Universal reference book for medicines
Product name: TAMIFLU ® (TAMIFLU ® )

Active substance: oseltamivir

Type: Antiviral drug

Manufacturer: F.Hoffmann-La Roche (Switzerland) manufactured by Roche (Italy) packed by FARMSTANDART-Lekssredstva (Russia)
Composition, form of production and packaging
Capsules
hard gelatinous, size 2, opaque, gray body, lid of light yellow color;
with the inscription "ROCHE" (on the body) and "75 mg" (on the lid) light blue; contents of capsules - powder from white to yellowish-white color.
1 caps.

oseltamivir phosphate 98.5 mg,

which corresponds to the content of oseltamivir 75 mg

[PRING] pregelatinized starch - 46.4 mg, povidone K30 - 6.7 mg, croscarmellose sodium - 3.4 mg, talc - 8.3 mg, sodium stearyl fumarate - 1.7 mg.

The composition of the capsule shell: (body - gelatin, iron dye oxide black (E172), titanium dioxide (E171), lid gelatin, iron oxide red (E172), iron oxide yellow oxide (E172), titanium dioxide (E171) 63 mg.

The composition of ink for applying the inscription on the capsule: ethanol, shellac, butanol, titanium dioxide (E171), aluminum based on indigo carmine, ethanol denatured (methyl alcohol).

10 pieces.
- blisters (1) - packs of cardboard.
Note: after 5 years of storage, there may be signs of "aging" of the capsules, which can lead to their increased brittleness or other physical disorders that do not affect the efficacy or safety of the drug.

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2015.

PHARMACHOLOGIC EFFECT

Mechanism of action

Antiviral drug.
Oseltamivir phosphate is a prodrug, its active metabolite (oseltamivir carboxylate, OK) is an effective and selective neuraminidase inhibitor of influenza A and B viruses, which catalyzes the release of newly formed viral particles from infected cells, their penetration into respiratory epithelial cells and further spread virus in the body.
It inhibits the growth of the influenza virus in vitro and suppresses the replication of the virus and its pathogenicity in vivo, reduces the isolation of influenza A and B viruses from the body.
Studies of clinical isolates of the influenza virus have shown that the OC concentration required to inhibit neuraminidase by 50% (IC 50 ) is 0.1-1.3 nM for influenza A virus and 2.6 nM for influenza B. According to published studies, the median of IC 50 values ​​for the virus influenza B is slightly higher and is 8.5 nM.
Clinical efficacy

Clinical efficacy of Tamiflu ® has been demonstrated in studies of experimental influenza in humans and in phase III studies with influenza infection that occurs in vivo.
In the studies conducted, Tamiflu ® did not affect the formation of anti-influenza antibodies, incl. on the production of antibodies in response to the introduction of an inactivated influenza vaccine.
Studies of natural influenza infection

In clinical studies of phase III, conducted in the Northern Hemisphere in 1997-1998,
during seasonal influenza infection, patients began to receive Tamiflu ® no later than 40 hours after the onset of the first symptoms of influenza infection. 97% of patients were infected with influenza A virus and 3% of patients with influenza B. B. Tamiflu significantly reduced the period of clinical manifestations of influenza infection (by 32 hours). In patients with confirmed influenza diagnosis who took Tamiflu ® , the severity of the disease, expressed as the area under the curve for the total symptom index, was 38% less than in patients receiving placebo. Moreover, in young patients without concomitant diseases, Tamiflu ® reduced by about 50% the incidence of complications of influenza requiring the use of antibiotics (bronchitis, pneumonia, sinusitis, otitis media). In these phase III clinical trials, clear evidence of the efficacy of the drug with respect to secondary efficacy criteria related to antiviral activity was obtained: Tamiflu ® caused both a shortening of the time of virus isolation from the body and a decrease in the area under the "viral titers-time" curve.
Data from the Tamiflu ® study in elderly and senile patients show that Tamiflu ® 75 mg twice daily for 5 days was accompanied by a clinically significant decrease in the average duration of the clinical course of influenza infection similar to that in adults patients younger, but the differences did not reach statistical significance.
In another study, patients with influenza older than 13 years who had concomitant chronic cardiovascular and / or respiratory diseases received Tamiflu ® in the same dosing regimen or placebo. Differences in median before the decrease in clinical manifestations of influenza infection in the Tamiflu ® and placebo groups were not, however, the febrile period with Tamiflu ® was reduced by approximately 1 day. The proportion of patients who isolated the virus on the 2 nd and 4 th days became significantly less. The safety profile of Tamiflu ® in patients at risk did not differ from that in the general population of adult patients.
Treatment of influenza in children

