Tamiflu 45 mg Hard Capsules

*
Pharmacy Only: Prescription
  • Company:

    Roche Registration GmbH
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    No Recent Update
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    Product subject to medical prescription which may not be renewed (A)
  • Active Ingredient(s):

    *Additional information is available within the SPC or upon request to the company

Updated on 25 January 2023

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Updated on 11 November 2021

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  • Change to section 6 - date of revision

Updated on 17 September 2021

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  • Change to section 3 - how to take/use
  • Change to section 4 - how to report a side effect
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Updated on 17 September 2021

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Updated on 17 September 2021

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  • Change to section 3 - how to take/use
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Updated on 17 September 2021

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  • Change to Section 4.8 – Undesirable effects - how to report a side effect

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Updated on 25 August 2020

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TAM PIL 45 mg hard capsules clean.pdf

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  • Change to section 2 - excipient warnings

Updated on 20 April 2020

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  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

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

Updated on 20 April 2020

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Tamiflu-45mg-capsules-PL-clean.pdf

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  • Change to section 3 - how to take/use
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

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

Updated on 03 April 2019

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uk-ie-mt-spc-Tamiflu-clean-210219-30mg-45mg-75mg-caps.pdf

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

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Update Shelf life for 30mg and 45mg capsule strengths from 7 years to 10 years on basis of real time stability data gathered.

Updated on 24 January 2019

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uk-ie-mt-pil-tamiflu-clean-19-01-11-45mg-caps.pdf

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  • Change to section 3 - how to take/use

Updated on 24 January 2019

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uk-ie-mt-spc-tamiflu-clean-19-01-11-caps.pdf

Reasons for updating

  • 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

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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

Patient Population

Patients with Resistance Mutations (%)

Phenotyping*

Geno- and Phenotyping*

Adults and adolescents

0.6288% (1421/22532377)

 

0.671.12% (1527/22532391)

 

Children (1-12 years)

3.89% (66/1698)

 

4.24% (72/1698)

 

Infants (<1year)

18.31% (13/71)

18.31% (13/71)

* 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.

 

 

Updated on 17 December 2018

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uk-ie-mt-pil-tamiflu-clean-18-11-15-45mg-caps.pdf

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  • Change to section 3 - how to take/use
  • Change to section 6 - date of revision

Updated on 14 December 2018

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uk-ie-mt-spc-tamiflu-clean-18-11-15-caps.pdf

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  • 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 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 17 August 2018

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uk-ie-mt-pil-Tamiflu-clean-18-08-09-45mg-Caps.pdf

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  • Change to section 6 - date of revision
  • Change to other sources of information section

Updated on 21 May 2018

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  • Other

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Updated on 26 April 2018

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  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

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Updated on 16 April 2018

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uk-ie-mt-pil-tamiflu-clean-18-04-12-45mg-caps.pdf

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  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - date of revision

Updated on 23 March 2018

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 23 March 2018

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

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 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

 





Updated on 18 January 2017

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.3 - Shelf life
  • Change to section 8 - Marketing authorisation number(s)

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company



1.       NAME OF THE MEDICINAL PRODUCT

 

Tamiflu 30 mg hard capsules
Tamiflu 45
 mg hard capsules
Tamiflu 75
 mg hard capsules

 

 

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Tamiflu 30 mg hard capsules

Each hard capsule contains oseltamivir phosphate equivalent to 30 mg of oseltamivir.

For the full list of excipients, see section 6.1.

 

Tamiflu 45 mg hard capsules
Each hard capsule contains oseltamivir phosphate equivalent to 45 mg of oseltamivir.

For the full list of excipients, see section 6.1.

 


Tamiflu 75
 mg hard capsules
Each hard capsule contains oseltamivir phosphate equivalent to 75 mg of oseltamivir.

For the full list of excipients, see section 6.1.

 

 

 

3.       PHARMACEUTICAL form

 

Tamiflu 30 mg hard capsules

Hard capsule (capsule)

The hard capsule consists of a light yellow opaque body bearing the imprint “ROCHE” and a light yellow opaque cap bearing the imprint “30 mg”. Imprints are blue.

 

Tamiflu 45 mg hard capsules

The hard capsule consists of a grey opaque body bearing the imprint “ROCHE” and a grey opaque cap bearing the imprint “45 mg”. Imprints are blue.



Tamiflu 75 mg hard capsules
The hard capsule consists of a grey opaque body bearing the imprint “ROCHE” and a light yellow opaque cap bearing the imprint “75 mg”. Imprints are blue.

