Tamiflu capsules 75mg №10×1

Name:
Tamiflu caps.75mg No. 10
Description:
Hard gelatin capsules, size No2, gray body, opaque, light yellow cap, opaque; with the inscription “ROCHE” (on the body) and “75 mg” (on the cap) in light blue; contents of capsules – powder from white to yellowish-white color. The main active ingredient Oseltamivir Release formHard gelatin capsules, size No2, gray body, opaque, light yellow cap, opaque; with the inscription “ROCHE” (on the body) and “75 mg” (on the cap) in 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 Excipients: pregelatinized starch, povidone K30, croscarmellose sodium, talc, sodium stearyl fumarate. The composition of the capsule shell: body – gelatin, iron dye black oxide (E172), titanium dioxide (E171); cap – gelatin, iron dye red oxide (E172), iron dye yellow oxide (E172), titanium dioxide (E171). The composition of the ink for writing on the capsule: ethanol, shellac, butanol, titanium dioxide (E171), aluminum lacquer based on indigo carmine, denatured ethanol (methylated alcohol). 10 pieces. – blisters (1) – packs of cardboard. Note: after 5 years of storage of the drug, signs of “aging” of the capsules may be observed, which can lead to their increased fragility or other physical disorders that do not affect the effectiveness or safety of the drug. Dosage 75mg No. 10 Special instructions In patients (mainly children and adolescents) who took Tamiflu® for the treatment of influenza, convulsions and delirium-like neuropsychiatric disorders have been reported. These cases were rarely accompanied by life-threatening activities. The role of Tamiflu® in the development of these phenomena is unknown. Similar neuropsychiatric disorders have also been noted in patients with influenza who did not receive Tamiflu®. The risk of developing neuropsychiatric disorders in patients receiving Tamiflu® does not exceed that in patients with influenza not receiving antiviral drugs. Careful monitoring of the behavior of patients, especially children and adolescents, is recommended in order to identify 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 Tamiflu® in any diseases caused by pathogens other than influenza A and B viruses. Tamiflu® is not a substitute for vaccination. Prophylactic administration of Tamiflu® is possible according to epidemiological indications. Tamiflu® in this dosage form should not be administered to children under the age of 1 year. 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 drug with wastewater or with household waste. If possible, special systems for the disposal of drugs should be used. Influence on the ability to drive vehicles and mechanisms Studies to study the effect of the drug on the ability to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions have not been conducted. Based on the safety profile, the impact of Tamiflu® on these activities is unlikely. Pharmacological action Mechanism of action Antiviral drug. Oseltamivir phosphate is a prodrug, its active metabolite (oseltamivir carboxylate, OK) is an effective and selective inhibitor of neuraminidase of influenza A and B viruses, an enzyme that catalyzes the release of newly formed viral particles from infected cells, their penetration into the epithelial cells of the respiratory tract 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 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 virus. The median IC50 values for influenza B virus are slightly higher and amount to 8.5 nM. Clinical efficacy 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 conducted during seasonal influenza infection, patients began receiving 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 virus. Tamiflu® significantly reduced the period of clinical manifestations of influenza infection (by 32 hours). Patients with a confirmed diagnosis of influenza treated with Tamiflu® had a 38% reduction in disease severity, expressed as area under the curve for the total symptom index, compared with patients treated with placebo. Moreover, in young patients without comorbidities, Tamiflu® reduced the incidence of influenza complications requiring antibiotics (bronchitis, pneumonia, sinusitis, otitis media) by about 50%. There was clear evidence of the effectiveness of the drug in relation to secondary efficacy criteria related to antiviral activity: Tamiflu® caused both a shortening of the time of virus excretion from the body and a decrease in the area under the viral titers-time curve. Data obtained in a study on Tamiflu® therapy in elderly and senile patients show that taking Tamiflu® at a dose of 75 mg 2 times / 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 adult patients younger age, but the differences did not reach statistical significance. In another study, influenza patients over 13 years of age who had concomitant chronic diseases of the cardiovascular and / or respiratory systems received Tamiflu® in the same dosing regimen or placebo. There was no difference in the median period to reduction of clinical manifestations of influenza infection in the Tamiflu® and placebo groups, however, the period of fever with Tamiflu® was reduced by about 1 day. The proportion of patients shedding virus on days 2 and 4 became significantly smaller. 