Natflu

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT NATFLU (NATFLU)

Composition:

Active substance: oseltamivir;

1 capsule contains oseltamivir phosphate equivalent to oseltamivir 30 mg, or 45 mg, or 75 mg;

Excipients: pregelatinized starch (starch 1500), sodium croscarmellose, povidone K-30, talc, sodium stearyl fumarate, hard gelatin capsules;

Capsule shell:

30 mg capsules: iron oxide red, iron oxide yellow, titanium dioxide, gelatin, blue ink;

45 mg capsules: iron oxide black, titanium dioxide, gelatin, blue ink;

75 mg capsules: iron oxide red, iron oxide yellow, iron oxide black, titanium dioxide, gelatin, blue ink;

Blue ink:

shellac, anhydrous alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, concentrated ammonia solution, FD & C Blue 2 Aluminium lake.

Pharmaceutical form. Hard capsules.

Main physicochemical characteristics:

30 mg capsules: size “4” capsules filled with white or almost white powder, with yellow cap printed “30mg” in blue ink and yellow body printed “NAT” in blue ink;

45 mg capsules: size “4” capsules filled with white or almost white powder, with grey cap printed “45mg” in blue ink and grey body printed “NAT” in blue ink;

75 mg capsules: size “2” capsules filled with white or almost white powder, with yellow cap printed “75mg” in blue ink and grey body printed “NAT” in blue ink.

Pharmacotherapeutic group.

Antiviral agents for systemic use. Direct-acting antiviral agents. Neuraminidase inhibitors. Oseltamivir. ATC code J05A H02.

Pharmacological properties

Pharmacodynamics

Oseltamivir phosphate is a prodrug of the active metabolite (oseltamivir carboxylate).

The active metabolite is a selective inhibitor of the neuraminidase enzyme of influenza viruses, which is a glycoprotein on the surface of the virion. Viral neuraminidase enzyme activity is essential for viral penetration into uninfected cells, release of newly formed viral particles from infected cells, and subsequent spread of the virus within the body.

Oseltamivir carboxylate inhibits neuraminidase of influenza virus types A and B in vitro. Oseltamivir phosphate inhibits viral replication and pathogenicity in vitro. Orally administered oseltamivir inhibits replication and pathogenicity of influenza virus types A and B in animal models of influenza infection in vivo, achieving antiviral exposure levels comparable to those achieved in humans when administered at a dose of 75 mg twice daily.

Antiviral activity of oseltamivir against influenza virus types A and B has been confirmed in experimental studies in healthy volunteers.

The IC50 values of oseltamivir for neuraminidase enzyme of clinical isolates of influenza virus A ranged from 0.1 to 1.3 nM, and for influenza virus B were 2.6 nM. Published study data have reported higher IC50 values for influenza virus B, with a median of 8.5 nM.

Pharmacokinetics

Absorption

After oral administration, oseltamivir phosphate is readily absorbed in the gastrointestinal tract and is extensively converted into the active metabolite (oseltamivir carboxylate) by hepatic esterases. At least 75% of the orally administered dose reaches systemic circulation as the active metabolite, while less than 5% remains as the parent drug. Plasma concentrations of both the prodrug and the active metabolite are dose-proportional and are not affected by concomitant food intake.

Distribution

In humans, the mean volume of distribution of the active metabolite at steady state is approximately 23 L, equivalent to the volume of extracellular fluid in the body. Since neuraminidase activity occurs extracellularly, oseltamivir carboxylate reaches all major sites of influenza infection. Plasma protein binding of the active metabolite is low (approximately 3%).

Metabolism

Oseltamivir phosphate is extensively converted to oseltamivir carboxylate by esterases, primarily located in the liver. Neither oseltamivir phosphate nor the active metabolite are substrates or inhibitors of cytochrome P450 isoenzymes in in vitro studies. No phase 2 conjugates of either compound have been identified in vivo.

Excretion

Oseltamivir is eliminated primarily (>90%) via conversion to oseltamivir carboxylate, which undergoes no further metabolism and is excreted in urine. In most patients, the maximum plasma concentration of the active metabolite declines with an elimination half-life of 6–10 hours. The active metabolite is eliminated entirely by the kidneys. Renal clearance (18.8 L/h) exceeds glomerular filtration rate (7.5 L/h), indicating that the drug is additionally eliminated via tubular secretion. Less than 20% of the orally administered radiolabeled drug is excreted in feces.