 

 

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 patientsChildren  who were found to carry oseltamivir-resistant virus in general shed the virus for a prolonged period compared with subjects with susceptible virusd.id 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 %)

Infants (<1year)

18.31% (13/71)

18.31% (13/71)

* Full genotyping was not performed in all studies.

 

[...]

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.       PHARMACEUTICAL PARTICULARS

 

6.1     List of excipients

 

Tamiflu 30 mg hard capsules

Capsule core

Pregelatinised starch (derived from maize starch)

Talc

Povidone

Croscarmellose sodium

Sodium stearyl fumarate

 

Capsule shell

Gelatin

Yellow iron oxide (E172)

Red iron oxide (E172)

Titanium dioxide (E171)

 

Printing ink

Shellac

Titanium dioxide (E171)

FD and C Blue 2 (indigo carmine, E132)

 

Tamiflu 45 mg hard capsules

Capsule core

Pregelatinised starch (derived from maize starch)

Talc

Povidone

Croscarmellose sodium

Sodium stearyl fumarate

 

Capsule shell

Gelatin

Black iron oxide (E172)

Titanium dioxide (E171)

 

Printing ink

Shellac

Titanium dioxide (E171)

FD and C Blue 2 (indigo carmine, E132)

 

 

Tamiflu 75 mg hard capsules

Capsule core

Pregelatinised starch (derived from maize starch)

Talc

Povidone

Croscarmellose sodium

Sodium stearyl fumarate

 

Capsule shell

Gelatin

Yellow iron oxide (E172)

Red iron oxide (E172)

Black iron oxide (E172)

Titanium dioxide (E171)

 

Printing ink

Shellac

Titanium dioxide (E171)

FD and C Blue 2 (indigo carmine, E132)

 

 

6.3       Shelf life

 

Tamiflu 30 mg hard capsules

7 years

 

Tamiflu 45 mg hard capsules

7 years

 

Tamiflu 75 mg hard capsules

10 years

 

 

8.       MARKETING AUTHORISATION NUMBER(S)

 

Tamiflu 30 mg hard capsules

EU/1/02/222/003

 

Tamiflu 45 mg hard capsules
EU/1/02/222/004

 

Tamiflu 75 mg hard capsules
EU/1/02/222/001

 


 

 


Updated on 27 May 2016

Reasons for 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

Legal category:Product subject to medical prescription which may not be renewed (A)

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 02 June 2015

Reasons for 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 - 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 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

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

 

Posology

 

Tamiflu hard capsules and Tamiflu suspension are bioequivalent formulations. 75 mg doses can be administered as either

-        one 75 mg capsule or

-           one 30 mg capsule plus one 45 mg capsule or

-        by administering one 30 mg dose plus one 45 mg dose of suspension.

 

Commercially manufactured Tamiflu powder for oral suspension (6 mg/ml) is the preferred product for paediatric and adult patients who have difficulties swallowing capsules or where lower doses are needed.  Adults, adolescents or infants and children (1 year of age or older) who are unable to swallow capsules may receive appropriate doses of Tamiflu suspension.

 

[...]

Iinfants 0 – 12 months of ageless than 1 year

 

In the absence of a suitable formulation, a pharmacy compounded preparation should preferentially be used as the syringe provided in the Tamiflu 12 mg/ml powder for oral suspension pack (with mg markings) does not allow for appropriate dose adjustments and commercially available syringes (with ml markings) may lead to unacceptable dosing inaccuracies (see section 6.6).

 

Treatment: The recommended treatment dose for infants less than 1 year0 - 12 months of 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 thiese 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). The following age-adjusted dosing regimen iss are recommended for treatment of infants 0 - 12 months below 1 year of age:

 

Body weight*

Recommended dose for 5 days

3 kg

9 mg twice daily

4 kg

12 mg twice daily

5 kg

15 mg twice daily

6 kg

18 mg twice daily

7 kg

21 mg twice daily

8 kg

24 mg twice daily

9 kg

27 mg twice daily

10 kg

30 mg twice daily

* This table is not intended to contain all possible weights for this population. For all patients under the age of 1 year of age, 3 mg/kg should be used to determine dose regardless of the weight of the patient.

