SKYCellflu Quadrivalent Prefilled Syringe Adverse Reactions

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. (Relatively common: 0.1 to <5%, Rare: <0.1%). (See Table 5.)

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20 out of 1,506 subjects developed 21 serious adverse events (449 subjects with 0.5 mL for 6 to 35 months after birth were followed by 1 month after vaccination) by 6 months after administration of SKYCellflu Quadrivalent vaccine (2 cases of gastroenteritis, 2 cases of pneumonia, 2 cases of mycoplasma pneumonia, 1 case of acute bronchitis, 1 case of acute stomachache, 1 case of acute pharyngitis, 1 case of bacterial pneumonia, 1 case of bronchopneumonia, 1 case of viral induced wheeze, 1 case of acute gastroenteritis, 1 case of diverticulitis, 1 case of wrist fracture, 1 case of tooth abscess, 1 case of benign prostatic hypertrophy, 1 case of deviated nasal septum, 1 case of benign neoplasm of breast, 1 case of cerebral hemorrhage, 1 case of enuresis) and all of which were concluded to be unrelated to SKYCellflu Quadrivalent except 1 case of acute pharyngitis.
Post Marketing Experience: During this 4-year post marketing surveillance (PMS) in South Korea, among 655 subjects on adults aged 19 years and older, adverse events were reported by 6.87% (45/655 subjects, 69 cases) regardless the causal relationship with the vaccine. No serious adverse events or serious adverse drug reactions were reported. In addition, unexpected adverse events and unexpected adverse drug reactions are shown as follows according to its frequency. (See Table 6.)

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During this 4-year post marketing surveillance (PMS), among 603 subjects on children and adolescents aged 3 to 18 years, adverse events were reported by 18.57% (112/603 subjects, 222 cases) regardless the causal relationship with the vaccine. No serious adverse events or serious adverse drug reactions were reported. In addition, unexpected adverse events and unexpected adverse drug reactions are shown as follows according to its frequency. (See Table 7.)

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At the point of re-examination, analysis and assessment were conducted by comparing the adverse events from the post-marketing surveillance of SKYCellflu Quadrivalent with adverse events reported from all of licensed medicines in South Korea (1989-September 30, 2020). The adverse events identified to occur more frequently in SKYCellflu Quadrivalent are as follows.
General disorders and administration site conditions: Chills, Vaccination site bruising.