Pharmacokinetics in special populations

Children aged 1 year and older

The pharmacokinetics of oseltamivir were studied in children aged 1 to 16 years in a single-dose pharmacokinetic study. Multiple-dose pharmacokinetics were studied in a small number of children in a clinical efficacy trial. In younger children, elimination of both the prodrug and active metabolite occurred more rapidly than in adults, resulting in lower exposure expressed as mg/kg dose. Following administration at a dose of 2 mg/kg, exposure to oseltamivir carboxylate was comparable to that achieved in adults after a single 75 mg dose (approximately equivalent to 1 mg/kg). Pharmacokinetics of oseltamivir in children and adolescents aged 12 years and older are similar to those in adults.

Elderly patients

In elderly patients (65–78 years), steady-state exposure to the active metabolite is 25–35% higher than in younger patients (<65 years) when receiving the same oseltamivir doses. Elimination half-life in elderly patients is similar to that in younger patients. Based on drug exposure and tolerability, dose adjustment is not required in elderly patients, except for those with moderate or severe renal impairment (creatinine clearance <60 mL/min).

Patients with renal impairment

Administration of oseltamivir phosphate 100 mg twice daily for 5 days to patients with varying degrees of renal impairment demonstrated that exposure to oseltamivir carboxylate is inversely proportional to the degree of renal function decline.

Patients with hepatic impairment

Based on in vitro data, no significant increase in oseltamivir exposure or significant decrease in active metabolite exposure is expected in patients with hepatic dysfunction.

Pregnant women

Population pharmacokinetic analysis indicates that the dosing regimen described in the section "Dosage and administration" results in lower exposure (on average 30% throughout pregnancy) to the active metabolite in pregnant women compared to non-pregnant individuals. However, the predicted lower exposure remains above inhibitory concentrations (IC95 values) and within the range effective against influenza virus strains. Additionally, data from observational studies support the benefit of the current dosing regimen in this patient population. Therefore, dose adjustment is not recommended for pregnant women during treatment or prophylaxis of influenza (see section "Use in pregnancy or lactation").

Immunocompromised patients

Population pharmacokinetic analyses have shown that administration of oseltamivir to immunocompromised adults and children (<18 years) according to the regimen specified in the section "Dosage and administration" results in increased predicted exposure (approximately 5–50%) to the active metabolite compared to immunocompetent patients with comparable creatinine clearance. Given the wide safety margin of the active metabolite, dose adjustment is not required in immunocompromised patients. However, for immunocompromised patients with renal impairment, the dose should be adjusted according to the recommendations in the section "Dosage and administration".

Analysis of pharmacokinetic and pharmacodynamic data from two studies involving immunocompromised patients demonstrated no significant additional benefit from doses exceeding the standard dose.

Clinical characteristics.

Indications.

Natflu is indicated for adults and children aged 1 year and older who have symptoms typical of influenza during periods of influenza virus circulation. Efficacy has been demonstrated when treatment was initiated within two days of symptom onset.

Prophylaxis of influenza

• Prophylaxis of influenza in adults and children aged 1 year and older following close contact with a person clinically diagnosed with influenza during periods of influenza virus circulation.
• The appropriate use of Natflu for influenza prophylaxis should be determined on a case-by-case basis, taking into account the circumstances and considering the patient population requiring protection. In exceptional situations (e.g., in case of a mismatch between the circulating influenza virus and the virus strain included in the vaccine, or during a pandemic), seasonal prophylaxis may be considered for individuals aged 1 year and older.

Use of Natflu does not replace influenza vaccination

The use of antiviral agents for the treatment and prophylaxis of influenza should be based on official recommendations. Decisions regarding the use of oseltamivir for the treatment and prophylaxis of influenza should take into account the characteristics of circulating influenza viruses, available information on the susceptibility of influenza viruses to antiviral drugs each season, and the impact of the disease in different geographical regions and patient populations (see section "Pharmacodynamics").

Contraindications.

Hypersensitivity to oseltamivir phosphate or to any component of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

The pharmacokinetic properties of oseltamivir, such as low protein binding and metabolism independent of the CYP450 and glucuronidase systems (see section "Pharmacokinetics"), suggest that clinically significant interactions with other medicinal products are unlikely.

Probenecid

No dose adjustment is required for patients with normal renal function when oseltamivir is co-administered with probenecid. Concomitant administration of probenecid, a potent inhibitor of the anion pathway of renal tubular secretion, results in approximately a doubling of exposure to the active metabolite of oseltamivir.