 

Age

Recommended dose for 5 days

0 to 1 month*

2 mg/kg twice daily

> 1 month to 3 months

2.5 mg/kg twice daily

> 3 months to 12 months

3 mg/kg twice daily

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

 

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

 

This ese age-based dosing recommendations isare not intended for premature infants, i.e. those with a post-conceptual postmenstrual 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.

 

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 regimens are is  recommended for infants below 1 year0 - 12 months of age:

 

Age

Recommended dose for 10 days

0 to 1 month*

2 mg/kg once daily

> 1 month to 3 months

2.5 mg/kg once daily

> 3 months to0 -  12 months

3 mg/kg once daily

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

 

Thisese age-based  dosing recommendation is are not intended for premature infants, i.e. those with a post-conceptual postmenstrual age less than 3637 weeks. Insufficient data are available for these patients, in whom different dosing may be required due to the immaturity of physiological functions.

 

Prevention during an influenza epidemic in the community: Prevention during an influenza epidemic has not been studied in children below 120-12 yearsmonths of age.

 


[...]

4.4     Special warnings and precautions for use

 

[...]

Paediatric population

No data allowing a dose recommendation for premature children (< 367 weeks post-conceptual agepost-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

 

[...]

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

 

ChildrenPaediatric population

 

Infants less than 1 year 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. 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.

 

[...]

 

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).

 


6.6     Special precautions for disposal and other handling

 

Any unused product or waste material should be disposed of in accordance with local requirements.

 

Extemporaneous formulation

 

When Tamiflu powder for oral suspension is not available

Commercially manufactured Tamiflu for oral suspension (6 mg/ml) is the preferred product for paediatric and adult patients who have difficulties swallowing capsules or where lower doses are needed.  In the event that When commercially manufactured Tamiflu powder for oral suspension is not available, the pharmacist may compound a suspension (6 mg/ml) from Tamiflu capsules or patients can prepare the suspension from capsules at patients who are unable to swallow capsules may receive appropriate doses of Tamiflu prepared in a pharmacy or prepared at home.

 

For infants less than 1 year of age, tThe pharmacy preparation should be preferred to home preparation. Detailed information on the home preparation can be found in the package leaflet of Tamiflu capsules under “Making liquid Tamiflu suspension at home”.

 

[...]

Dosing chart for pharmacy compounded 6 mg/ml suspension prepared from Tamiflu capsules for infants less than 1 year of age

Body Weight

(rounded to the nearest 0.5 kg)

Dose

(mg)

Volume

per dose

(6 mg/ml)

Treatment Dose
(for 5 days)

Prophylaxis Dose
(for 10 days)

Dispenser size

to use

(grading 0.1 ml)

3 kg

9 mg

1.5 ml

1.5 ml twice daily

1.5 ml once daily

2.0 ml or 3.0 ml

3.5 kg

10.5 mg

1.8 ml

1.8 ml twice daily

1.8 ml once daily

2.0 ml or 3.0 ml

4 kg

12 mg

2.0 ml

2.0 ml twice daily

2.0 ml once daily

3.0 ml

4.5 kg

13.5 mg

2.3 ml

2.3 ml twice daily

2.3 ml once daily

3.0 ml

5 kg

15 mg

2.5 ml

2.5 ml twice daily

2.5 ml once daily

3.0 ml

5.5 kg

16.5 mg

2.8 ml

2.8 ml twice daily

2.8 ml once daily

3.0 ml

6 kg

18 mg

3.0 ml

3.0 ml twice daily

3.0 ml once daily

3.0 ml (or 5.0 ml)

6.5 kg

19.5 mg

3.3 ml

3.3 ml twice daily

3.3 ml once daily

5.0 ml

7 kg

21 mg

3.5 ml

3.5ml twice daily

3.5 ml once daily

5.0 ml

7.5 kg

22.5 mg

3.8 ml

3.8 ml twice daily

3.8 ml once daily

5.0 ml

8 kg

24 mg

4.0 ml

4.0 ml twice daily

4.0 ml once daily

5.0 ml

8.5 kg

25.5 mg

4.3 ml

4.3 ml twice daily

4.3 ml once daily

5.0 ml

9 kg

27 mg

4.5 ml

4.5 ml twice daily

4.5 ml once daily

5.0 ml

9.5 kg

28.5 mg

4.8 ml

4.8 ml twice daily

4.8 ml once daily

5.0 ml

10 kg

30 mg

5.0 ml

5.0 ml twice daily

5.0 ml once daily

5.0 ml

 

 

