FluMist

FluMist® Quadrivalent is a vaccine indicated for active immunization for the prevention of influenza disease caused by influenza A subtype viruses and type B viruses contained in the vaccine [see DESCRIPTION].

FluMist Quadrivalent is approved for use in persons 2 through 49 years of age.

FluMist® Quadrivalent
(pronounced FLEW-mist Kwä-dre-VA-lent)
(Influenza Vaccine Live, Intranasal)

Please read this Patient Information carefully before you or your child is vaccinated with FluMist Quadrivalent.

This is a summary of information about FluMist Quadrivalent. It does not take the place of talking with your healthcare provider about influenza vaccination. If you have questions or would like more information, please talk with your healthcare provider.

What is FluMist Quadrivalent?

FluMist Quadrivalent is a vaccine that is sprayed into the nose to help protect against influenza. It can be used in children, adolescents, and adults ages 2 through 49. FluMist Quadrivalent is similar to MedImmune's trivalent Influenza Vaccine Live, Intranasal (FluMist) except FluMist Quadrivalent provides protection against an additional influenza strain. FluMist Quadrivalent may not prevent influenza in everyone who gets vaccinated.

Who should not get FluMist Quadrivalent?

You should not get FluMist Quadrivalent if you:

• have a severe allergy to eggs or to any inactive ingredient in the vaccine (see “What are the ingredients in FluMist Quadrivalent?”)
• have ever had a life-threatening reaction to influenza vaccinations
• are 2 through 17 years old and take aspirin or medicines containing aspirin. Children or adolescents should not be given aspirin for 4 weeks after getting FluMist or FluMist Quadrivalent unless your healthcare provider tells you otherwise.

Please talk to your healthcare provider if you are not sure if the items listed above apply to you or your child.

Children under 2 years old have an increased risk of wheezing (difficulty with breathing) after getting FluMist Quadrivalent.

Who may not be able to get FluMist Quadrivalent?

Tell your healthcare provider if you or your child:

• are currently wheezing
• have a history of wheezing if under 5 years old
• have had Guillain-Barré syndrome
• have a weakened immune system or live with someone who has a severely weakened immune system
• have problems with your heart, kidneys, or lungs
• have diabetes
• are pregnant or nursing
• are taking Tamiflu®, Relenza®, amantadine, or rimantadine

If you or your child cannot take FluMist Quadrivalent, you may still be able to get an influenza shot. Talk to your healthcare provider about this.

How is FluMist Quadrivalent given?

• FluMist Quadrivalent is a liquid that is sprayed into the nose.
• You can breathe normally while getting FluMist Quadrivalent. There is no need to inhale or “sniff” it.
• People 9 years of age and older need one dose of FluMist Quadrivalent each year.
• Children 2 through 8 years old may need 2 doses of FluMist Quadrivalent, depending on their history of previous influenza vaccination. Your healthcare provider will decide if your child needs to come back for a second dose.

What are the possible side effects of FluMist Quadrivalent?

The most common side effects are:

• runny or stuffy nose
• sore throat
• fever over 100 degrees F

Other possible side effects include:

• decreased appetite
• headache
• irritability
• muscle ache
• tiredness
• chills
• cough

Call your healthcare provider or go to the emergency department right away if you or your child experience:

• hives or a bad rash
• trouble breathing
• swelling of the face, tongue, or throat

These are not all the possible side effects of FluMist Quadrivalent. You can ask your healthcare provider for a complete list of side effects that is available to healthcare professionals.

Call your healthcare provider for medical advice about side effects. You may report side effects to VAERS at 1-800-822-7967 or http://vaers.hhs.gov.

What are the ingredients in FluMist Quadrivalent?

Active Ingredient: FluMist Quadrivalent contains 4 influenza virus strains that are weakened (A(H1N1), A(H3N2), B Yamagata lineage, and B Victoria lineage).

Inactive Ingredients: monosodium glutamate, gelatin, arginine, sucrose, dibasic potassium phosphate, monobasic potassium phosphate, and gentamicin.

