Vaxigrip

The vaccine, after shaking gently, is a colourless opalescent liquid.
Influenza virus (inactivated, split) of the following strains*: A/Victoria/4897/2022 (H1N1) pdm09-like strain (A/Victoria/4897/2022, IVR-238)15 micrograms HA**.
A/Croatia/10136RV/2023 (H3N2)-like strain (A/Croatia/10136RV/2023, X-425A) 15 micrograms HA**.
B/Austria/1359417/2021-like strain (B/Michigan/01/2021, wild type) 15 micrograms HA**.
Per 0.5 mL dose.
* Propagated in fertilised hens' eggs from healthy chicken flocks.
** Haemagglutinin.
This vaccine complies with the WHO recommendations (Northern Hemisphere) and European Union decision for the 2025/2026 season.
Vaxigrip may contain traces of eggs, such as ovalbumin, and of neomycin, formaldehyde and octoxynol-9, which are used during the manufacturing process (see Contraindications).
Excipients/Inactive Ingredients: Buffer solution: Sodium chloride, Potassium chloride, Disodium phosphate dihydrate, Potassium dihydrogen phosphate, Water for injections.

Pharmacotherapeutic group: influenza vaccine. ATC code: J07BB02.
Pharmacology: Pharmacodynamics: Mechanism of action: Vaxigrip provides active immunisation against three influenza virus strains (two A subtypes and one B type) contained in the vaccine.
Vaxigrip induces humoral antibodies against the haemagglutinins within 2 to 3 weeks. These antibodies neutralise influenza viruses.
In infants less than 6 months of age born to women vaccinated with Vaxigrip during pregnancy, protection is due to transplacental transfer of these neutralizing antibodies.
There is no correlation between specific levels of antibody titres after vaccination with inactivated influenza virus vaccines, measured by haemagglutination inhibition (HAI), with protection against influenza, but HAI antibody titres have been used as a measure of vaccine activity. In some human studies, HAI antibody titres ≥1/40 have been associated with protection against influenza in up to 50% of subjects.
Since influenza viruses constantly evolve, the virus strains selected for the vaccine are reviewed annually by the WHO.
Annual influenza vaccination is recommended given the duration of immunity provided by the vaccine and because circulating strains of influenza virus change from year to year.
Efficacy: Efficacy data of Vaxigrip are available in pregnant women and in infants less than 6 months of age born to vaccinated pregnant women (passive protection).
No efficacy studies have been performed with Vaxigrip in children and adolescents from 9 to 17 years of age, in adults and in the elderly.
In children from 6 to 35 months of age and from 3 to 8 years of age (active immunisation), Vaxigrip efficacy is based on extrapolation of Vaxigrip Tetra efficacy.
Infants less than 6 months of age born to women vaccinated during their pregnancies (passive protection): Infants less than 6 months of age are at high risk of influenza, resulting in high rates of hospitalisation. However, influenza vaccines are not indicated for active immunisation in this age group.
Efficacy in infants born of women who received a single 0.5 mL dose of Vaxigrip during the second or third trimester of pregnancy has been demonstrated in clinical trials.
The efficacy of Vaxigrip in infants born to women vaccinated during the first trimester of pregnancy was not studied in these trials. If influenza vaccination is considered necessary during the first trimester of pregnancy, it should not be postponed (see Use in Pregnancy & Lactation).
In randomized, controlled phase IV clinical studies conducted in Mali, Nepal and South Africa, approximately 5,000 pregnant women received Vaxigrip and approximately 5,000 pregnant women received placebo or control vaccine (quadrivalent meningococcal conjugate vaccine) during the second or third trimester of pregnancy. Vaccine efficacy in the prevention of laboratory confirmed influenza in pregnant women was evaluated as a secondary endpoint in all three studies.
The studies conducted in Mali and South Africa demonstrated the efficacy of Vaxigrip in the prevention of influenza in pregnant women following vaccination during these trimesters of pregnancy (see Table 1). In the study conducted in Nepal, the efficacy of Vaxigrip in the prevention of influenza in pregnant women following vaccination during these trimesters of pregnancy was not demonstrated. (See Table 1.)

