Flustop

General characteristics. Structure:

Active ingredient: 75 mg of an oseltamivir (in the form of an oseltamivir of phosphate).

Excipients: povidone, lactose anhydrous, croscarmellose sodium, talc, magnesium stearate, potato starch;

Structure of a cover of the capsule: gelatin, glycerin, methylparahydroxybenzoate, пропилпарагидроксибензоат, sodium lauryl sulfate, titanium dioxide (Е 171), dye carmoisin (Е 122).

The antiviral drug reducing incidence of flu among the contacting persons reduces the frequency of allocation of a virus and prevents transfer of a virus from one family member to another.

Pharmacological properties:

Pharmacodynamics. Antiviral drug FLUSTOP contains phosphate which is pro-medicine in quality of an effective agent of Oseltamivir. Its active metabolite (an oseltamivir of carboxyarmour) competitively and selectively inhibits a neuraminidase of influenza viruses of type A and B - the enzyme catalyzing process of release of again formed virus particles of the infected cells, their penetrations into cells of an epithelium of respiratory tracts and further spread of a virus in an organism.

Oseltamivira of carboxyarmour acts out of cells. Growth of an influenza virus of in vitro oppresses and suppresses replication of a virus and its pathogenicity of in vivo, reduces allocation of influenza viruses And yes In from an organism. Its concentration necessary for suppression of activity of enzyme for 50% (IC50), are at the lower bound of nanomolar range

Efficiency. It is proved that Oseltamivir is an effective remedy of prevention and treatment of flu at teenagers (12 years are more senior), adults, persons of advanced and senile age.

At reception for the purpose of prevention, Oseltamivir significantly and authentically reduces incidence of flu (by 92%) among the contacting persons, reduces the frequency of allocation of a virus and prevents transfer of a virus from one family member to another.

Pharmacokinetics. Absorption. After oral administration of an oseltamivir phosphate is easily soaked up in digestive tract and highly turns into an active metabolite under the influence of hepatic esterases. Concentration of an active metabolite in plasma are defined within 30 minutes, reach almost maximum level in 2-3 hours after reception and significantly (more than by 20 times) exceed concentration of pro-medicine. Not less than 75% of the dose accepted inside get to a system blood stream in the form of an active metabolite, less than 5% - in the form of initial drug. Plasma concentration both pro-drugs, and an active metabolite are proportional to a dose and do not depend on meal.

Distribution. At the person the average volume of distribution (Vss) of an active metabolite equals to about 23 liters

Linkng of an active metabolite with proteins of plasma of the person is insignificant (about 3%). Linkng of pro-medicine with proteins of plasma of the person makes 42% that it is not enough to serve as the reason of essential medicinal interactions.

Metabolism. Oseltamivira phosphate highly turns into an active metabolite under the influence of the esterases which are preferential in a liver and intestines. Neither an oseltamivira phosphate, nor an active metabolite are not substrates or inhibitors of isoenzymes of system of P450 cytochrome.

Removal. The soaked-up Oseltamivir is brought, mainly (> 90%), by transformation into an active metabolite. The active metabolite is not exposed to further transformation and is removed with urine (> 99%). At most of patients the elimination half-life of an active metabolite makes 6-10 hours of plasma.

The active metabolite is removed completely (> 99%) by renal excretion. The renal clearance (18,8 l/hour) exceeds a glomerular filtration rate (7,5 l/hour) that indicates that drug is removed also by canalicular secretion. With a stake less than 20% accepted inside are removed it is radioactive marked drug.

Pharmacokinetics in special groups. Patients with damage of kidneys. At Oseltamivir's appointment on 100 mg 2 times a day within 5 days the patient with various extent of damage of kidneys of the area under a curve "concentration of an active metabolite in plasma – time" are inversely proportional (AUC) to depression of function of kidneys.

Patients with damage of a liver. Experiments of in vitro showed that at patients with hepatic pathology the size AUC of an oseltamivir of phosphate is much not increased, and AUC of an active metabolite is not lowered.

Patients of senile age. The drug elimination half-life at elderly (65 years are also more senior) significantly does not differ from that at younger patients of adult age. Taking into account data on AUC drug and portability, at treatment and prevention of flu it is not required to patients of senile age of dose adjustment.

Children. The pharmacokinetics of an oseltamivir at children is more senior than 12 years same, as at adults.

Indications to use:

- Treatment of flu A and B at adults and children is aged more senior than 12 years.
 
- Prevention of flu A and B at adults and teenagers is aged more senior than 12 years which are in groups of the increased risk of infection with a virus (in military units and big work collectives, at the weakened patients).

