Skip to content
SPC Logo

Tamiflu 6 mg/ml Powder for Oral Suspension

Last Updated on eMC 18-Jan-2017 View document  | Roche Products Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Updated on 18-Jan-2017 and displayed until Current

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic properties

Date of revision of text on the SPC: 15-Dec-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



5.       PHARMACOLOGICAL PROPERTIES

 

5.1     Pharmacodynamic properties


[....]

Specific studies have not been conducted to assess the reduction in the risk of complications.

 

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.

 

 

Patient Population

Patients with Resistance Mutations (%)

Phenotyping*

Geno- and Phenotyping*

Adults and adolescents

0.62% (14/2253)

4/1,245 (0.32 %)

0.67% (15/2253)

5/1,245 (0.4 %)

Children (1-12 years)

3.89% (66/1698)

19/464 (4.1 %)

4.24% (72/1698)

25/464 (5.4 %)

Infant (<1 year)

18.31% (13/71)

18.31 (13/71)

* 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.

 

 

Updated on 16-Jun-2016 and displayed until 18-Jan-2017

Reasons for adding or updating:

  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 09-Jun-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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

 

Updated on 27-May-2016 and displayed until 16-Jun-2016

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 28-Apr-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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

[....]

Updated on 01-Jun-2015 and displayed until 27-May-2016

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text
  • Change to section 2 - Qualitative and quantitative composition

Date of revision of text on the SPC: 05-May-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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.

[...]

4.1     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

Body weight

Recommended dose for 5 days

Amount of oral suspension to withdraw

3 kg

6 mg twice daily

1.0 ml twice daily

3.5 kg

7 mg twice daily

1.2 ml twice daily

4 kg

8 mg twice daily

1.3 ml twice daily

4.5 kg

9 mg twice daily

1.5 ml 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

Body weight

Recommended dose for 5 days

Amount of oral suspension to withdraw

4 kg

10 mg twice daily

1.7 ml twice daily

4.5 kg

11.25 mg twice daily

1.9 ml twice daily

5 kg

12.5 mg twice daily

2.1 ml twice daily

5.5 kg

13.75 mg twice daily

2.3 ml twice daily

6 kg

15 mg twice daily

2.5 ml twice daily

6.5 kg

16.25 mg twice daily

2.7 ml 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

Body Weight*

Recommended dose for 5 days

Amount of oral suspension to withdraw

Dispenser size

to use

3 kg

9 mg twice daily

1.5 ml twice daily

3 ml

3.5 kg

10.5 mg twice daily

1.8 ml twice daily

3 ml

4 kg

12 mg twice daily

2.0 ml twice daily

3 ml

4.5 kg

13.5 mg twice daily

2.3 ml twice daily

3 ml

5 kg

15 mg twice daily

2.5 ml twice daily

3 ml

5.5 kg

16.5 mg twice daily

2.8 ml twice daily

3 ml

6 kg

18 mg twice daily

3.0 ml twice daily

3 ml

6.5 kg

19.5 mg twice daily

3.3 ml twice daily

 

> 6 - 7 kg7 kg

21 mg twice daily

3.5 ml twice daily

10 ml

7.5 kg

22.5 mg twice daily

3.8 ml twice daily

 

> 7 - 8 kg8 kg

24 mg twice daily

4.0 ml twice daily

10 ml

8.5 kg

25.5 mg twice daily

4.3 ml twice daily

 

> 8 - 9 kg9 kg

27 mg twice daily

4.5 ml twice daily

10 ml

9.5 kg

28.5 mg twice daily

4.8 ml twice daily

 