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 a fever (≤37.8°C) and one of the symptoms of the respiratory system (cough or rhinitis) during the period of influenza virus circulation in the population, it was carried out double-blind, placebo-controlled study. 67% of patients were infected with influenza A virus and 33% of patients with influenza B virus. Tamiflu® (when taken no later than 48 hours after 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 until cough relief, nasal congestion, disappearance of fever, return to normal activity. In the group of children treated with Tamiflu®, the incidence of acute otitis media was reduced by 40% compared with the placebo group. Recovery and return to normal activity occurred almost 2 days earlier in children treated with Tamiflu® compared to the placebo group. Another study included children aged 6-12 with asthma; 53.6% of patients had influenza infection confirmed serologically and/or in culture. The median duration of illness in the Tamiflu® group did not decrease significantly. But by the last 6 days of Tamiflu® therapy, forced expiratory volume in 1 second (FEV1) 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 natural influenza A and B infections has been proven in 3 separate phase III clinical trials. While taking Tamiflu®, about 1% of patients fell ill with influenza. Tamiflu® also significantly reduced the frequency of virus shedding from the respiratory tract and prevented the transmission of the virus from one family member to another. Adults and adolescents who were in contact with a sick family member started Tamiflu® within two days of the onset of flu symptoms in family members and continued for 7 days, which significantly reduced the incidence of influenza in contact persons by 92%. In unvaccinated and generally healthy adults aged 18-65 years, taking Tamiflu® during an influenza epidemic significantly reduced the incidence of influenza (by 76%). Patients took the drug for 42 days. In elderly and senile residents of 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 influenza complications: bronchitis, pneumonia, sinusitis. Patients took the drug for 42 days. Influenza prophylaxis in children The prophylactic efficacy of Tamiflu® against natural influenza infection was demonstrated in a study in children aged 1 to 12 years after contact with an ill family member or with someone from a permanent environment. The main efficacy parameter was the frequency of laboratory-confirmed influenza infection. In children who received Tamiflu® /powder for oral suspension / at a dose of 30 to 75 mg 1 time / day for 10 days, and did not shed the virus at baseline, the frequency of laboratory-confirmed influenza decreased to 4% (2/47) compared to 21% (15/70) in the placebo group. Influenza prophylaxis in immunocompromised individuals In immunocompromised individuals with seasonal influenza infection and no shedding at baseline, prophylactic use of Tamiflu resulted in a reduction in laboratory-confirmed symptomatic influenza infection to 0.4% (1/232) compared with 3% (7/231) in the placebo group. A laboratory-confirmed symptomatic influenza infection was diagnosed with oral temperature above 37.2°C, cough and/or coryza (all reported on the same day while taking the drug/placebo), and a positive return transcriptase polymerase chain reaction for influenza virus RNA. Resistance Clinical Studies The risk of the emergence of influenza viruses with reduced susceptibility or resistance to the drug has been studied in clinical studies sponsored by Roche. In all patients carrying 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) 19/464 (4.1%) 25/464 (5.4%) * Complete genotyping was not performed in any of the studies. When taking Tamiflu® for the purpose of post-exposure prophylaxis (7 days), prophylaxis of family contacts (10 days) and seasonal prophylaxis (42 days), there were no cases of resistance to the drug in persons with normal immune system function. In a 12-week study on seasonal prophylaxis, no cases of resistance were observed in immunocompromised individuals. Data from individual clinical cases and observational studies In patients who did not receive oseltamivir, naturally occurring mutations of influenza A and B viruses were found, which had a reduced sensitivity to oseltamivir. In 2008, the resistance