1. Name Of The Medicinal Product
Tamiflu 30 mg hard capsule.
Tamiflu 45 mg hard capsule.
2. Qualitative And Quantitative Composition
Tamiflu 30 mg hard capsule: Each hard capsule contains oseltamivir phosphate equivalent to 30 mg of oseltamivir.
Tamiflu 45 mg hard capsule: Each hard capsule contains oseltamivir phosphate equivalent to 45 mg of oseltamivir.
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Hard capsule
Tamiflu 30 mg hard 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 capsule: 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.
4. Clinical Particulars
4.1 Therapeutic Indications
Treatment of influenza
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 below 12 months of age during a pandemic influenza outbreak (see section 5.2).
Prevention of influenza
- Post-exposure prevention in individuals one year of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community.
- The appropriate use of Tamiflu for prevention of influenza should be determined on a case by case basis by the circumstances and the population requiring protection. In exceptional situations (e.g., in case of a mismatch between the circulating and vaccine virus strains, and a pandemic situation) seasonal prevention could be considered in individuals one year of age or older.
- Tamiflu is indicated for post-exposure prevention of influenza in infants below 12 months of age during a pandemic influenza outbreak (see section 5.2).
Tamiflu is not a substitute for influenza vaccination.
The use of antivirals for the treatment and prevention of influenza should be determined on the basis of official recommendations. Decisions regarding the use of oseltamivir for treatment and prophylaxis should take into consideration what is known about the characteristics of the circulating influenza viruses, available information on influenza drug susceptibility patterns for each season and the impact of the disease in different geographical areas and patient populations (see section 5.1).
Based on limited pharmacokinetic and safety data, Tamiflu can be used in infants below 12 months of age for treatment during a pandemic influenza outbreak. 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
Tamiflu 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.
Adults, adolescents or children (1 year of age or older) who are unable to swallow capsules may receive appropriate doses of Tamiflu suspension.
For infants below 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 below 4.2).
Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza.
• For adolescents (13 to 17 years of age) and adults: The recommended oral dose is 75 mg oseltamivir twice daily for 5 days.
• For infants older than 1 year of age and for children 2 to 12 years of age: Tamiflu 30 mg and 45 mg capsules and oral suspension are available.
The following weight-adjusted dosing regimens are recommended for children 1 year of age and older:
Body Weight
|
Recommended dose for 5 days
|
|
30 mg twice daily
|
> 15 kg to 23 kg
|
45 mg twice daily
|
> 23 kg to 40 kg
|
60 mg twice daily
|
> 40 kg
|
75 mg twice daily
|
Children who are able to swallow capsules may receive treatment with Tamiflu capsules (30 mg, 45 mg, 75 mg) twice daily for 5 days as an alternative to the recommended dose of Tamiflu suspension.
• For infants below 12 months of age: The recommended treatment dose for infants less than 12 months is between 2 mg/kg twice daily and 3 mg/kg twice daily during a pandemic influenza outbreak. This is based upon limited pharmacokinetic 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 weight-adjusted dosing regimens are recommended for treatment of infants below 1 year of age:
Age
|
Recommended dose for 5 days
|
> 3 months to 12 months
|
3 mg/kg twice daily
|
> 1 month to 3 months
|
2.5 mg/kg twice daily
|
0 to 1 month*
|
2 mg/kg twice daily
|
* 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.
These age-based dosing recommendations are not intended for premature infants, i.e. those with a postmenstrual age less than 37 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
• For adolescents (13 to 17 years of age) and adults: The recommended dose for prevention of influenza following close contact with an infected individual is 75 mg oseltamivir once daily for 10 days. Therapy should begin as soon as possible within two days of exposure to an infected individual.
• For infants older than 1 year of age and for children 2 to 12 years of age: Tamiflu 30 mg and 45 mg capsules and oral suspension are available.
The recommended post-exposure prevention dose of Tamiflu is:
Body Weight
|
Recommended dose for 10 days
|
|
30 mg once daily
|
> 15 kg to 23 kg
|
45 mg once daily
|
> 23 kg to 40 kg
|
60 mg once daily
|
> 40 kg
|
75 mg once daily
|
Children who are able to swallow capsules may receive prevention Tamiflu capsules (30 mg, 45 mg, 75 mg) once daily for 10 days as an alternative to the recommended dose of Tamiflu suspension.