> 9 - 10 kg10 kg

30 mg twice daily

5.0 ml twice daily

10 ml

* 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

Body Weight

Recommended dose for 10 days

Amount of oral suspension to withdraw

3 kg

6 mg once daily

1.0 ml once daily

3.5 kg

7 mg once daily

1.2 ml once daily

4 kg

8 mg once daily

1.3 ml once daily

4.5 kg

9 mg once daily

1.5 ml 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

Body Weight

Recommended dose for 10 days

Amount of oral suspension to withdraw

4 kg

10 mg once daily

1.7 ml once daily

4.5 kg

11.25 mg once daily

1.9 ml once daily

5 kg

12.5 mg once daily

2.1 ml once daily

5.5 kg

13.75 mg once daily

2.3 ml once daily

6 kg

15 mg once daily

2.5 ml once daily

6.5 kg

16.25 mg once daily

2.7 ml 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

Body Weight*

Recommended dose for 10 days

Amount of oral suspension to withdraw

Dispenser size

to use

3 kg

9 mg once daily

1.5 ml once daily

3 ml

3.5 kg

10.5 mg once daily

1.8 ml once daily

3 ml

4 kg

12 mg once daily

2.0 ml once daily

3 ml

4.5 kg

13.5 mg once daily

2.3 ml once daily

3 ml

5 kg

15 mg once daily

2.5 ml once daily

3 ml

5.5 kg

16.5 mg once daily

2.8 ml once daily

3 ml

6 kg

18 mg once daily

3.0 ml once daily

3 ml

6.5 kg

19.5 mg once daily

3.3 ml once daily

> 6 - 7 kg7 kg

21 mg once daily

3.5 ml once daily

10 ml

7.5 kg

22.5 mg once daily

3.8 ml once daily

> 7 - 8 kg8 kg

24 mg once daily

4.0 ml once daily

10 ml

8.5 kg

25.5 mg once daily

4.3 ml once daily

> 8 - 9 kg9 kg

27 mg once daily

4.5 ml once daily

10 ml

9.5 kg

28.5 mg once daily

4.8 ml once daily

> 9 - 10 kg10 kg

30 mg once daily

5.0 ml once daily

10 ml

* 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.

 

Safety information available on oseltamivir administered for treatment of influenza in infants less than one year of age from prospective and retrospective observational studies (comprising together more than 2,400 infants of that age class), epidemiological databases research and postmarketing reports suggest that the safety profile in infants less than one year of age is similar to the established safety profile of children aged one year and older.

 

Elderly patientsOlder people and patients with chronic cardiac and/or respiratory disease

The population included in the influenza treatment studies is comprised of otherwise healthy adults/adolescents and patients “at risk” (patients at higher risk of developing complications associated with influenza, e.g. elderly patientsolder people and patients with chronic cardiac or respiratory disease). In general, the safety profile in the patients “at risk” was qualitatively similar to that in otherwise healthy adults/adolescents.

[...]

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.

Oseltamivir is effective only against illnesses caused by influenza virus. Statistical analyses are therefore presented only for influenza-infected subjects. In the pooled treatment study population, which included both influenza-positive and -negative subjects (ITT), primary efficacy was reduced proportionally to the number of influenza-negative individuals. In the overall treatment population, influenza infection was confirmed in 67 % (range 46 % to 74 %) of the recruited patients. Of the elderly older subjects, 64 % were influenza-positive and of those with chronic cardiac and/or respiratory disease 62 % were influenza-positive. In all phase III treatment studies, patients were recruited only during the period in which influenza was circulating in the local community.

[...]

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.


[...]

[...]

[...]

[...]

[...][...]

Updated on 22-May-2015 and displayed until 01-Jun-2015

Reasons for adding or updating:

  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 23-Apr-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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

 

Updated on 18-May-2015 and displayed until 22-May-2015

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 05-May-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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