In children aged 1-12 years (mean age 5.3 years) who had fever (≥37.8 ° C) and one of the symptoms on the part of the respiratory system (cough or runny nose) during the circulation of the influenza virus among the population, a double-blind, placebo- controlled trial.
67% of patients were infected with influenza A virus and 33% of patients with influenza B. The drug Tamiflu ® (when 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 with placebo. The duration of the disease was defined as the time to return to normal activity, accompanied by the disappearance of symptoms of coughing, nasal congestion, fever. In the group of children receiving Tamiflu ® , the incidence of acute otitis media decreased by 40% compared with the placebo group. Recovery and return to normal activity occurred almost 2 days earlier in children receiving Tamiflu ® , compared with the placebo group.
Another study involved children aged 6-12 years suffering from bronchial asthma;
53.6% of patients had an influenza infection confirmed serologically and / or in culture. The median duration of the disease in the group of patients receiving Tamiflu ® did not significantly decrease. But by the last day of therapy with Tamiflu ®, the volume of forced expiration in 1 sec (FEV 1 ) increased by 10.8% compared with 4.7% in patients receiving placebo (p = 0.0148).
Prevention of influenza in adults and adolescents

The prophylactic efficacy of Tamiflu ® in the case of natural influenza A and B infection was demonstrated in 3 separate clinical trials of Phase III.

In the Phase III study, adults and adolescents who were in contact with a sick family member began taking Tamiflu ® within two days of the onset of flu symptoms in family members and continued it for 7 days, which significantly reduced the incidence of influenza in contacting individuals 92%.

In a double-blind, placebo-controlled trial in unvaccinated and generally healthy adults aged 18-65 years, the administration of Tamiflu ® during the flu epidemic significantly reduced the incidence of influenza (by 76%).
Participants in this study took the drug for 42 days.
In a double-blind, placebo-controlled study in elderly and elderly people in nursing homes, 80% of whom were vaccinated before the season when the study was conducted, Tamiflu ® significantly reduced the incidence of influenza by 92%.
In the same study, Tamiflu ® significantly (by 86%) reduced the incidence of complications of influenza: bronchitis, pneumonia, sinusitis. Participants in this study took the drug for 42 days.
In all three clinical trials, with the use of Tamiflu ® influenza, about 1% of patients became ill.

In these clinical trials, Tamiflu ® also significantly reduced the frequency of viral release from the respiratory tract and prevented transmission of the virus from one family member to another.

Prevention of influenza in children

The prophylactic efficacy of Tamiflu ® with natural influenza infection was demonstrated in a study in children aged 1 to 12 years after contact with an affected family member or someone from a constant environment.
The main efficacy parameter in this study was the frequency of a laboratory-confirmed influenza infection.In a study in children who received Tamiflu ® / powder to prepare a suspension for oral administration at a dose of 30 to 75 mg once a day for 10 days and did not isolate the virus initially, the frequency of laboratory-confirmed influenza decreased to 4% (2 / 47) compared with 21% (15/70) in the placebo group.
Prevention of influenza in immunocompromised individuals