Amoxicillin

Oseltamivir does not exhibit kinetic interaction with amoxicillin, which is eliminated via the same pathway as oseltamivir, suggesting minimal interaction via this route.

Renal excretion

Clinically significant interaction with other medicinal products involving competition for renal tubular secretion is unlikely due to the known safety margins of most such drugs, the elimination characteristics of active metabolites (glomerular filtration and anion tubular secretion), and the extent of excretion via these pathways. However, caution should be exercised when prescribing oseltamivir to patients taking medicinal products with a similar excretion pathway and a narrow therapeutic index (e.g., chlorpropamide, methotrexate, phenylbutazone).

Additional information

No pharmacokinetic interactions between oseltamivir and its main metabolite were observed when co-administered with paracetamol, acetylsalicylic acid, cimetidine, antacids (magnesium hydroxide and aluminum hydroxide, calcium carbonate), rimantadine, or warfarin (in patients receiving stable warfarin doses and not suffering from influenza).

In phase III clinical trials of oseltamivir for the treatment and prophylaxis of influenza, the drug was administered concomitantly with commonly used medicinal products such as ACE inhibitors (enalapril, captopril), thiazide diuretics (bendroflumethiazide), antibiotics (penicillin, cephalosporins, azithromycin, erythromycin, and doxycycline), H2-receptor blockers (ranitidine, cimetidine), beta-blockers (propranolol), xanthines (theophylline), sympathomimetics (pseudoephedrine), opioids (codeine), corticosteroids, inhaled bronchodilators, and analgesics (acetylsalicylic acid, ibuprofen, and paracetamol). No changes in the safety profile or frequency of adverse reactions were observed when oseltamivir was used concomitantly with these agents.

No interaction mechanism with oral contraceptives has been identified.

Special precautions.

Oseltamivir is effective only against illnesses caused by influenza viruses. There are no data on the efficacy of oseltamivir in any illnesses caused by pathogens other than influenza viruses.

Oseltamivir use does not replace influenza vaccination

Oseltamivir use should not influence decisions regarding annual influenza vaccination. Protection against influenza lasts only during oseltamivir administration. The drug should be used for treatment and prevention of influenza only when reliable epidemiological data indicate virus circulation. It has been demonstrated that susceptibility of circulating influenza virus strains to oseltamivir shows high variability; therefore, the physician should consider the most up-to-date information on susceptibility of currently circulating viruses to oseltamivir before deciding on its use.

Severe skin reactions and hypersensitivity reactions

During post-marketing use of oseltamivir, cases of anaphylaxis and severe skin reactions, including toxic epidermal necrolysis, Stevens–Johnson syndrome, and erythema multiforme, have been reported. Oseltamivir should be discontinued and appropriate treatment initiated if such reactions occur or are suspected.

Severe underlying conditions

There is no information on the safety and efficacy of oseltamivir use in patients with severe or unstable conditions associated with an inevitable risk of hospitalization.

Immunocompromised patients

The safety and efficacy of oseltamivir for treatment and prevention of influenza in immunocompromised patients have not been established.

Cardiac/respiratory diseases

The efficacy of oseltamivir for treatment of patients with chronic cardiac and/or respiratory diseases has not been established. In such patients, no difference in the frequency of complications was observed between treatment and placebo groups.

Severe renal impairment

Dose adjustment of oseltamivir is recommended for adults and adolescents (13–17 years) with severe renal impairment when used for treatment and prophylaxis. There is insufficient clinical data on the use of the drug in children with renal impairment aged 1 year and older to provide dosing recommendations (see section "Pharmacokinetics").

Neuropsychiatric disorders

Neuropsychiatric disorders have been reported in influenza patients (predominantly in children and adolescents) treated with oseltamivir. Such disorders have also been reported in influenza patients not receiving this drug. Patients should be closely monitored for behavioral changes, and the benefit and risk of continuing treatment should be carefully evaluated for each patient (see section "Adverse reactions").

Disposal of unused or expired medication

Environmental contamination by medicinal products should be minimized. The drug must not be disposed of via wastewater or household waste. A designated waste collection system should be used for disposal, if available.

