Seasonal Influenza Vaccine Safety: A Summary for Clinicians

• Pain and other injection site reactionsexternal icon are frequently reported after IIV vaccination in both children and adults. In IIV clinical trialsexternal icon, up to 65% of people vaccinated with IIV experience pain at the injection site during the first week after vaccination which usually did not interfere with activity.
• Fever, malaise, myalgia, and other systemic symptoms can occur after vaccination with IIV, most often affecting individuals who have had no previous exposure to the influenza virus antigens in the vaccine (e.g., young children). In adults, the rate of having these symptoms is similar after IIV and after a placebo injection.
• Vaccine components can on rare occasions cause allergic reactions (immediate hypersensitivity). Manifestations of immediate hypersensitivity range from mild urticaria (hives) and angioedema (swelling beneath the skin) to anaphylaxis.
• In some seasons, IIV has been associated with febrile seizures in young children, particularly when given together with 13-valent pneumococcal conjugate vaccine (PCV13) and diphtheria, tetanus and pertussis (DTaP) vaccines. Flu vaccine composition often changes year-to-year, and CDC and FDA will continue to closely monitor the safety of influenza vaccines each season.
• Guillain–Barré Syndrome (GBS) following IIV occurs rarely. The cause of GBS, a serious neurological condition that can cause paralysis, is unknown, however, gastrointestinal and upper respiratory infections are known risk factors.
  • Safety monitoring of seasonal IIV over the course of many years has not detected a clear link to GBS. However, if there is a risk of GBS from IIV, it would be no more than 1 or 2 cases per million people vaccinated.
  • Each year, about 3,000 to 6,000 people in the United States develop GBS whether or not they received a vaccination —1 to 2 people per 100,000.
  • Even though GBS following influenza illness is rare, studiesexternal icon suggest that the risk of developing GBS after having influenza is higher than the potential risk of developing GBS after vaccination.
• IIV, like other injections, can also cause syncope (fainting).

IIV should not be administered to the following individuals:

• Infants younger than 6 months of age.
• People who have experienced a severe (life threatening) allergy to a prior dose of a seasonal influenza vaccine (IIV or LAIV).
• People who have a severe allergy to a component of the IIV vaccine. Health care providers should consult the package insertsexternal icon for vaccine components.

Recommendations for vaccinating patients who are allergic to eggs are available. RIV is approved in individuals aged 18 years and older, and people in this age group who are allergic to eggs may receive RIV. If RIV is not available or the recipient is not 18 years or older, most egg-allergic patients can safely receive IIV. Those who have only experienced hives as a reaction to egg may receive IIV, with some additional safety precautions. Individuals with a history of severe (life threatening) allergy to eating eggs may receive IIV if it is administered by a physician experienced in the recognition and management of severe allergic conditions.

In general, vaccinations should be deferred when a precaution is present. However, a health care provider may determine that vaccination is indicated in the presence of a precaution because the benefit of protection from the vaccine outweighs the risk for an adverse reaction. The following are precautions for IIV:

• GBS within 6 weeks of a previous dose of an influenza vaccine (IIV or LAIV)
• Presence of a moderate or severe acute illness with or without a fever. Individuals who were hospitalized with an acute illness but who are now well enough to be discharged from a hospital can be vaccinated.

Before administering IIV, health care providers should ask the patient about the following:

• Egg allergies: Individuals who report egg allergy should be evaluated using the algorithm in Figure 2 of the 2015-16 ACIP influenza guidelines.
• Reactions or adverse events, including GBS, after prior doses of influenza vaccine. Individuals who have had severe allergies after previous vaccine doses should not be vaccinated.
• Current health status, including any current (acute) illness: patients with mild illnesses should be able to be safety vaccinated; those with moderate to severe acute illnesses (with or without fever) should be vaccinated at the discretion of the doctor and patient.

To reduce the risk of adverse events after vaccination, health care providers should take the following steps:

• IIV should be administered by intramuscular injection, or intradermal injection in the case of intradermal IIV, using appropriate technique pdf icon[480 KB, 28 pages].
• Providers vaccinating children and adolescents aged <19 years of age should be sure the IIV formulation is approved for use in children in their patients’ age group and the proper dose is used. No influenza vaccines are approved for use in infants aged <6 months.

Providers should consult the ACIP General Recommendations regarding other steps to take that may help prevent adverse events after IIV vaccination.

