Tamiflu 6 mg/ml Powder for Oral Suspension

Update to SPC following completion of paediatric studies NV25719 & NV20234 & downstream population PK & PK/PD analysis

Update to PL following completion of paediatric studies NV25719 & NV20234 & downstream population PK & PK/PD analysis

4.2     Posology and method of administration

[….]

Immunocompromised patients

Treatment: The recommended oral dose is 75 mg oseltamivir twice daily for 10 days for adults (see sections 4.4, 4.8 and 5.1). Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza.

Seasonal prophylaxis: Longer duration of seasonal prophylaxis up to 12 weeks has been evaluated in immunocompromised patients (see sections 4.4, 4.8 and 5.1).

[….]

4.4     Special warnings and precautions for use

[….]

Immunocompromised patients

The efficacy of oseltamivir in either treatment or prophylaxis of influenza in immunocompromised patients has not been firmly established. However, the duration of treatment of influenza in immunocompromised adult patients should be 10 days, as there are no studies of a shorter course of oseltamivir in this patient group (see section 5.1).

[….]

4.8     Undesirable effects

[….]

Summary of the safety profile

The overall safety profile of Tamiflu is based on data from 6049 adult/adolescent and 1473 paediatric patients treated with Tamiflu or placebo for influenza, and on data from 3990 adult/adolescent and 253 paediatric patients receiving Tamiflu or placebo/no treatment for the prophylaxis of influenza in clinical trials. In addition, 199 immunocompromised adult patients received Tamiflu for the treatment of influenza and 475 immunocompromised patients (including 18 children, of these 10 Tamiflu and 8 placebo) received Tamiflu or placebo for the prophylaxis of influenza.

[….]

Immunocompromised patients

In a double blind study for the treatment of influenza, a total of 199 adult immunocompromised patients (evaluable for safety) were randomized to receive Tamiflu for 10 days: 98 patients received the standard dose (75 mg twice daily) and 101 patients received the double dose (150 mg twice daily). The safety profile of Tamiflu observed in this study was consistent with that observed in previous clinical trials where Tamiflu was administered for treatment of influenza in non-immunocompromised patients (otherwise healthy patients or “at risk” patients [i.e., those with respiratory and/or cardiac co-morbidities]). The percentage of patients reporting adverse events was lower in the standard dose group compared to the double dose group (49.0% vs 59.4 %, respectively) (See section 5.1).

[….]

5.       PHARMACOLOGICAL PROPERTIES

5.1     Pharmacodynamic properties

[….]

Treatment of influenza in immunocompromised adults: A randomized, double blind study, to evaluate safety and characterize the effects of oseltamivir on the development of resistant influenza virus (primary analysis) in influenza-infected adult immunocompromised patients, included 151 patients evaluable for efficacy of oseltamivir (secondary analysis, not powered). The study included solid organ transplant [SOT] patients, haematopoietic stem cell transplant [HSCT] patients, HIV positive patients with a CD4+ cell count <500 cells/mm3, patients on systemic immunosuppressive therapy, and those with haematological malignancy. These patients were randomized to be treated, within 96 hours of symptoms onset, with standard dose (73 patients) or double dose (78 patients) of oseltamivir, for a duration of 10 days.

The median time to resolution of symptoms (TTRS) was similar between the standard dose group (103 hours [90% CI 75.4-110.0]) and double dose group (104 hours [90% CI 65.8-131.0]).  The proportion of patients with secondary infections in the standard dose group and double dose group was comparable (8.2% vs 5.1%).

[….]

An overall higher incidence of oseltamivir-resistance was observed in adult immunocompromised patients treated with standard dose or double dose of oseltamivir for a duration of 10 days [14.9% (10/67) in standard dose group and 2.8% (2/71) in double dose group], compared to data from studies with oseltamivir-treated otherwise healthy adult patients. The majority of patients that developed resistance were transplant recipients (8/10 patients in the standard dose group and 2/2 patients in the double dose group). Most of the patients with oseltamivir-resistant virus were infected with influenza type A and had prolonged viral shedding.

Incidence of Oseltamivir Resistance in Clinical Studies

* Full genotyping was not performed in all studies.

Prophylaxis of Influenza

There has been no evidence for emergence of drug resistance associated with the use of Tamiflu in clinical studies conducted to date in post-exposure (7 days), post-exposure within household groups (10 days) and seasonal (42 days) prevention of influenza in immunocompetent patients. There was no resistance observed during a 12-week prophylaxis study in immunocompromised patients.

