Flublok

Quadrivalent influenza vaccine (recombinant, prepared in cell culture, contains influenza virus haemagglutinin proteins).

One dose (0.5 mL) contains: Influenza virus haemagglutinin (HA) proteins, of the following strains*: A/Hawaii/70/2019 (H1N1) 45 micrograms HA; A/Minnesota/41/2019 (H3N2) 45 micrograms HA; B/Washington/02/2019 45 micrograms HA; B/Phuket/3073/2013 45 micrograms HA.
* Produced by recombinant DNA technology using a baculovirus expression system in a continuous insect cell line that is derived from Sf9 cells of the fall armyworm, Spodoptera frugiperda.
This vaccine complies with the World Health Organization (WHO) recommendation (Northern Hemisphere) and EU recommendation for the 2020/2021 season.
Flublok may contain traces of octylphenol ethoxylate.
Excipients/Inactive Ingredients: Polysorbate 20 (E432), Sodium chloride, Monohydrate sodium phosphate monobasic, Dodecahydrate sodium phosphate dibasic, Water for injections.

Pharmacotherapeutic group: Influenza vaccine. ATC code: J07BB02.
Pharmacology: Pharmacodynamics: Immunogenicity: Flublok was evaluated in healthy adults of 18-49 years of age in a randomized, observer-blind, active controlled, non-inferiority immunogenicity, multi-center trial conducted during the 2014-2015 influenza season in the United States (study 1).
In the study 1, subjects received Flublok (N=998) or an egg-based quadrivalent inactivated influenza vaccine (IIV4) (N=332). Immunogenicity was assessed before and 28 days after administration of a single dose of study vaccine.
Haemagglutination inhibition (HAI) geometric mean titers (GMTs) were determined for the two vaccine groups for each vaccine antigen. Immunogenicity was compared by calculating the difference in seroconversion rates (SCR) and the ratios of GMTs of Comparator to Flublok.
Study 1 had two co-primary endpoints: GMTs and Day 28 HAI seroconversion rates for each of the four antigens contained in the study vaccines.
Flublok met the success criterion for GMTs for three of the four antigens but did not meet the success criteria for the B/Victoria lineage antigen (Table 1). Antibody titres against the B/Victoria were low in both vaccine groups. (See Table 1.)

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Flublok met the success criterion for SCRs for three of the four antigens (Table 2), but not for the B/Victoria lineage. The HAI response to the B/Victoria lineage antigen was low in both vaccine groups. (See Table 2.)

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The study 1 in adults 18-49 years of age was conducted in parallel to the study 2 in adults of 50 years of age and older. These adults 18-49 years of age were vaccinated during the same influenza season (2014-2015 Northern Hemisphere influenza season) and received the same Flublok formulation (same vaccine strain composition) as adults of 50 years of age and older in the study 2. The immune response induced by Flublok was assessed by the same HAI assay and performed by the same laboratory for both studies. The immunogenicity results in adults 18-49 years of age (study 1) and adults 50 years of age and older (study 2) are presented in Table 3. (See Table 3.)

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These immunogenicity data provide supportive information for the 18-49 years of age group in addition to vaccine efficacy data available in adults ≥50 years of age (see Clinical Efficacy as follows).
Clinical efficacy: Flublok efficacy in terms of prevention of laboratory-confirmed influenza-like illness (ILI) caused by any strain of influenza, was evaluated in adults ≥50 years of age and conducted during the 2014-2015 influenza season in the United States (study 2).
A total of 8963 healthy, medically stable adults were randomized in a 1:1 ratio to receive a single dose of Flublok (n=4474) or an egg-based quadrivalent inactivated influenza vaccine (n=4489). A total of 5412 (60.4%) subjects were 50-64 years of age, 2532 (28.2%) were 65-74 years of age and 1019 (11.4%) were ≥75 years of age.
The primary efficacy endpoint of Study 2 was reverse transcriptase polymerase chain reaction (rtPCR)-positive, protocol-defined ILI due to any strain of influenza.
Laboratory-confirmed protocol defined ILI was defined as having at least one symptom in each of two categories of respiratory and systemic symptoms, which could include sore throat, cough, sputum production, wheezing and difficulty breathing, or systemic symptoms such as fever >99°F (>37°C), chills, fatigue, headache and myalgia, laboratory-confirmed by rtPCR.
US epidemiological data for the 2014-2015 influenza season indicated that Influenza A (H3N2) viruses predominated and that most influenza A/H3N2 viruses were antigenically dissimilar while A/H1N1 and B viruses were antigenically similar to vaccine antigens. Flublok met the pre-specified success criterion for non-inferiority to the comparator pre-defined as a lower bound of the two sided 95% CI >-20%.
Of the 4474 participants exposed to Flublok in a phase 3 active-controlled study (Study 2), a total of 1761 were 65 years or older. Although no differences in safety or efficacy were observed between older and younger participants, the number of patients aged 65 and over in this study was not sufficient to determine statistically whether this age group will respond differently from younger individuals. (See Table 4.)