FluMist Quadrivalent does not contain preservatives.

How is FluMist Quadrivalent Stored?

FluMist Quadrivalent is stored in a refrigerator (not the freezer) between 35-46 degrees F (2-8 degrees C) upon receipt. FluMist Quadrivalent sprayer must be kept in the carton until use in order to protect from light. FluMist Quadrivalent must be used before the expiration date on the sprayer label.

If you would like more information, talk to your healthcare provider or visit www.flumistquadrivalent.com or call 1-877-633-4411.

Contraindications

• Severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine, including egg protein.1 (See Sensitivity Reactions under Cautions.)

• Severe allergic reaction (e.g., anaphylaxis) to previous dose of any influenza vaccine.1

• Children and adolescents 2 through 17 years of age receiving aspirin or aspirin-containing therapy; possible association of Reye’s syndrome with aspirin use and wild-type influenza infection.1 (See Specific Drugs under Interactions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions (e.g., anaphylactic reaction, facial edema, urticaria) reported.1

Prior to administration, review patient’s history with respect to possible sensitivity reactions to the vaccine or vaccine components, including egg protein, and prior vaccination-related adverse effects and assess benefits versus risks.100 112

Appropriate medical treatment and supervision must be readily available in case anaphylaxis occurs.1

Do not administer additional vaccine doses to any individual who had a severe allergic reaction to a previous dose.1 (See Contraindications under Cautions.)

Seasonal intranasal live influenza vaccine is produced using eggs;1 contains residual egg protein (<24 mcg of ovalbumin per dose).1

Manufacturer states that seasonal intranasal live influenza vaccine contraindicated in individuals who have had a severe allergic reaction (e.g., anaphylaxis) to egg protein.1 Although Vaccine Adverse Event Reporting System (VAERS) has received occasional reports of anaphylaxis in egg-allergic individuals after administration of influenza vaccines, ACIP states that influenza vaccines produced using eggs may be administered safely to individuals with a history of egg allergy.100

Individuals who are able to eat lightly cooked eggs (e.g., scrambled eggs) without reaction are unlikely to be allergic.100 Egg-allergic individuals may tolerate egg in baked products (e.g., bread, cake).100 Egg allergy can be confirmed by a consistent medical history of adverse reactions to eggs and egg-containing foods in addition to skin and/or blood testing for immunoglobulin E antibodies to egg proteins.100

ACIP states that individuals with a history of egg allergy involving only urticaria after exposure to eggs may receive any licensed and recommended influenza vaccine that is appropriate based on age and health status, including those produced using eggs.100

These experts state that individuals with a history of egg allergy involving symptoms other than urticaria (e.g., angioedema, respiratory distress, lightheadedness, recurrent emesis, reactions requiring epinephrine or another emergency medical intervention) also may receive any licensed and recommended influenza vaccine that is appropriate based on age and health status; however, administer the vaccine in an inpatient or outpatient medical setting (including but not necessarily limited to hospitals, clinics, health departments, and physician offices) under supervision of a health-care provider able to recognize and manage severe allergic reactions.100

ACIP states that a previous severe allergic reaction to influenza vaccine, regardless of the component suspected of being responsible for the reaction, is a contraindication to future receipt of influenza vaccine.100 112

Infants <24 Months of Age

Do not use in infants <24 months of age; increased risk of wheezing and hospitalization reported in clinical trials in this age group.1 (See Pediatric Use under Cautions.)

Individuals with Asthma or Recurrent Wheezing

Individuals of any age with asthma and children <5 years of age with history of recurrent wheezing or a recent wheezing episode (i.e., during the past 12 months) may be at increased risk of wheezing after receiving intranasal live influenza vaccine.1

Manufacturer states that intranasal live influenza vaccine has not been studied in individuals with severe asthma or active wheezing.1

ACIP states that data are insufficient to determine the level of severity of asthma for which administration of intranasal live influenza vaccine would be inadvisable.100 These experts state that intranasal live influenza vaccine should not be used in individuals with asthma or in children 24 through 59 months of age who have had a wheezing episode within the past 12 months.100 (See Pediatric Use under Cautions.)