Body weight

Recommended dose for 5 days

Amount of oral suspension to withdraw

3 kg

6 mg twice daily

1.0 ml twice daily

3.5 kg

7 mg twice daily

1.2 ml twice daily

4 kg

8 mg twice daily

1.3 ml twice daily

4.5 kg

9 mg twice daily

1.5 ml 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

Body weight

Recommended dose for 5 days

Amount of oral suspension to withdraw

4 kg

10 mg twice daily

1.7 ml twice daily

4.5 kg

11.25 mg twice daily

1.9 ml twice daily

5 kg

12.5 mg twice daily

2.1 ml twice daily

5.5 kg

13.75 mg twice daily

2.3 ml twice daily

6 kg

15 mg twice daily

2.5 ml twice daily

6.5 kg

16.25 mg twice daily

2.7 ml 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

Body Weight*

Recommended dose for 5 days

Amount of oral suspension to withdraw

Dispenser size

to use

3 kg

9 mg twice daily

1.5 ml twice daily

3 ml

3.5 kg

10.5 mg twice daily

1.8 ml twice daily

3 ml

4 kg

12 mg twice daily

2.0 ml twice daily

3 ml

4.5 kg

13.5 mg twice daily

2.3 ml twice daily

3 ml

5 kg

15 mg twice daily

2.5 ml twice daily

3 ml

5.5 kg

16.5 mg twice daily

2.8 ml twice daily

3 ml

6 kg

18 mg twice daily

3.0 ml twice daily

3 ml

6.5 kg

19.5 mg twice daily

3.3 ml twice daily

 

> 6 - 7 kg7 kg

21 mg twice daily

3.5 ml twice daily

10 ml

7.5 kg

22.5 mg twice daily

3.8 ml twice daily

 

> 7 - 8 kg8 kg

24 mg twice daily

4.0 ml twice daily

10 ml

8.5 kg

25.5 mg twice daily

4.3 ml twice daily

 

> 8 - 9 kg9 kg

27 mg twice daily

4.5 ml twice daily

10 ml

9.5 kg

28.5 mg twice daily

4.8 ml twice daily

 

> 9 - 10 kg10 kg

30 mg twice daily

5.0 ml twice daily

10 ml

* 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

Body Weight

Recommended dose for 10 days

Amount of oral suspension to withdraw

3 kg

6 mg once daily

1.0 ml once daily

3.5 kg

7 mg once daily

1.2 ml once daily

4 kg

8 mg once daily

1.3 ml once daily

4.5 kg

9 mg once daily

1.5 ml 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

Body Weight

Recommended dose for 10 days

Amount of oral suspension to withdraw

4 kg

10 mg once daily

1.7 ml once daily

4.5 kg

11.25 mg once daily

1.9 ml once daily

5 kg

12.5 mg once daily

2.1 ml once daily

5.5 kg

13.75 mg once daily

2.3 ml once daily

6 kg

15 mg once daily

2.5 ml once daily

6.5 kg

16.25 mg once daily

2.7 ml 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

Body Weight*

Recommended dose for 10 days

Amount of oral suspension to withdraw

Dispenser size

to use

3 kg

9 mg once daily

1.5 ml once daily

3 ml

3.5 kg

10.5 mg once daily

1.8 ml once daily

3 ml

4 kg

12 mg once daily

2.0 ml once daily

3 ml

4.5 kg

13.5 mg once daily

2.3 ml once daily

3 ml

5 kg

15 mg once daily

2.5 ml once daily

3 ml

5.5 kg

16.5 mg once daily

2.8 ml once daily

3 ml

6 kg

18 mg once daily

3.0 ml once daily

3 ml

6.5 kg

19.5 mg once daily

3.3 ml once daily

> 6 - 7 kg7 kg

21 mg once daily

3.5 ml once daily

10 ml

7.5 kg

22.5 mg once daily

3.8 ml once daily

> 7 - 8 kg8 kg

24 mg once daily

4.0 ml once daily

10 ml

8.5 kg

25.5 mg once daily

4.3 ml once daily

> 8 - 9 kg9 kg

27 mg once daily

4.5 ml once daily

10 ml

9.5 kg

28.5 mg once daily

4.8 ml once daily

> 9 - 10 kg10 kg

30 mg once daily

5.0 ml once daily

10 ml

* 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.

 

[...]

4.8     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.       PHARMACOLOGICAL PROPERTIES

 

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.

 

[...]

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.

 

[...]

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.

[...]