• For infants below 12 months of age: The recommended prophylaxis dose for infants less than 12 months during a pandemic influenza outbreak is half of the daily treatment dose. This is based upon clinical data in children > 1 year of age and adults showing that a prophylaxis dose equivalent to half the daily treatment dose is clinically efficacious for the prevention of influenza. The following weight-adjusted dosing prophylaxis regimens are recommended for infants below 1 year of age:
Age
|
Recommended dose for 10 days
|
> 3 months to 12 months
|
3 mg/kg once daily
|
> 1 month to 3 months
|
2.5 mg/kg once daily
|
0 to 1 month*
|
2 mg/kg once daily
|
* 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 prophylaxis versus any potential risk to the infant.
These age-based dosing recommendations are not intended for premature infants, i.e. those with a postmenstrual age less than 37 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
The recommended dose for prevention of influenza during a community outbreak is 75 mg oseltamivir once daily for up to 6 weeks.
Extemporaneous formulation
|
When Tamiflu powder for oral suspension is not available
When commercially manufactured Tamiflu powder for oral suspension is not available, patients who are unable to swallow capsules may receive appropriate doses of Tamiflu prepared in a pharmacy or prepared at home.
For infants below 12 months, the pharmacy preparation should be preferred to home preparation. Detailed information on the home preparation can be found in section 3 of the package leaflet of Tamiflu capsules.
Pharmacy compounding
• Adults and children greater than 1 year who are unable to swallow intact capsules
This procedure describes the preparation of a 15 mg/ml solution that will provide one patient with enough medication for a 5-day course of treatment or a 10-day course of prophylaxis.
The pharmacist may compound a suspension (15 mg/ml) from Tamiflu 30 mg, 45 mg or 75 mg capsules using water containing 0.1% w/v sodium benzoate added as a preservative.
First, calculate the Total Volume needed to be compounded and dispensed to provide a 5-day course of treatment or a 10=day course of prophylaxis for the patient. The Total Volume required is determined by the weight of the patient according to the recommendation in the table below:
Volume of Compounded Suspension (15 mg/ml) Prepared Based Upon the Patient's Weight
Body Weight
(kg)
|
Total Volume to Compound per Patient Weight
(ml)
|
10 to 15 kg
|
30 ml
|
> 15 to 23 kg
|
40 ml
|
> 23 to 40 kg
|
50 ml
|
> 40 kg
|
60 ml
|
Second, determine the number of capsules and the amount of vehicle (water containing 0.1% w/v sodium benzoate added as a preservative) that is needed to prepare the Total Volume (calculated from the table above: 30 ml, 40 ml, 50 ml or 60 ml) of compounded suspension (15 mg/ml) as shown in the table below:
Number of Capsules and Amount of Vehicle Needed to Prepare the Total Volume of a Compounded Suspension (15 mg/ml)
Total Volume of Compounded Suspension to be Prepared
|
Required Number of Tamiflu Capsules
(mg of oseltamivir)
|
Required Volume of Vehicle
|
|
|
75 mg
|
45 mg
|
30 mg
|
|
|
30 ml
|
6 capsules
(450 mg)
|
10 capsules
(450 mg)
|
15 capsules
(450 mg)
|
29 ml
|
40 ml
|
8 capsules
(600 mg)
|
Please use alternative capsule strength*
|
20 capsules
(600 mg)
|
38.5 ml
|
50 ml
|
10 capsules
(750 mg)
|
Please use alternative capsule strength*
|
25 capsules
(750 mg)
|
48 ml
|
60 ml
|
12 capsules
(900 mg)
|
20 capsules
(900 mg)
|
30 capsules
(900 mg)
|
57 ml
|
* No integral number of capsules can be used to achieve the target concentration; therefore, please use either the 30 mg or 75 mg capsules.
Third, follow the procedure below for compounding the suspension (15 mg/ml) from Tamiflu capsules:
1. Carefully separate the capsule body and cap and transfer the contents of the required number of Tamiflu capsules into a clean mortar.