Guillain-Barré Syndrome (GBS)

If GBS occurred within 6 weeks after previous influenza vaccination, manufacturer states base decision to administer influenza vaccine on careful consideration of potential benefits and risks.1

Unclear whether influenza vaccination increases risk of recurrence of GBS.100 Temporal association was noted between administration of 1976 swine influenza vaccine and GBS.1 100 Investigations to date suggest no large increase in GBS associated with influenza vaccine (other than 1976 swine influenza vaccine) and if influenza vaccine does pose a risk it probably is quite small (i.e., approximately 1 additional case of GBS per 1 million vaccinees).1 100

ACIP states that, as a precaution, individuals who are not at high risk for severe influenza complications and who developed GBS within 6 weeks of a previous dose of influenza vaccine generally should not receive influenza vaccination;100 clinicians might consider use of antiviral prophylaxis for such individuals.100 However, ACIP states that benefits of influenza vaccine may outweigh risks for certain individuals with a history of GBS who are at high risk for severe complications from influenza.100

Individuals with Altered Immunocompetence and Their Close Contacts

Efficacy not studied in immunocompromised individuals.1 Limited data in immunocompromised adults, adolescents, and children with HIV or cancer indicate adverse effects and frequency and duration of vaccine virus shedding in such individuals are similar to that reported in healthy individuals.1

CDC, NIH, IDSA, AAP, and other experts state that HIV-infected children, adolescents, and adults should receive annual vaccination against seasonal influenza with parenteral inactivated influenza vaccine (not the intranasal live vaccine).100 112 155 156

ACIP states that live viral vaccines (including intranasal live influenza vaccine) usually should not be used in immunocompromised individuals, except in certain circumstances.134 These experts state that use of live virus vaccines can be considered in patients with leukemia, lymphoma, or other malignancies if the disease is in remission and chemotherapy was terminated at least 3 months prior to vaccination.134 (See Specific Drugs under Interactions.)

Because of possible transmission of live vaccine viruses, intranasal live influenza vaccine should not be administered to close contacts of severely immunocompromised individuals who are hospitalized and require care in a protective environment (e.g., HSCT recipients);100 235 the vaccine may be administered to close contacts of less severely immunocompromised individuals (e.g., those not requiring a protective environment).100 235

In addition, because of possible transmission of live vaccine viruses, ACIP states that health-care workers who have received the intranasal vaccine should avoid contact with severely immunocompromised patients requiring a protective environment (e.g., HSCT recipients) for 7 days after vaccination.100 Hospital visitors who have received the vaccine should avoid contact with severely immunosuppressed patients for 7 days after vaccination but may visit patients who are not severely immunosuppressed.100

Individuals with Medical Conditions that Increase Risk of Influenza Complications

Safety not established in individuals with underlying medical conditions that increase risk for complications following wild-type influenza infection.1

Transmission of Vaccine Virus

Intranasal influenza vaccine contains live, attenuated virus.1 Vaccine virus capable of infection and replication is present in nasal secretions of vaccine recipients1 and viral shedding occurs in adults and children who have received the intranasal live vaccine.1

Relationship between vaccine virus replication in vaccine recipients and transmission of vaccine virus to other individuals not established.1 Transmission of vaccine virus has occurred rarely between recipients of intranasal influenza vaccine and their contacts.1

Limitations of Vaccine Effectiveness

Following seasonal influenza vaccination, up to 2 weeks may be required to develop antibody protection against infection.100

May not protect all vaccine recipients against influenza.1

Seasonal influenza vaccines are formulated annually to contain influenza A and B antigens predicted to represent strains of influenza virus likely to circulate in the US during the upcoming influenza season.1 567 (See Actions.) Efficacy of seasonal vaccine during any given year depends on how closely viral strains represented in the vaccine match viral strains circulating during the season.100 166