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

 

 

 

 

 

Updated on 23-May-2014 and displayed until 18-May-2015

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects - how to report a side effect
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 25-Apr-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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

 

 

 

Updated on 27-Nov-2013 and displayed until 23-May-2014

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 24-Oct-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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

Body weight

Recommended dose for 5 days

Amount of oral suspension to withdraw

3 kg

6 mg twice daily

1.0 ml twice daily

3.5 kg

7 mg twice daily

1.2 ml twice daily

4 kg

8 mg twice daily

1.3 ml twice daily

4.5 kg

9 mg twice daily

1.5 ml 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

Body weight

Recommended dose for 5 days

Amount of oral suspension to withdraw

4 kg

10 mg twice daily

1.7 ml twice daily

4.5 kg

11.25 mg twice daily

1.9 ml twice daily

5 kg

12.5 mg twice daily

2.1 ml twice daily

5.5 kg

13.75 mg twice daily

2.3 ml twice daily

6 kg

15 mg twice daily

2.5 ml twice daily

6.5 kg

16.25 mg twice daily

2.7 ml 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

Body weight

Recommended dose for 5 days

Amount of oral suspension to withdraw

6 kg

18 mg twice daily

3.0 ml twice daily

6.5 kg

19.5 mg twice daily

3.3 ml twice daily

7 kg

21 mg twice daily

3.5 ml twice daily

7.5 kg

22.5 mg twice daily

3.8 ml twice daily

8 kg

24 mg twice daily

4.0 ml twice daily

8.5 kg

25.5 mg twice daily

4.3 ml twice daily

9 kg

27 mg twice daily

4.5 ml twice daily

9.5 kg

28.5 mg twice daily

4.8 ml twice daily

10 kg

30 mg twice daily

5.0 ml twice daily

 

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

 

 

[….]

 

 

The following weight-adjusted dosing regimens 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 oncetwice daily

Body Weight

Recommended dose for 10 days

Amount of oral suspension to withdraw

3 kg

6 mg once daily

1.0 ml once daily

3.5 kg

7 mg once daily

1.2 ml once daily

4 kg

8 mg once daily

1.3 ml once daily

4.5 kg

9 mg once daily

1.5 ml 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 twice once daily

Body Weight

Recommended dose for 10 days

Amount of oral suspension to withdraw

4 kg

10 mg once daily

1.7 ml once daily

4.5 kg

11.25 mg once daily

1.9 ml once daily

5 kg

12.5 mg once daily

2.1 ml once daily

5.5 kg

13.75 mg once daily

2.3 ml once daily

6 kg

15 mg once daily

2.5 ml once daily

6.5 kg

16.25 mg once daily

2.7 ml once 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 once daily

Body Weight

Recommended dose for 10 days

Amount of oral suspension to withdraw

6 kg

18 mg once daily

3.0 ml once daily

6.5 kg

19.5 mg once daily

3.3 ml once daily

7 kg

21 mg once daily

3.5 ml once daily

7.5 kg

22.5 mg once daily

3.8 ml once daily

8 kg

24 mg once daily

4.0 ml once daily

8.5 kg

25.5 mg once daily

4.3 ml once daily

9 kg

27 mg once daily

4.5 ml once daily

9.5 kg

28.5 mg once daily

4.8 ml once daily

10 kg

30 mg once daily

5.0 ml once daily

 

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

 

[….]

 

 

 

 

 

 

10.     DATE OF REVISION OF THE TEXT

 

24 October 2013

 

Updated on 17-Dec-2012 and displayed until 27-Nov-2013

Reasons for adding or updating:

  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 15-Nov-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Underlined text = new text

 

Strike through text = deleted text

 

 

4.9     Overdose

 

Reports of overdoses with Tamiflu have been received from clinical trials and during post-marketing experience. In the majority of cases reporting overdose, no adverse events were reported.

 

Adverse events reported following overdose were similar in nature and distribution to those observed with therapeutic doses of Tamiflu, described in section 4.8 Undesirable effects.

 

There is no experience with overdose. However, the anticipated manifestations of acute overdose would be nausea, with or without accompanying vomiting, and dizziness. Patients should discontinue the treatment in the event of overdose. No specific antidote is known.

 

Paediatric population

Overdose has been reported more frequently for children than adults and adolescents. Caution should be exercised when preparing Tamiflu oral suspension and when administering Tamiflu products to children.