• The most common (≥10%) local and systemic reactions in adults 18-64 years of age were injection site pain (28%), injection site erythema (13%), headache (16%), fatigue (12%), muscle pain (11%) and malaise (10%).

ccIIV3 should not be administered to the following:

• Individuals who have had a severe allergic reaction to any component of the vaccine or after previous dose of any influenza vaccine.

In general, vaccinations should be deferred when a precaution is present. However, a healthcare provider may determine that vaccination is indicated in the presence of a precaution because the benefit of protection from the vaccine outweighs the risk for an adverse reaction. The following are precautions for ccIIV3:

• Moderate or severe acute illness with or without fever.
• History of GBS within 6 weeks of previous influenza vaccination.

Before administering ccIIV3, health care providers should ask the patient about the following:

• Egg allergies: Individuals who report egg allergy should be evaluated using the algorithm in Figure 2 of the ACIP General Influenza Recommendations.
• Reactions or adverse events, including GBS, after prior doses of influenza vaccine: individuals who have had severe allergies after previous vaccine doses should not be vaccinated.
• Current health status, including any current (acute) illness: patients with mild illnesses should be able to be safety vaccinated; those with moderate to severe acute illnesses (with or without fever) should be vaccinated at the discretion of the doctor and patient.

To reduce the risk of adverse events after vaccination, health care providers should take the following steps:

• ccIIV3 should be administered by intramuscular injection using appropriate technique pdf icon[480 KB, 28 pages].
• ccIIV3 should be used in individuals 18 years of age and older.
• Providers should consult the ACIP General Recommendations regarding other steps to take that may help prevent adverse events after influenza vaccination

• During clinical trialsexternal icon, the most common injection-site reaction was pain (37%); the most common solicited systemic adverse reactions were headache (15%), fatigue (15%) and muscle pain (11%).

RIV should not be administered to the following:

• Individuals who have had a severe allergic reaction (e.g., anaphylaxis) after previous dose of RIV or to a vaccine component.

In general, vaccinations should be deferred when a precaution is present. However, a healthcare provider may determine that vaccination is indicated in the presence of a precaution because the benefit of protection from the vaccine outweighs the risk for an adverse reaction. The following are precautions for RIV:

• Moderate or severe acute illness with or without fever.
• History of GBS within 6 weeks of previous influenza vaccination.

Before administering RIV, health care providers should ask the patient about the following:

• Allergies
• Reactions or adverse events, including GBS, after prior doses of influenza vaccine: individuals who have had severe allergies after previous vaccine doses should not be vaccinated.
• Current health status, including any current (acute) illness: patients with mild illnesses should be able to be safety vaccinated; those with moderate to severe acute illnesses (with or without fever) should be vaccinated at the discretion of the doctor and patient.

Current health status, including any current (acute) illness: patients with mild illnesses should be able to be safety vaccinated; those with moderate to severe acute illnesses should be vaccinated at the discretion of the doctor and patient.

To reduce the risk of adverse events after vaccination, health care providers should take the following steps:

• RIV should be administered by intramuscular injection using appropriate technique pdf icon[480 KB, 28 pages].
• RIV should be used in individuals 18 years of age and older.
• Providers should consult the ACIP General Recommendations regarding other steps to take that may help prevent adverse events after influenza vaccination

Studies support the safety of LAIV. In clinical trialsexternal icon, quadrivalent LAIV had a safety profile similar to the previously used trivalent LAIV, with the exception of slightly more reports of fever after the first dose of quadrivalent LAIV compared to trivalent LAIV. This occurred in a subset of children 2 years through 8 years of age who were getting vaccinated for the first time. Rhinitis (runny nose) and nasal congestion pdf icon[1.1 MB, 26 pages]external icon occur more commonly after LAIV than IIV or placebo in adults and children.

• The most common adverse reactions to LAIV pdf icon[1.1 MB, 26 pages]external icon are runny nose or nasal congestion in all ages, fever >100°F in children 2-6 years of age, and sore throat in adults.
• One studyexternal icon of 8,352 children aged 6 through 59 months showed that younger children aged 6 through 23 months (an age group for which LAIV is not licensed) had increased rates of wheezing in the 42 days after LAIV (6%) than after IIV (4%). Children aged 24 through 59 months had similar rates of wheezing after LAIV (2%) pdf icon[1.1 MB, 26 pages]external icon and IIV (3%).
• According to the LAIV package insertexternal icon:
  • In children aged 2 through 6 years, fever >100° F occurred more often after first dose LAIV (16%) than placebo (11%). Adults receiving LAIV did not have an increased risk for fever after vaccination compared with placebo.
  • In adults the following other adverse events were reported more often after LAIV than after an intranasal placebo: headache, sore throat, tiredness/weakness, muscles aches, cough, chills, and sinusitis.