2. Triturate the granules to a fine powder.
3. Add one-third (1/3) of the specified amount of vehicle (water containing 0.1% w/v sodium benzoate added as a preservative) and triturate the powder until a uniform suspension is achieved.
4. Transfer the suspension to an amber glass or amber polyethyleneterephthalate (PET) bottle. A funnel may be used to eliminate any spillage.
5. Add another one-third (1/3) of the vehicle to the mortar, rinse the pestle and mortar by a triturating motion and transfer the vehicle into the bottle.
6. Repeat the rinsing (Step 5) with the remainder of the vehicle.
7. Close the bottle using a child-resistant cap.
8. Shake well to completely dissolve the active drug and to ensure homogeneous distribution of the dissolved drug in the resulting suspension.
(Note: Undissolved residue may be visible but is comprised of inert ingredients of Tamiflu capsules, which are insoluble. However, the active drug, oseltamivir phosphate, readily dissolves in the specified vehicle and therefore forms a uniform solution.)
9. Put an ancillary label on the bottle indicating “Shake Gently Before Use”.
10. Instruct the parent or caregiver that after the patient has completed the full course of therapy any remaining solution must be discarded. It is recommended that this information be provided by affixing an ancillary label to the bottle or adding a statement to the pharmacy label instructions.
11. Place an appropriate expiration date label according to storage condition (see below).
Storage of the pharmacy-compounded suspension (15 mg/ml)
Room temperature storage conditions: Stable for 3 weeks (21 days) when stored at room temperature “do not store above 25 °C”.
Refrigerated storage conditions: Stable for 6 weeks when stored at 2 °C - 8 °C.
Place a pharmacy label on the bottle that includes the patient's name, dosing instructions, use by date, drug name and any other required information to be in compliance with local pharmacy regulations. Refer to the table below for the proper dosing instructions.
Dosing Chart for Pharmacy-Compounded Suspension from Tamiflu Capsules for Children One Year of Age or Older
Body Weight
(kg)
|
Dose
(mg)
|
Volume per Dose
15 mg/ml
|
Treatment Dose
(for 5 days)
|
Prophylaxis Dose
(for 10 days)
|
10 kg to 15 kg
|
30 mg
|
2 ml
|
2 ml twice daily
|
2 ml once daily
|
> 15 to 23 kg
|
45 mg
|
3 ml
|
3 ml twice daily
|
3 ml once daily
|
> 23 to 40 kg
|
60 mg
|
4 ml
|
4 ml twice daily
|
4 ml once daily
|
> 40 kg
|
75 mg
|
5 ml
|
5 ml twice daily
|
5 ml once daily
|
Note: This compounding procedure results in a 15 mg/ml suspension, which is different from the commercially available Tamiflu powder for oral suspension.
Dispense the suspension with a graduated oral syringe for measuring small amounts of suspension. If possible, mark or highlight the graduation corresponding to the appropriate dose (2 ml, 3 ml, 4 ml or 5 ml) 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.
• Infants less than 1 year of age
This procedure describes the preparation of a 10 mg/ml solution that will provide one patient with enough medication for a 5-day course of treatment or a 10-day course of prophylaxis.
The pharmacist may compound a suspension (10 mg/ml) from Tamiflu 30 mg, 45 mg or 75 mg capsules using water containing 0.1% w/v sodium benzoate added as a preservative.
First, calculate the Total Volume needed to be compounded and dispensed for each patient. The Total Volume required is determined by the weight of the patient according to the recommendation in the table below:
Volume of Compounded Suspension (10 mg/ml) Prepared Based Upon the Patient's Weight
Body Weight
(kg)
|
Total Volume to Compound per Patient Weight
(ml)
|
|
30 ml
|
> 7 to 12 kg
|
45 ml
|
Second, determine the number of capsules and the amount of vehicle (water containing 0.1% w/v sodium benzoate added as a preservative) that is needed to prepare the Total Volume (calculated from the table above: 30 ml, 45 ml) of compounded suspension (10 mg/ml) as shown in the table below:
Number of Capsules and Amount of Vehicle Needed to Prepare the Total Volume of a Compounded Suspension (10 mg/ml)
Total Volume of Compounded Suspension to be Prepared
|
Required Number of Tamiflu Capsules
(mg of oseltamivir)
|
Required Volume of Vehicle
|
|
|
75 mg
|
45 mg
|
30 mg
|
|
|
30 ml
|
4 capsules
(300 mg)
|
Please use alternative capsule strength*
|
10 capsules
(300 mg)
|
29.5 ml
|
45 ml
|
6 capsules
(450 mg)
|
10 capsules
(450 mg)
|
15 capsules
(450 mg)
|
44 ml
|
* No integral number of capsules can be used to achieve the target concentration; therefore, please use either the 30 mg or 75 mg capsules.