 

 

 

10.     DATE OF REVISION OF THE TEXT

 

15 November 2012

 

 

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu

Updated on 21-Sep-2012 and displayed until 17-Dec-2012

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC: 10-Sep-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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

4.8     Undesirable effects

 

Summary of the safety profile

The overall safety profile of Tamiflu is based on data from 46246049 adult/adolescent and1480 1473 paediatric patients treated with Tamiflu or placebo for influenza, and on data from3533 3990 adult/adolescent and148 253 paediatric patients receiving Tamiflu or placebo/no treatment for the prophylaxis of influenza in clinical trials. In addition, 475 immunocompromised patients (including 18 children, of these 10 Tamiflu and 8 placebo) received Tamiflu or placebo for the prophylaxis of influenza.

 

In adults/adolescents, the most commonly reported adverse reactions (ARs) were nausea and vomitingand headache in the treatment studies, and nausea , vomiting, headache and pain in the prevention studies. The majority of these ARs were reported on a single occasion on either the first or second treatment day and resolved spontaneously within 1-2 days. In children, the most commonly reported adverse reactions were was vomiting. , nausea, dyspepsia, abdominal pain and headache. In the majority of patients, these ARs did not lead to discontinuation of Tamiflu.

 

The following serious clinically important adverse reactions have been rarely reported since oseltamivir has been marketed: Anaphylactic and anaphylactoid reactions, hepatic disorders (fulminant hepatitis, hepatic function disorder and jaundice), angioneurotic oedema, Stevens-Johnson syndrome and toxic epidermal necrolysis, gastrointestinal bleeding and neuropsychiatric disorders.

(Regarding neuropsychiatric disorders, see section 4.4.)

 

Tabulated summary list of adverse reactions

The ARs listed in the tables below fall into the following categories: Very common (³ 1/10), common (³ 1/100 to < 1/10), uncommon (³ 1/1,000 to < 1/100), rare (³ 1/10,000 to < 1/1,000), and very rare (< 1/10,000). ARs are added to the appropriate category in the tables according to the pooled analysis from clinical studies.

 

Treatment and prevention of influenza in adults and adolescents:

In adult/adolescent treatment and prophylaxis prevention studies, ARs that occurred the most frequently (³ 1 %) at the recommended dose (75  mg bid for 5  days for treatment and 75  mg od for up to 6  weeks for prophylaxis) are shown in Table 1.

 

The safety profile reported in subjects who received the recommended dose of Tamiflu for prophylaxis (75 mg once daily for up to 6 weeks) was qualitatively similar to that seen in the treatment studies, despite a longer duration of dosing in the prophylaxis studies.

 

Table 1       Adverse reactions in studies investigating Tamiflu for treatment and prevention of influenza in adults and adolescents or through post-marketing surveillance

 

System Organ Class (SOC)

Adverse reactions according to frequency

Very common

Common

Uncommon

Rare

Infections and infestations

 

Bronchitis,

Herpes simplex,

Influenza,

Nasopharyngitis,

Upper respiratory tract infections,

Sinusitis

 

 

Blood and lymphatic system disorders

 

 

 

Thrombocytopenia

Immune system disorders

 

 

Hypersensitivity reaction

Anaphylactic reactions, Anaphylactoid reactions

Psychiatric disorders

 

 

 

Agitation,
Abnormal behaviour, Anxiety,
Confusion, Delusions, Delirium, Hallucination, Nightmares,
Self-injury

Nervous system disorders

Headache

Insomnia

Altered level of consciousness, Convulsion

 

Eye disorders

 

 

 

Visual disturbance

Cardiac disorders

 

 

Cardiac arrhythmia

 

Respiratory, thoracic and mediastinal disorders

 

Cough,

Nasal congestion,

Sore throat,

Rhinorrhea

 

 

Gastrointestinal disorders

Nausea

Vomiting

Abdominal pain (incl. upper abdominal pain), Diarrhoea, Dyspepsia

 

Gastrointestinal bleedings, Hemorrhagic colitis

Hepatobiliary disorders

 

 