The efficacy of Tamiflu ® for seasonal influenza prevention was demonstrated in a double-blind, placebo-controlled trial in immunocompromised patients (involving 475 patients, including 18 children aged 12 years and under).
In immunocompromised individuals, with the initial absence of viral release, the prophylactic use of Tamiflu ® led to a reduction in the frequency of laboratory-confirmed influenza accompanied by clinical symptoms to 0.4% (1/232) compared to 3% (7/231) in the placebo group. Laboratory-confirmed influenza, accompanied by clinical symptoms, was diagnosed with a temperature in the oral cavity above 37.2 ° C, cough and / or acute rhinitis (symptoms recorded simultaneously on the same day while taking the drug / placebo), and a positive result back transcriptase polymerase chain reaction to influenza RNA.
Resistance

Clinical researches

The risk of the emergence of influenza viruses with reduced sensitivity or resistance to the drug has been studied in clinical trials sponsored by Roche.
In all patients with OC-resistant virus carriers had a temporary character, did not affect the elimination of the virus and did not cause deterioration of the clinical state.
Patients with mutations leading to resistance (Table 1)

Population of patients Phenotyping * Geno-and phenotyping *

Adults and teenagers 4/1245 (0.32%) 5/1245 (0.4%)

Children (1-12 years old) 19/464 (4.1%) 25/464 (5.4%)

* Complete genotyping has not been carried out in any of the studies.

When Tamiflu ® was administered for the purpose of post-exposure prophylaxis (7 days), prevention of family contact (10 days) and seasonal prophylaxis (42 days), there was no evidence of resistance to the drug in individuals with normal immune function.
In a 12-week study on seasonal prophylaxis in immunocompromised patients, the occurrence of resistance was also not observed.
Data from selected clinical cases and observational studies

In patients who did not receive oseltamivir, mutations of influenza A and B viruses, which appeared in the wild, had a reduced sensitivity to oseltamivir.
In 2008, a H275Y-type mutation, leading to resistance, was detected in more than 99% of strains of the 2008 H1N1 virus circulating in Europe. The influenza virus 2009 H1N1 ("swine flu") was in most cases sensitive to oseltamivir. Resistant to oseltamivir strains were found in individuals with normal immune system function and persons with weakened immunity who took oseltamivir. The degree of decrease in sensitivity to oseltamivir and the frequency of occurrence of such viruses may differ depending on the season and the region. Resistance to oseltamivir was found in patients with pandemic H1N1 flu, who received the drug for both treatment and prevention.
The incidence of resistance may be higher in younger patients and in immunocompromised patients.
Oseltamivir-resistant laboratory strains of influenza viruses and influenza viruses from patients treated with oseltamivir carry mutations of neuraminidase N1 and N2. Mutations that lead to resistance are often specific for the subtype of neuraminidase.
When deciding on the use of Tamiflu ® , the seasonal sensitivity of the influenza virus to the drug should be taken into account (the latest information can be found on the WHO website).

Preclinical data

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

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

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

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

Teratogenicity: no effect on embryonic development was observed 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 (rabbits).
In studies on antenatal and postnatal developmental periods in rats, when oseltamivir was administered at a dose of 1500 mg / kg / day, there was an increase in the period of labor: the safety margin between exposure for humans and the maximum non-effecting dose in rats (500 mg / kg / day) for rats Oseltamivir is 480 times higher, and for its active metabolite 44 times. Exposure of the fetus was 15-20% of that of the mother.
Other: oseltamivir and active metabolite penetrate the milk of lactating rats.
According to limited data, oseltamivir and its active metabolite penetrate the human breast milk. Based on the results of extrapolation of data obtained in studies in animals, their amount in breast milk can be 0.01 mg / day and 0.3 mg / day, respectively.
Approximately 50% of the guinea pigs tested, when the maximum doses of the active substance of oseltamivir were administered, skin sensitization in the form of erythema was observed.
Also, reversible eye irritation in rabbits has been identified.
While very high oral single doses (657 mg / kg and above) of oseltamivir phosphate did not affect adult rats, these doses had toxic effects on immature 7-day-old rat cubs, including rats.
led to the death of animals. Undesirable effects were not observed with chronic administration at a dose of 500 mg / kg / day from day 7 to day 21 of the postnatal period.
PHARMACOKINETICS

Suction

Oseltamivir phosphate is readily absorbed into the digestive tract and is highly converted into an active metabolite under the action of hepatic and intestinal esterases.The concentrations of the active metabolite in plasma are determined within 30 minutes and more than 20 times higher than the concentration of the prodrug, the time to reach C max is 2-3 hours. At least 75% of the ingested dose enters the systemic bloodstream as an active metabolite, less than 5% in the form of the starting drug.The plasma concentrations of both the prodrug and the active metabolite are proportional to the dose and do not depend on the intake of food.