mutation H275Y was found in more than 99% of the 2008 H1N1 virus strains circulating in Europe. The 2009 H1N1 influenza virus (“swine flu”) was in most cases susceptible to oseltamivir. Oseltamivir-resistant strains have been found in immunocompromised and normal individuals treated with oseltamivir. The degree of desensitization to oseltamivir and the frequency of occurrence of such viruses may differ depending on the season and region. Resistance to oseltamivir has been found in patients with pandemic H1N1 influenza who received the drug for both treatment and prophylaxis. The incidence of resistance may be higher in younger and immunocompromised patients. Oseltamivir-resistant laboratory strains of influenza viruses and influenza viruses from patients treated with oseltamivir carry neuraminidase N1 and N2 mutations. Mutations leading to resistance are often specific to the neuraminidase subtype. 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 from standard studies on pharmacological safety, genotoxicity and chronic toxicity did not reveal any particular hazard to humans. Carcinogenicity: Results from 3 studies evaluating carcinogenic potential (two 2-year studies in rats and mice for oseltamivir and one 6-month study in Tg:AC transgenic mice 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 embryonic development was found. In studies on the antenatal and postnatal periods of development in rats with the introduction of oseltamivir at a dose of 1500 mg / kg / day, an increase in the period of labor was observed: the margin of safety between human exposure and the maximum ineffective dose in rats (500 mg / kg / day) for oseltamivir is 480 times higher, and for its active metabolite – 44 times. The exposure in the fetus was 15-20% of that in the mother. Miscellaneous: Oseltamivir and the active metabolite pass into the milk of lactating rats. Based on limited data, oseltamivir and its active metabolite pass into human breast milk. According to 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. Skin sensitization in the form of erythema was observed in approximately 50% of the tested guinea pigs with the introduction of maximum doses of the active substance of oseltamivir. Reversible eye irritation has also been found in rabbits. While very high oral single doses (657 mg/kg and above) of oseltamivir phosphate had no effect on adult rats, these doses had a toxic effect on immature 7-day-old pups of rats, incl. led to the death of animals. No adverse effects were observed with chronic administration at a dose of 500 mg / kg / day from 7 to 21 days of the postnatal period. Pharmacokinetics Absorption Oseltamivir is readily absorbed from the gastrointestinal tract and extensively converted to the active metabolite by hepatic and intestinal esterases. Plasma concentrations of the active metabolite are determined within 30 minutes and are more than 20 times higher than the concentrations of the prodrug, the time to reach Cmax is 2-3 hours. form of the original drug. Plasma concentrations of both the prodrug and the active metabolite are dose-proportional and independent of food intake. The distribution of Vd 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 washings, nasal mucosa, middle ear and trachea) at concentrations that provide an antiviral effect. The binding of the active metabolite to plasma proteins is 3%. Plasma protein binding of the prodrug is 42%, which is insufficient to cause significant drug interactions. Metabolism Oseltamivir is extensively converted to the active metabolite by esterases, predominantly in the liver. Neither oseltamivir nor the active metabolite are substrates or inhibitors of isoenzymes of the cytochrome P450 system. Withdrawal Excreted (> 90%) as an active metabolite, mainly by the kidneys. The 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 the glomerular filtration rate (7.5 l / h), which indicates that the drug is also excreted by tubular secretion. Less than 20% of the drug taken is excreted through the intestines. T1 / 2 active metabolite 6-10 hours. Pharmacokinetics in special clinical situations Patients with kidney damage. When using Tamiflu® (100 mg 2 times / day for 5 days) in patients with varying degrees of kidney damage, AUC is inversely proportional to the decrease in kidney function. The pharmacokinetics of oseltamivir in patients with end-stage renal disease (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 that there was no significant increase in the AUC of oseltamivir or its active metabolite in mild to moderate hepatic impairment were also confirmed in clinical studies. The safety and pharmacokinetics of oseltamivir have not been studied in patients with severe hepatic impairment. Patients of elderly and senile age. In elderly and senile patients (65-78 years old), the exposure of the active metabolite in the equilibrium state is 25-35% higher than in younger patients when prescribing similar doses of Tamiflu®. T1 / 2 of the drug in elderly and senile patients did not differ significantly from that in younger patients. Given the data on the exposure of the drug and its tolerability in elderly and senile patients, dose adjustment in the treatment and prevention of influenza is not required. Children aged 1 to 8 years and adolescents. The pharmacokinetics of Tamiflu® was 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 rate of excretion of the active metabolite, adjusted for body weight, is higher in young children than in adults, resulting in lower AUC relative to a specific dose. Taking the drug at a dose of 2 mg / kg and single doses of 30 mg or 45 mg in accordance with the dosing recommendations for children given in the "Dosage regimen" section provides the same AUC of oseltamivir carboxylate, which is achieved in adults after a single dose of a capsule with 75 mg of the drug (equivalent to about 1 mg/kg). The pharmacokinetics of oseltamivir in children over 12 years of age is the same as in adults. Indications for use - 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 who are at high risk of infection with the virus (in military units and large production teams, in debilitated patients); - prevention of influenza in children older than 1 year. Dosage and administration Take orally, during meals or regardless of food intake. Tolerability of the drug can be improved if taken with food. Adults, adolescents or children who cannot swallow a capsule may also receive Tamiflu® treatment in powder form for oral suspension. In cases where Tamiflu® in the form of powder for oral suspension is not available, or if there are signs of "aging" of the capsules (for example, increased fragility or other physical disorders), it is necessary to open the capsule and empty its contents into a small amount (maximum 1 teaspoon) of a suitable sweetened food item (normal or unsweetened chocolate syrup, honey, light brown sugar or table sugar dissolved in water, sweet dessert, sweetened condensed milk, applesauce or yogurt) in order to hide the bitter taste. The mixture must be thoroughly mixed and given to the patient as a whole. The mixture should be swallowed immediately after preparation. Detailed recommendations are given in the subsection "Preparation of suspension ex tempore". Standard dosage regimen Treatment The drug should be started no later than 2 days after the onset of symptoms of the disease. Adults and adolescents aged 12 years and older - 75 mg 2 times / day orally for 5 days. Increasing the dose of more than 150 mg / day does not increase the effect. Children weighing over 40 kg or aged 8 years and older who can swallow capsules can also be treated with one 75 mg capsule twice daily. For children aged 1 to 8 years, Tamiflu® powder for oral suspension 12 mg / ml or capsules 30 and 45 mg (for children over 2 years) is recommended. To determine the recommended dosing regimen, see the instructions for medical use of Tamiflu®: powder for oral suspension 12 mg/ml or capsules 30 and 45 mg. It is possible to prepare an ex tempore suspension using 75 mg capsules (see subsection "Ex tempore suspension preparation"). Prevention The drug should be started no later than 2 days after contact with patients. Adults and adolescents aged >12 years – 75 mg 1 time / day orally for at least 10 days after contact with the patient. During a seasonal influenza epidemic – 75 mg 1 time / day for 6 weeks. The prophylactic effect lasts as long as the drug is taken. Children weighing > 40 kg or aged 8 to 12 years who can swallow the capsules can also receive prophylactic therapy by taking one 75 mg capsule once a day. For children aged 1 year and older, Tamiflu® powder for oral suspension 12 mg/ml or capsules 30 and 45 mg is recommended. For the recommended dosing regimen, see the instructions for medical use of Tamiflu® powder for oral suspension 12 mg/ml or capsules 30 and 45 mg. It is possible to prepare an ex tempore suspension using 75 mg capsules (see “Preparation of an ex tempore suspension”.). Dosing in special cases Patients with kidney damage Treatment Patients with CC more than 60 ml / min dose adjustment is not required. In patients with CC 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 CC 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 chronic hemodialysis, Tamiflu® at the initial dose of 30 mg can be taken prior to dialysis if influenza symptoms appear within 48 hours between dialysis sessions. To maintain plasma concentrations at therapeutic levels, Tamiflu® should be taken at 30 mg after each dialysis session. Patients on peritoneal dialysis should take Tamiflu at