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In the same randomized, controlled phase IV clinical studies conducted in Mali, Nepal and South Africa, 4530 of 4898 (92%) infants born to pregnant women who received Vaxigrip and 4532 of 4868 (93%) infants born to pregnant women who received a placebo or control vaccine (quadrivalent meningococcal conjugate vaccine) (see Table 2) during the second or third trimester of pregnancy, were followed up until approximately 6 months of age.
The studies confirmed the efficacy of Vaxigrip in the prevention of influenza in infants born to women vaccinated during these trimesters of pregnancy, from birth until approximately 6 months of age. Women in their first trimester of pregnancy were not included in these studies; Vaxigrip efficacy in infants born to mothers vaccinated during the first trimester could therefore not be evaluated. (See Table 2.)

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The efficacy data indicate a decrease over time after birth in the protection of infants born to mothers vaccinated during their pregnancies.
In the trial conducted in South Africa, vaccine efficacy was higher in infants 8 weeks of age or younger (85.8% [95% CI: 38.3; 98.4]) and decreased over time; vaccine efficacy was 25.5% (95% CI: -67.9; 67.8) in infants from 8 to 16 weeks of age and 30.4% (95% CI: -154.9; 82.6) in infants from 16 to 24 weeks of age.
In the trial conducted in Mali, there was also a trend for higher efficacy of Vaxigrip in infants during the first four months after birth, with lower efficacy within the 5^th month of surveillance and a marked fall within the 6^th month when protection is no longer evident.
The prevention of influenza can only be expected if the infant(s) are exposed to strains included in the vaccine administered to the mother.
Children from 6 to 35 months of age (active immunisation): A randomized placebo controlled study was conducted in 4 regions (Africa, Asia, Latina America and Europe) over 4 influenza seasons, in more than 5,400 children from 6 to 35 months of age who received two doses (0.5 mL) of Vaxigrip Tetra (N=2,722), or placebo (N=2,717) 28 days apart to assess Vaxigrip Tetra efficacy in the prevention of laboratory-confirmed influenza caused by any strain A and/or B and caused by strains to those of the vaccine (as determined by sequencing).
Laboratory-confirmed influenza was defined as influenza like-illness (ILI) [occurrence of fever ≥38°C (lasting at least 24 hours) concurrently with at least one of the following symptoms: cough, nasal congestion, rhinorrhoea, pharyngitis, otitis, vomiting, or diarrhoea], laboratory-confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and/or viral culture. (See Table 3.)