[….]

5.2     Pharmacokinetic properties

[….]

Immunocompromised Patients

Population pharmacokinetic analysis indicates that treatment of adult immunocompromised patients with oseltamivir (as described in Section 4.2. Posology and method of administration) results in an increased exposure (of up to 50%) to the active metabolite when compared to adult non-immunocompromised patients with comparable creatinine clearance. Due to the wide safety margin of the active metabolite, no dose adjustments are required in adults due to their immunocompromised status. However, for adult immunocompromised patients with renal impairment, doses should be adjusted as outlined in section 4.2. Posology and method of administration.

4.6     Fertility, pregnancy and lactation

Pregnancy

While no controlled clinical studies have been conducted on the use of oseltamivir in pregnant women data on use in pregnancy has been collected Influenza is associated with adverse pregnancy and foetal outcomes, with a risk of major congenital malformations, including congenital heart defects. A large amount of data on oseltamivir exposure of pregnant women from post-marketing reports and observational studies (please refer to section 5.1 “Treatment of influenza in pregnant women”; for data on exposure in pregnant women please refer to section 5.2.).  These data in conjunction with animal studies do not (more than 1000 exposed outcomes during the first trimester) indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal or postnatal development (see section 5.3) no malformative nor feto/neonatal toxicity by oseltamivir.

However, in one observational study, while the overall malformation risk was not increased, the results for major congenital heart defects diagnosed within 12 months of birth were not conclusive. In this study, the rate of major congenital heart defects following oseltamivir exposure during the first trimester was 1.76% (7 infants out of 397 pregnancies) compared to 1.01% in unexposed pregnancies from the general population (Odds Ratio 1.75, 95% Confidence Interval 0.51 to 5.98). The clinical significance of this finding is not clear, as the study had limited power. Additionally, this study was too small to reliably assess individual types of major malformations; moreover women exposed to oseltamivir and women unexposed could not be made fully comparable, in particular whether or not they had influenza.

Animal studies do not indicate reproductive toxicity (see section 5.3).

The use of Tamiflu Pregnant women may receive Tamiflu may be considered during pregnancy if necessary and, after considering the available safety and benefit information (for data on benefit in pregnant women please refer to section 5.1 “Treatment of influenza in pregnant women”), and the pathogenicity of the circulating influenza virus strain and the underlying condition of the pregnant woman.

10.     DATE OF REVISION OF THE TEXT

22 February 2018

Oseltamivir resistance

Clinical studies: The risk of emergence of influenza viruses with reduced susceptibility or frank resistance to oseltamivir has been examined during Roche-sponsored clinical studies. Developing oseltamivir-resistant virus during treatment was more frequent in children than adults, ranging from less than 1% in adults to 18% in infants aged below 1 year. All patients Children who were found to carry oseltamivir-resistant virus in general shed the virus for a prolonged period compared with subjects with susceptible virus. did so transiently, cleared the virus normally and showed no clinical deterioration. However treatment-emergent resistance to oseltamivir did not affect treatment response and caused no prolongation of influenza symptoms.

* Full genotyping was not performed in all studies.

There has been no evidence for emergence of drug resistance associated with the use of Tamiflu in clinical studies conducted to date in post-exposure (7 days), post-exposure within household groups (10 days) and seasonal (42 days) prevention of influenza in immunocompetent patients. There was no resistance observed during a 12-week prophylaxis study in immunocompromised patients.

Clinical and surveillance data: Natural mutations associated with reduced susceptibility to oseltamivir in vitro have been detected in influenza A and B viruses isolated from patients without exposure to oseltamivir. Resistant strains selected during oseltamivir treatment have been isolated from both immunocompetent and immunocompromised patients. Immunocompromised patients and young children are at a higher risk of developing oseltamivir-resistant virus during treatment.

Oseltamivir-resistant viruses isolated from oseltamivir-treated patients and oseltamivir-resistant laboratory strains of influenza viruses have been found to contain mutations in N1 and N2 neuraminidases. Resistance mutations tend to be viral sub-type specific. Since 2007 naturally occurring resistance associated with the H275Y mutation in seasonal H1N1 strains has been sporadically detectedbecome widespread. The susceptibility to oseltamivir and the prevalence of such viruses appear to vary seasonally and geographically. In 2008, H275Y was found in > 99 % of circulating H1N1 influenza isolates in Europe. The 2009 H1N1 influenza (“swine flu”) was almost uniformly susceptible to oseltamivir, with only sporadic reports of resistance in connection with both therapeutic and prophylactic regimens.

