Fluenz Tetra nasal spray Influenza vaccine
Aug 5, 2020 19:20:25 GMT
Post by Admin on Aug 5, 2020 19:20:25 GMT
Fluenz Tetra nasal spray suspension Influenza vaccine (live attenuated, nasal)
1. Name of the medicinal product
Fluenz Tetra nasal spray suspension
Influenza vaccine (live attenuated, nasal)
2. Qualitative and quantitative composition
Reassortant influenza virus* (live attenuated) of the following four strains**:
A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09 - like strain
(A/Hawaii/66/2019, MEDI 326775)
107.0±0.5 FFU***
A/Hong Kong/2671/2019 (H3N2) - like strain
(A/Hong Kong/2671/2019, MEDI 325078)
107.0±0.5 FFU***
B/Washington/02/2019 - like strain
(B/Washington/02/2019, MEDI 323797)
107.0±0.5 FFU***
B/Phuket/3073/2013 - like strain
(B/Phuket/3073/2013, MEDI 306444)
107.0±0.5 FFU***
..................................................................................................................per 0.2 ml dose
* propagated in fertilised hens' eggs from healthy chicken flocks.
** produced in VERO cells by reverse genetic technology. This product contains genetically modified organisms (GMOs).
*** fluorescent focus units.
This vaccine complies with the WHO recommendation (Northern Hemisphere) and EU decision for the 2020/2021 season.
The vaccine may contain residues of the following substances: egg proteins (e.g. ovalbumin) and gentamicin.
The maximum amount of ovalbumin is less than 0.024 micrograms per 0.2 ml dose (0.12 micrograms per ml).
For the full list of excipients, see section 6.1.
www.medicines.org.uk/emc/medicine/29112
AstraZeneca UK Limited
Active ingredient
influenza vaccine
What is a Patient Information Leaflet and why is it useful?
The Patient Information Leaflet (PIL) is the leaflet included in the pack with a medicine. It is written for patients and gives information about taking or using a medicine. It is possible that the leaflet in your medicine pack may differ from this version because it may have been updated since your medicine was packaged.
4.3 Contraindications
- Hypersensitivity to the active substances, to any of the excipients listed in section 6.1 (e.g. gelatin), or to gentamicin (a possible trace residue).
- Severe allergic reaction (e.g. anaphylaxis) to eggs or to egg proteins (e.g. ovalbumin).
- Children and adolescents with clinical immunodeficiency due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids.
Fluenz Tetra is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency.
- Children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection.
4.8 Undesirable effects
Summary of the safety profile
The safety experience with trivalent Fluenz is relevant to the use of Fluenz Tetra because Fluenz Tetra (influenza vaccine-live attenuated, nasal) is identical to Fluenz with the only difference being the addition of a fourth strain (a second B strain) to Fluenz Tetra.
Safety data regarding use of Fluenz Tetra are based on data from Fluenz Tetra clinical studies in 2,231 children and adolescents 2 to 17 years of age, Fluenz clinical studies in over 29,000 children and adolescents 2 to 17 years of age and Fluenz post-authorisation safety studies in over 84,000 children and adolescents 2 to 17 years of age. Additional experience has occurred with marketed use of Fluenz.
In clinical studies, the safety profile of Fluenz Tetra was similar to the safety profile of Fluenz. The most common adverse reaction observed in clinical studies was nasal congestion/rhinorrhoea.
List of adverse reactions
Adverse reaction frequencies are reported as:
Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Immune system disorders
Uncommon: Hypersensitivity reactions (including facial oedema, urticaria and very rare anaphylactic reactions)
Metabolism and nutrition disorders
Very common: Decreased appetite
Nervous system disorders
Common: Headache
Respiratory, thoracic and mediastinal disorders
Very common: Nasal congestion/rhinorrhoea
Uncommon: Epistaxis
Skin and subcutaneous tissue disorders
Uncommon: Rash
Musculoskeletal and connective tissue disorders
Common: Myalgia
General disorders and administration site conditions
Very common: Malaise
Common: Pyrexia
Paediatric population
In an active-controlled clinical study (MI-CP111), an increased rate of hospitalisations (for any cause) through 180 days after final vaccination dose was observed in infants and toddlers 6-11 months of age (6.1% Fluenz versus 2.6% injectable influenza vaccine).
Most hospitalisations were due to gastrointestinal and respiratory tract infections and occurred more than 6 weeks post vaccination.
The rate of hospitalisations was not increased in Fluenz recipients 12 months and older.
In the same study, an increased rate of wheezing through 42 days was observed in infants and toddlers 6-23 months of age (5.9% Fluenz versus 3.8% injectable influenza vaccine).
The rate of wheezing was not increased in Fluenz recipients 24 months and older. Fluenz Tetra is not indicated for use in infants and toddlers younger than 24 months (see section 4.2).