an initial dose of 30 mg prior to dialysis, then 30 mg every 5 days. Pharmacokinetics in patients with end-stage renal disease (CC? 10 ml / min) who are not on dialysis have not been studied. In this regard, there are no recommendations for dosing in this group of patients. Prevention Patients with CC more than 60 ml / min dose adjustment is not required. In patients with CC from 30 to 60 ml / min, the dose of Tamiflu® should be reduced to 30 mg 1 time / day. In patients with CC from 10 to 30 ml / min, it is recommended to reduce the dose of Tamiflu® to 30 mg every other day. For patients on permanent hemodialysis, Tamiflu® at the initial dose of 30 mg can be taken prior to the start of dialysis (“1st session”). To maintain plasma concentrations at therapeutic levels, Tamiflu® should be taken at a dose of 30 mg after each successive odd dialysis session. Patients on peritoneal dialysis should take Tamiflu 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 disease (CC? 10 ml / min) who are not on dialysis have not been studied. In this regard, there are no recommendations for dosing in this group of patients. Patients with hepatic impairment Dose adjustments in the treatment and prevention of influenza in patients with mild to moderate hepatic impairment are not required. The safety and pharmacokinetics of Tamiflu in patients with severe hepatic impairment have not been studied. Elderly and senile patients Dose adjustment is not required for the prevention or treatment of influenza. Immunocompromised patients (after transplantation) For seasonal prophylaxis of influenza in immunocompromised patients over the age of 1 year – for 12 weeks, dose adjustment is not required. Children Tamiflu® in this dosage form should not be administered to children under the age of 1 year. Preparation of Tamiflu® ex tempore suspension In cases where adults, adolescents and children have a problem with swallowing capsules, and Tamiflu® in the dosage form “powder for oral suspension” is not available or if there are signs of “aging” of the capsules, it is necessary to open the capsule and pour its contents into a small amount (maximum 1 teaspoon) of a suitable sweetened food (see above) in order to mask the bitter taste. The mixture must be thoroughly mixed and given to the patient as a whole. The mixture should be swallowed immediately after preparation. If patients require a dose of 75 mg, the following instructions should be followed: 1. Holding one Tamiflu® 75 mg capsule over a small container, carefully 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 item (to cover the bitter taste) and mix well. 3. Thoroughly mix the mixture and drink it immediately after preparation. If a small amount of the mixture remains in the container, then 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 correct dosing: 1. Holding one Tamiflu® 75 mg capsule over a small container, carefully open the capsule and pour the powder into the container. 2. Add 5 ml of water to the powder using a syringe with marks indicating the amount of liquid collected. Mix thoroughly for 2 minutes. 3. Draw the required amount of the mixture from the container into the syringe according to the table below. Body weight Recommended dose Amount of Tamiflu® mixture per dose ? 15 kg 30 mg 2 ml > 15-23 kg 45 mg 3 ml > 23-40 kg 60 mg 4 ml There is no need to collect undissolved white powder, since it is an inactive excipient. By pressing the plunger of the syringe, inject all its contents into the second container. The remaining unused mixture must be discarded. 4. In the second container, add a small amount (no more than 1 teaspoon) of a suitable sweetened food item to cover the bitter taste and mix well. 5. Thoroughly mix the mixture and drink it immediately after preparation. If a small amount of the mixture remains in the container, then rinse the container with a small amount of water and drink the remaining mixture. This procedure should be repeated before each dose of the drug. Use during pregnancy and lactation No controlled studies have been conducted in pregnant women. However, the results of post-marketing and observational studies have demonstrated the benefit of the proposed standard dosing regimen for this patient population. The results of the pharmacokinetic analysis showed a lower exposure of the active metabolite (approximately 30% during all trimesters of pregnancy) in pregnant women compared to non-pregnant women. However, the calculated exposure value remains above inhibitory concentrations (IC95 value) and therapeutic values for many strains of influenza virus. Changing the dosage regimen in pregnant women during therapy or prophylaxis is not recommended. No direct or indirect adverse effects of the drug on pregnancy, embryofetal or postnatal development were