6.3     Shelf life

2 4 years

After reconstitution, store below 25 °C for 10 days.

10.     DATE OF REVISION OF THE TEXT

9 June 2016

4.2     Posology and method of administration

[....]

 

Post-exposure prevention: The recommended prophylaxis dose for infants less than 1 year of age during a pandemic influenza outbreak is half of the daily treatment dose. This is based upon clinical data in infants and children 1 year of age or older and adults showing that a prophylaxis dose equivalent to half the daily treatment dose is clinically efficacious for the prevention of influenza. The following age-adjusted dosing prophylaxis regimen is recommended for infants 0 - 12 months of age (see Section 5.2 for exposure simulation):

Older peopleElderly

No dose adjustment is required, unless there is evidence of moderate or severe renal impairment.

5.1     Pharmacodynamic properties

[....]

Post-exposure prevention of influenza in infants less than 1 year of age during a pandemic:

Prevention during an influenza pandemic has not been studied in controlled clinical studies in children 0-12 months of age. See Section 5.2 for exposure simulation details.

[....]

5.2     Pharmacokinetic properties

[....]

Post-exposure prevention of influenza in infants less than 1 year of age during a pandemic: Simulation of once daily dosing of 3mg/kg in infants <1 year shows an exposure in the same range or higher than for once daily dosing of 75 mg in adults. Exposure does not exceed that for treatment of infants < 1 year (3 mg/kg twice daily) and is anticipated to result in a comparable safety profile (see Section 4.8). No clinical studies of prophylaxis in infants aged <1 have been performed.   

[....] 

Older peopleElderly

10.     DATE OF REVISION OF THE TEXT

28 April 2016

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of reconstituted suspension contains 6 mg oseltamivir phosphate equivalent to 6 mg of oseltamivir.

4.1     Therapeutic indications

Treatment of influenza

Tamiflu is indicated in adults and children including full term neonates In patients one year of age and older who present with symptoms typical of influenza, when influenza virus is circulating in the community. Efficacy has been demonstrated when treatment is initiated within two days of first onset of symptoms. This indication is based on clinical studies of naturally occurring influenza in which the predominant infection was influenza A (see section 5.1).

Tamiflu is indicated for the treatment of infants less than 1 year of age during a pandemic influenza outbreak (see section 5.2).

The treating physician should take into account the pathogenicity of the circulating strain and the underlying condition of the patient to ensure there is a potential benefit to the child.

[...]

 

4.2     Posology and method of administration

 [...]

For infants less than 1 year of age: The recommended treatment dose for infants 0 - 12 months less than 12 monthsof age is between 2 mg/kg twice daily and 3 mg/kg twice daily during a pandemic influenza outbreak. This is based upon limited pharmacokinetic and safety data indicating that thisese doses in infants 0 - 12 months provides plasma concentrations of the pro-drug and active metabolite that are anticipated to be clinically efficacious with a safety profile comparable to that seen provide plasma drug exposures in the majority of patients similar to those shown to be clinically efficacious in older children and adults (see section 5.2).

In case of a pandemic, aA 3 ml oral dispenser (graduated in 0.1 ml steps) should be used for dosing children 0 - 12 months below 12 months of age requiring 1 ml to 3 ml of Tamiflu 6 mg/ml oral suspension. For higher doses the 10 ml syringe should be used. 6 mg to 18 mg of oseltamivir. The following dosing regimen is recommended for treatment of infants below 1 year of age:

Information should be provided to the patient´s parents or caregivers on where to obtain the 3 ml oral dispenser.

Dosing table of oseltamivir for children aged from 0 to 30 days (less than one month of age): 2 mg/kg twice daily

Dosing table of oseltamivir for children aged from 31 to 90 days (more than one month to three months of age): 2.5 mg/kg twice daily

Dosing table of oseltamivir for children less than 1 year of age aged from 91 to < 365 days (more than three months to twelve months of age): 3 mg/kg twice daily

* This table is not intended to contain all possible weights for this population.

There is no data available regarding the administration of Tamiflu to infants less than one month of age.

Administration of Tamiflu to infants less than one year of age should be based upon the judgment of the physician after considering the potential benefit of treatment versus any potential risk to the infant.

