Clinical Guidance for Seasonal Influenza Vaccine Safety

Some people experience no adverse events after receiving egg-based IIV3s. Some adverse events are relatively common (such as mild tenderness or pain at the injection site), and some are rare (such as Guillain-Barre syndrome).

• Pain and other injection site reactions are frequently reported after administration of inactivated influenza vaccines in both children and adults. They include symptoms such as pain, redness, and swelling at the injection site. These side effects may affect your ability to do daily activities, but they should go away in a few days.
• Fever, malaise, myalgia, and other systemic symptoms can also occur after inactivated influenza vaccination. These reactions are more common among individuals who have had no previous exposure to the influenza virus antigens in the vaccine (e.g., young children). These symptoms are generally less common in adults.
• Influenza vaccines can be associated with allergic (immediate hypersensitivity) reactions that range in severity from mild reactions 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.
• Guillain–Barré Syndrome (GBS), a serious neurological condition that can cause paralysis occurs rarely following influenza vaccination. The cause of GBS is unknown. GBS is also associated with some gastrointestinal and upper respiratory infections.
  • Safety monitoring of seasonal IIVs over the course of many years has not detected an increased risk of GBS in most seasons. When an increased risk has been detected it has been small (approximately 1 or 2 additional cases for every million people vaccinated).
  • Each year, about 3,000 to 6,000 people in the United States develop GBS regardless of whether they received a vaccination —a rate of 1 or 2 people per 100,000.
  • Even though GBS following influenza illness is rare, studies suggest that the risk of developing GBS after having influenza is higher than the potential risk of developing GBS after influenza vaccination.
• IIVs, like other injections, can also be associated with syncope (fainting).

IIV should not be administered to infants younger than 6 months of age, because they are not approved for this age group.

Egg-based IIV3s are contraindicated for the following groups:

• People who have experienced a severe or life threatening allergic reaction (e.g., anaphylaxis) to a prior dose of any influenza vaccine (any egg-based IIV, ccIIV, RIV, or LAIV of any valency).
• People who have had a severe allergic reaction to any component of a specific influenza vaccine (other than egg protein) should not receive that vaccine or other vaccines containing that component. Health care providers should consult the package inserts for vaccine components.

Although a history of severe allergic reaction (e.g., anaphylaxis) to egg is a labeled contraindication to the use of egg-based IIV3s and LAIV3, ACIP recommends that persons with a history of egg allergy may receive any licensed, recommended influenza vaccine that is otherwise appropriate for their age and health status. See, Vaccination of Persons with Egg Allergies, below.

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

The safety profile of ccIIV3 is similar to that of other (egg-based) IIV3s. (See, Adverse Events Following Egg-Based IIV3s, above).

ccIIV3 should not be administered to infants younger than 6 months of age, because it is not approved for this age group.

In addition, ccIIV3 is contraindicated for individuals who have had a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency, or to any component of ccIIV3.

Precautions to the use of cell culture-based IIV3s include:

• GBS within six weeks of a previous dose of any influenza vaccine.
• Presence of a moderate or severe acute illness with or without a fever. Individuals who were hospitalized with an acute illness but now are well enough to be discharged can be vaccinated
• History of severe allergic reaction to a previous dose of any other influenza vaccine (i.e., any egg-based IIV, RIV, or LAIV of any valency). If administered in these instances, vaccination should occur in a medical setting under supervision of a provider who can recognize and manage a severe allergic reaction. Providers can also consider consultation with an allergist to help identify the vaccine component responsible for the previous severe allergic reaction.

Like other injectable influenza vaccines, RIV3 may cause pain, redness, and swelling at the injection site as well as fever, malaise, and myalgias. In some studies, some local injection site reactions were less common with RIV than with IIVs.

RIV3 should not be administered to persons younger than 18 years of age, because it is not approved for this age group.

In addition RIV3 is contraindicated for individuals who have had a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency, or to any component of RIV3.

• History of GBS within six weeks of previous dose of any influenza vaccine.
• Presence of a moderate or severe acute illness with or without a fever. Individuals who were hospitalized with an acute illness but now are well enough to be discharged can be vaccinated
• History of severe allergic reaction to a previous dose of any other influenza vaccine (i.e., any egg-based IIV, ccIIV, or LAIV of any valency). If administered in these instances, vaccination should occur in a medical setting under supervision of a provider who can recognize and manage a severe allergic reaction. Providers can also consider consultation with an allergist to help identify the vaccine component responsible for the previous severe allergic reaction.

LAIV should not be administered to children aged <2 years of age or to adults aged ≥50 years of age, because it is approved only for persons aged 2 through 49 years.

In addition, conditions and situations in which LAIV3 is either contraindicated or in which ACIP recommends that it should not be used include:

• Individuals with a history of severe allergic reaction (e.g., anaphylaxis) to a previous dose of any influenza vaccine (any egg-based IIV, ccIIV, RIV, or LAIV of any valency), or to any component of LAIV3 (other than egg protein).
• Children or adolescents receiving aspirin or other salicylates (because of the association of Reye syndrome with wild-type influenza virus infection).
• Children aged 2 through 4 years who have received a diagnosis of asthma, or whose parents or caregivers report that a health care provider has told them during the preceding 12 months that their child had wheezing or asthma, or whose medical record indicates a wheezing episode has occurred during the preceding 12 months
• Children and adults who are immunocompromised due to any cause, including but not limited to immunosuppression caused by medications, congenital or acquired immunodeficiency states, HIV infection, anatomic asplenia, or functional asplenia (e.g., due to sickle cell anemia).
• Close contacts and caregivers of severely immunosuppressed persons who require a protected environment (alternatively, they should avoid contact with such persons for 7 days after receipt of LAIV.)
• Pregnancy
• Persons with active communication between the cerebrospinal fluid (CSF) and the oropharynx, nasopharynx, nose, or ear or any other cranial CSF leak
• Persons with cochlear implants
• Individuals who have recently taken influenza antiviral medications: LAIV3 contains live influenza viruses, and it is possible that influenza antiviral medications might interfere with replication of these viruses. This has not been studied, and the time frame for possible interference is not known. Based on the half-lives of the medications, interference might be possible if influenza antivirals are taken:
  • From 48 hours before to two weeks after LAIV3 administration for oseltamivir and zanamivir.
  • From five days before to two weeks after LAIV3 administration for peramivir.
  • From 17 days before to two weeks after LAIV3 administration for baloxavir.

• These time intervals might be longer in the presence of medical conditions that delay clearance of medications.

Although a history of severe allergic reaction (e.g., anaphylaxis) to egg is a labeled contraindication to the use of egg-based IIV4s and LAIV4, ACIP recommends that persons with a history of egg allergy may receive any licensed, recommended influenza vaccine that is otherwise appropriate for their age and health status.

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