found. When prescribing Tamiflu® to pregnant women, both safety data and the course of pregnancy and the pathogenicity of the circulating strain of the influenza virus should be taken into account. During preclinical studies, oseltamivir and the active metabolite were excreted into the milk of lactating rats. Data on the excretion of oseltamivir in human breast milk and the use of oseltamivir in lactating women are limited. Oseltamivir and its active metabolite pass into breast milk in small amounts, creating sub-therapeutic concentrations in the blood of an infant. When prescribing oseltamivir to lactating women, the concomitant disease and pathogenicity of the circulating influenza virus strain should also be taken into account. During pregnancy and during breastfeeding, oseltamivir is used only if the intended benefit to the mother outweighs the potential risk to the fetus and child. Precautions Dose adjustment in the treatment and prevention of influenza in patients with mild to moderate hepatic impairment is not required. The safety and pharmacokinetics of Tamiflu in patients with severe hepatic impairment have not been studied. For the treatment of patients with kidney damage with CC more than 60 ml / min, dose adjustment is not required. In patients with CC 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 CC 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 chronic hemodialysis, Tamiflu® at the initial dose of 30 mg can be taken prior to dialysis if influenza symptoms appear within 48 hours between dialysis sessions. To maintain plasma concentrations at therapeutic levels, Tamiflu® should be taken at 30 mg after each dialysis session. Patients on peritoneal dialysis should take Tamiflu at an initial dose of 30 mg prior to dialysis, then 30 mg every 5 days. Pharmacokinetics in patients with end-stage renal disease (CC less than 10 ml / min) who are not on dialysis have not been studied. In this regard, there are no recommendations for dosing in this group of patients. For prophylaxis in patients with CC more than 60 ml / min, dose adjustment is not required. In patients with CC from 30 to 60 ml / min, the dose of Tamiflu® should be reduced to 30 mg 1 time / day. In patients with CC from 10 to 30 ml / min, it is recommended to reduce the dose of Tamiflu® to 30 mg every other day. For patients on permanent hemodialysis, Tamiflu® at the initial dose of 30 mg can be taken prior to the start of dialysis (“1st session”). To maintain plasma concentrations at therapeutic levels, Tamiflu® should be taken at a dose of 30 mg after each successive odd dialysis session. Patients on peritoneal dialysis should take Tamiflu 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 disease (CC less than 10 ml / min) who are not on dialysis have not been studied. In this regard, there are no recommendations for dosing in this group of patients. Tamiflu® in this dosage form should not be administered to children under the age of 1 year. Dose adjustment for the prevention or treatment of influenza in elderly and senile patients is not required. Interaction with other drugs Clinically significant drug interaction is unlikely based on pharmacological and pharmacokinetic studies. Oseltamivir is extensively converted to the active metabolite by esterases, mainly found in the liver. Drug interaction due to competition for binding to the active sites of esterases is not widely represented in the literature. The low degree of binding of oseltamivir and its active metabolite to plasma proteins does not suggest the presence of an interaction associated with the displacement of drugs from protein binding. In vitro studies indicate that neither oseltamivir phosphate nor its active metabolite is a preferred substrate for polyfunctional oxidases of the cytochrome P450 system or for glucuronyltransferases. There are no grounds for interaction with oral contraceptives. Cimetidine, a non-specific inhibitor of isoenzymes of the cytochrome P450 system 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. A clinically significant drug-drug interaction associated with competition for tubular secretion is unlikely, given the margin of safety for most of these drugs, the routes of elimination of the active metabolite of oseltamivir (glomerular filtration and anionic tubular secretion), and the excretion capacity of each of the routes. Probenecid leads to an increase in the AUC of the active metabolite of oseltamivir by about 2 times (due to a decrease in active tubular secretion in the kidneys). However, dose adjustment is not required when co-administered with probenecid, given the safety margin of the active metabolite. Simultaneous administration with amoxicillin does not affect the plasma concentrations of oseltamivir and its metabolites, demonstrating