This ese age-based dosing recommendation is are not intended for premature infants, i.e. those with a post-conceptualpostmenstrual age less than 37 36 weeks. Insufficient data are available for these patients, in whom different dosing may be required due to the immaturity of physiological functions.

[...]

In case of a pandemic, a 3 ml oral dispenser (graduated in 0.1 ml steps) should be used for dosing children below 1 year of age requiring 1 ml to 3 ml of Tamiflu 6 mg/ml oral suspension. For higher doses the 10 ml syringe should be used. requiring 6 mg to 18 mg of oseltamivir.

Information should be provided to the patient´s parents or caregivers on where to obtain the 3 ml oral dispenser.

[...]

The following weight-adjusted dosing regimen is are recommended for infants less than 1 year of age:

Dosing table of oseltamivir for children aged from 0 to 30 days (less than one month of age): 2 mg/kg once daily

Dosing table of oseltamivir for children aged from 31 to 90 days (more than one month to three months of age): 2.5 mg/kg once daily

Dosing table of oseltamivir for children below one year of age aged from 91 to < 365 days (more than three months to twelve months of age): 3 mg/kg once daily

* This table is not intended to contain all possible weights for this population.

There is no data available regarding the administration of Tamiflu to infants less than 1 month of age.

Administration of Tamiflu to infants less than 1year of age should be based upon the judgment of the physician after considering the potential benefit of prophylaxis versus any potential risk to the infant.

Thisese age-based dosing recommendation is are not intended for premature infants, i.e. those with a post-conceptualpostmenstrual age less than 37 36 weeks. Insufficient data are available for these patients, in whom different dosing may be required due to the immaturity of physiological functions.

[...]

4.4     Special warnings and precautions for use

[...]

Paediatric population

No data allowing a dose recommendation for premature children (<36 weeks post-conceptual  37 weeks post-menstrual age*) are currently available.

*          Time between first day of last normal menstrual period and day of assessment, gestational age plus post-natal age.

[...]

4.6     Fertility, pregnancy and lactation

Pregnancy

While no controlled clinical studies have been conducted on the use of oseltamivir in pregnant women data on use in pregnancy has been collected from post-marketing and observational studies (please refer to section 5.1 “Treatment of influenza in pregnant women”; for data on exposure in pregnant women please refer to section 5.2.). While no controlled clinical studies have been conducted on the use of oseltamivir in pregnant women, there is limited data available from post-marketing and retrospective observational surveillance reports. These data in conjunction with animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal or postnatal development (see section 5.3). Pregnant women may receive Tamiflu, after considering the available safety information, the pathogenicity of the circulating influenza virus strain and the underlying condition of the pregnant woman.

[...]

4.8     Undesirable effects

[...]

Other special populations

Paediatric population (infants less than one year of age)

In two studies to characterise the pharmacokinetics, pharmacodynamics and safety profile of oseltamivir therapy in 124135 influenza infected children less than one year of age, the safety profile was similar among age cohorts with vomiting, diarrohea and diaper rash being the most frequently reported adverse events (see section 5.2). Insufficient data are available for infants who have a post-conceptual age of less than 36 weeks.

[...]

5.1     Pharmacodynamic properties

[...]

Clinical studies

Treatment of influenza infection

The indication is based on clinical studies of naturally occurring influenza in which the predominant infection was influenza A.

[...]

Treatment of influenza in pregnant women: No controlled clinical studies have been conducted on the use of oseltamivir in pregnant women, however, there is evidence from post-marketing and retrospective observational studies showing benefit of the current dosing regimen in this patient population in terms of lower morbidity/mortality. Results from pharmacokinetic analyses indicate a lower exposure to the active metabolite, however dose adjustments are not recommended for pregnant women in the treatment or prophylaxis of influenza (see section 5.2, Pharmacokinetics, Special Population).

[...]

The indication in infants below the age of 1 is based upon extrapolation of efficacy data from older children and the recommended posology is based upon pharmacokinetic modelling data (see Section 5.2).

[...]

5.2     Pharmacokinetic properties

[...]