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In addition, a predefined complementary analysis showed Vaxigrip Tetra prevented 56.6% (95% CI: 37.0; 70.5) of severe laboratory-confirmed influenza due to any strain, and 71.7% (95% CI: 43.7; 86.9) of severe laboratory-confirmed influenza due to strains similar to those of the vaccine. Furthermore, subjects receiving Vaxigrip Tetra were 59.2% (95% CI: 44.4; 70.4) less likely to experience influenza requiring a medical consultation than subjects receiving placebo.
Severe laboratory-confirmed influenza was defined as influenza-like illness laboratory-confirmed by RT-PCR and/or viral culture with at least one of the following: fever >39.5°C for subjects aged <24 months or ≥39.0°C for subjects aged ≥24 months, and/or at least one significant flu-like symptom which prevents daily activity (cough, nasal congestion, rhinorrhoea, pharyngitis, otitis, vomiting, diarrhoea), and/or one of the following events: acute otitis media, acute lower respiratory infection (pneumonia, bronchiolitis, bronchitis, croup), inpatient hospitalisation.
Children from 3 to 8 years of age (active immunisation): Based on immune responses of Vaxigrip observed in children 3 to 8 years of age, the efficacy of Vaxigrip in this population is expected to be at least similar to the efficacy observed in children from 6 to 35 months (see "Children from 6 to 35 months of age (active immunisation) as previously mentioned and "Immunogenicity of Vaxigrip" as follows).
Immunogenicity: Clinical studies performed in adults from 18 to 60 years of age, in the elderly over 60 years of age, and in children from 3 to 8 years of age and from 6 to 35 months of age, evaluated the immune response to Vaxigrip (TIV) and Vaxigrip Tetra (QIV) as regards the geometric mean titres (GMTs) in IHA antibodies at Day 21 (for adults) and at Day 28 (for children), the HAI seroconversion rate (4-fold rise in reciprocal titre or change from an undetectable titre [<10] to a reciprocal titre ≥40), and the geometric mean of individual titre ratios (GMTRs) of HAI (post-/pre-vaccination titres).
One clinical study performed in adults from 18 to 60 years of age and in children from 9 to 17 years of age described the immune response of Vaxigrip Tetra and Vaxigrip as regards the GMT in HAI antibodies on Day 21. Another clinical study performed in children from 9 to 17 years of age described the immune response of Vaxigrip Tetra.
One clinical study performed in pregnant women described the immune response of Vaxigrip and Vaxigrip Tetra as regards the GMT in for HAI antibodies at Day 21, the HAI seroconversion rate, and the HAI GMTR after one dose administered during the second or third trimester of pregnancy. In this study, transplacental transfer was evaluated using GMTs in HAI antibodies of maternal blood, of cord blood and the ratio of cord blood/maternal blood, at delivery.
Overall, Vaxigrip induced an immune response to the 3 influenza strains contained in the vaccine.
In children from 3 years of age and in adults including pregnant women and in elderly, Vaxigrip was as immunogenic as Vaxigrip Tetra for the strains in common.
Antibody persistence was assessed in adults, the elderly and children aged 6 months to 35 months. The duration of the immunity induced by vaccination is at least 12 months.
Adults and the elderly: In one clinical study, the immune response was described in adults from 18 to 60 years of age and the elderly over 60 years of age who received one 0.5-mL dose of Vaxigrip or Vaxigrip Tetra.
The immunogenicity results by HAI method in adults from 18 to 60 years of age and elderly over 60 years of age are presented in Table 4. (See Table 4.)

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Pregnant women and transplacental transfer: In one clinical study, a total of 116 pregnant women received Vaxigrip and 230 pregnant women received Vaxigrip Tetra during the second or third trimester of pregnancy (from 20 to 32 weeks of pregnancy).
Immunogenicity results by HAI method, in pregnant women 21 days after vaccination with Vaxigrip or Vaxigrip Tetra are presented in Table 5. (See Table 5.)

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A descriptive analysis of immunogenicity by HAI method, at delivery, in a sample of mother's blood (BL03M), and in a sample of cord blood (BL03B) and of transplacental transfer (BL03B/BL03M) are presented in Table 6. (See Table 6.)

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At delivery, the higher level of antibodies in the cord sample compared to the maternal sample is consistent with transplacental antibody transfer from mother to the foetus following vaccination of women with Vaxigrip or Vaxigrip Tetra during the second or third trimester of pregnancy.
These data are consistent with the passive protection demonstrated in infants from birth to approximately 6 months of age born of women vaccinated during the second or third trimester of pregnancy with Vaxigrip in studies conducted in Mali, Nepal, and South Africa (see Efficacy).
Paediatric population: Children from 9 to 17 years of age: In a total of 55 children from 9 to 17 years of age who received one dose of Vaxigrip and 429 who received one dose of Vaxigrip Tetra, the immune response against the strains contained in the vaccine was similar to the immune response induced in adults 18 to 60 years of age.
Children from 3 years to 8 years of age: In one clinical study, the immune response was described in children from 3 to 8 years of age who received either one or two 0.5 mL doses of Vaxigrip or Vaxigrip Tetra, depending on their previous influenza vaccination history.
Children who received a one- or two-dose schedule of Vaxigrip or Vaxigrip Tetra presented a similar immune response following the last dose of the respective schedule.
The immunogenicity results by HAI method 28 days after receipt of the last injection are presented in Table 7.
Children from 6 months to 35 months of age: In one clinical trial, the immune response was described in children from 6 to 35 months of age who received two 0.5-mL doses of Vaxigrip or Vaxigrip Tetra.
The immunogenicity results by HAI method, 28 days after receipt of the last injection are presented in Table 7. (See Table 7.)

