Quadrivalent Influenza Vaccine (Split Virion, Inactivated)

Registered South African indications:

• Prevention of influenza disease caused by the two influenza A virus subtypes and two influenza B virus types contained in the vaccine for
  - Active immunisation
  - Passive protection of infant(s) from birth to <6 months of age following vaccination of pregnant women

Contraindications

South African recommendations

• History of severe allergic reaction to egg proteins (eggs or egg products), to chicken proteins, to any component of the vaccine (including manufacturing residuals
• History of severe allergic reaction after previous administration of quadrivalent influenza vaccine (split virion, inactivated) or a vaccine containing the same components
• Administration of quadrivalent influenza vaccine (split virion, inactivated) should be postponed in subjects suffering from moderate or severe febrile disease or acute disease

Recommendations in other jurisdictions

• Hypersensitivity to the active substances, to any of the excipients, or to any component that may be present as traces such as eggs (ovalbumin, chicken proteins), neomycin, formaldehyde, and octoxinol-9
• Vaccination should be postponed in case of moderate or severe febrile disease or acute disease

Cautions

South African recommendations

• Hypersensitivity to antibiotics in the same class as neomycin
• Renal impairment
• Hepatic impairment
• Influenza strains not covered in the vaccine preparation
• Immunocompromised persons whether due to genetic, immunodeficiency disease, or immunosuppressive therapy
• Thrombocytopenia or a bleeding disorder

Recommendations in other jurisdictions

• Renal impairment
• Hepatic impairment
• Influenza strains not covered in the vaccine preparation
• Endogenous or iatrogenic immunosuppression
• Thrombocytopenia or a bleeding disorder

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Due to the variation of the influenza virus and the duration of immunity provided by the vaccine, it is recommended to perform vaccination against influenza every year at the beginning of the risk period

Prevention of influenza disease caused by the two influenza A virus subtypes and two influenza B virus types contained in the vaccine for
- Active immunisation

• IM/SC: 0.5ml, as a single dose

The vaccine should be given by intramuscular or deep subcutaneous injection

The preferred sites for intramuscular injection are the deltoid muscle

Do not administer the quadrivalent influenza vaccine by intravascular injection

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Due to the variation of the influenza virus and the duration of immunity provided by the vaccine, it is recommended to perform vaccination against influenza every year at the beginning of the risk period

Prevention of influenza disease caused by the two influenza A virus subtypes and two influenza B virus types contained in the vaccine for
- Active immunisation

Younger than 6 months

• Not established for use

Between 6 months-17 years

• IM/SC: 0.5ml, as a single dose

- Passive protection of infant(s) from birth to <6 months of age following vaccination of pregnant women

• See adult dosage (adult active immunisation dosage applicable for pregnant women)

For children less than 9 years of age who have not previously been vaccinated, a second dose of 0.5ml should be given after an interval of at least 4 weeks

The vaccine should be given by intramuscular or deep subcutaneous injection. 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

Regarding passive protection: one 0,5ml dose given to pregnant women may protect infants from birth to less than 6 months of age; however, not all these infants will be protected

Do not administer the quadrivalent influenza vaccine by intravascular injection

Pregnancy

• Safe; no evidence of risk in studies
• Pregnant women are at high risk of influenza complications, including premature labour and delivery, hospitalisation, and death; therefore, pregnant women should receive an influenza vaccine, whatever their stage of pregnancy during the influenza season
• The quadrivalent influenza vaccine (split virion, inactivated) can be administered in all stages of pregnancy based on the safety data from clinical studies and post-marketing experience with the trivalent influenza vaccine, thiomersal free
• In these clinical studies, none of the serious adverse events reported in women, foetuses or infants were considered related to the quadrivalent influenza vaccine (split virion, inactivated)
  (See additional prescribing points)

Breastfeeding

South African recommendations

• Compatible
• Based on inactivated influenza vaccines experience, the quadrivalent influenza vaccine (split virion, inactivated) may be used during breastfeeding
• There are no data on the effect of the vaccine in breastfed newborns/ infants of women vaccinated with the quadrivalent influenza vaccine (split virion, inactivated) during the breastfeeding period

Recommendations in other jurisdictions

• Compatible
• The quadrivalent influenza vaccine (split virion, inactivated) may be used during breastfeeding

Fertility

• There are no fertility data available in humans
• One animal study with the quadrivalent influenza vaccine (split virion, inactivated) did not indicate harmful effects on female fertility

Renal Impairment

• Caution; no information available
• Studies conducted with inactivated influenza vaccine, split virion in renal transplant patients showed no major differences in terms of safety profile of inactivated influenza vaccine, split virion in these populations

Hepatic Impairment 

• Caution; no information available 

Elderly

• No dose adjustment recommended 

Porphyria Information

• Probably not porphyrinogenic (PNP) 

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Paraesthesia
• Somnolence
• Malaise
• Moaning
• Restlessness
• Irritability
• Abnormal crying
• Drowsiness
• Guillain-Barré syndrome
• Neuritis
• Neuralgia
• Seizures
• Encephalomyelitis

Cardiovascular Disorders

• Hot flushes
• Vasculitis
  - Henoch-Schönlein purpura (with transient renal involvement in certain cases)