Distribution

V d of active metabolite - 23 liters.
According to studies conducted in animals, after taking oseltamivir phosphate inside, its active metabolite was found in all major foci of infection (lungs, bronchial washings, nasal mucosa, middle ear and trachea) in concentrations providing antiviral effect. Binding of active metabolite with plasma proteins - 3%. The binding of a prodrug with plasma proteins is 42%, which is not enough to cause a significant drug interaction.
Metabolism

Oseltamivir phosphate is highly converted into an active metabolite by the action of esterases, which are predominantly in the liver.
Neither oseltamivir phosphate nor active metabolite are substrates or inhibitors of cytochrome P450 isoenzymes.
Excretion

It is excreted (> 90%) in the form of active metabolite mainly by the kidneys.
The active metabolite is not further transformed and is excreted by the kidneys (> 99%) by glomerular filtration and tubular secretion. The renal clearance (18.8 l / h) exceeds the glomerular filtration rate (7.5 l / h), which indicates that the drug is also excreted by tubular secretion. Through the intestine, less than 20% of the drug taken is excreted. T 1/2 active metabolite 6-10 h.
Pharmacokinetics in special clinical cases

Patients with renal involvement

When using Tamiflu ® (100 mg 2 times / day for 5 days) in patients with varying degrees of kidney damage, the AUC is inversely proportional to a decrease in renal function.

In the treatment of patients with CK more than 60 ml / min dose adjustment is not required.
In patients with SC from 30 to 60 ml / min, the dose of Tamiflu ® should be reduced to 30 mg 2 times / day for 5 days. In patients with SC from 10 to 30 ml / min, the dose of Tamiflu ® should be reduced to 30 mg 1 time / day for 5 days.
For patients on permanent hemodialysis, Tamiflu ® in an initial dose of 30 mg can be taken before dialysis begins, if flu symptoms have appeared within 48 hours between dialysis sessions.
To maintain plasma concentrations at the therapeutic level, Tamiflu ® should be taken at 30 mg after each dialysis session. Patients who are on peritoneal dialysis, Tamiflu ® must be taken in the initial dose of 30 mg before the start of dialysis, then to 30 mg every 5 days. Pharmacokinetics of oseltamivir for patients with end-stage renal failure (CS <10 ml / min) and not on dialysis, has not been studied. In this regard, recommendations for dosing in this group of patients are missing.
For the prevention of patients with CC more than 60 ml / min the dose correction is not required. In patients with CC from 30 to 60 ml / min the dose Tamiflu ®should be reduced to 30 mg 1 time / day. In patients with CC from 10 to 30 ml / min is recommended to reduce the dose of Tamiflu ® 30 mg in a day. Patients in hemodialysis constant, Tamiflu ®in an initial dose of 30 mg may be taken prior to dialysis ( "1st session"). To maintain plasma concentrations at therapeutic levels Tamiflu ® should take 30 mg after each subsequent odd dialysis session. Patients who are on peritoneal dialysis, Tamiflu ® must be taken in the initial dose of 30 mg before the start of dialysis, then to 30 mg every 7 days. Pharmacokinetics of oseltamivir for patients with end-stage renal failure (CS <10 ml / min) and not on dialysis, has not been studied. In this regard, recommendations for dosing in this group of patients are missing.
Patients with liver disease
Obtained in vitro and in animal studies lack information about a significant increase in AUC of oseltamivir phosphate in violation of liver function mild or moderate and were confirmed in clinical studies. The safety and pharmacokinetics of oseltamivir phosphate in patients with severe hepatic impairment has not been studied.
Patients elderly
patients elderly (65-78 years) exposure of the active metabolite at steady state at a 25-35% higher than in younger patients with similar doses of Tamiflu appointment® . T 1/2the drug in elderly patients did not significantly differ from that in younger patients. Given the data on the drug exposure and patient tolerance elderly dose adjustment in the treatment and prevention of influenza is required.
Children aged? 1, the
pharmacokinetics of Tamiflu ®studied in children aged 1 year to 16 years in a pharmacokinetic study with a single dose of the drug in a clinical trial to study the multi-dose of the drug in a small number of children aged 3-12 years. The rate of excretion of the active metabolite after adjusting for body weight in younger children is higher than adults, resulting in a lower AUC with respect to a particular dose. The drug dose of 2 mg / kg single doses of 30 mg or 45 mg, in accordance with the recommendations of dosing children, described in "Dosage", provides the same AUC oseltamivir carboxylate, which in adults is achieved after a single dose capsules 75 mg of the drug (equivalent to about 1 mg / kg). The pharmacokinetics of oseltamivir in children over 12 years is the same as in adults.
INDICATIONS