Duration of Immunity

Immunity declines during the year after seasonal influenza vaccination.100 In addition, circulating strains of seasonal influenza virus change from year to year.100 Annual vaccination is needed for prevention of seasonal influenza.100

Do not administer influenza vaccine from a previous influenza season (e.g., 2015–2016) in an attempt to provide protection during a subsequent influenza season.100 112

Concomitant Illness

Delay administration in individuals with moderate to severe acute illness (with or without fever) until symptoms have subsided.134

ACIP states that mild diarrhea or mild upper respiratory tract illness or other acute illness (with or without fever) does not preclude vaccination.134

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune responses in vaccinees.134

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.134 (See Storage under Stability.)

Do not administer vaccine that has been mishandled or has not been stored at the recommended temperature.1 134 If there are concerns about mishandling, contact the manufacturer or state or local immunization or health departments for guidance on whether the vaccine is usable.134

Specific Populations

Category B.1

Manufacturer states use in pregnant women only when clearly needed.1

ACIP, ACOG, American College of Physicians (ACP), and other experts state that parenteral inactivated influenza vaccine (not intranasal live influenza vaccine) should be used for prevention of seasonal influenza in pregnant women.100 134

Not known whether influenza virus live is distributed into milk.1 Manufacturer recommends caution.1

Safety and efficacy established only in children ≥2 years of age.1

Not indicated in infants <24 months of age.1 Increased incidence of wheezing and hospitalization reported in a clinical trial in infants 6 through 23 months of age† who received intranasal live influenza vaccine compared with those who received parenteral seasonal inactivated influenza vaccine.1

ACIP states that intranasal live influenza vaccine should not be used in children with asthma or children 24 through 59 months of age with a history of recurrent wheezing or recent wheezing episode (i.e., during the past 12 months) and should be used with caution in those ≥5 years of age with asthma.100

Protection of young infants against seasonal influenza virus depends on immunization of their close contacts.100 112 All household contacts, health-care and day-care providers, and other close contacts of young infants should receive seasonal influenza vaccination appropriate for their age and target group.100 112

Not indicated for use in adults 50–64 years of age.1 Efficacy not demonstrated in adults 50–64 years of age.1

Not indicated for use in geriatric individuals ≥65 years of age.1

Common Adverse Effects

Children 2 through 6 years of age: Runny nose/nasal congestion, decreased appetite, irritability, lethargy, sore throat, fever, headache, muscle aches, chills.1

Older children and adolescents through 17 years of age: Adverse effects similar to those reported in younger children; in addition, abdominal pain and decreased activity.1

Adults 18 through 49 years of age: Runny nose, headache, sore throat, tiredness/weakness, muscle aches, cough, chills, nasal congestion, sinusitis.1

• Influenza vaccine live intranasal contains live, attenuated (cold-adapted) influenza virus types A and B,1 and is prepared by culturing live attenuated influenza virus reassortants in specific pathogen-free eggs.1

• Seasonal influenza vaccines are formulated annually to contain antigens representative of the influenza A (H1N1), influenza A (H3N2), and influenza B viruses likely to circulate during the upcoming influenza season.1 100 567 For the 2016–2017 season, antigenic components recommended by FDA for US formulations of seasonal influenza vaccines are the same as those recommended by WHO (Northern Hemisphere).567 568

• Intranasal live influenza vaccine 2016–2017 is a quadrivalent vaccine containing 2 influenza type A antigens (H1N1 and H3N2) and 2 influenza type B antigens (B/Yamagata lineage and B/Victoria lineage).1

• Intranasal live influenza vaccine 2016–2017 for the US contains A/Bolivia/559/2013 (H1N1) (an A/California/7/2009 (H1N1)pdm09-like virus), A/New Caledonia/71/2014 (H3N2) (an A/Hong Kong/4801/2014-like virus), B/Phuket/3073/2013 (B/Yamagata/16/88 lineage), and B/Brisbane/60/2008 (B/Victoria/2/87 lineage) virus antigens.1