Route of administration and doses:

Oseltamivir is accepted inside, during food or irrespective of meal. At some patients portability of drug improves if it is accepted during food.

Standard mode of dosing. Treatment. Treatment needs to be begun in the first or second day (ideally the first 36 hours) after emergence of symptoms of flu.

Adults and teenagers 12 are also more senior than 12 years. The recommended drug dosing mode – on one capsule of 75 mg 2 times a day inside within 5 days. Increase in a dose does not lead more than 150 mg/days to strengthening of effect.

Prevention. Adults and teenagers 12 are also more senior than 12 years. On 75 mg of 1 times a day inside within not less than 10 days after contact with infected. Administration of drug needs to be begun no later than in the first 2 days after contact. During a seasonal flu epidemic – on 75 mg of 1 times a day; within 6 weeks. Preventive action continues so much how many administration of drug lasts.

Dosing in special cases. Patients with damage of kidneys. Treatment of flu. More than 60 ml/min. dose adjustment is not required to patients with clearance of creatinine. Dose adjustment is required from patients with clearance of creatinine from 30 to 60 ml/min. - it is necessary to reduce Oseltamivir's dose to 75 mg within 5 days once a day. Recommendations about dosing at the patients who are on a constant hemodialysis or chronic peritoneal dialysis concerning an end-stage of a chronic renal failure and for patients with clearance of creatinine ≤ 10 ml/min. are absent (see. "Pharmacokinetics in special groups").

Prevention of flu. More than 60 ml/min. dose adjustment is not required to patients with clearance of creatinine. Dose adjustment is required from patients with clearance of creatinine from 30 to 60 ml/min. - it is recommended to reduce Oseltamivir's dose to 75 mg every other day. Recommendations about dosing at the patients who are on a constant hemodialysis or chronic peritoneal dialysis concerning an end-stage of a chronic renal failure and for patients with clearance of creatinine ≤ 10 ml/min. are absent (see. "Pharmacokinetics in special groups").

At clearance of creatinine less than 30 ml/min. this dosage form of medicine is contraindicated to use.

Patients with damage of a liver. Dose adjustment at treatment and prevention of flu is not required.

Patients of senile age. Dose adjustment for prevention or treatment of flu is not required.

Use at pregnancy and a lactation. Now data on use of drug for pregnant women are not enough to estimate teratogenic or fetotoksichny action of an oseltamivir of phosphate. Taking into account it, Oseltamivir it is necessary to appoint during pregnancy or a lactation only if possible advantages of its use exceed potential risk for a fruit or the baby.

Features of use:

Data on efficiency of drug at any diseases caused by other activators except influenza viruses And yes In, no.

At treatment and prevention of flu dose adjustment is required from patients with clearance of creatinine from 30 to 60 ml/min.: at treatment of flu it is necessary to reduce Oseltamivir's dose to 75 mg within 5 days once a day; at prevention of flu it is recommended to reduce Oseltamivir's dose to 75 mg every other day.

At clearance of creatinine less than 30 ml/min. this dosage form of medicine is contraindicated to use.

At the patients (generally at teenagers) accepting Oseltamivir for the purpose of treatment of flu spasms and delirium-like psychoneurological disturbances were registered. In rare instances these disturbances led to inadvertent injuries, seldom or never – from the death. Similar psychoneurological disturbances are also noted at the patients with flu who were not receiving Oseltamivir. Careful observation of behavior of patients, especially teenagers, for the purpose of identification of signs of abnormal behavior is recommended.

Oseltamivir's efficiency at treatment of patients with chronic diseases of cardiovascular system and/or diseases of a respiratory path is still not studied. However on the frequency of complications distinctions between groups of treatment and placebo were not noted.

Oseltamivir's use is not replacement of vaccination against flu. Oseltamivir it is necessary to use for treatment and prevention of flu only when reliable epidemiological data demonstrate that the influenza virus circulates in population.

Influence on ability to drive the car and to work with mechanisms. Influence of medicine on ability to drive the car and to work with mechanisms is noted, but disturbance of these abilities can be caused by action of an influenza virus on the central nervous system.

Side effects:

At Oseltamivir's reception for treatment of flu at adults the most frequent undesirable phenomena - nausea and vomiting which arise, as a rule, after reception of the first dose have tranzitorny character and in most cases do not demand drug withdrawal.

Other undesirable phenomena arising with a frequency of 1% at Oseltamivir's reception on 75 mg 2 times a day include diarrhea, bronchitis, abdominal pains, a rotatory and not rotatory vertigo, a headache, cough, sleep disorders, weakness.