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These immunogenicity data provide supportive information in addition to efficacy data available in children from 6 to 35 months of age (see Efficacy).
Pharmacokinetics: Not applicable.
Toxicology: Preclinical Safety Data: Data in animals generated with Vaxigrip Tetra (60 μg of total HA/dose) can be extrapolated to Vaxigrip (45 μg of total HA/dose): these data revealed no unexpected findings and no target organ toxicity.

Vaxigrip is indicated for the prevention of influenza disease caused by the two influenza A virus subtypes and the influenza B virus type contained in the vaccine for: active immunisation of adults, including pregnant women, and children from 6 months of age and older, passive protection of infant(s) from birth to less than 6 months of age following vaccination of pregnant women (see Precautions, Use in Pregnancy & Lactation and Pharmacology: Pharmacodynamics under Actions).
The use of Vaxigrip should be based on official recommendations on vaccination against influenza.

Posology: Adults: one dose of 0.5 mL.
Paediatric population: Children from 6 months to 17 years of age: one dose of 0.5 mL.
For children less than 9 years of age who have not previously been vaccinated, a second dose of 0.5 mL should be given after an interval of at least 4 weeks.
Infants less than 6 months of age: the safety and efficacy of Vaxigrip administration (active immunisation) have not been established. No data are available.
Regarding passive protection: one 0.5 mL dose given to pregnant women may protect infants from birth to less than 6 months of age (see Precautions, Use in Pregnancy & Lactation and Pharmacology: Pharmacodynamics under Actions).
Method of Administration: The preferred route of administration for this vaccine is intramuscular although it can also be given subcutaneously.
The preferred sites for 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 in children from 36 months of age and adults.
Precautions to be taken before handling or administering the medicinal product: For instructions on preparation of the medicinal product before administration, see Special Precautions for Disposal and Other Handling under Cautions for Usage.

Cases of administration of more than the recommended dose (overdose) have been reported with Vaxigrip. When adverse reactions were reported, the information was consistent with the known safety profile of Vaxigrip described in Adverse Reactions.

Hypersensitivity to the active substances, to any of the excipients listed in Description or to any component that may be present as traces such as eggs (ovalbumin, chicken proteins), neomycin, formaldehyde and octoxinol-9.

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: As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine.
Concurrent illness: Vaccination should be postponed in patients with acute febrile illness until the fever is resolved.
Precautions for use: Vaxigrip should under no circumstances be administered intravascularly.
Thrombocytopenia and coagulation disorders: As with other vaccines administered intramuscularly, the vaccine should be administered with caution to subjects with thrombocytopenia or a coagulation disorder since bleeding may occur following an intramuscular administration to these subjects.
Syncope: Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent injury from fainting and manage syncopal reactions.
Protection: Vaxigrip is intended to provide protection against those strains of influenza virus from which the vaccine is prepared.
As with any vaccine, vaccination with Vaxigrip may not protect all vaccinees.
Regarding passive protection, not all infants less than 6 months of age born to women vaccinated during pregnancy will be protected (see Pharmacology: Pharmacodynamics under Actions).
Immunodeficiency: Antibody response in patients with congenital or acquired immunodeficiency may be insufficient.
Potassium and sodium content: This medicinal product contains less than 1 mmol (39 mg) of potassium and less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially "potassium-free" and "sodium-free".
Effects on Ability to Drive and Use Machines: Vaxigrip has no or negligible influence on the ability to drive and use machines.