Very rare reports of Guillain-Barré syndrome and exacerbation of symptoms of Leigh syndrome (mitochondrial encephalomyopathy) have also been observed in the post-marketing setting with Fluenz.
Fluenz safety
Chronic conditions
Although safety in children and adolescents with mild to moderate asthma has been established, data in children with other pulmonary diseases or with chronic cardiovascular, metabolic or renal diseases are limited.
In a study (D153-P515) of children 6 to 17 years of age with asthma (trivalent Fluenz: n=1,114, trivalent injectable influenza vaccine: n=1,115), there were no significant differences between treatment groups in the incidence of asthma exacerbations, mean peak expiratory flow rate, asthma symptom scores, or night-time awakening scores.
The incidence of wheezing within 15 days after vaccination was lower in Fluenz recipients relative to inactivated vaccine recipients (19.5% vs. 23.8%, P=0.02).
In a study of children and adolescents 9 to 17 years of age with moderate to severe asthma (trivalent Fluenz: n=24, placebo: n=24), the primary safety criterion, change in percent predicted forced expiratory volume in 1 second (FEV1) measured before and after vaccination, did not differ between treatment arms.
In studies of adults in which a high percentage of individuals had underlying chronic medical conditions, the safety profile of trivalent Fluenz was comparable to the safety profile observed in individuals without these conditions.
Fluenz Tetra immunogenicity
A multicentre, randomised, double-blind, active-controlled, non-inferiority study was conducted to assess the immunogenicity of Fluenz Tetra compared to Fluenz (active control) in children and adolescents 2-17 years of age.
A total of 2,312 children and adolescents were randomised by site at a 3:1:1 ratio to receive either Fluenz Tetra or one of two formulations of comparator vaccine Fluenz, each containing a B strain that corresponded to one of the two B strains in Fluenz Tetra (a B strain of the Yamagata lineage and a B strain of the Victoria lineage).
Immunogenicity was evaluated by comparing geometric mean titres (GMTs) of strain-specific serum haemagglutination inhibition (HAI) antibodies post dosing. Fluenz Tetra demonstrated immunologic non-inferiority to the two formulations of Fluenz as the upper bound for each of the four 95% CIs for the post-dose strain-specific GMT HAI antibody ratios was ≤ 1.5.
6. Pharmaceutical particulars
6.1 List of excipients
Sucrose
Dipotassium phosphate
Potassium dihydrogen phosphate
Gelatin (porcine, Type A)
Arginine hydrochloride
Monosodium glutamate monohydrate
Water for injections
Full report in the link below.
www.medicines.org.uk/emc/medicine/29112
www.medicines.org.uk/emc/files/pil.3296.pdf
Active ingredient
influenza vaccine
What is a Patient Information Leaflet and why is it useful?
The Patient Information Leaflet (PIL) is the leaflet included in the pack with a medicine. It is written for patients and gives information about taking or using a medicine. It is possible that the leaflet in your medicine pack may differ from this version because it may have been updated since your medicine was packaged.
4.3 Contraindications
- Hypersensitivity to the active substances, to any of the excipients listed in section 6.1 (e.g. gelatin), or to gentamicin (a possible trace residue).
- Severe allergic reaction (e.g. anaphylaxis) to eggs or to egg proteins (e.g. ovalbumin).
- Children and adolescents with clinical immunodeficiency due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids.
Fluenz Tetra is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency.
- Children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection.
4.8 Undesirable effects
Summary of the safety profile
The safety experience with trivalent Fluenz is relevant to the use of Fluenz Tetra because Fluenz Tetra (influenza vaccine-live attenuated, nasal) is identical to Fluenz with the only difference being the addition of a fourth strain (a second B strain) to Fluenz Tetra.
Safety data regarding use of Fluenz Tetra are based on data from Fluenz Tetra clinical studies in 2,231 children and adolescents 2 to 17 years of age, Fluenz clinical studies in over 29,000 children and adolescents 2 to 17 years of age and Fluenz post-authorisation safety studies in over 84,000 children and adolescents 2 to 17 years of age. Additional experience has occurred with marketed use of Fluenz.
In clinical studies, the safety profile of Fluenz Tetra was similar to the safety profile of Fluenz. The most common adverse reaction observed in clinical studies was nasal congestion/rhinorrhoea.
List of adverse reactions
Adverse reaction frequencies are reported as:
Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Immune system disorders
Uncommon: Hypersensitivity reactions (including facial oedema, urticaria and very rare anaphylactic reactions)
Metabolism and nutrition disorders
Very common: Decreased appetite
Nervous system disorders
Common: Headache
Respiratory, thoracic and mediastinal disorders
Very common: Nasal congestion/rhinorrhoea
Uncommon: Epistaxis
Skin and subcutaneous tissue disorders
Uncommon: Rash
Musculoskeletal and connective tissue disorders
Common: Myalgia
General disorders and administration site conditions
Very common: Malaise
Common: Pyrexia
Paediatric population
In an active-controlled clinical study (MI-CP111), an increased rate of hospitalisations (for any cause) through 180 days after final vaccination dose was observed in infants and toddlers 6-11 months of age (6.1% Fluenz versus 2.6% injectable influenza vaccine).