Other sSpecial populations

Paediatric population

Children

Infants less than 1 year of age: The pharmacokinetics, pharmacodynamics and safety of Tamiflu have been evaluated in two uncontrolled open-label studies including influenza infected children less than one year of age (n=12435). The rate of clearance of the active metabolite, corrected for body-weight, decreases with ages below one year. Metabolite exposures are also more variable in the youngest infants. The available data indicates that the exposure following a 3 mg/kg dose in infants 0-12 months of age provides pro-drug and metabolite exposures anticipated to be efficacious with a safety profile comparable to that seen in older children and adults using the approved dose (see sections 4.1 and 4.2).The reported adverse events were consistent with the established safety profile in older children.

There are no data available for infants below 1 year of age for post exposure prevention of influenza. Prevention during an influenza epidemic in the community has not been studied in children below 12 years of age.

 Limited pharmacokinetic and safety data are available for infants less than 1 year of age. Pharmacokinetic modeling was undertaken using these data in addition to data from studies in adults and infants and children 1 year of age or older. The results demonstrate that doses of 3 mg /kg twice daily for infants aged 3 to 12 months and 2.5 mg /kg twice daily for infants aged between 1 and 3 months provide exposures similar to those shown to be clinically efficacious in adults and infants and children 1 year of age or older (see sections 4.1 and 4.2). There are currently no data available in infants less than 1 month of age using Tamiflu.

[...]

Pregnant Women

A pooled population pharmacokinetic analysis indicates that the Tamiflu dosage regimen described in Section 4.2 Posology and method of administration results in lower exposure (30% on average across all trimesters) to the active metabolite in pregnant women compared to non-pregnant women. The lower predicted exposure however, remains above inhibitoy concentrations (IC95 values) and at a therapeutic level for a range of influenza virus strains. In addition, there is evidence from observational studies showing benefit of the current dosing regimen in this patient population. Therefore, dose adjustments are not recommended for pregnant women in the treatment

or prophylaxis of influenza (see section 4.6 Fertility, pregnancy and lactation).

[...]

6.5     Nature and contents of container

100 ml amber glass bottle (with child-resistant polypropylene screw cap, outer part: polyethylene; inner part: polypropylene; liner: polyethylene) with 13 g of powder for oral suspension, a plastic adapter (low density polyethylene) , a plastic 3 ml  oral dispenser (0.1 ml graduation) and 10 ml oral dispensers (0.5 ml graduation)  (barrel and plunger: polypropylene, silicon based seal ring) and a plastic measuring cup (polypropylene).

Pack-size of one bottle.

10.     DATE OF REVISION OF THE TEXT

5 May 2015

4.6     Fertility, pregnancy and lactation

Pregnancy

While no controlled clinical studies have been conducted on the use of oseltamivir in pregnant women, data on use in pregnancy has been collected from post-marketing and observational  studies (please refer to section 5.1 “Treatment of influenza in pregnant women”; for data on exposure in pregnant women please refer to section 5.2.). While nNo controlled clinical studies have been conducted on the use of oseltamivir in pregnant women; however, there is evidence limited data available from post-marketing and retrospective observational studies showing benefit of the current dosing regimen in this patient population.surveillance reports.  Results from pharmacokinetic analyses indicate a lower exposure to the active metabolite, however dose adjustments are not recommended for pregnant women in the treatment or prophylaxis of influenza (see section 5.2, Pharmacokinetics, Special Population). These data in conjunction with animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal or postnatal development (see section 5.3). Pregnant women may receive Tamiflu, after considering the available safety information, the pathogenicity of the circulating influenza virus strain and the underlying condition of the pregnant woman.

5.       PHARMACOLOGICAL PROPERTIES

5.1     Pharmacodynamic properties

Treatment of influenza in pregnant women: No controlled clinical studies have been conducted on the use of oseltamivir in pregnant women, however, there is evidence from post-marketing and retrospective observational studies showing benefit of the current dosing regimen in this patient population in terms of lower morbidity/mortality. Results from pharmacokinetic analyses indicate a lower exposure to the active metabolite, however dose adjustments are not recommended for pregnant women in the treatment or prophylaxis of influenza (see section 5.2, Pharmacokinetics, Special Population).

5.2     Pharmacokinetic properties

Pregnant Women

A pooled population pharmacokinetic analysis indicates that the Tamiflu dosage regimen described in Section 4.2 Posology and method of administration results in lower exposure (30% on average across all trimesters) to the active metabolite in pregnant women compared to non-pregnant women. The lower predicted exposure however, remains above inhibitoy concentrations (IC95 values) and at a therapeutic level for a range of influenza virus strains. In addition, there is evidence from observational studies showing benefit of the current dosing regimen in this patient population. Therefore, dose adjustments are not recommended for pregnant women in the treatment

or prophylaxis of influenza (see section 4.6 Fertility, pregnancy and lactation).