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Upper abdominal pain

Endocrine and Metabolic Disorders

• Shivering
• Loss of appetite

Musculoskeletal Disorders

• Myalgia
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Injection site reactions
  - Pain/ tenderness
  - Erythema
  - Swelling
  - Induration
  - Ecchymosis
  - Pruritus
  - Rash
  - Warmth
  - Discomfort
• Allergic dermatitis
• Generalised pruritus
• Papular rash
• Urticaria
• Pruritus
• Erythema
• Hyperhidrosis

Immune, Blood and Lymphatic System Disorders

• Fever
• Lymphadenopathy
• Hypersensitivity
• Allergic reactions
• Angioedema
• Influenza-like illness
• Thrombocytopenia
• Anaphylactic reactions
• Transient thrombocytopenia
• Shock

Other

• Interference with serological testing (See additional prescribing points)

None routine

Additional observations

• Anaphylaxis and syncope (for 15mins following administration)
• Seizure-like activity associated with syncope

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

Administration directions

• DO NOT administer as IV
• The vaccine should be allowed to reach room temperature before use
• Shake before use to distribute the suspension uniformly before administration
• Inspect the vaccine visually for particulate matter and/or discolouration prior to administration
• If either of these conditions exists, the vaccine should not be administered
• Any unused medicine or waste material should be disposed of in accordance with local requirements

Special precautions

• The vaccine must be administered with caution to subjects with thrombocytopenia or a bleeding disorder, since bleeding may occur following an intramuscular administration to these subjects
• Appropriate medical treatment and supervision should be readily available for immediate use in case of an anaphylactic reaction following the administration of the vaccine
• As a precautionary measure, adrenaline (epinephrine) injection (1:1000) must be immediately available in case of unexpected anaphylactic or serious allergic reactions
• 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 falling injury and manage syncopal reactions

Interference with serological testing

• Following influenza vaccination, false positive results in serology tests using the ELISA method to detect antibodies against HIV-1, hepatitis C and especially HTLV-1 have been observed
• The western blot technique disproves the false-positive ELISA test results
• The transient false positive reactions could be due to the IgM response by the vaccine

Studies conducted in pregnancy

• One developmental and reproductive toxicity study conducted in rabbits with quadrivalent influenza vaccine (split virion, inactivated) did not show any effects on mating performance, embryo-foetal development and early postnatal development 
• Data from worldwide use of inactivated influenza vaccines, including experience with use of quadrivalent influenza vaccine (split virion, inactivated) and the trivalent inactivated influenza vaccine in countries where inactivated influenza vaccines are recommended in all stages of pregnancy, and data from a clinical study conducted in Finland with the quadrivalent influenza vaccine (split virion, inactivated) administered in pregnant women during the second or third trimester (230 exposed pregnancies and 231 live births) did not indicate any adverse foetal or maternal outcomes attributable to the vaccine
• Data from four clinical studies conducted with the trivalent inactivated influenza vaccine, thiomersal free, administered to pregnant women during the second and third trimesters (more than 5000 exposed pregnancies and more than 5000 live births, followed up to approximately 6 months post-partum), did not indicate any adverse foetal, newborn, infant or maternal outcomes attributable to the vaccine
• In clinical studies conducted in South Africa and Nepal, there were no significant differences between the trivalent inactivated influenza vaccine and placebo groups with regards to foetal, newborn, infant and maternal outcomes (including miscarriage, stillbirth, premature birth, low birth weight)
• In a study conducted in Mali, there were no significant differences between the trivalent inactivated influenza vaccine and control vaccine (quadrivalent meningococcal conjugate vaccine) groups with regards to prematurity rate, stillbirth rate and low birth weight/small for gestational age rate

The quadrivalent influenza vaccine (split virion, inactivated) provides active immunisation against four influenza virus strains (two A subtypes and two B types) contained in the vaccine. The vaccine induces humoral antibodies against the haemagglutinins within 2 to 3 weeks. These antibodies neutralise influenza viruses. Specific levels of haemagglutination inhibition (HAI) antibody titer post vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza illness but the HAI antibody titers have been used as a measure of vaccine activity. In some human challenge studies, HAI antibody titers of ≥1:40 have been associated with protection from influenza illness in up to 50% of subjects.

Since influenza viruses constantly evolve, the virus strains selected in the vaccine are reviewed annually by the World Health Organisation (WHO). Annual revaccination with the quadrivalent influenza vaccine (split virion, inactivated) has not been studied. However, based on clinical experience with the trivalent vaccine, 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.

Split influenza virus, inactivated strains for 2023 Southern Hemisphere
A/Sydney/5/2021 (H1N1)pdm09 - like strain (A/Sydney/5/2021, SAN-013)
A/Darwin/9/2021 (H3N2) - like strain (A/Darwin/9/2021, IVR-228)
B/Austria/1359417/2021 - like strain (B/Michigan/01/2021, wild type)
B/Phuket/3073/2013 - like strain (B/Phuket/3073/2013, wild type)

Injection 0.5ml

• Vaxigrip Tetra (Sanofi-Aventis)