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Efficacy of trivalent recombinant influenza vaccine (RIV3): The efficacy of trivalent recombinant influenza vaccine (RIV3) is relevant to Flublok because both vaccines are manufactured using the same process and have overlapping compositions.
The efficacy of trivalent recombinant influenza vaccine in protecting against influenza illness was evaluated in a randomized, observer-blind, placebo-controlled multicenter trial conducted in the United States during the 2007-2008 influenza season in adults 18-49 years of age (Study 3).
Study 3 enrolled and vaccinated 4648 healthy adults randomized in a 1:1 ratio to receive a single dose of RIV3 (n=2344) or saline placebo (n=2304).
The primary efficacy endpoint of Study 3 was defined as an influenza-like illness (ILI) with a positive culture for an influenza virus strain antigenically resembling a strain represented in RIV3. ILI is defined as fever of ≥100°F (37.8°C) oral accompanied by cough, sore throat, or both, on the same or consecutive days. Attack rates and vaccine efficacy (VE), defined as the reduction in the influenza rate for RIV3 relative to placebo, were calculated for the total vaccinated cohort (n=4648).
Due to very small number of cultured confirmed influenza cases with matched strains, an exploratory analysis of VE of RIV3 against all strains, regardless of antigenic match, isolated from any subject with an ILI, not necessarily meeting ILI criteria was done, demonstrated an efficacy estimate of 44.8% (95% CI 24.4, 60.0). See Table 5 for VE by case definition. (See Table 5.)

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Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Non-clinical safety data on the trivalent formulation revealed no special hazard for humans based on conventional studies of repeat dose and local toxicity, reproductive and developmental (including teratogenicity) toxicity and safety pharmacology studies. The results of these studies with trivalent recombinant influenza vaccine are relevant to Flublok because both vaccines are manufactured using the same process and have overlapping compositions.

Flublok is indicated for active immunization for the prevention of influenza disease in adults.
Flublok should be used in accordance with official recommendations.

Posology: One dose of 0.5 mL.
Paediatric population: Safety and efficacy of Flublok have not yet been established in individuals below 18 years of age.
Method of administration: For intramuscular injection only. The preferred site is in the deltoid muscle.
The vaccine must not be injected intravascularly and must not be mixed with other vaccines in the same syringe.
For instructions on the handling of the vaccine before administration, see Special precautions for disposal and other handling under Cautions for Usage.

No cases of overdose reported.

Hypersensitivity to the active substances, to any of the excipients listed in Description or to any trace residuals such as octylphenol ethoxylate.

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hypersensitivity: Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.
Intercurrent illness: Vaccination should be postponed in patients with acute febrile illness until the fever is resolved.
Immunodeficiency: Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient to prevent influenza.
Thrombocytopenia and coagulation disorders: As with all injectable vaccines, Flublok must be administered with caution to individuals with thrombocytopaenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects.
Syncope: Syncope can occur following or even before any vaccination as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. Procedures should be in place to prevent falling and injury and to manage syncope.
Protection: As with any vaccine, vaccination with Flublok may not protect all vaccinees.
Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say is essentially "sodium free".
Effects on ability to drive and use machines: Flublok has no or negligible influence on the ability to drive and use machines.

Pregnancy: There is a limited amount of data from the use of Flublok in pregnant women.
One animal study performed with trivalent recombinant influenza vaccine did not indicate direct or indirect harmful effects with respect to pregnancy, embryo-foetal development or early post-natal development.
An assessment of the risks and benefits should be performed by a health care professional before administering Flublok to a pregnant woman.
Breast-feeding: It is not known whether Flublok vaccine is excreted in human milk.
An assessment of the risks and benefits should be performed by a health care professional before administering Flublok to a breast-feeding woman.
Fertility: No human fertility data are available.
The animal study with trivalent recombinant influenza vaccine did not indicate harmful effects on female fertility.

Summary of the safety profile: Flublok has been administered to and safety data collected from 998 adults 18-49 years of age (Study 1) and 4328 adults 50 years of age and older (Study 2).
The most common reactions occurring after vaccine administration were injection-site reactions (tenderness and pain) reported overall by 48% and 37% of study participants 18-49 years of age receiving Flublok respectively. In study participants 50 years of age and older, injection site tenderness was reported by 34% and injection site pain reported by 19%.
The severity of the reactions was mild to moderate. Onset usually occurred within the first 3 days after vaccination. All resolved without sequelae.
Tabulated list of adverse reactions: The adverse reactions are listed by MedDRA system organ class under headings of frequency using the following convention: 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); Frequency not known (adverse reactions from post-marketing experience; cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. (See Table 6.)

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Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

No interaction studies have been performed, nor data to assess the concomitant administration of Flublok with other vaccines.
If Flublok is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

Special precautions for disposal and other handling: The vaccine should be inspected visually for particulate matter and/or discoloration prior to administration. If either of these conditions exists, the vaccine should be discarded.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Store in a refrigerator (2°C - 8°C).
Do not freeze.
Keep the pre-filled syringe in the outer carton in order to protect from light.
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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