Use during pregnancy or breastfeeding

Pregnancy

Influenza is associated with harmful effects on pregnancy outcomes and fetal development, including significant congenital malformations, such as congenital heart defects. A large amount of post-marketing and observational study data on oseltamivir use during pregnancy (more than 1000 exposures during the first trimester) indicates no evidence of teratogenic or fetal/neonatal toxicity of oseltamivir. However, in one observational study, while no increase in overall congenital malformations was observed, results regarding significant congenital heart defects diagnosed within 12 months after birth were inconclusive. In this study, the rate of significant congenital heart defects after oseltamivir exposure during the first trimester of pregnancy was 1.76% (7 infants out of 397 pregnancies), compared to 1.01% in pregnancies without oseltamivir exposure in the general population (risk ratio 1.75, 95% confidence interval (CI) 0.51 to 5.98). The clinical significance of these data is unclear due to the study's limited sample size. Additionally, the study was not sufficiently large to reliably assess individual types of significant congenital malformations. Furthermore, a complete comparison between women exposed and unexposed to oseltamivir was not possible, including determining whether they had influenza.

Animal studies do not indicate reproductive toxicity.

If oseltamivir use during pregnancy is necessary, available information on the safety and efficacy of the drug, as well as the pathogenicity of the circulating influenza virus strain, should be considered.

Breastfeeding period

In lactating rats, oseltamivir and its active metabolite are excreted into breast milk. There is very limited information on infants who were breastfed and exposed to oseltamivir, and on the excretion of oseltamivir into human breast milk. Limited data show that oseltamivir and its active metabolite were detected in breast milk, but at low levels, potentially resulting in subtherapeutic exposure in infants. Considering these data, the pathogenicity of the circulating influenza virus strain, and the health status of the breastfeeding woman, oseltamivir may be considered if there is a clear potential benefit to the breastfeeding woman.

Fertility

Based on preclinical data, there is no evidence of an effect of oseltamivir on fertility in men or women.

Ability to affect reaction speed when driving or operating machinery

The drug does not affect the ability to drive or operate machinery.

Administration and Dosage

Administration

For oral use.

Dosage

75 mg doses can be administered as follows:

1 capsule of 75 mg or

1 capsule of 30 mg plus 1 capsule of 45 mg.

Adults and adolescents aged 13 years and older

Treatment

The recommended dosage regimen of Natflu is one 75 mg capsule twice daily orally for 5 days in adults and adolescents (13–17 years) with body weight over 40 kg.

Treatment should be initiated as early as possible, within the first two days of symptom onset.

For immunocompromised patients (adults and adolescents aged 13–17 years with body weight over 40 kg), the recommended dosage regimen of Natflu is one 75 mg capsule twice daily orally for 10 days (see section "Dosage in special situations. Immunocompromised patients").

Treatment should be initiated as early as possible, within the first two days of symptom onset.

Post-exposure prophylaxis following contact with an influenza patient

The recommended dose of Natflu for post-exposure prophylaxis of influenza after close contact with an infected individual is 75 mg once daily orally for 10 days in adults and adolescents (13–17 years) with body weight over 40 kg. Treatment should be initiated as soon as possible within two days of contact with an infected individual.

Prophylaxis during seasonal influenza outbreaks

The recommended dose for prophylaxis during seasonal influenza outbreaks is 75 mg once daily for 6 weeks.

Children aged 1 to 12 years

Treatment

The recommended weight-adjusted dosage regimen for treatment of children aged 1 year and older:

Treatment should be initiated as soon as possible within the first two days of onset of influenza symptoms.

Post-exposure prophylaxis

The recommended dosage regimen of Natflu for post-exposure prophylaxis:

Influenza seasonal epidemic prophylaxis

Prophylaxis during influenza seasonal epidemics in children under 12 years of age has not been studied.

Dosage in special cases

Patients with hepatic impairment

There is no need to adjust the dose for treatment or prophylaxis in patients with hepatic impairment. The safety and pharmacokinetics of oseltamivir in children with hepatic impairment have not been studied.

Patients with renal impairment

Treatment of influenza. Dose adjustment of oseltamivir is required for adults and adolescents (13–17 years) with moderate or severe renal impairment, as shown in the table below:

*Data obtained from studies in patients undergoing continuous ambulatory peritoneal dialysis (CAPD); clearance of oseltamivir carboxylate is expected to be higher with the use of automated continuous cycling peritoneal dialysis (CCPD). The treatment regimen may be switched from CCPD to CAPD if deemed necessary by the nephrologist.

Influenza prophylaxis. Dose adjustment of oseltamivir required for adults and adolescents (13–17 years) with moderate or severe renal impairment is shown in the table:

* Data obtained from studies in patients undergoing intermittent hemodialysis (IHD); the clearance of oseltamivir carboxylate is expected to be higher with continuous ambulatory peritoneal dialysis (CAPD). The treatment regimen may be changed from CAPD to IHD if deemed necessary by the nephrologist.

