International non-proprietary name: Oseltamivir
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Size 0 hard gelatin capsules, white body, orange cap.
Active ingredient: oseltamivir, 75 mg (as oseltamivir phosphate);
Excipients: povidone, anhydrous lactose, croscarmellose sodium, talc, magnesium stearate, potato starch;
Capsule shell composition: gelatin, titanium dioxide (E 171), red iron oxide (E 172).
Antivirals for systemic use. Neuraminidase inhibitors.
Oseltamivir phosphate is a prodrug of the active metabolite (oseltamivir carboxylate). The active metabolite is a selective inhibitor of the virus neuraminidase – glycoprotein enzymes located on the surface of the virion. The activity of the viral enzyme neuraminidase is important for the release of the formed viral particles from infected cells and further spread of the virus in the body.
Oseltamivir carboxylate in vitro inhibits the neuraminidase of influenza A and B viruses.
Oseltamivir phosphate inhibits the growth of the influenza virus and suppresses its replication in vitro. Oral oseltamivir inhibits influenza A and B virus replication and pathogenicity in vivo in animal models of influenza, at doses similar to human administration of 75 mg twice daily.
The antiviral activity of oseltamivir against influenza A and B has been confirmed by experimental studies with provocative tests in healthy volunteers.
The value of the median inhibitory concentration (IC50) of oseltamivir in relation to the neuraminidase enzyme for clinically isolated influenza A ranged from 0.1 nM to 1.3 nM, for influenza B it was 2.6 nM. Published studies have reported higher IC50 values for influenza B, up to 8.5 nM.
Treatment of influenza in adults and children over 12 years of age and weighing more than 40 kg with typical influenza symptoms in the mass spread of the influenza virus among the population. Efficacy was found in cases where treatment was started within 2 days of the first onset of symptoms. This indication is based on clinical studies of naturally occurring influenza, primarily influenza A.
- post-exposure prophylaxis in adults and children over 12 years of age and weighing more than 40 kg after contact with clinically diagnosed influenza in case of mass spread of the influenza virus among the population;
- proper use of Flustop for prevention of influenza should be determined on a case-by-case basis according to the circumstances and the needs of the population to be protected.
In exceptional cases (for example, in the event of a mismatch between the circulating strain of the virus and the vaccine, as well as during a pandemic), seasonal prophylaxis may be considered in people aged 12 years, weighing more than 40 kg, and older.
Flustop does not replace flu vaccination
The use of antivirals for treatment and prevention of influenza should be based on official recommendations. Decisions regarding the use of oseltamivir for treatment and prophylaxis should be made taking into account data on circulating influenza viruses, available information on drug susceptibility patterns for each season, and the impact of the disease in different geographic regions and patient populations.
Adolescents 13-17 years old and adults.
The recommended oral dose is 75 mg oseltamivir twice daily for 5 days in adolescents (13–17 years of age >40 kg) and adults.
Treatment should be started as early as possible, but no later than 2 days after the onset of influenza symptoms.
The recommended dose for preventing influenza after close contact with an influenza patient is 75 mg oseltamivir once daily for 10 days in adolescents (13-17 years) and adults. Treatment should be started as early as possible, but no later than 2 days from the moment of contact with the patient.
Prevention during an epidemic in community
Oseltamivir 75 mg once daily for up to 6 weeks is recommended to prevent influenza during an outbreak.
Dose adjustment in the treatment and prevention of influenza in patients with hepatic insufficiency is not required. Studies of pediatric patients with hepatic insufficiency have not been conducted.
Patients with creatinine clearance greater than 60 ml/min dose adjustment is not required. With a creatinine clearance of less than 10 ml / min, the use of oseltamivir is contraindicated. With a creatinine clearance of less than 60 ml / min, including patients on hemodialysis, this dosage form of the drug is contraindicated for use.
Dose adjustment is not required, except in patients with renal insufficiency.
Patients with immunodeficiency
For patients with immunodeficiency, the possibility of extending seasonal prophylaxis up to 12 weeks is being considered.
Mode of administration
Oseltamivir is taken by mouth.
Overall safety profile
The overall safety profile of oseltamivir is based on data from clinical studies of 6049 adults/adolescents and 1473 pediatric patients who received oseltamivir or placebo for the treatment of influenza, and 3990 adults/adolescents and 253 children who received oseltamivir or placebo (or no treatment) for the prevention of influenza. Additionally, 245 immunocompromised patients (including 7 adolescents and 39 children) received oseltamivir for the treatment of influenza and 475 immunocompromised patients (including 18 children, of which 10 on oseltamivir and 8 on placebo) received oseltamivir or placebo for influenza prevention.