Dosing chart for pharmacy compounded 6 mg/ml suspension prepared from Tamiflu capsules for infants 0 to 30 days of age (less than one month of age)

Body Weight

(rounded to the nearest 0.5 kg)

Dose

(mg)

Volume

per dose

(6 mg/ml)

Treatment Dose
(for 5 days)

Prophylaxis Dose
(for 10 days)

Dispenser size

to use

(grading 0.1 ml)

3 kg

6 mg

1.0 ml

1.0 ml twice daily

1.0 ml once daily

1.0 ml (or 2.0 ml)

3.5 kg

7 mg

1.2 ml

1.2 ml twice daily

1.2 ml once daily

2.0 ml

4 kg

8 mg

1.3 ml

1.3 ml twice daily

1.3 ml once daily

2.0 ml

4.5 kg

9 mg

1.5 ml

1.5 ml twice daily

1.5 ml once daily

2.0 ml

 

Dosing chart for pharmacy compounded 6 mg/ml suspension prepared from Tamiflu capsules for infants of 31 to 90 days of age (more than one month to three months of age)

Body Weight

(rounded to the nearest 0.5 kg)

Dose

(mg)

Volume

per dose

(6 mg/ml)

Treatment Dose
(for 5 days)

Prophylaxis Dose
(for 10 days)

Dispenser size

to use

(grading 0.1 ml)

4 kg

10 mg

1.7 ml

1.7 ml twice daily

1.7 ml once daily

2.0 ml (or 3.0 ml)

4.5 kg

11.25 mg

1.9 ml

1.9 ml twice daily

1.9 ml once daily

2.0 ml (or 3.0 ml)

5 kg

12.5 mg

2.1 ml

2.1 ml twice daily

2.1 ml once daily

3.0 ml

5.5 kg

13.75 mg

2.3 ml

2.3 ml twice daily

2.3 ml once daily

3.0 ml

6 kg

15 mg

2.5 ml

2.5 ml twice daily

2.5 ml once daily

3.0 ml

6.5 kg

16.25 mg

2.7 ml

2.7 ml twice daily

2.7 ml once daily

3.0 ml

 

Dosing chart for pharmacy compounded 6 mg/ml suspension prepared from Tamiflu capsules for infants 91 to less than 365 days of age (more than three months to twelve months of age)

Body Weight
(rounded to the nearest 0.5 kg)

Dose

(mg)

Volume

per dose

(6 mg/ml)

Treatment Dose
(for 5 days)

Prophylaxis Dose
(for 10 days)

Dispenser size

to use

(grading 0.1 ml)

6 kg

18 mg

3.0 ml

3.0 ml twice daily

3.0 ml once daily

3.0 ml (or 5.0 ml)

6.5 kg

19.5 mg

3.3 ml

3.3 ml twice daily

3.3 ml once daily

5.0 ml

7 kg

21 mg

3.5 ml

3.5ml twice daily

3.5 ml once daily

5.0 ml

7.5 kg

22.5 mg

3.8 ml

3.8 ml twice daily

3.8 ml once daily

5.0 ml

8 kg

24 mg

4.0 ml

4.0 ml twice daily

4.0 ml once daily

5.0 ml

8.5 kg

25.5 mg

4.3 ml

4.3 ml twice daily

4.3 ml once daily

5.0 ml

9 kg

27 mg

4.5 ml

4.5 ml twice daily

4.5 ml once daily

5.0 ml

9.5 kg

28.5 mg

4.8 ml

4.8 ml twice daily

4.8 ml once daily

5.0 ml

10 kg

30 mg

5.0 ml

5.0 ml twice daily

5.0 ml once daily

5.0 ml

 

Dispense the pharmacy compounded suspension with a graduated oral syringe for measuring small amounts of suspension. If possible, mark or highlight the graduation corresponding to the appropriate dose (according to the dosing tables above) on the oral syringe for each patient.

 

The appropriate dose must be mixed by the caregiver with an equal quantity of sweet liquid food, such as sugar water, chocolate syrup, cherry syrup, dessert toppings (like caramel or fudge sauce) to mask the bitter taste.

 

Home preparation

 

When commercially manufactured Tamiflu oral suspension is not available, a pharmacy compounded suspension prepared from Tamiflu capsules mustcan be used (see detailed instructions above). If the commercially manufactured Tamiflu oral suspension and the pharmacy compounded suspension is also not available, Tamiflu suspension may be prepared at home. The pharmacy compounded suspension is the preferred option in infants less than 1 year of age.

