SKYCellflu Quadrivalent Prefilled Syringe

Inactivated quadrivalent sub-unit influenza vaccine [(surface antigens, (hemagglutinin & neuraminidase)].

Influenza virus surface antigens (hemagglutinin and neuraminidase)*, inactivated, of the following strains: [A/Guangdong-Maonan/SWL1536/2019, CNIC-1909 (H1N1)] 15 μg HA**, [A/Hong Kong/2671/2019, NIB-121 (H3N2)] 15 μg HA**, [B/Washington/02/2019] 15 μg HA**, [B/Phuket/3073/2013] 15 μg HA** per 0.5 mL dose.
*propagated in Madin Darby Canine Kidney (MDCK) cells.
**hemagglutinin.
The vaccine complies with the WHO recommendation (northern hemisphere) for the 2020-2021 season.
Excipients/Inactive Ingredients: Sodium chloride, Potassium chloride, Potassium dihydrogen phosphate, Disodium phosphate dihydrate, Magnesium chloride hexahydrate, Calcium chloride dihydrate, Water for injection.

Pharmacotherapeutic group: Influenza vaccine. ATC code: J07BB02.
Pharmacology: Pharmacodynamics: The efficacy of SKYCellflu Quadrivalent is supported by the immunogenicity data from a Phase I/II clinical trial and three Phase III clinical trials. The immunogenicity was assessed based on the seroprotection rate, seroconversion rate, GMR (Geometric Mean Ratio) and GMT (Geometric Mean Titer), in which were calculated using pre-vaccination and post-vaccination of HI (Hemagglutination inhibition) antibody titers. Throughout the Phase III clinical trials, the immunogenicity was evaluated in total of 1,435 subjects who completed the clinical trial without any major protocol violations. Data obtained from 1,435 subjects administered with SKYCellflu Quadrivalent were as follows.
Adults and elderly aged 19 years or older: Immunogenicity was assessed on 1,495 subjects (Test group: 748 subjects, Control group 1: 371 subjects, Control group 2: 376 subjects) included in the per protocol study (PPS), and the pre-determined efficacy criteria for this vaccine were met and the criteria for non-inferiority and superiority were also met. (See Table 1.)

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Children and adolescents aged 3 to 18 years: Immunogenicity was assessed on 314 subjects (Test group: 253 subjects, Control group: 61 subjects) included in the PPS, and the pre-determined efficacy criteria for this drug were met. (See Table 2.)

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Children aged 6 months to 35 months of age: Immunogenicity was assessed on 653 subjects (Test group: 434 subjects, Control group: 219 subjects) included in the PPS, and the pre-determined efficacy criteria for this drug were met and the criteria for non-inferiority and superiority were also met. (See Table 3.)

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In conclusion, the immunogenicity results of four clinical trials suggest that SKYCellflu Quadrivalent has a satisfactory immunogenicity profile for all four strains (A/H1N1, A/H3N2, B/Yamagata and B/Victoria).
Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Nonclinical data reveal no special hazard based on conventional repeat dose toxicity studies. SKYCellflu Quadrivalent was well tolerated and immunogenic in mice. In a repeat-dose toxicity study in rabbits and mice, there was no evidence of systemic toxicity and the vaccine was locally well tolerated.
No evidence of reproductive or developmental toxicity was seen in a study where the human dose was administered prior to and during gestation to female rabbits.

Active immunization for the prevention of influenza disease caused by influenza virus subtypes A and type B contained in the vaccine, for adults and children 6 months of age and older.
The use of SKYCellflu Quadrivalent should be based on official recommendations.

Posology: Adults and children 6 months of age and older: 0.5 mL as a single injection.
For children below 9 years of age who have not been previously vaccinated or infected, a second dose should be administered after an interval of at least 4 weeks.
Method of administration: Administration should be carried out by intramuscular injection. The sites of intramuscular injection are the anterolateral aspect of the thigh (or the deltoid muscle if muscle mass is adequate) in children 6 months through 35 months of age, or the deltoid muscle of the upper arm in children from 36 months of age and adults.

No information.

If deemed necessary after a medical interview and visual inspection, examine the subject's health condition further using methods such as auscultation and percussion. Do not administer the vaccine to subjects with following conditions. As an exception, the vaccine may be administered to subjects who are at risk of possible influenza infection and determined to have no likelihood of developing serious disabilities due to the administration of the vaccine.
Hypersensitivity reaction to active ingredient and/or any other ingredient (including formalin) in SKYCellflu Quadrivalent.
Febrile disease or acute infection.
History of severe hypersensitivity reaction and/or convulsive symptom to previous influenza vaccination.
History of Guillain-Barre syndrome or other neurological disorder within 6 weeks of previous influenza vaccination.
Fever.
History of anaphylaxis reaction to any ingredient in SKYCellflu Quadrivalent.
History of suspected allergic reaction, including systemic rash, to previous vaccination.
Other medical conditions that are diagnosed to be inappropriate for administration of SKYCellflu Quadrivalent vaccine.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.
As with other intramuscular injection, patients with bleeding disorder such as hemophilia and thrombocytopenia or patients on anticoagulant therapy should not receive SKYCellflu Quadrivalent unless the potential benefit outweighs the risk of administration. If the decision is made to administer SKYCellflu Quadrivalent in such persons, it should be administered with caution to avoid the risk of hematoma formation following injection.
Effects on ability to drive and use machines: The vaccine is unlikely to produce an effect on the ability to drive and use machines.