LAIV should not be administered to the following:

• Children aged <2 years of age.
• Adults aged ≥50 years of age.
• Individuals with a history of severe allergic reaction to any component of the vaccine or to a previous dose of any influenza vaccine.
• People who are allergic to eggs.
• Children or adolescents receiving aspirin or other salicylates (because of the association of Reye syndrome with wild-type influenza virus infection).
• Pregnant women.
• Individuals with known or suspected immunodeficiency diseases or immunosuppressed states (including those caused by HIV).
• Children 2 through 4 years of age who have asthma or who have had a wheezing episode noted in their medical record within the past 12 months, or for whom parents report that a health care provider stated that they had wheezing or asthma within the last 12 months.
• Individuals who have taken influenza antiviral medications within the previous 48 hours
• Persons who care for severely immunosuppressed persons who require a protective environment, or these individuals should avoid contact with such persons for 7 days after receipt.

In general, vaccinations should be deferred when a precaution is present. However, a health care provider may determine that vaccination is indicated in the presence of a precaution because the benefit of protection from the vaccine outweighs the risk for an adverse reaction. The following are precautions for LAIV:

• GBS within 6 weeks of a previous dose of an influenza vaccine (IIV or LAIV)
• Presence of a moderate or severe acute illness with or without a fever.⁵ Individuals who were hospitalized with an acute illness but who are now well enough to be discharged from a hospital can be vaccinated.
• Asthma in children aged 5 years and older.
• Individuals who have other medical conditions that place them at increased risk for complications from influenza, including:
  • Other chronic disorders of the pulmonary or cardiovascular system (except hypertension)
  • Neurological/neuromuscular diseases
  • Metabolic disease, such as diabetes mellitus
  • Renal or hepatic dysfunction
  • Hematologic disorders, such as hemoglobinopathies

Before administering an influenza vaccine, health care providers should ask patients about the following:

• Egg allergies: Individuals who report egg allergy should be evaluated using the algorithm in Figure 2 of the ACIP General Influenza Recommendations.
• Reactions or adverse events, including GBS, after prior doses of influenza vaccine: individuals who have had severe allergies after previous vaccine doses should not be vaccinated.
• Current health status, including any current (acute) illness: patients with mild illnesses should be able to be safety vaccinated; those with moderate to severe acute illnesses (with or without fever) should be vaccinated at the discretion of the doctor and patient.
• Young children may experience episodes of wheezing in association with certain respiratory viruses. Some young children might have a history of wheezing but have not been diagnosed with asthma. The following screening recommendations should be used to assist individuals who administer influenza vaccines in providing the appropriate vaccine for children aged 2 through 4 years of age.¹
  • Screen for possible reactive airways diseases when considering use of LAIV for children aged 2 through 4 years, and avoid use of LAIV in children with asthma or a recent wheezing episode.
  • Consult the medical record, when available, to identify children 2 through 4 years of age with asthma or recurrent wheezing that might indicate asthma.
  • Ask parents or caregivers of children aged 2 through 4 years: “In the past year, has a health care provider ever told you that your child had wheezing or asthma?”
  • Do not administer LAIV to children whose parents or caregivers answer “yes” to this question, or to children who have asthma or who had a wheezing episode noted in the medical record during the preceding 12 months should not receive LAIV. IIV is available for use in children with asthma or possible reactive airways disease.

• Health care providers who treat severely immunocompromised patients (e.g., those who require a protective environment, such as patients with hematopoietic stem cell transplants) and close contacts of these patients should receive IIV rather than LAIV, or should avoid contact with these patients for 7 days after vaccination. A live, attenuated vaccine virus could be transmitted to the severely immunosuppressed person.
• LAIV should be administered by an intranasal squirt using appropriate technique described in the package insertexternal icon.
• Providers should consult the ACIP General Recommendations regarding other steps to take that may help prevent adverse events after LAIV vaccination.