 

When appropriate capsule strengths are available for the dose needed, the dose is given by opening the capsule and mixing its contents with no more than one teaspoon of a suitable sweetened food product. The bitter taste can be masked by products such as sugar water, chocolate syrup, cherry syrup, dessert toppings (like caramel or fudge sauce). The mixture should be stirred and given entirely to the patient. The mixture must be swallowed immediately after its preparation.

 

When only 75 mg capsules are available, and doses of 30 mg or 45 mg are needed, the preparation of Tamiflu suspension involves additional steps. Detailed instructions can be found in the package leaflet of Tamiflu capsules under “Making liquid Tamiflu suspension at home”.

 

 

10.     DATE OF REVISION OF THE TEXT

 

5 May 2015

 




[...][...][...][...][...][...][...][...][...][...][...][...][...]

Updated on 21 May 2015

Reasons for updating

  • Change to section 4.6 - 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

Legal category:Product subject to medical prescription which may not be renewed (A)

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,; however there is evidence limited data available from post-marketing and retrospective observational surveillance 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.). showing benefit of the current dosing regimen in this patient populationreports. 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.       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 inhibitory 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 15 May 2015

File name

PIL_14467_911.pdf

Reasons for updating

  • New PIL for new product

Updated on 15 May 2015

Reasons for 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

Legal category:Product subject to medical prescription which may not be renewed (A)

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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

 

Posology

 

Tamiflu hard capsules and Tamiflu suspension are bioequivalent formulations. 75 mg doses can be administered as either

-        one 75 mg capsule or

-           one 30 mg capsule plus one 45 mg capsule or

-        by administering one 30 mg dose plus one 45 mg dose of suspension.

 

Commercially manufactured Tamiflu powder for oral suspension (6 mg/ml) is the preferred product for paediatric and adult patients who have difficulties swallowing capsules or where lower doses are needed.  Adults, adolescents or infants and children (1 year of age or older) who are unable to swallow capsules may receive appropriate doses of Tamiflu suspension.


[...] 


 

Paediatric population

 

Children 1 to 12 years of age


[...]

Iinfants 0 – 12 months of ageless than 1 year

 

In the absence of a suitable formulation, a pharmacy compounded preparation should preferentially be used as the syringe provided in the Tamiflu 12 mg/ml powder for oral suspension pack (with mg markings) does not allow for appropriate dose adjustments and commercially available syringes (with ml markings) may lead to unacceptable dosing inaccuracies (see section 6.6).

 

Treatment: The recommended treatment dose for infants less than 1 year0 - 12 months of 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 thiese 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). The following age-adjusted dosing regimen iss are recommended for treatment of infants 0 - 12 months below 1 year of age:

 

Body weight*

Recommended dose for 5 days

3 kg

9 mg twice daily

4 kg

12 mg twice daily

5 kg

15 mg twice daily

6 kg

18 mg twice daily

7 kg

21 mg twice daily

8 kg

24 mg twice daily

9 kg

27 mg twice daily

10 kg

30 mg twice daily

* This table is not intended to contain all possible weights for this population. For all patients under the age of 1 year of age, 3 mg/kg should be used to determine dose regardless of the weight of the patient.

 

Age

Recommended dose for 5 days

0 to 1 month*

2 mg/kg twice daily

> 1 month to 3 months

2.5 mg/kg twice daily

> 3 months to 12 months

3 mg/kg twice daily

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

 


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

 

This ese age-based dosing recommendations isare not intended for premature infants, i.e. those with a post-conceptual postmenstrual 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.

 

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 regimens are is  recommended for infants below 1 year0 - 12 months of age:

 

Age

Recommended dose for 10 days

0 to 1 month*

2 mg/kg once daily

> 1 month to 3 months

2.5 mg/kg once daily

> 3 months to0 -  12 months

3 mg/kg once daily

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

 

Thisese age-based  dosing recommendation is are not intended for premature infants, i.e. those with a post-conceptual postmenstrual age less than 3637 weeks. Insufficient data are available for these patients, in whom different dosing may be required due to the immaturity of physiological functions.

 

Prevention during an influenza epidemic in the community: Prevention during an influenza epidemic has not been studied in children below 120-12 yearsmonths of age.

 

For instructions on preparing the extemporaneous formulation, see section 6.6.

 

[...]

Method of administration

Oral use..