10.     DATE OF REVISION OF THE TEXT

23 April 2015

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of reconstituted suspension contains 6 mg oseltamivir phosphate equivalent to 6 mg of oseltamivir.

One bottle of reconstituted suspension (65 ml) contains 390 mg of oseltamivir.

4.       Clinical particulars

4.1     Therapeutic indications

Treatment of influenza

Tamiflu is indicated in adults and children including full term neonates In patients one year of age and older who present with symptoms typical of influenza, when influenza virus is circulating in the community. Efficacy has been demonstrated when treatment is initiated within two days of first onset of symptoms. This indication is based on clinical studies of naturally occurring influenza in which the predominant infection was influenza A (see section 5.1).

Tamiflu is indicated for the treatment of infants less than 1 year of age during a pandemic influenza outbreak (see section 5.2).

The treating physician should take into account the pathogenicity of the circulating strain and the underlying condition of the patient to ensure there is a potential benefit to the child.

4.2     Posology and method of administration

For infants less than 1 year of age: The recommended treatment dose for infants 0 - 12 months less than 12 monthsof age is between 2 mg/kg twice daily and 3 mg/kg twice daily during a pandemic influenza outbreak. This is based upon limited pharmacokinetic and safety data indicating that thisese doses in infants 0 - 12 months provides plasma concentrations of the pro-drug and active metabolite that are anticipated to be clinically efficacious with a safety profile comparable to that seen provide plasma drug exposures in the majority of patients similar to those shown to be clinically efficacious in older children and adults (see section 5.2).

In case of a pandemic, aA 3 ml oral dispenser (graduated in 0.1 ml steps) should be used for dosing children 0 - 12 months below 12 months of age requiring 1 ml to 3 ml of Tamiflu 6 mg/ml oral suspension. For higher doses the 10 ml syringe should be used. 6 mg to 18 mg of oseltamivir. The following dosing regimen is recommended for treatment of infants below 1 year of age:

Information should be provided to the patient´s parents or caregivers on where to obtain the 3 ml oral dispenser.

Dosing table of oseltamivir for children aged from 0 to 30 days (less than one month of age): 2 mg/kg twice daily

Dosing table of oseltamivir for children aged from 31 to 90 days (more than one month to three months of age): 2.5 mg/kg twice daily

Dosing table of oseltamivir for children less than 1 year of age aged from 91 to < 365 days (more than three months to twelve months of age): 3 mg/kg twice daily

* This table is not intended to contain all possible weights for this population.

There is no data available regarding the administration of Tamiflu to infants less than one month of age.

Administration of Tamiflu to infants less than one year of age should be based upon the judgment of the physician after considering the potential benefit of treatment versus any potential risk to the infant.

This ese age-based dosing recommendation is are not intended for premature infants, i.e. those with a post-conceptualpostmenstrual age less than 37 36 weeks. Insufficient data are available for these patients, in whom different dosing may be required due to the immaturity of physiological functions.

Underlined text has been added, text with strike through deleted:

4.2       Posology and method of administration

[…]

ElderlyOlder people

No dose adjustment is required, unless there is evidence of moderate or severe renal impairment.

[…]

4.8    Undesirable effects

“Reporting of suspected adverse reactions” added in line with QRD 9

5.2       Pharmacokinetic properties

[…]

ElderlyOlder people

Exposure to the active metabolite at steady state was 25 to 35 % higher in elderly (age 65 to 78 years) compared to adults less than 65 years of age given comparable doses of oseltamivir. Half-lives observed in the elderly were similar to those seen in young adults. On the basis of drug exposure and tolerability, dosage adjustments are not required for elderly patients unless there is evidence of moderate or severe renal impairment (creatinine clearance below 60 ml /min) (see section 4.2).

[…]

10.       DATE OF REVISION OF THE TEXT

25 April 2014

4.2     Posology and method of administration

[….]

Dosing table of oseltamivir for children aged from 0 to 30 days (less than one month of age): 2 mg/kg twice daily

Dosing table of oseltamivir for children aged from 31 to 90 days (more than one month to three months of age): 2.5 mg/kg twice daily

Dosing table of oseltamivir for children aged from 91 to < 365 days (more than three months to twelve months of age): 3 mg/kg twice daily