Insufficient data are available to provide dosing recommendations for children under 12 years of age with impaired renal function.

Elderly patients

Dose adjustment is not required, except in cases of moderate or severe renal impairment.

Immunocompromised patients

Treatment. The recommended dose of oral oseltamivir is 75 mg twice daily for 10 days in adults (see sections "Special instructions", "Side effects"). Treatment should be initiated as soon as possible within the first two days of onset of influenza symptoms.

Seasonal prophylaxis. Longer durations (up to 12 weeks) of seasonal prophylaxis have been studied in immunocompromised patients (see sections "Special instructions", "Side effects").

Children

Recommended for children aged 1 year and older with body weight above 10 kg, who are able to swallow capsules.

Overdose

Reports of oseltamivir overdose have been received during clinical trials and post-marketing use. In most cases, overdose was not associated with adverse outcomes.

Adverse reactions reported following overdose were similar in nature and distribution to those observed with therapeutic doses of oseltamivir (see section "Side effects").

There is no specific antidote.

Children

Overdose has been reported more frequently in children than in adults and adolescents. Caution should be exercised when administering oseltamivir to children.

Adverse Reactions

The overall safety profile of oseltamivir is based on data from treatment of influenza in 6049 adults/adolescents and 1473 children who received oseltamivir or placebo, as well as on prophylaxis data from 3990 adults/adolescents and 253 children who received oseltamivir or placebo in clinical trials. Additionally, 199 adult patients with impaired immunity received oseltamivir for treatment of influenza, and 475 immunocompromised patients (including 18 children: 10 in the oseltamivir group, 8 in the placebo group) received oseltamivir or placebo for influenza prophylaxis.

In adults/adolescents, the most commonly reported adverse events during oseltamivir treatment in influenza treatment studies were nausea and vomiting; in prophylaxis studies, nausea was the most common adverse event. Most of these adverse reactions occurred as single events, were transient in nature, typically occurred on the first or second day of treatment, and resolved spontaneously within 1–2 days. In children, vomiting was the most common adverse event. In most cases, adverse reactions did not lead to discontinuation of oseltamivir.

During post-marketing use of oseltamivir, rare but serious adverse reactions have been reported, including anaphylactic and anaphylactoid reactions, hepatic disorders (fulminant hepatitis, liver function abnormalities, and jaundice), angioneurotic edema, Stevens–Johnson syndrome, toxic epidermal necrolysis, gastrointestinal hemorrhage, and neuropsychiatric disorders (for neuropsychiatric disorders, see section "Special Warnings and Precautions for Use").

The following frequency categories were used to describe the incidence of adverse reactions: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), and not known (cannot be estimated from available data). Adverse reactions were assigned to a specific category based on pooled analysis of clinical trial data.

Treatment and Prophylaxis of Influenza in Adults and Adolescents

The most frequently reported adverse reactions observed in clinical studies of oseltamivir for treatment and prophylaxis of influenza in adults and adolescents, as well as during post-marketing experience with the recommended dose (75 mg twice daily for 5 days for treatment and 75 mg once daily for up to 6 weeks for prophylaxis), are listed below.

The safety profile in patients who received oseltamivir at the recommended prophylactic dose (75 mg once daily for up to 6 weeks) was similar to that observed in treatment studies, despite the longer duration of prophylactic studies:

Infections and infestations: common – bronchitis, herpes simplex, upper respiratory tract infections, nasopharyngitis, sinusitis;

Blood and lymphatic system disorders: rare – thrombocytopenia;

Immune system disorders: uncommon – hypersensitivity reaction; rare – anaphylactic and anaphylactoid reactions;

Psychiatric disorders: rare – agitation, abnormal behavior, anxiety, confusion, delirium, hallucinations, nightmares, self-injury;

Nervous system disorders: very common – headache; common – insomnia; uncommon – altered consciousness, seizures;

Eye disorders: rare – visual disturbances;

Cardiac disorders: uncommon – cardiac arrhythmias;

Respiratory, thoracic and mediastinal disorders: common – cough, rhinorrhea, sore throat;

Gastrointestinal disorders: very common – nausea; common – vomiting, abdominal pain (including in the upper abdomen), dyspepsia; rare – gastrointestinal hemorrhage, hemorrhagic colitis;

Hepatobiliary disorders: uncommon – increased liver enzymes; rare – fulminant hepatitis, hepatic failure, hepatitis;

Skin and subcutaneous tissue disorders: uncommon – dermatitis, rash, eczema, urticaria; rare – angioneurotic edema, erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis; frequency not known – allergy, facial swelling;

General disorders and administration site conditions: common – dizziness (including vertigo), weakness, pain, hyperthermia, limb pain.