The safety of SKYCellflu Quadrivalent in pregnant women and breast-feeding women has not been assessed in clinical trials.
Pregnant women: Direct and/or indirect adverse effect related to reproduction and developmental toxicity was not observed in animal studies. Because of the consequences of influenza infection in pregnant women, WHO recommends vaccination of pregnant women.
Breast-feeding women: Since it is not known whether SKYCellflu Quadrivalent is excreted in breast milk, caution should be exercised when SKYCellflu Quadrivalent is administered to a nursing mother.
Fertility: No human fertility data are available. Animal data have not shown effects on female fertility. Male fertility has not been assessed in animals.

Summary of safety profile: The safety of SKYCellflu Quadrivalent was assessed through phase I/II clinical trial and three phase III clinical trials. Four human clinical studies have been performed with SKYCellflu Quadrivalent and the safety was evaluated in the Safety Analysis Set of 1,506 subjects who were enrolled and received the vaccination with SKYCellflu Quadrivalent. Of 1,506 subjects who received the SKYCellflu Quadrivalent, and 449 healthy infant subjects, 255 healthy pediatric subjects and 802 healthy adult subjects received 0.5 mL. Safety evaluations were performed for all subjects during the first 3 weeks for adults or 4 weeks for pediatric subjects, 6 months to 18 years of age following vaccination. SAEs have been collected during six months of follow-up, except 449 subjects aged 6 through 35 months for whom SAE has been collected 1 month after vaccination.
Summary of adverse reactions: Local reaction: adverse reactions including injection site tenderness, pain, erythema/redness, and induration/swelling may occur; these reactions usually disappear instantly.
Systemic reaction: systemic reactions including myalgia, fatigue/malaise, headache, diarrhea, and vomiting may occur after vaccination; these reactions usually disappear within 3-4 days.
Encephalomyelitis: rarely, acute disseminated encephalomyelitis (ADEM) is reported. Fever, headache, convulsion, motor disorder, cognitive disorder, etc. may occur generally within 2 weeks after vaccination. In a case of suspected ADEM, diagnosis with MRI and proper intervention should be instituted.
Very rarely, allergic reaction to anaphylaxis may occur.
Temporary disorder of systemic and/or local neural network may occur. Sensitivity to stimulus or pain may be abnormal. Vascular, cerebral, or neuronal inflammation (e.g., Guillain-Barre syndrome) resulting in paralysis, neuropathic pain, bleeding, and internal bleeding has been reported.
Safety of SKYCellflu Quadrivalent was assessed in a study with 449 children 6 months through 35 months of age, 255 pediatric and adolescent subjects 3 through 18 years of age, and 802 adults ≥ 19 years of age, and followings were reported for adverse reactions. 701 out of 1,506 (46.55%) subjects developed adverse reactions after vaccination. The incidence rate was 50.11% in children 6 through 35 months of age, 46.27% in pediatric and adolescent subjects 3 through 18 years of age, 49.00% in adult 19 through 59 years of age, and 26.14% in subjects ≥ 60 years of age.
Solicited adverse reactions observed during the 7-day period after SKYCellflu Quadrivalent vaccination are shown as follows. (See Table 4.)

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Unsolicited adverse reactions observed during the 21-day (adults) or 28-day (children and adolescents) period after SKYCellflu Quadrivalent vaccination were reported in 35 out of 1,506 (2.32%) subjects. Adverse reactions related to respiratory system in 14 subjects (0.93%) was most frequently observed. Adverse reactions observed during the study period are shown as follows.
Uncommon: 0.1 to <5%, Rare: <0.1%. (See Table 5.)

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Concurrent immunosuppressive therapy or immunodeficiency may affect immunological response to the vaccine.
Co-administration of SKYCellflu Quadrivalent with other vaccine has not been studied. If concomitant vaccination cannot be avoided, injections should be administered on different sites, and the patients should be informed of possible increases in the severity of the adverse effects due to the co-administration.
False positive response has been reported from the serum test after influenza vaccination which measures antibody against HIV1, HCV, and particularly HTLV1 using ELISA assay (false positivity confirmed with Western Blot technique). Such temporary false positive result is attributed to IgM reaction from vaccination.
Immunosuppressive therapy (radiotherapy, anti-metabolic agent, alkylating agent, cytotoxic agent, and supraphysiological doses of corticosteroid) may reduce the immunological response to influenza vaccine.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Special precautions for disposal and other handling: 1) Inspect the vaccine visually for any particulate matter or change in physical appearance prior to administration.
2) Before administering a dose of vaccine, shake the vaccine well until colorless or opalescent solution is achieved. Do not use the vaccine in case of any abnormality are observed.
3) Remove the vaccine from the refrigerator and allow reaching room temperature. Shake well to achieve homogenous solution before use (storage condition is 2°C to 8°C refrigeration).
4) Upon long-term storage, vaccine may show slight aggregation. This does not indicate abnormal quality, and is easily resuspended by shaking the vaccine.
5) Do not administer SKYCellflu Quadrivalent via intravenous injection.
6) Lateral upper arm is the typical administration site, and should be disinfected with ethanol or iodine tincture before the administration. In addition, it is advised to avoid repeating vaccination at the same site.
Any unused medicinal product or other waste material should be disposed of in accordance with local rules for the disposal of products of this nature.

Store SKYCellflu Quadrivalent refrigerated at 2°C to 8°C away from light. Do NOT freeze.
Do not use the vaccine if the contents have been frozen, because it may cause changes in product quality.
Shelf-life: 1 year.

Vaccines, Antisera & Immunologicals

J07BB02 - influenza, inactivated, split virus or surface antigen ; Belongs to the class of influenza viral vaccines.

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