Adults, adolescents (13 to 17 years of age) or infants and children (1 year of age or older) Patients  who are unable to swallow capsules, may receive appropriate doses of Tamiflu suspension.

 

4.4     Special warnings and precautions for use

 

[...]

 

Paediatric population

No data allowing a dose recommendation for premature children (< 367 weeks post-conceptual agepost-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.

 

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.       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.

 

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 high risk populations: The median duration of influenza illness in olderelderly subjects (≥ 65 years) and in subjects with chronic cardiac and/or respiratory disease receiving oseltamivir 75 mg twice daily for 5 days was not reduced significantly. The total duration of fever was reduced by one day in the groups treated with oseltamivir. In the influenza-positive older people elderly, oseltamivir significantly reduced the incidence of specified lower respiratory tract complications (mainly bronchitis) treated with antibiotics from 19 % (52/268) in the placebo group to 12 % (29/250) in the oseltamivir treated population (p = 0.0156).


[...]

 

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

 

ChildrenPaediatric population

 

Infants less than 1 year 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. 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.

 

[...]

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

 

[...]

6.6     Special precautions for disposal and other handling

 

Any unused product or waste material should be disposed of in accordance with local requirements.

 

Extemporaneous formulation

 

When Tamiflu powder for oral suspension is not available

Commercially manufactured Tamiflu for oral suspension (6 mg/ml) is the preferred product for paediatric and adult patients who have difficulties swallowing capsules or where lower doses are needed.  In the event that When commercially manufactured Tamiflu powder for oral suspension is not available, the pharmacist may compound a suspension (6 mg/ml) from Tamiflu capsules or patients can prepare the suspension from capsules at patients who are unable to swallow capsules may receive appropriate doses of Tamiflu prepared in a pharmacy or prepared at home.

 

For infants less than 1 year of age, tThe pharmacy preparation should be preferred to home preparation. Detailed information on the home preparation can be found in the package leaflet of Tamiflu capsules under “Making liquid Tamiflu suspension at home”.

 

[...]


10.     DATE OF REVISION OF THE TEXT

 

5 May 2015

 








Updated on 15 May 2015

Reasons for updating

  • Change to packaging
  • Change to side-effects
  • Change to date of revision
  • Change to dosage and administration
  • Changes to therapeutic indications

Updated on 10 July 2014

Reasons for updating

  • Change to date of revision
  • Addition of information on reporting a side effect.

Updated on 20 May 2014

Reasons for 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

Legal category:Product subject to medical prescription which may not be renewed (A)

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 19 May 2014

Reasons for updating

  • Change to date of revision
  • Addition of information on reporting a side effect.

Updated on 27 November 2013

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 6.3 - Shelf life
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.2     Posology and method of administration

 

Posology

 

[…]

 

 

 

Adults, and Aadolescents (13 to 17 years of age) and adultsand over

 

Treatment: The recommended oral dose is 75 mg oseltamivir twice daily for 5 days for adolescents (13 to 17 years of age) and adults.

 

Body Weight

Recommended dose for 5 days

> 40 kg

75 mg twice daily

 

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

 

Post-exposure prevention: The recommended dose for prevention of influenza following close contact with an infected individual is 75 mg oseltamivir once daily for 10 days for adolescents (13 to 17 years of age) and adults.

 

Body Weight

Recommended dose for 10 days

> 40 kg

75 mg once daily

 

Therapy should begin as soon as possible within two days of exposure to an infected individual.

 

Prevention during an influenza epidemic in the community: The recommended dose for prevention of influenza during a community outbreak is 75 mg oseltamivir once daily for up to 6 weeks.

 

Infants and cChildren 1 to 12 years of age or older

 

Tamiflu 30 mg, 45 mg and 75 mg capsules and oral suspension are available for infants and children 1 year of age or older

 

 

[….]

 

 

For Iinfants below less than 1 year of age

 

In the absence of a suitable formulation, a pharmacy compounded preparation should preferentially be used as the syringe provided in the Tamiflu 12 mg/ml powder for oral suspension pack (with mg markings) does not allow for appropriate dose adjustments and commercially available syringes (with ml markings) may lead to unacceptable dosing inaccuracies (see section 6.6).

 

Treatment: The recommended treatment dose for infants less than 1 year of 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 these doses 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). The following age-adjusted dosing regimens are recommended for treatment of infants below 1 year of age:

 

Age

Recommended dose for 5 days

0 to 1 month*

2 mg/kg twice daily

> 3 months to 12 months