for tubular secretion are unlikely, given the safety reserve for most of these drugs, the elimination pathways of the active metabolite of oseltamivir (glomerular filtration and anionic tubular secretion), as well as the excretory capacity of each of the pathways.

Probenecid leads to an increase in the AUC of the active metabolite of oseltamivir by approximately 2 times (due to a decrease in active tubular secretion in the kidneys). However, no dose adjustment is required when used concomitantly with probenecid, given the safety reserve of the active metabolite.

Concomitant use with amoxicillin does not affect the plasma concentrations of oseltamivir and its components, demonstrating weak competition for elimination by anionic tubular secretion.

Concomitant use with paracetamol does not affect the plasma concentrations of oseltamivir and its active metabolite or paracetamol.

No pharmacokinetic interactions were found between oseltamivir, its main metabolite, when co-administered with paracetamol, acetylsalicylic acid, cimetidine, antacids (magnesium and aluminum hydroxide, calcium carbonate), warfarin, rimantadine or amantadine.

When using oseltamivir with commonly used medications such as ACE inhibitors (enalapril, captopril), thiazide diuretics (bendroflumethiazide), antibiotics (penicillin, cephalosporins, azithromycin, erythromycin and doxycycline), H2-histamine receptor blockers (ranitidine, cimetidine), beta-blockers (propranolol), xanthines (theophylline), sympathomimetics (pseudoephedrine), opiates (codeine), corticosteroids, inhaled bronchodilators and non-narcotic analgesics (acetylsalicylic acid, ibuprofen and paracetamol), changes in the nature or frequency of adverse events were not observed.

Oseltamivir should be used with caution in combination with drugs that have a narrow therapeutic range (for example, chlorpropamide, methotrexate, butadione).

How to take, course of use and dosage

Treatment

Taking the drug should be started no later than 2 days after the development of symptoms of the disease.

Adults and adolescents aged ≥12 years

75 mg (one 75 mg capsule or one 30 mg capsule + one 45 mg capsule) 2 times a day orally for 5 days. An increase in the dose of more than 150 mg / day does not lead to an increased effect.

Children weighing >40 kg or aged 8-12 years>

Children who can swallow capsules can also receive treatment by taking one 75 mg capsule or one 30 mg capsule + one 45 mg capsule 2 times a day for 5 days.

Children aged 1 to 8 years

The recommended dosage regimen of oseltamivir in capsules of 30 mg and 45 mg:

Body weight	Recommended dose for 5 days
≤ 15 kg > 15-23 kg> > 23-40 kg> > 40 kg>	30 mg twice daily 45 mg twice daily 60 mg twice daily 75 mg twice daily

It is possible to use an extemporal suspension (see the subsection “Extemporal preparation of oseltamivir suspension”).

Prevention

The drug should be started no later than 2 days after contact with patients.

Adults and adolescents aged ≥12 years

75 mg (one capsule of 75 mg or one capsule of 30 mg + one capsule of 45 mg) 1 time a day inside for at least 10 days after contact with the patient. During a seasonal flu epidemic-75 mg once a day for 6 weeks. The preventive effect lasts as long as the drug is taken.

Children weighing >40 kg or aged 8-12 years>

Children who can swallow capsules can also receive preventive therapy by taking one 75 mg capsule or one 30 mg capsule + one 45 mg capsule once a day for 10 days.

Children aged 1 to 8 years

The recommended dosage regimen of oseltamivir in capsules of 30 mg and 45 mg:

Body weight	Recommended dose for 5 days
≤ 15 kg > 15-23 kg> > 23-40 kg> > 40 kg>	30 mg twice daily 45 mg twice daily 60 mg twice daily 75 mg twice daily

It is possible to use an extemporal suspension (see the subsection “Extemporal preparation of oseltamivir suspension”).

Dosage in special cases

Patients with impaired renal function

Treatment

In patients with creatinine clearance greater than 60 ml/min, no dose adjustment is required. In patients with a creatinine clearance of 30 to 60 ml/min, the dose of oseltamivir should be reduced to 30 mg twice daily for 5 days.

In patients with creatinine clearance from 10 to 30 ml/min, the dose of oseltamivir should be reduced to 30 mg once a day for 5 days. In patients on continuous hemodialysis, oseltamivir at an initial dose of 30 mg can be taken before dialysis if flu symptoms appear within 48 hours between dialysis sessions. To maintain plasma concentrations at therapeutic levels, oseltamivir should be taken 30 mg after each dialysis session. In patients undergoing peritoneal dialysis, oseltamivir should be taken at an initial dose of 30 mg prior to dialysis, followed by 30 mg every 5 days. The pharmacokinetics of oseltamivir in patients with end-stage renal insufficiency (with creatinine clearance < 10 ml/min) who are not on dialysis have not been studied. Therefore, there are no recommendations on dosage in this group of patients.

Prevention

In patients with creatinine clearance greater than 60 ml/min, no dose adjustment is required. In patients with a creatinine clearance of 30 to 60 ml/min, the dose of oseltamivir should be reduced to 30 mg once a day.

In patients with creatinine clearance from 10 to 30 ml/min, it is recommended to reduce the dose of oseltamivir to 30 mg every other day. In patients on permanent hemodialysis, oseltamivir at an initial dose of 30 mg can be taken before the start of dialysis (“1st session”). To maintain plasma concentrations at therapeutic levels, oseltamivir should be taken 30 mg after each subsequent odd dialysis session. In patients undergoing peritoneal dialysis, oseltamivir should be taken at an initial dose of 30 mg prior to dialysis, then 30 mg every 7 days. The pharmacokinetics of oseltamivir in patients with end-stage renal insufficiency (with creatinine clearance < 10 ml/min) who are not on dialysis have not been studied. Therefore, there are no recommendations on dosage in this group of patients.

Patients with impaired liver function

No dose adjustment is required for the treatment and prevention of influenza in patients with mild to moderate hepatic impairment. The safety and pharmacokinetics of oseltamivir in patients with severe hepatic impairment have not been studied.

Elderly and senile patients

No dose adjustment is required to prevent or treat influenza.

Immunocompromised patients (after transplantation)

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

Children

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

Overdose

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

Special instructions

Mental disorders

Psychiatric disorders, seizures, and delirium-like neuropsychiatric disorders have been reported in patients (mainly children and adolescents) taking oseltamivir for the treatment of influenza. These cases were rarely accompanied by life-threatening actions. The role of oseltamivir in the development of these phenomena is unknown. Similar neuropsychiatric disorders were also reported in patients with influenza who did not receive oseltamivir.

The risk of developing neuropsychiatric disorders in patients receiving oseltamivir does not exceed that in patients with influenza who do not receive antiviral drugs.

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

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

Oseltamivir is not a substitute for vaccination.

Prophylactic use of oseltamivir is possible for epidemiological reasons.

Recommendations for dose adjustment in patients with renal impairment are presented in the section “Dosage in special cases”.

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

Instructions for use, handling and disposal

The release of medicinal products into the environment should be kept to a minimum. Do not dispose of the product using waste water or together with household waste. If possible, it is necessary to use special systems for disposing of medicines.

Influence on the ability to drive vehicles and mechanisms

Studies on the effect of the drug on the ability to drive vehicles and engage in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions have not been conducted. Based on the safety profile, the effect of oseltamivir on these activities is unlikely.

Storage conditions

Keep out of the reach of children in a dark place at a temperature not exceeding 25 °

C.

Shelf

life is 2 years.

Do not use after the expiration date.

Active ingredient

Oseltamivir

Conditions of release from pharmacies

By prescription

Dosage form

Capsules