- treatment of influenza in adults and children older than 1 year;
- prevention of influenza in adults and adolescents aged over 12 years who are in a group of viruses increased risk of infection (in military units and large production teams, in debilitated patients);
- prevention of influenza in children older than 1 year.
DOSING MODE

The drug is taken orally, during a meal or without food. Tolerability can be improved if you take it during the meal.
Adults, adolescents or children who can not swallow a capsule, can also be treated with Tamiflu ® in the form of a powder for suspension for oral administration.
In cases where Tamiflu ®in the form of a powder for suspension for oral administration is missing, or when there are indications of "aging" capsule, open the capsule and pour the contents into a small amount (at most 1 teaspoon) suitable sweetened food product (chocolate syrup with a normal sugar content or containing no sugar, honey, light brown sugar or table sugar dissolved in water, sweet dessert, sweetened condensed milk, apple sauce or yogurt) to hide the bitter taste. Stir thoroughly and give the patient as a whole. It should swallow the mixture immediately after preparation. Detailed recommendations are given in the section "Preparation of the suspension."
The standard dosing regimen
Treatment
The drug should be started no later than 2 days from the date of onset of symptoms.
Adults and adolescents aged 12 years and older - 75 mg 2 times / day orally for 5 days. Increasing the dose of 150 mg / day did not lead to increased effect.
Children weighing more than 40 kg or aged 8 years and older , who are able to swallow capsules, may also be treated by taking one capsule of 75 mg of 2 times / day.
Children under the age of 1 year and older recommended Tamiflu ® powder for suspension for oral administration of 12 mg / ml or capsules 30 and 45 mg (children over 2 years). To determine the recommended dosing regimen of Tamiflu, see the instructions for medical use ®: Powder for suspension for oral administration of 12 mg / ml or capsules 30 and 45 mg. Perhaps the extemporaneous preparation of suspensions using capsules of 75 mg (cm. Below).
Prevention
The drug should be started no later than 2 days after contact with patients.
Adults and adolescents aged 12 years and older - 75 mg 1 time / day orally for at least 10 days after contact with the patient. During flu season - 75 mg 1 time / day for 6 weeks. Preventive action continues as long as the drug lasts.
Children weighing more than 40 kg or aged 8 years and above , which can swallow capsules, may also receive prophylactic therapy, taking one capsule 75 mg 1 time / day.
Children under the age of 1 year and older recommended Tamiflu ® powder for suspension for oral administration of 12 mg / ml or capsules 30 and 45 mg. To determine the recommended dosing regimen refer to the medical application of Tamiflu instructions ® powder for suspension for oral administration of 12 mg / ml or capsules 30 and 45 mg. Perhaps the extemporaneous preparation of suspensions using capsules of 75 mg (cm. Below).
Dosing in special cases
for the treatment of patients with renal impairment CS 60 ml / min dose adjustment is required. In patients with CC from 30 to 60 ml / min the dose Tamiflu®should be reduced to 30 mg of 2 times / day for 5 days. In patients with CC from 10 to 30 ml / min the dose Tamiflu ® should be reduced to 1 to 30 mg once / day for 5 days. Patients in hemodialysis constant, Tamiflu ® in the initial dose of 30 mg may be taken prior to dialysis, if flu symptoms appeared within 48 hours between sessions of dialysis. To maintain plasma concentrations at therapeutic levels Tamiflu ® should take 30 mg after each dialysis session. Patients who are on peritoneal dialysis, Tamiflu ®should be taken in the initial dose of 30 mg before the start of dialysis, then to 30 mg every 5 days. Pharmacokinetics in patients with end-stage renal failure (creatinine clearance less than 10 mL / min), not been studied in dialysis. In this regard, recommendations for dosing in this group of patients are missing.