Third, follow the procedure below for compounding the suspension (10 mg/ml) from Tamiflu capsules:
1. Carefully separate the capsule body and cap and transfer the contents of the required number of Tamiflu capsules into a clean mortar.
2. Triturate the granules to a fine powder.
3. Add one-third (1/3) of the specified amount of vehicle and triturate the powder until a uniform suspension is achieved.
4. Transfer the suspension to an amber glass or amber polyethyleneterephthalate (PET) bottle. A funnel may be used to eliminate any spillage.
5. Add another one-third (1/3) of the vehicle to the mortar, rinse the pestle and mortar by a triturating motion and transfer the vehicle into the bottle.
6. Repeat the rinsing (Step 5) with the remainder of the vehicle.
7. Close the bottle using a child-resistant cap.
8. Shake well to completely dissolve the active drug and to ensure homogeneous distribution of the dissolved drug in the resulting suspension.
(Note: Undissolved residue may be visible but is comprised of inert ingredients of Tamiflu capsules, which are insoluble. However, the active drug, oseltamivir phosphate, readily dissolves in the specified vehicle and therefore forms a uniform solution.)
9. Put an ancillary label on the bottle indicating “Shake Gently Before Use”.
10. Instruct the parent or caregiver that after the patient has completed the full course of therapy any remaining solution must be discarded. It is recommended that this information be provided by affixing an ancillary label to the bottle or adding a statement to the pharmacy label instructions.
11. Place an appropriate expiration date label according to storage condition (see below).
Storage of the pharmacy-compounded suspension (10 mg/ml)
Room temperature storage conditions: Stable for 3 weeks (21 days) when stored at room temperature “do not store above 25 °C”.
Refrigerated storage conditions: Stable for 6 weeks when stored at 2 °C - 8 °C.
Place a pharmacy label on the bottle that includes the patient's name, dosing instructions, use by date, drug name and any other required information to be in compliance with local pharmacy regulations. Refer to the table below for the proper dosing instructions.
Dosing Chart for Pharmacy-Compounded Suspension (10 mg/ml) from Tamiflu Capsules for Infants Less Than One Month of Age
Body Weight
(rounded to the nearest 0.5 kg)
|
Treatment Dose
(for 5 days)
|
Prophylaxis Dose
(for 10 days)
|
3 kg
|
0.60 ml twice daily
|
0.60 ml once daily
|
3.5 kg
|
0.70 ml twice daily
|
0.70 ml once daily
|
4 kg
|
0.80 ml twice daily
|
0.80 ml once daily
|
4.5 kg
|
0.90 ml twice daily
|
0.90 ml once daily
|
Dosing Chart for Pharmacy-Compounded Suspension (10 mg/ml) from Tamiflu Capsules for Infants One to Twelve Months of Age
Body Weight
(rounded to the nearest 0.5 kg)
|
Treatment Dose
(for 5 days)
|
Prophylaxis Dose
(for 10 days)
|
4 kg
|
1.00 ml twice daily
|
1.00 ml once daily
|
4.5 kg
|
1.10 ml twice daily
|
1.10 ml once daily
|
5 kg
|
1.30 ml twice daily
|
1.30 ml once daily
|
5.5 kg
|
1.40 ml twice daily
|
1.40 ml once daily
|
6 kg
|
1.50 ml twice daily
|
1.50 ml once daily
|
7 kg
|
2.10 ml twice daily
|
2.10 ml once daily
|
8 kg
|
2.40 ml twice daily
|
2.40 ml once daily
|
9 kg
|
2.70 ml twice daily
|
2.70 ml once daily
|
|
3.00 ml twice daily
|
3.00 ml once daily
|
Note: This compounding procedure results in a 10 mg/ml suspension, which is different from the commercially available Tamiflu powder for oral suspension.