In influenza treatment studies in adults or adolescents, side effects such as nausea and vomiting were more frequently described, in prevention studies, nausea was more often described. Most of these side effects were reported once on the first or second day of treatment, and they spontaneously resolved within 1-2 days. In children, vomiting was most often described as a side effect. In most cases, these side effects did not lead to discontinuation of treatment.
The following serious adverse reactions to oseltamivir have been rarely reported during the postmarketing stage: anaphylactic and anaphylactoid reactions, liver disease (fulminant hepatitis, abnormal liver function and jaundice), angioedema, Steven-Johnson syndrome, toxic epidermal necrolysis, gastrointestinal bleeding and neuropsychiatric disorders.
(See Section Warnings and precautions for details on neuropsychiatric disorders.)
Tabular list of adverse reactions
The adverse reactions listed in the table below fall into the following categories:
Very common (≥1/10);
Common (≥1/100 to <1/10);
Uncommon (≥1/1000 to <1/100);
Rare (≥1/10000 to < 1/1000);
Very rare (< 1/10000);
Frequency not known (cannot be estimated from available data).
Adverse events are added to the appropriate category of the table based on the combined analysis of clinical studies.
Treatment and prevention in adults and adolescents
In the treatment and prevention studies in adults and adolescents, the most commonly reported adverse reactions at the recommended doses (75 mg twice daily for 5 days and 75 mg once daily for up to 6 weeks) were quantitatively similar to those in the treatment studies. despite longer dosing durations in prevention studies (Table 1).
Table 1. Adverse events in studies of oseltamivir for the treatment and prevention of influenza in adults and adolescents or during post-marketing surveillance
|Class of organ systems||Side effects according to frequency|
|Infectious and parasitic diseases||Bronchitis, herpes simplex, nasopharyngitis, upper respiratory infections, sinusiti|
|Blood and lymphatic system disorders||Thrombocytopenia|
|Immune system disorders||Hypersensitivity reactions||Anaphylactic reactions, anaphylactoid reactions|
|Psychiatric disorders||Agitation, bizarre behavior, anxiety, confusion, mania, delusions, hallucinations, nightmares, self-mutilation|
|Nervous system disorders||Headache||Insomnia||Clouding of consciousness, convulsions|
|Eye disorders||Visual impairment|
|Cardiac disorders||Cardiac arrhythmias|
|Respiratory, thoracic and mediastinal disorders||Cough, sore throat, rhinorrhea|
|Gastrointestinal disorders||Nausea||Vomiting, abdominal pain (including upper abdominal pain), dyspepsia||Gastrointestinal bleeding, hemorrhagic colitis|
|Liver and biliary tract disorders||Increased liver enzymes||Fulminant hepatitis, renal failure, hepatitis|
|Skin and subcutaneous tissue disorders||Eczema, dermatitis, rash, urticaria||Angioedema, erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis|
|General disorders and disorders at the injection site||Pain, dizziness (including vestibular), fatigue, pyrexia, pain in the extremities|
Additional information on individual adverse reactions:
Psychiatric and nervous system disorders
Influenza may be associated with a variety of neurological and behavioral symptoms, which may include events such as hallucinations, delirium, and unusual behavior, in some cases fatal. These disorders may occur in the presence of encephalitis or encephalopathy, or in the absence of significant severe disease.
Seizures and delirium (including symptoms such as clouding of consciousness, confusion, unusual behavior, mania, hallucinations, agitation, anxiety, nightmares) have been reported in patients with influenza treated with oseltamivir in the postmarketing period, which in very rare cases led to self-mutilation or fatality. These events have been reported mainly in children and adolescents. Often they started suddenly and quickly passed. The role of oseltamivir in causing these disorders is unknown. Such neuropsychiatric manifestations have also been reported in patients with influenza who did not receive oseltamivir.
Liver and biliary tract disorders
Liver and biliary disorders, including hepatitis and increased liver enzymes, in patients with influenza-like illness. They cover cases of fulminant hepatitis/liver failure with a fatal outcome.
Inform your healthcare provider if any of the side effects listed in the instructions get worse, or if you notice any other side effects not listed in this patient information leaflet.
Hypersensitivity to the active substance or any of the excipients listed in Section Ingredients of this patient information leaflet.
Oseltamivir overdose has been reported from clinical trials and post-marketing monitoring. In most cases, reports of overdose, adverse events were not reported.
Side effects reported in connection with overdose were similar in nature and frequency to those observed with oseltamivir at therapeutic dosages and are described in the section Side Effects.