For prevention in patients with CC more than 60 ml / min dose adjustment is required. In patients with CC from 30 to 60 ml / min Tamiflu dose ® should be reduced to 30 mg 1 time / day. In patients with CC from 10 to 30 ml / min is recommended to reduce the dose of Tamiflu ® 30 mg in a day. Patients in hemodialysis constant, Tamiflu ®in an initial dose of 30 mg may be taken prior to dialysis ( "1st session"). To maintain plasma concentrations at therapeutic levels Tamiflu ®should take 30 mg after each subsequent odd dialysis session. Patients who are on peritoneal dialysis, Tamiflu ® must be taken in the initial dose of 30 mg before the start of dialysis, then to 30 mg every 7 days. Pharmacokinetics of oseltamivir for patients with end-stage renal failure (creatinine clearance less than 10 mL / min) and not on dialysis, has not been studied. In this regard, recommendations for dosing in this group of patients are missing.
Dose adjustment for treatment and prevention of influenza in patients with impaired liver function mild to moderate severitynot required. The safety and pharmacokinetics of Tamiflu ® in patients with severely impaired function of the liver has not been studied.
No dose adjustment for the prevention or treatment of influenza in patients with middle and old age is not required.
For seasonal prophylaxis of influenza during the 12 weeks in immunocompromised patients (transplant) over the age of 1 year, a dose adjustment is required.
Tamiflu ® in the dosage form should not be administered to children under the age of 1 year.
Slurry preparation Tamiflu ®
Slurry preparation may be required in cases where adults, adolescents and children, there is a problem with swallowing capsules and Tamiflu ® in the dosage form of "powder for suspension for oral administration" is missing or if there is evidence of "aging" capsules.
If patients required 75 mg dose, it must follow the following steps:
1. Keeping one capsule 75 mg Tamiflu ® over a small capacitance accurately reveal the capsule and pour the powder into the container.
2. Add a small amount (less than 1 teaspoon) suitable sweetened food product (to hide the bitter taste) and mix well.
3. Stir the mixture and drink it immediately after preparation. If the container is left a small amount of the mixture, the container should be rinsed with a little water and drink the remaining mixture.
If patients required a dose of 30-60 mg, the need for correct dosing the following instructions:
1. Keeping one capsule 75 mg Tamiflu ® over a small capacitance accurately reveal the capsule and pour the powder into the container.
2. Add powder 5 ml of water via syringe with labels showing the number dialed liquid. Stir for 2 minutes.
3. Dial the syringe the required amount of the mixture from the vessel the following table.
Body weight Recommended dose amount of the mixture Tamiflu ®single dose
of <15 kg 30 mg 2 mL
> 45 mg 15-23kg 3ml
> 23-40 kg 60 mg of 4 ml
No need for fence undissolved white powder, as it is an inactive filler. By clicking on the syringe plunger to enter all its contents into the second container. The remaining unused mixture must be discarded.
4. In a second container add a small amount (less than 1 teaspoon) of sweetened food product suitable to hide the bitter taste and mix well.
5. Stir the mixture and drink it immediately after preparation. If the container is left a small amount of the mixture, the container should be rinsed with a little water and drink the remaining mixture.
This procedure must be repeated before each administration of the drug.
SIDE EFFECT