Elevated liver enzymes

Fulminant hepatitis, Hepatic failure, Hepatitis

Skin and subcutaneous tissue disorders

 

 

Eczema, Dermatitis, Rash,
Urticaria

Angioneurotic oedema,
Erythema multiforme, Stevens-Johnson syndrome,
Toxic epidermal necrolysis

Musculoskeletal and connective tissue disorders

 

Arthralgia,

Back pain,

Myalgia

 

 

Reproductive system and breast disorders

 

Dysmenorrhea

 

 

General disorders and administration site conditions

 

Pain

Dizziness (incl. vertigo),

Fatigue,

Pyrexia ,

Pain in limb

Influenza like illness

 

 

Below is a list of commonly occurring ARs from treatment studies (n = 2,647) and prophylaxis studies (n = 1,945). These events occurred either more frequently in patients on placebo compared to patients on oseltamivir, or the difference in frequency between the two arms was less than 1 %. Commonly occurring ARs are those which occur with a frequency of greater than 1 per 100 patients, and less than 1 per 10 patients.

 

·        Infections and infestations: Bronchitis, herpes simplex, influenza, nasopharyngitis, upper respiratory tract infections, sinusitis

 

·        Nervous system disorders: Insomnia

 

·        Respiratory, thoracic and mediastinal disorders: Cough, nasal congestion, sore throat, rhinorrhea

 

·        Gastrointestinal disorders: Abdominal pain (incl. upper abdominal pain), diarrhoea, dyspepsia

 

·        Musculoskeletal and connective tissue disorders: Arthralgia, back pain, myalgia

 

·        Reproductive system and breast disorders: Dysmenorrhea

 

·        General disorders: Dizziness (incl. vertigo), fatigue, influenza like illness, pain in limb, pyrexia

 

Treatment and prevention of influenza in children:

 

A total of 14801473 children (including otherwise healthy children aged 1-12 years old and asthmatic children aged 6-12 years old) participated in clinical studies of oseltamivir given for the treatment of influenza. Of those, 858851 children received treatment with oseltamivir suspension. A total of 148 158 children received the recommended dose of Tamiflu once daily in a post-exposure prophylaxis study in households (n = 99), a 6-week paediatric seasonal prophylaxis study (n = 49) and a 12-week paediatric seasonal prophylaxis study in immunocompromised subjects (n = 10).

and in a separate 6-week paediatric prophylaxis study (n = 49).

Table 2 shows the most frequently reported ARs from paediatric clinical trials.

 

Table 2       Adverse reactions in studies investigating Tamiflu for treatment and prevention of influenza in children (age/weight-based dosing [30 mg to 75 mg o.d.])

 

System Organ Class (SOC)

Adverse reactions according to frequency

Very common

Common

Uncommon

Rare

Infections and infestations

 

Bronchitis,

Nasopharyngitis,

Otitis media,

Pneumonia,

Sinusitis,

Upper respiratory tract infection

 

 

Blood and lymphatic system disorders

 

 

Lymphadenopathy

 

Nervous system disorders

 

Headache

 

 

Eye disorders:

 

Conjunctivitis (including red eyes, eye discharge and eye pain)

 

 

Ear and labyrinth disorders:

 

Earache

Tympanic membrane disorder

 

Respiratory, thoracic and mediastinal disorders

Cough,

Nasal congestion

Asthma (including aggravated asthma),

Epistaxis,

Rhinorrhoea

 

 

Gastrointestinal disorders

Vomiting

Abdominal pain (incl. upper abdominal pain), Dyspepsia,

Nausea

Diarrhoea

 

 

Skin and subcutaneous tissue disorders

 

 

Dermatitis (including allergic and atopic dermatitis)

 

General disorders

 

Pyrexia

 

 

 

Below is a list of commonly occurring ARs from treatment studies (n = 858) and prophylaxis studies (n = 148). These events occurred either more frequently in patients on placebo/no prophylaxis compared to patients on oseltamivir, or the difference in frequency between the two groups was less than 1 %. Commonly occurring ARs are those which occur with a frequency of greater than 1 per 100 patients, and less than 1 per 10 patients.