• Influenza vaccines stimulate active immunity to influenza virus strains represented in the vaccines.1

• Following administration of intranasal live influenza vaccine, vaccine virus replicates in cells lining the nasopharynx.1 Protective mechanism not completely understood; may involve both serum and nasal secretory antibodies and cell-mediated immune responses (influenza-specific T-cells).1

• Efficacy of influenza vaccines in preventing seasonal influenza virus infection depends on whether the virus strains represented in the vaccines are antigenically similar to influenza virus strains circulating during the influenza season.100 166

0.2 mL pre-filled, single-use intranasal spray.

Each 0.2 mL dose of Flumist is formulated to contain 106.5-7.5 FFU (fluorescent focus units) of each of three live attenuated influenza virus reassortants:  A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2), and B/Brisbane/60/2008.

Flumist (Influenza Vaccine Live, Intranasal) is a live trivalent vaccine for administration by intranasal spray. The influenza virus strains in Flumist are (a) cold-adapted (ca) (i.e., they replicate efficiently at 25°C, a temperature that is restrictive for replication of many wild-type influenza viruses); (b) temperature-sensitive (ts) (i.e., they are restricted in replication at 37°C (Type B strains) or 39°C (Type A strains), temperatures at which many wild-type influenza viruses grow efficiently); and (c) attenuated (att) (they do not produce classic influenza-like illness in the ferret model of human influenza infection). The cumulative effect of the antigenic properties and the ca, ts, and att phenotypes is that the attenuated vaccine viruses replicate in the nasopharynx to induce protective immunity.

No evidence of reversion has been observed in the recovered vaccine strains that have been tested (135 of possible 250 recovered isolates) [see Clinical Studies (14.5)]. For each of the three reassortant strains in Flumist, the six internal gene segments responsible for ca, ts, and att phenotypes are derived from a master donor virus (MDV), and the two segments that encode the two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), are derived from the corresponding antigenically relevant wild-type influenza viruses that have been recommended by the USPHS for inclusion in the annual vaccine formulation. Thus, the three viruses contained in Flumist maintain the replication characteristics and phenotypic properties of the MDV and express the HA and NA of wild-type viruses that are related to strains expected to circulate during the 2010-2011 influenza season. For the Type A MDV, at least five genetic loci in three different internal gene segments contribute to the ts and att phenotypes. For the Type B MDV, at least three genetic loci in two different internal gene segments contribute to both the ts and att properties; five genetic loci in three gene segments control the ca property.

Specific pathogen-free (SPF) eggs are inoculated with each of the reassortant strains and incubated to allow vaccine virus replication. The allantoic fluid of these eggs is harvested, pooled and then clarified by filtration. The virus is concentrated by ultracentrifugation and diluted with stabilizing buffer to obtain the final sucrose and potassium phosphate concentrations. Ethylene diamine tetracetic acid (EDTA) is added to the dilution buffer for H3N2 strains. The viral harvests are then sterile filtered to produce the monovalent bulks. Each lot is tested for ca, ts, and att phenotypes and is also tested extensively by in vitro and in vivo methods to detect adventitious agents. Monovalent bulks from the three strains are subsequently blended and diluted as required to attain the desired potency with stabilizing buffers to produce the trivalent bulk vaccine. The bulk vaccine is then filled directly into individual sprayers for nasal administration.

Each pre-filled refrigerated Flumist sprayer contains a single 0.2 mL dose. Each 0.2 mL dose contains 106.5-7.5 FFU of live attenuated influenza virus reassortants of each of the three strains:  A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2), and B/Brisbane/60/2008. Each 0.2 mL dose also contains 0.188 mg/dose monosodium glutamate, 2.00 mg/dose hydrolyzed porcine gelatin, 2.42 mg/dose arginine, 13.68 mg/dose sucrose, 2.26 mg/dose dibasic potassium phosphate, 0.96 mg/dose monobasic potassium phosphate, and <0.015 mcg/mL gentamicin sulfate. Flumist contains no preservatives.