Treatment and Prophylaxis of Influenza in Children

A total of 1473 children (including healthy children aged 1–12 years and children with asthma aged 6–12 years) participated in clinical trials of oseltamivir for treatment of influenza. Of these, 851 children received oseltamivir suspension. A total of 158 children received the recommended dose of oseltamivir once daily in post-exposure prophylaxis studies in household settings (n = 99), in 6-week seasonal prophylaxis studies (n = 49), and in 12-week seasonal prophylaxis studies in immunocompromised children (n = 10).

The most frequently reported adverse reactions observed in clinical studies of oseltamivir for treatment and prophylaxis of influenza in children (using age-based dosing from 30 mg to 75 mg once daily) are as follows:

Infections and infestations: common – otitis media; frequency not known – bronchitis, pneumonia, sinusitis;

Nervous system disorders: common – headache;

Blood and lymphatic system disorders: frequency not known – lymphadenopathy;

Eye disorders: common – conjunctivitis (including eye redness, eye discharge, and eye pain);

Ear and labyrinth disorders: common – ear pain; uncommon – tympanic membrane disorders;

Respiratory, thoracic and mediastinal disorders: very common – cough, nasal congestion; common – rhinorrhea; frequency not known – asthma (including exacerbations), epistaxis;

Gastrointestinal disorders: very common – vomiting; common – nausea, abdominal pain (including in the upper abdomen), dyspepsia; frequency not known – diarrhea;

Skin and subcutaneous tissue disorders: uncommon – dermatitis (including allergic and atopic dermatitis).

Description of Selected Adverse Reactions

Psychiatric and Neurological Disorders

Influenza may be associated with various neurological and behavioral symptoms, including hallucinations, delirium, and abnormal behavior, sometimes resulting in fatal outcomes. These events may occur as manifestations of encephalitis or encephalopathy, but may also arise without apparent severe illness.

In influenza patients treated with oseltamivir during the post-marketing period, cases of seizures and delirium (including symptoms such as altered level of consciousness, confusion, abnormal behavior, hallucinations, agitation, anxiety, nightmares) have been reported. In some isolated cases, these events led to accidental self-injury or death. These events were primarily observed in children and adolescents and often had sudden onset and rapid resolution. It is unknown whether these neuropsychiatric events are related to oseltamivir use, as similar neuropsychiatric disorders have also been reported in influenza patients not treated with this drug.

Hepatobiliary Disorders

Hepatobiliary disorders, including cases of hepatitis and elevated liver enzymes, have been observed in patients with influenza-like illness. These cases included fatal fulminant hepatitis/hepatic failure.

Additional Information on Specific Patient Groups

Elderly Patients and Patients with Chronic Cardiac and/or Respiratory Diseases

The studied population for influenza treatment included healthy adults/adolescents and patients with risk factors (e.g., elderly patients and patients with chronic cardiac or respiratory diseases). Overall, the safety profile in adolescents and adults with chronic cardiac and/or respiratory diseases was qualitatively comparable to that in healthy volunteers.

Immunocompromised Patients

Influenza treatment in immunocompromised patients was evaluated in two studies using standard or high (double or triple) doses of oseltamivir. The safety profile observed in these studies was consistent with that observed in previous clinical trials of oseltamivir for influenza treatment in non-immunocompromised patients of all age groups (patients without other conditions or with risk factors [underlying cardiac and/or respiratory diseases]). The most common adverse reaction in immunocompromised children was vomiting (28%).

In a 12-week prophylaxis study involving 475 immunocompromised individuals, including 18 children aged 1–12 years, the safety profile in 238 patients who received oseltamivir was comparable to that observed in clinical trials of oseltamivir for prophylaxis.

Children with Bronchial Asthma

The overall adverse reaction profile in children with bronchial asthma was qualitatively similar to that in otherwise healthy children.

Shelf Life

3 years.

Do not use after the expiry date.

Storage Conditions

Store at temperatures not exceeding 30 °C.

Keep out of reach of children.

Packaging

10 capsules in a blister. 1 blister in a cardboard box.

Prescription Category

Prescription only.

Manufacturer

Natco Pharma Limited.

Manufacturer's Address and Place of Business

Pharma Division, Kothur, Rangareddy, Telangana 509228, India.