Pregnancy: Pregnant women are at high risk of influenza complications, including premature labour and delivery, hospitalisation, and death: pregnant women should receive an influenza vaccine.
Vaxigrip can be used in all stages of pregnancy.
More data are available on the safety of inactivated influenza vaccines for the second and third trimesters than for the first trimester. Data from worldwide use of inactivated influenza vaccines, including Vaxigrip and Vaxigrip Tetra (quadrivalent inactivated influenza vaccine), do not indicate any adverse foetal and maternal outcomes attributable to the vaccine.
This is consistent with results observed in one clinical study in which Vaxigrip and Vaxigrip Tetra were administered in pregnant women during the second or third trimester (116 exposed pregnancies and 119 live births for Vaxigrip, 230 exposed pregnancies and 231 live births for Vaxigrip Tetra).
Data from four clinical studies with Vaxigrip administered in pregnant women during the second or third trimester (more than 5,000 exposed pregnancies and more than 5,000 live births followed up to approximately 6 months post-partum) did not indicate any adverse foetal, newborn, infant and maternal outcomes attributable to the vaccine.
In clinical studies conducted in South Africa and Nepal, there were no significant differences between the Vaxigrip and placebo groups with regards to foetal, newborn, infant and maternal outcomes (including miscarriage, stillbirth, premature birth and low birth weight).
In a study conducted in Mali, there were no significant differences between the Vaxigrip and control vaccine (quadrivalent meningococcal conjugate vaccine) groups with regard to premature births, rate of stillbirths and rates of low birth weight/small for gestational age.
For additional information, see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions.
The results of one reproductive and developmental toxicity study in rabbits conducted with Vaxigrip Tetra (60 μg of total HA/dose) can be extrapolated to Vaxigrip (45 μg of total HA/dose): this study did not indicate direct or indirect harmful effects with respect to pregnancy, embryo-foetal development or early post-natal development.
Breast-feeding: Vaxigrip can be used during breast-feeding.
Fertility: No fertility data are available in humans. One animal study with Vaxigrip Tetra did not indicate harmful effects on female fertility.

Summary of the safety profile: The safety profile of Vaxigrip is based on data from 46 clinical studies in which approximately 17,900 participants from 6 months of age received Vaxigrip or Vaxigrip Tetra, and data from post-marketing surveillance.
Most of the adverse reactions usually occurred within the first 3 days after vaccination and resolved spontaneously within 1 to 3 days of their onset. The intensity of most of these effects was mild to moderate.
The most frequently reported undesirable effect after vaccination, in all populations including the whole group of children from 6 to 35 months of age, was injection site pain.
Tabulated list of adverse reactions: Adverse events are ranked 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); Not known (cannot be estimated from available data).
Adults and the elderly: The safety profile is based on data: from clinical studies in more than 8,000 adults (5,064 for Vaxigrip, 3,040 for Vaxigrip Tetra) and more than 5,800 elderly subjects over 60 years of age (4,468 for Vaxigrip, 1,392 for Vaxigrip Tetra); from worldwide post-marketing surveillance in the general population.
In adults, the most frequently reported adverse reactions after vaccination were injection site pain (52.8%), headache (27.8%), myalgia (23.0%) and malaise (19.2%).
In the elderly, the most frequently reported adverse reactions after vaccination were injection site pain (25.8%), headache (15.6%) and myalgia (13.9%). (See Table 8.)