Clinical Studies
The overall safety profile of Tamiflu ® in clinical studies based on data from 2647 adult / adolescent patients and 858 patients childhood, receiving Tamiflu ® for treatment of influenza, as well as data 1945 adult / adolescent patients and 148 pediatric patients treated with Tamiflu ®for the prevention of influenza. As for influenza treatment studies in adult / adolescent patients the most common adverse reactions (HP) were nausea, vomiting and headache. Most HP occurred in the first or second day of therapy and resolve spontaneously within 1-2 days. In studies on the prevention of influenza in adults and adolescents the most frequent HP were nausea, vomiting, headache and pain. In children, the most frequently encountered vomiting. HP described in most cases did not require discontinuation of therapy.
Treatment and prevention of influenza in adults and adolescents
Table 1 shows the HP, occur most frequently (≥ 1%) when taking the recommended dose of Tamiflu ®in the prevention and treatment of influenza studies in adults and adolescents (75 mg, 2 times / day for 5 days treatment and 75 mg of 1 time / day to 6 weeks for prophylaxis) and whose frequency is at least 1% higher than placebo. The study on treatment of influenza included adults / adolescents without comorbidity and patients at high risk for influenza complications (patients aged and elderly patients with chronic heart disease or respiratory). In general, patients at risk the safety profile consistent with that of the adult / adolescent patients without comorbidity.
The Influenza prevention safety profile trials in patients treated with the recommended dose of Tamiflu ®(75 mg 1 times / day up to 6 weeks), did not differ from that in the treatment of flu research, despite the long-term use of the drug.
Table 1. Percentage of adults / adolescents with HP, occur with a frequency ≥1% in the oseltamivir group in the studies for the treatment and prevention of influenza (difference from placebo? 1%).
The system-organ class / Adverse Drug Reaction Treatment Prevention frequency Category and
Oseltamivir (75 mg, 2 times / day) n = 2647 Placebo n = 1977 Oseltamivir (75 mg 1 time / day) n = 1945 Placebo n = 1588
Disorders Gastrointestinal
Nausea 10 % 6% 8% 4% very often
Vomiting 8% 3% 2% 1% often
Disorders of the nervous system
Headache 2% 1% 17% 16% often
Common disorders
pain <1% <1% 4% 3% often
a category of frequency is shown only for the group of oseltamivir. For HP frequency estimation, the following frequency categories: very common (1/10?); often (? 1/100, <1/10).
The following are adverse events that occurred with a frequency of ≥ 1% in adults and adolescents who received oseltamivir treatment studies (n = 2647) and prophylaxis (n = 1945) influenza infection. These adverse events either observed more frequently in patients treated with a placebo or the difference in frequency between oseltamivir and placebo groups were less than 1%.
Violations of the gastrointestinal tract (Tamiflu ® vs. placebo):
Treatment - diarrhea (6% versus 7%), abdominal pain (including pain in the upper abdomen, 2% to 3%);
prevention - diarrhea (3% to 4%), pain in the upper abdomen (2% vs. 2%), dyspepsia (1% vs. 1%).
Infections and infestations (Tamiflu ® vs. placebo):
treatment - bronchitis (3% to 4%), sinusitis (1% vs. 1%), herpes simplex (1% vs. 1%);
Prevention - nasopharyngitis (4% vs. 4%), upper respiratory tract infection (3% vs 3%), influenza infection (2% to 3%).
Common disorders (Tamiflu ® vs. placebo):
treatment - vertigo (including vertigo, 2% to 3%);
Prevention - fatigue (7% vs. 7%), pyrexia (2% vs. 2%), influenza-like illness (1% to 2%), dizziness (1% vs. 1%), pain in the limbs (1% vs. 1%).
Disorders of the nervous system (Tamiflu ® vs. placebo):
treatment - insomnia (1% vs. 1%);
Prevention - insomnia (1% vs. 1%).
Disorders of the respiratory system of chest and mediastinum (Tamiflu ® vs. placebo):
treatment - cough (2% vs. 2%), nasal congestion (1% n
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