Most hospitalisations were due to gastrointestinal and respiratory tract infections and occurred more than 6 weeks post vaccination.
The rate of hospitalisations was not increased in Fluenz recipients 12 months and older.
In the same study, an increased rate of wheezing through 42 days was observed in infants and toddlers 6-23 months of age (5.9% Fluenz versus 3.8% injectable influenza vaccine).
The rate of wheezing was not increased in Fluenz recipients 24 months and older. Fluenz Tetra is not indicated for use in infants and toddlers younger than 24 months (see section 4.2).
Very rare reports of Guillain-Barré syndrome and exacerbation of symptoms of Leigh syndrome (mitochondrial encephalomyopathy) have also been observed in the post-marketing setting with Fluenz.
Fluenz safety
Chronic conditions
Although safety in children and adolescents with mild to moderate asthma has been established, data in children with other pulmonary diseases or with chronic cardiovascular, metabolic or renal diseases are limited.
In a study (D153-P515) of children 6 to 17 years of age with asthma (trivalent Fluenz: n=1,114, trivalent injectable influenza vaccine: n=1,115), there were no significant differences between treatment groups in the incidence of asthma exacerbations, mean peak expiratory flow rate, asthma symptom scores, or night-time awakening scores.
The incidence of wheezing within 15 days after vaccination was lower in Fluenz recipients relative to inactivated vaccine recipients (19.5% vs. 23.8%, P=0.02).
In a study of children and adolescents 9 to 17 years of age with moderate to severe asthma (trivalent Fluenz: n=24, placebo: n=24), the primary safety criterion, change in percent predicted forced expiratory volume in 1 second (FEV1) measured before and after vaccination, did not differ between treatment arms.
In studies of adults in which a high percentage of individuals had underlying chronic medical conditions, the safety profile of trivalent Fluenz was comparable to the safety profile observed in individuals without these conditions.
Fluenz Tetra immunogenicity
A multicentre, randomised, double-blind, active-controlled, non-inferiority study was conducted to assess the immunogenicity of Fluenz Tetra compared to Fluenz (active control) in children and adolescents 2-17 years of age.
A total of 2,312 children and adolescents were randomised by site at a 3:1:1 ratio to receive either Fluenz Tetra or one of two formulations of comparator vaccine Fluenz, each containing a B strain that corresponded to one of the two B strains in Fluenz Tetra (a B strain of the Yamagata lineage and a B strain of the Victoria lineage).
Immunogenicity was evaluated by comparing geometric mean titres (GMTs) of strain-specific serum haemagglutination inhibition (HAI) antibodies post dosing. Fluenz Tetra demonstrated immunologic non-inferiority to the two formulations of Fluenz as the upper bound for each of the four 95% CIs for the post-dose strain-specific GMT HAI antibody ratios was ≤ 1.5.
6. Pharmaceutical particulars
6.1 List of excipients
Sucrose
Dipotassium phosphate
Potassium dihydrogen phosphate
Gelatin (porcine, Type A)
Arginine hydrochloride
Monosodium glutamate monohydrate
Water for injections
Full report in the link below.
www.medicines.org.uk/emc/medicine/29112
www.medicines.org.uk/emc/files/pil.3296.pdf
1. Name of the medicinal product
Fluenz Tetra nasal spray suspension
Influenza vaccine (live attenuated, nasal)
2. Qualitative and quantitative composition
Reassortant influenza virus* (live attenuated) of the following four strains**:
A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09 - like strain
(A/Hawaii/66/2019, MEDI 326775)
107.0±0.5 FFU***
A/Hong Kong/2671/2019 (H3N2) - like strain
(A/Hong Kong/2671/2019, MEDI 325078)
107.0±0.5 FFU***
B/Washington/02/2019 - like strain
(B/Washington/02/2019, MEDI 323797)
107.0±0.5 FFU***
B/Phuket/3073/2013 - like strain
(B/Phuket/3073/2013, MEDI 306444)
107.0±0.5 FFU***
..................................................................................................................per 0.2 ml dose
* propagated in fertilised hens' eggs from healthy chicken flocks.
** produced in VERO cells by reverse genetic technology. This product contains genetically modified organisms (GMOs).
*** fluorescent focus units.
This vaccine complies with the WHO recommendation (Northern Hemisphere) and EU decision for the 2020/2021 season.
The vaccine may contain residues of the following substances: egg proteins (e.g. ovalbumin) and gentamicin.
The maximum amount of ovalbumin is less than 0.024 micrograms per 0.2 ml dose (0.12 micrograms per ml).
For the full list of excipients, see section 6.1.
www.medicines.org.uk/emc/medicine/29112