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Paediatric population: The safety profile is based on data: from clinical studies in 1 247 children from 3 to 8 years of age (363 for Vaxigrip, 884 for Vaxigrip Tetra) and in 725 children/adolescents from 9 to 17 years of age (296 for Vaxigrip, 429 for Vaxigrip Tetra); from one clinical study in 1 981 children from 6 to 35 months of age (367 for Vaxigrip, 1 614 for Vaxigrip Tetra); from worldwide post-marketing surveillance in the general population.
Depending on immunisation history, children from 6 months to 8 years of age received one or two doses of Vaxigrip or Vaxigrip Tetra. Children/adolescents from 9 to 17 years of age received one dose.
In children from 6 months to 8 years of age, the safety profile was similar after the first and the second injections with a trend for a lower incidence of adverse reactions after the second injection compared to the first one in children from 6 to 35 months.
In children/adolescents from 9 to 17 years of age, the most frequently reported adverse reactions after vaccination were injection site pain (65.3%), myalgia (29.1%), headache (28.6%), malaise (20.3%), chills (13.0%), injection site erythema (11.7%) and injection site swelling (11.4%).
In children from 3 to 8 years of age, the most frequently reported adverse reactions after vaccination were injection site pain (59.1%), malaise (30.7%), injection site erythema (30.3%), myalgia (28.5%), headache (25.7%), injection site swelling (22.1%), injection site induration (17.6%), and chills (11.2%).
In children from 6 to 35 months of age, the most frequently reported adverse reactions after vaccination were: injection site pain/tenderness (29.4%), fever (20.4%) and injection site erythema (17.2%).
In the subpopulation of children from 6 to 23 months of age, the most frequently reported adverse reactions after vaccination were irritability (34.9%), abnormal crying (31.9%), lost appetite (28.9%), somnolence (19.2%) and vomiting (17.0%).
In the subpopulation of children from 24 to 35 months of age, the most frequently reported adverse reactions after vaccination were malaise (26.8%), myalgia (14.5%) and headache (11.9%). (See Table 9.)

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Other special populations: Although only a limited number of subjects with co-morbidities were enrolled, studies conducted in patients with co-morbidities such as renal transplant or asthmatic patients, showed no major differences in terms of safety profile of Vaxigrip and Vaxigrip Tetra in these populations.
Pregnant women: In clinical studies conducted in pregnant women in South Africa and Mali with Vaxigrip (see Use in Pregnancy & Lactation and Pharmacology: Pharmacodynamics under Actions), frequencies of local and systemic solicited reactions reported within 7 days following administration of the vaccine, were consistent with those reported for the adult population during clinical studies. In the study conducted in South Africa, local reactions were more frequent in the Vaxigrip group than in the placebo group in both HIV-negative and HIV-positive cohorts. There were no other significant differences in solicited reactions between Vaxigrip and placebo groups in both cohorts.
In one clinical study conducted in pregnant women in Finland with Vaxigrip and Vaxigrip Tetra (see Use in Pregnancy & Lactation and Pharmacology: Pharmacodynamics under Actions), frequencies of reported local and systemic solicited reactions were consistent with those reported for the non-pregnant adult population during clinical studies conducted with Vaxigrip or Vaxigrip Tetra even though higher for some adverse reactions (injection site pain, injection site erythema, malaise, chills, headache, myalgia).
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 via the national reporting system.

Vaxigrip could be given at the same time as other vaccines if needed.
Data showing that Vaxigrip can be administered concomitantly with other vaccines are available for the following vaccines: pneumococcal polysaccharide vaccine, tetanus, diphtheria, pertussis and polio vaccine (DTAP/IPV, Repevax), and a shingles vaccine. If Vaxigrip is given at the same time as other vaccines, separate injection sites and separate syringes should be used.
The immunological response may be reduced if the patient is undergoing immunosuppressant treatment.

Incompatibilities: In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.
Special Precautions for Disposal and Other Handling: The vaccine should be allowed to reach room temperature before use.
Shake before use. Inspect visually prior to administration.
The vaccine should not be used if foreign particles are present in the suspension.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store in a refrigerator (2°C-8°C). Do not freeze. Keep the syringe in the outer carton in order to protect from light.
Vaxigrip remains stable for 72 hours at temperatures up to 25°C ±2°C. This is not a recommended storage condition; it is only intended to guide healthcare professionals in case of temporary temperature excursion.
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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