The tip attached to the sprayer is equipped with a nozzle that produces a fine mist that is primarily deposited in the nose and nasopharynx. Flumist is a colorless to pale yellow liquid and is clear to slightly cloudy.

You may not be able to receive FluMist if you are allergic to eggs, or if you have:

• a history of severe allergic reaction to a flu vaccine;

• a history of Guillain-Barré syndrome (within 6 weeks after receiving a flu vaccine);

• a weak immune system caused by disease, bone marrow transplant, or by using certain medicines or receiving cancer treatments;

• if someone in your household has a weak immune system; or

• if you are under 18 years old and have recently taken aspirin.

To make sure FluMist is safe for you, tell your doctor if you have (or the child receiving this vaccine has):

• asthma, wheezing, or other breathing disorder;

• a history of seizures;

• a neurologic disorder or disease affecting the brain (or if this was a reaction to a previous vaccine); or

• used a flu medication such as oseltamivir (Tamiflu) or zanamivir (Relenza) within the past 48 hours.

You can still receive a vaccine if you have a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving FluMist.

FluMist nasal influenza vaccine is not recommended for use in pregnant women. However, the Centers for Disease Control and Prevention recommends that pregnant women get a flu shot during any trimester of pregnancy to protect themselves and their newborn babies from flu.

It is not known whether influenza virus nasal vaccine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

FluMist is not approved for anyone younger than 2 or older than 49 years of age.

Before receiving this vaccine, tell the doctor about all other vaccines you have recently received.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• amantadine;

• aspirin;

• oseltamivir (Tamiflu);

• rimantadine; or

• zanamivir (Relenza).

This list is not complete. Other drugs may interact with influenza virus nasal vaccine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Applies to influenza virus vaccine, live, trivalent: nasal solution, nasal spray

In 1976, a number of people who received the “swine flu” influenza vaccine developed Guillain-Barré syndrome (GBS), which is a disease that may cause paralysis. Most of these people were over 25 years of age. Although only 10 out of every one million people who received the vaccine actually developed GBS, this number was 6 times higher than would normally have been expected. Most of the people who got GBS recovered completely.

It is assumed that the “swine flu” virus included in the 1976 vaccine caused the problem, but this has not been proven. Since that time, the “swine flu” virus has not been used in influenza vaccines, and there has been no recurrence of GBS that was associated with influenza vaccinations.

Along with its needed effects, influenza virus vaccine, live, trivalent (the active ingredient contained in FluMist) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking influenza virus vaccine, live, trivalent:

• Chills
• cough
• decreased appetite
• fever
• headache
• muscle aches
• sore throat
• stuffy or runny nose
• tiredness or weakness

• Earache
• pain or tenderness around the eyes and cheekbones
• redness or swelling in the ear
• shortness of breath or troubled breathing
• sneezing
• tightness of the chest or wheezing

• Difficulty with breathing or swallowing
• hives
• itching, especially of the feet or hands
• reddening of the skin, especially around the ears
• swelling of the eyes, face, or inside of the nose
• unusual tiredness or weakness (sudden and severe)

• Anxiety
• bloody nose
• blue or pale skin
• chest pain, possibly moving to the left arm, neck, or shoulder
• confusion
• diarrhea
• dizziness
• drowsiness
• fast heartbeat
• general feeling of illness
• hoarseness
• inability to move the arms and legs
• irritation
• itching
• joint pain, stiffness, or swelling
• nausea
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• severe headache
• skin rash
• stiff neck and/or back
• sudden numbness and weakness in the arms and legs
• swelling or puffiness of the face
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• unusual tiredness or weakness
• vomiting
• weakness of the muscles in your face

Some side effects of influenza virus vaccine, live, trivalent may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain
• irritability
• loss of appetite

• Welts

Use is not recommended. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: -Because some viruses are excreted in human milk, caution is advised.