Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Actavis Group PTC ehf., Reykjavíkurvegi 76-78, 220 Hafnarfjörður, Iceland
Ebilfumin is indicated in adults and children including full-term neonates 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.
Post-exposure prevention in individuals 1 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 Ebilfumin 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.
Ebilfumin is indicated for post-exposure prevention of influenza in infants less than 1 year of age during a pandemic influenza outbreak (see section 5.2).
Ebilfumin 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).
Ebilfumin hard capsules are bioequivalent formulations. 75 mg doses can be administered as either:
Commercially manufactured oseltamivir 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.
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.
The recommended dose for prevention of influenza during a community outbreak is 75 mg oseltamivir once daily for up to 6 weeks.
Ebilfumin 30 mg, 45 mg and 75 mg capsules are available for infants and children 1 year of age or older
Treatment:
The following weight-adjusted dosing regimens are recommended for treatment of infants and children 1 year of age or older:
| Body Weight | Recommended dose for 5 days |
|---|---|
| 10 kg to 15 kg | 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 |
Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza.
Post-exposure prevention:
The recommended post-exposure prevention dose of Ebilfumin is:
| Body Weight | Recommended dose for 10 days |
|---|---|
| 10 kg to 15 kg | 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 |
Prevention during an influenza epidemic in the community:
Prevention during an influenza epidemic has not been studied in children below 12 years of age.
Treatment:
The recommended treatment dose for infants 0-12 months of age is 3 mg/kg twice daily. This is based upon pharmacokinetic and safety data indicating that this dose 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 in older children and adults (see section 5.2). The following dosing regimen is recommended for treatment of infants 0-12 months of age:
Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza.
This dosing recommendation is not intended for premature infants, i.e. those with a postconceptual age less than 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 regimen is recommended for infants 0–12 months of age (see Section 5.2 for exposure simulation):
| Age | Recommended dose for 10 days |
|---|---|
| 0-12 months | 3 mg/kg once daily |
This dosing recommendation is not intended for premature infants, i.e. those with a postconceptual age less than 36 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 0-12 months of age.
For instructions on preparing the extemporaneousformulation, see section 6.6.
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.
Treatment of influenza: Dose adjustment is recommended for adults and adolescents (13 to 17 years of age) 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 twice daily |
| >10 to 30 (ml/min) | 30 mg once daily |
| ≤10 (ml/min) | Not recommended (no data available) |
| Haemodialysis patients | 30 mg after each haemodialysis session |
| Peritoneal dialysis patients* | 30 mg 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 and adolescents (13 to 17 years of age) 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 once daily |
| >10 to 30 (ml/min) | 30 mg every second day |
| ≤10 (ml/min) | Not recommended (no data available) |
| Haemodialysis patients | 30 mg after every second haemodialysis session |
| Peritoneal dialysis patients* | 30 mg 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.
There is insufficient clinical data available in infants and children (12 years of age and younger) with renal impairment to be able to make any dosing recommendation.
No dose adjustment is required, unless there is evidence of moderate or severe renal impairment.
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.
Longer duration of seasonal prophylaxis up to 12 weeks has been evaluated in immunocompromised patients (see sections 4.4, 4.8 and 5.1).
Oral use.
Patients who are unable to swallow capsules may receive appropriate extemporaneous formulation, see section 6.6 for preparation.
Reports of overdoses with oseltamivir have been received from clinical trials and during postmarketing 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 oseltamivir, described in section 4.8 Undesirable effects.
No specific antidote is known.
Overdose has been reported more frequently for children than adults and adolescents. Caution should be exercised when preparing oseltamivir oral suspension and when administering oseltamivir products to children.
6 years.
Shelf life of 3 weeks when stored below 25°C.
Shelf life of 6 weeks at 2°C-8°C.
Store below 25°C.
For storage conditions of the pharmacy compounded suspension, see section 6.3.
PVC/PE/PVdC/Al blisters or HDPE containers with LDPE lid (and a desiccant).
Pack-size 10 capsules.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Commercially manufactured oseltamivir 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. In the event that commercially manufactured oseltamivir powder for oral suspension is not available, the pharmacist may compound a suspension (6 mg/ml) from Ebilfumin capsules or patients can prepare the suspension from capsules at home.
The pharmacy preparation should be preferred to home preparation. Detailed information on the home preparation can be found in the package leaflet of Ebilfumin capsules under “Making liquid Ebilfumin at home”.
Syringes of appropriate volume and grading should be provided for administering the pharmacy compounded suspension as well as for the procedures involved in the home preparation. In both cases, the correct volumes should preferably be marked on the syringes.
Adults, adolescents and infants and children 1 year of age or older who are unable to swallow intact capsules:
This procedure describes the preparation of a 6 mg/ml suspension that will provide one patient with enough medicine for a 5-day course of treatment or a 10-day course of prophylaxis.
The pharmacist may compound a 6 mg/ml suspension from Ebilfumin 30 mg, 45 mg or 75 mg capsules using water containing 0.05% 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. To allow for accurate volume withdrawal of up to 10 doses (2 withdrawals per daily treatment dose for 5 days), the column indicating measurement loss is to be considered for compounding.
Volume of pharmacy compounded 6 mg/ml suspension prepared based upon the patient’s weight:
| Body weight (kg) | Total volume to compound per patient weight (ml) Measurement loss not considered | Total volume to compound per patient weight (ml) Measurement loss considered |
|---|---|---|
| 10 kg to 15 kg | 50 ml | 60 ml or 75 ml* |
| >15 kg to 23 kg | 75 ml | 90 ml or 100 ml* |
| >23 kg to 40 kg | 100 ml | 125 ml |
| >40 kg | 125 ml | 137.5 ml (or 150 ml)* |
* Depending on the capsule strength used.