There is no specific antidote.
The pharmacokinetic properties of oseltamivir, such as low plasma protein binding and metabolism independent of CYP450 and the glucuronidase system, suggest that clinically significant interactions through these mechanisms are unlikely.
In patients with normal renal function, no dose adjustment is required when oseltamivir and probenecid are co-administered. Co-administration of probenecid, a potent inhibitor of renal tubular anionic secretion, resulted in an approximately two-fold increase in the concentration of the active metabolite of oseltamivir.
Oseltamivir has no pharmacokinetic interaction with amoxicillin, which is eliminated by the same route, and oseltamivir is expected to compete weakly for this elimination route.
Clinically significant drug interactions involving competition for renal tubular secretion are unlikely due to the known safety profile of most of these substances, the elimination patterns of the active metabolite (glomerular filtration and tubular anionic secretion), and due to their excretion mechanisms. However, caution should be exercised when prescribing oseltamivir to patients using drugs with a narrow therapeutic interval that are excreted by the same route (eg, chlorpropamide, methotrexate, phenylbutazone).
No pharmacokinetic interactions have been observed between oseltamivir or its main metabolite when oseltamivir is co-administered with paracetamol, acetylsalicylic acid, cimetidine, or antacids (magnesium and aluminum hydroxide and calcium carbonate), rimantadine, or warfarin (in warfarin-stable patients without influenza).
Oseltamivir is effective only in diseases caused by influenza viruses. There is no evidence that oseltamivir is effective against diseases caused by agents other than the influenza virus.
Flustop is not a substitute for the flu vaccine.
The use of Flustop should not affect the determination of individuals for annual influenza vaccination. Protection against influenza lasts only while taking Flustop. Flustop should be used for the treatment and prevention of influenza only with reliable epidemiological data confirming the fact that influenza is circulating in the population. The sensitivity of circulating influenza strains to oseltamivir is highly variable. Therefore, prescribers should take into account the most recent information on the nature of susceptibility of currently circulating viruses to oseltamivir when deciding whether to use Flustop.
Associated severe conditions
There are no data on the safety and efficacy of oseltamivir in patients with any sufficiently severe or unstable medical condition for which the risk of hospitalization is considered imminent.
Patients with immunodeficiency
The efficacy of oseltamivir for both the treatment and prevention of influenza in immunocompromised patients has not been clearly established.
Heart and respiratory diseases
The efficacy of oseltamivir in patients with chronic heart and/or respiratory diseases has not been established. In these patients, there were no differences in the incidence of complications between the medicine and placebo groups.
Severe kidney failure
Dose adjustments are recommended for treatment and prophylaxis in adults and adolescents (13-17 years of age) with severe renal insufficiency.
Neuropsychiatric events have been reported with oseltamivir in patients with influenza, especially in children and adolescents. The same events were also observed in patients with influenza who did not take oseltamivir. Patients should be carefully monitored for behavioral changes and the benefits and risks of continuing treatment should be carefully assessed for each patient (see Section Possible side effects).
Since no controlled clinical trials have been conducted with oseltamivir in pregnant women, only limited data are available from post-marketing reports and retrospective observational studies. Data from animal studies have shown no direct or indirect damaging effects on pregnancy, fetal/embryo development or postnatal development. Pregnant women may take Flustop, taking into account the available data on the safety, pathogenicity of the circulating strain of the influenza virus and the condition of the pregnant woman.
In lactating rats, oseltamivir and its active metabolite, oseltamivir carboxylate, were excreted in breast milk. Limited data on infants whose mothers took oseltamivir and on the excretion of oseltamivir in breast milk demonstrated that oseltamivir and its active metabolite were found in breast milk at very low doses, which are below the therapeutic dose for an infant. Given this information, the pathogenicity of the circulating influenza virus strain, and the condition of the mother, oseltamivir may be considered if there is potential benefit to the nursing mother.
Based on preclinical data, there is no evidence of the effect of Flustop on male or female fertility.
There was no effect of the drug on the ability to drive a car and work with mechanisms, but a violation of these abilities may be caused by the action of the influenza virus on the central nervous system.
10 capsules in a blister pack. One blister pack with instructions for medical use is placed in a cardboard pack.
Protect from light and moisture. Store at a temperature not exceeding 25°C. Keep out of the reach of children.
2 years. Do not use after the expiration date.
State enterprise ACADEMPHARM
220141, 5/3 Kuprevicha Street, Minsk, Belarus
Phone / Fax +375 17 268 63 64
To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en