Dispense the suspension with a graduated oral syringe for measuring small amounts of suspension. If possible, mark or highlight the graduation corresponding to the appropriate dose 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 preparation from Tamiflu capsules can be used (detailed instructions above in section 4.2). If the pharmacy preparation is not available either, Tamiflu doses may be prepared at home. The pharmacy preparation is the preferred option in infants below 12 months of age.
When appropriate capsule strengths are available, 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 involves additional steps. Detailed instructions can be found in section 3 in the package leaflet of Tamiflu capsules.
Special populations
Hepatic impairment
No dose adjustment is required either for treatment or for prevention in patients with hepatic dysfunction. No studies have been carried out in paediatric patients with hepatic disorder.
Renal impairment
Treatment of influenza: Dose adjustment is recommended for adults with moderate or severe renal impairment. Recommended doses are detailed in the table below.
Creatinine clearance
|
Recommended dose for treatment
|
> 60 (ml/min)
|
75 mg twice daily
|
> 30 to 60 (ml/min)
|
30 mg (suspension or capsules) twice daily
|
> 10 to 30 (ml/min)
|
30 mg (suspension or capsules) once daily
|
|
Not recommended (no data available)
|
Hemodialysis patients
|
30 mg after each hemodialysis session
|
Peritoneal dialysis patients*
|
30 mg (suspension or capsules) single dose
|
* Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients; the clearance of oseltamivir carboxylate is expected to be higher when automated peritoneal dialysis (APD) mode is used. Treatment mode can be switched from APD to CAPD if considered necessary by a nephrologist.
Prevention of influenza: Dose adjustment is recommended for adults with moderate or severe renal impairment as detailed in the table below.
Creatinine clearance
|
Recommended dose for prevention
|
> 60 (ml/min)
|
75 mg once daily
|
> 30 to 60 (ml/min)
|
30 mg (suspension or capsules) once daily
|
> 10 to 30 (ml/min)
|
30 mg (suspension or capsules) every second day
|
|
Not recommended (no data available)
|
Hemodialysis patients
|
30 mg after every second hemodialysis session
|
Peritoneal dialysis patients*
|
30 mg (suspension or capsules) once weekly
|
* Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients; the clearance of oseltamivir carboxylate is expected to be higher when automated peritoneal dialysis (APD) mode is used. Treatment mode can be switched from APD to CAPD if considered necessary by a nephrologist.
Elderly
No dose adjustment is required, unless there is evidence of severe renal impairment.
Children
There is insufficient clinical data available in children with renal impairment to be able to make any dosing recommendation.
Immunocompromised patients
Longer duration of seasonal prophylaxis up to 12 weeks has been evaluated in immunocompromised patients (see sections 4.4, 4.8 and 5.1).
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special Warnings And Precautions For Use
Oseltamivir is effective only against illness caused by influenza viruses. There is no evidence for efficacy of oseltamivir in any illness caused by agents other than influenza viruses.
No information is available regarding the safety and efficacy of oseltamivir in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalisation.
The efficacy of oseltamivir in either treatment or prophylaxis of influenza in immunocompromised patients has not been firmly established (see section 5.1).
Efficacy of oseltamivir in the treatment of subjects with chronic cardiac disease and/or respiratory disease has not been established. No difference in the incidence of complications was observed between the treatment and placebo groups in this population (see section 5.1).
No data allowing a dose recommendation for premature children (< 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.
Tamiflu is not a substitute for influenza vaccination. Use of Tamiflu must not affect the evaluation of individuals for annual influenza vaccination. The protection against influenza lasts only as long as Tamiflu is administered. Tamiflu should be used for the treatment and prevention of influenza only when reliable epidemiological data indicate that influenza virus is circulating in the community.
Susceptibility of circulating influenza virus strains to oseltamivir has been shown to be highly variable (see section 5.1). Therefore, prescribers should take into account the most recent information available on oseltamivir susceptibility patterns of the currently circulating viruses when deciding whether to use Tamiflu.
Severe renal impairment
Dose adjustment is recommended for both treatment and prevention in adults with sev