Second, determine the number of capsules and the amount of vehicle (water containing 0.05% w/v sodium benzoate added as a preservative) that is needed to prepare the total volume (calculated from the table above) of pharmacy compounded 6 mg/ml suspension as shown in the table below:
Number of capsules and amount of vehicle needed to prepare the total volume of a pharmacy compounded 6 mg/ml suspension:
| Total volume of compounded suspension to be prepared | Required number of Ebilfumin capsules (mg of oseltamivir) | Required volume of vehicle | ||
|---|---|---|---|---|
| 75 mg | 45 mg | 30 mg | ||
| 60 ml | Please use alternative capsule strength* | 8 capsules (360 mg) | 12 capsules (360 mg) | 59.5 ml |
| 75 ml | 6 capsules (450 mg) | 10 capsules (450 mg) | 15 capsules (450 mg) | 74 ml |
| 90 ml | Please use alternative capsule strength* | 12 capsules (540 mg) | 18 capsules (540 mg) | 89 ml |
| 100 ml | 8 capsules (600 mg) | Please use alternative capsule strength* | 20 capsules (600 mg) | 98.5 ml |
| 125 ml | 10 capsules (750 mg) | Please use alternative capsule strength* | 25 capsules (750 mg) | 123.5 ml |
| 137.5 ml | 11 capsules (825 mg) | Please use alternative capsule strength* | Please use alternative capsule strength* | 136 ml |
* There is no combination of this capsule strength that can be used to achieve the target concentration; therefore, please use an alternative capsule strength.
Third, follow the procedure below for compounding the 6 mg/ml suspension from Ebilfumin capsules:
Place a pharmacy label on the bottle that includes the patient’s name, dosing instructions, use by date, name of medicinal product 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 6 mg/ml suspension prepared from Ebilfumin capsules for infants and children 1 year of age or older:
| Body weight (kg) | Dose (mg) | Volume per dose 6 mg/ml | Treatment dose (for 5 days) | Prophylaxis dose (for 10 days) |
|---|---|---|---|---|
| 10 kg to 15 kg | 30 mg | 5 ml | 5 ml twice daily | 5 ml once daily |
| >15 kg to 23 kg | 45 mg | 7.5 ml | 7.5 ml twice daily | 7.5 ml once daily |
| >23 kg to 40 kg | 60 mg | 10 ml | 10 ml twice daily | 10 ml once daily |
| >40 kg | 75 mg | 12.5 ml | 12.5 ml twice daily | 12.5 ml once daily |
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 table 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.
Infants less than 1 year of age:
This procedure describes the preparation of a 6 mg/ml suspension 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 6 mg/ml suspension from Ebilfumin 30 mg, 45 mg or 75 mg capsules using water containing 0.05% 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. To allow for accurate volume withdrawal of up to 10 doses (2 withdrawals per daily treatment dose for 5 days), the column indicating measurement loss is to be considered for compounding.
Volume of pharmacy compounded 6 mg/ml suspension prepared based upon the patient’s weight:
| Body weight (kg) | Total volume to compound per patient weight (ml) Measurement loss not considered | Total volume to compound per patient weight (ml) Measurement loss considered |
|---|---|---|
| ≤7 kg | up to 40 ml | 50 ml |
| >7 kg to 10 kg | 50 ml | 60 ml or 75 ml* |
* Depending on the capsule strength used.
Second, determine the number of capsules and the amount of vehicle (water containing 0.05% w/v sodium benzoate added as a preservative) that is needed to prepare the total volume (calculated from the table above) of pharmacy compounded 6 mg/ml suspension as shown in the table below:
Number of capsules and amount of vehicle needed to prepare the total volume of a pharmacy compounded 6 mg/ml suspension:
| Total volume of compounded suspension to be prepared | Required number of Ebilfumin capsules (mg of oseltamivir) | Required volume of vehicle | ||
|---|---|---|---|---|
| 75 mg | 45 mg | 30 mg | ||
| 50 ml | 4 capsules (300 mg) | Please use alternative capsule strength* | 10 capsules (300 mg) | 49.5 ml |
| 60 ml | Please use alternative capsule strength* | 8 capsules (360 mg) | 12 capsules (360 mg) | 59.5 ml |
| 75 ml | 6 capsules (450 mg) | 10 capsules (450 mg) | 15 capsules (450 mg) | 74 ml |
* There is no combination of this capsule strength that can be used to achieve the target concentration; therefore, please use an alternative capsule strength.
Third, follow the procedure below for compounding the 6 mg/ml suspension from Ebilfumin capsules:
Place a pharmacy label on the bottle that includes the patient’s name, dosing instructions, use by date, name of medicinal product 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 6 mg/ml suspension prepared from Ebilfumin 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 | 3.5 ml 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.
When commercially manufactured oseltamivir powder for oral suspension is not available, a pharmacy compounded suspension prepared from Ebilfumin capsules must be used (see detailed instructions above). If the commercially manufactured oseltamivir powder for oral suspension and the pharmacy compounded suspension is also not available, Ebilfumin suspension may be prepared at home.
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 Ebilfumin suspension involves additional steps. Detailed instructions can be found in the package leaflet of Ebilfumin capsules under “Making liquid Ebilfumin at home”.
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