At the patients accepting Oseltamivir for prevention of flu, a little more often than in group of placebo and more often than in researches on therapy, pains of various localization, a rhinorrhea, dyspepsia and upper respiratory tract infections were noted. However distinctions in the frequency of these undesirable phenomena between groups with drug and placebo made less than 1%.

Post-marketing observation. For assessment of frequency of undesirable effects the following categories are used: very often (≥ 1/10); often (≥ 1/100 and <1/10); infrequently (≥ 1/1000 and <1/100); seldom (≥ 1/10000 and <1/1000); very seldom (<1/10000) and frequency is not known (according to the available data frequency cannot be determined).

From skin and a hypodermic fatty tissue: seldom – hypersensitivity reactions: dermatitis, skin rash, eczema, small tortoiseshell; very seldom – a multiformny exudative erythema, Stephen-Johnson's syndrome and a toxic epidermal necrolysis; seldom - anaphylactic and anaphylactoid reactions, a Quincke's edema.

From a liver: very seldom – hepatitis, increase in activity of liver enzymes at the patients with grippopodobny symptoms receiving Oseltamivir.

From the psychological sphere: at the patients (generally at children and teenagers) accepting Oseltamivir for the purpose of treatment of flu spasms and a delirium were registered (including such symptoms as consciousness disturbance, a disorientation in time and space, abnormal behavior, nonsense, hallucinations, excitement, alarm, nightmares). Similar psychoneurological disturbances are also noted at the patients with flu who were not receiving Oseltamivir.

From digestive tract: cases of gastrointestinal bleedings after Oseltamivir's reception were seldom observed (in particular, it is impossible to exclude communication between the phenomena of hemorrhagic colitis and Oseltamivir's reception as the specified phenomena disappeared both after recovery of the patient from flu, and after medicine cancellation).

From an organ of sight: a vision disorder (frequency is not known

From heart: cardiac arrhythmia (frequency is not known).

In some cases - pancreatitis, an eosinophilia, a leukopenia and a hamaturia.

Interaction with other medicines:

Information obtained in pharmacological and pharmacokinetic researches of an oseltamivir of phosphate allows to consider clinically significant medicinal interactions improbable.

The medicinal interactions caused by the competition and linkng with active centers of the esterases turning an oseltamivir phosphate into active agent in literature in detail are not lit. Low extent of binding of an oseltamivir and an active metabolite with proteins do not give the grounds to assume existence of the interactions connected with replacement of medicines from communication with proteins.

Experiments of in vitro showed that neither an oseltamivira phosphate, nor an active metabolite are not preferable substrate for multifunctional oxidases of system of P450 cytochrome or for глюкуронилтрансфераз. There is no formal basis for interaction with oral contraceptives.

Cimetidinum, nonspecific inhibitor of isoenzymes of system of P450 cytochrome, does not influence plasma concentration of an oseltamivir and its active metabolite.

Co-administration of a probenetsid leads to increase in AUC of an active metabolite approximately twice. However dose adjustment at simultaneous use with probenetsidy is not required.

The concomitant use with amoxicillin does not influence plasma concentration of both drugs. The concomitant use with paracetamol does not influence plasma concentration of an oseltamivir, its active metabolite and paracetamol.

At Oseltamivir's appointment together with often applied drugs, such as APF inhibitors (enalapril, captopril), thiazide diuretics (бендрофлюазид), antibiotics (penicillin, cephalosporins, azithromycin, erythromycin and doxycycline), H2 receptors blockers to a histamine (ranitidine, Cimetidinum), beta-blockers (propranolol), xanthines (theophylline), sympathomimetics (pseudoephedrine), opiates (codeine), corticosteroids, inhalation bronchial spasmolytics and analgetics (aspirin, an ibuprofen and paracetamol), changes of character or frequency of the undesirable phenomena were not observed.

Contraindications:

- Hypersensitivity to an oseltamivir to phosphate or any component of drug.
- Chronic renal failure (constant hemodialysis, chronic peritoneal dialysis, clearance of creatinine ≤ 10 ml/min.). At clearance of creatinine less than 30 ml/min. this dosage form of medicine is contraindicated to use.

Overdose:

Now cases of overdose are not described, however nausea with vomiting or without it can be estimated symptoms of acute overdose. Single doses of Oseltamivir to 1000 mg were transferred well, except for nausea and vomiting.

Storage conditions:

In the place protected from light and moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

On 10 capsules in a blister strip packaging. One blister strip packaging with the instruction on a medical use is placed in a pack cardboard.