 

·        Infections and infestations: Bronchitis, nasopharyngitis, otitis media, pneumonia, sinusitis, upper respiratory tract infection

 

·        Eye disorders: Conjunctivitis (including red eyes, eye discharge and eye pain)

 

·        Ear and labyrinth disorders: Earache

 

·        Respiratory, thoracic and mediastinal disorders: Asthma (including aggravated asthma), cough, epistaxis, nasal congestion, rhinorrhoea

 

·        Gastrointestinal disorders: Diarrhoea

 

·        Skin and subcutaneous tissue disorders: Dermatitis (including allergic and atopic dermatitis)

 

·        General disorders: Pyrexia

 

The following additional Uncommon (frequency > 1/1,000 to < 1/100) ARs were reported in the paediatric treatment studies. These ARs previously qualified as Common (frequency > 1/100 to < 1/10) but in the larger datasets no longer fulfil the criteria to be included in the previous section.

 

·        Blood and lymphatic system disorders: Lymphadenopathy

 

·        Ear and labyrinth disorders: Tympanic membrane disorder

 

Description of selected adverse reactions:

 

Psychiatric disorders and nervous system disorders

Influenza can be associated with a variety of neurologic and behavioural symptoms which can include events such as hallucinations, delirium, and abnormal behaviour, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease.

 

In patients with influenza who were receiving Tamiflu, there have been postmarketing reports of convulsions and delirium (including symptoms such as altered level of consciousness, confusion, abnormal behaviour, delusions, hallucinations, agitation, anxiety, nightmares), in a very few cases resulting in self-injury or fatal outcomes. These events were reported primarily among paediatric and adolescent patients and often had an abrupt onset and rapid resolution. The contribution of Tamiflu to those events is unknown. Such neuropsychiatric events have also been reported in patients with influenza who were not taking Tamiflu.

 

Hepato-biliary disorders

Hepato-biliary system disorders, including hepatitis and elevated liver enzymes in patients with influenza-like illness. These cases include fatal fulminant hepatitis/hepatic failure.

 

Other special populations

 

Paediatric population (infants less than one year of age)

Safety information available on oseltamivir administered for treatment of influenza in infants less than one year of age from prospective and retrospective observational studies (comprising together more than 2,400 infants of that age class), epidemiological databases research and postmarketing reports suggest that the safety profile in infants less than one year of age is similar to the established safety profile of children aged one year and older.

 

Elderly patients and patients with chronic cardiac and/or respiratory disease

The population included in the influenza treatment studies is comprised of otherwise healthy adults/adolescents and patients “at risk” (patients at higher risk of developing complications associated with influenza, e.g. elderly patients and patients with chronic cardiac or respiratory disease). In general, the safety profile in the patients “at risk” was qualitatively similar to that in otherwise healthy adults/adolescents.

 

Immunocompromised patients

In a 12-week prophylaxis study in 475 immunocompromised patients, including 18 children 1 to 12 years of age and older, the safety profile in the 238 patients who received oseltamivir was consistent with that previously observed in Tamiflu prophylaxis clinical studies.

 

Children with pre-existing bronchial asthma

In general, the adverse reaction profile in children with pre-existing bronchial asthma was qualitatively similar to that of otherwise healthy children.

10.     DATE OF REVISION OF THE TEXT

 

 

 

10 September 2012

 

 

Updated on 20-Aug-2012 and displayed until 21-Sep-2012

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC

Legal Category:POM

Black Triangle (CHM): NO

Company contact details

Roche Products Limited

Company image
Address

Hexagon Place, 6 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW

Fax

+44 (0)1707 338 297

Medical Information e-mail
Medical Information Fax

+44 (0)1707 384555

Telephone

+44 (0)1707 366 000

Medical Information Direct Line

+44 (0)800 328 1629

Customer Care direct line

+44 (0)800 731 5711

Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why?

Active ingredients

oseltamivir phosphate

Legal categories

POM - Prescription Only Medicine

This site uses cookies. By continuing to browse the site you are agreeing to our policy on the use of cookies. Continue