FluMist (influenza nasal vaccine live)

FluMist (influenza nasal vaccine live) is a nasal vaccine that protects against infection with the influenza virus or the "flu." 

FluMist contains live influenza virus that has been weakened so that it causes minimal or no symptoms. When FluMist is inhaled, the body responds to the weakened viruses in FluMist by developing antibodies that fight influenza viruses. These antibodies protect against later infections by the naturally-occurring influenza virus. 

FluMist is effective only against the strains of influenza virus that are included in it, and the strains of virus change from year to year. FluMist has no effect on the flu once infection has begun. 

FluMist should be given shortly before the flu season begins to allow time for antibodies to be produced and for protection throughout the entire flu season. 

FluMist and FluMist Quadrivalent are similar except for the addition of one additional virus strain to Flumist Quadrivalent. FluMist is a trivalent vaccine because it has three flu virus strains (two type A viruses and one B type) and FluMist Quadrivalent has four virus strains (two A type and two B types).

Common side effects of FluMist include

• cough,
• runny nose,
• nasal congestion,
• sore throat,
• headache,
• restlessness,
• muscle aches,
• tiredness or weakness,
• chills, and
• fever.

Other important side effects of FluMist include

• decreased appetite,
• abdominal pain,
• sneezing, and
• hypersensitivity reactions.

Serious side effects includeDrug interactions of FluMist include aspirin therapy in children 5 to 17 years of age, because of the association between aspirin, influenza infection, and Reye's syndrome, a serious disease of the liver. 

Use of FluMist together with antiviral drugs that are active against the influenza virus has not been evaluated. Since there is a potential for antiviral drugs to reduce the effectiveness of FluMist (by preventing infection with the weakened viruses in FluMist), antiviral drugs should not be administered until 2 weeks after FluMist therapy, and FluMist should not be administered until 48 hours after antiviral therapy is discontinued. 

Administering FluMist with inactivated virus vaccines was not evaluated in FluMist clinical trials, and combining FluMist with other intranasal products has not been evaluated. FluMist did not interfere with, and was not affected by measles, mumps, rubella, or varicella live vaccines. 

FluMist should not be given to pregnant women. 

Use of FluMist during breastfeeding has not been adequately evaluated, and it is unknown if FluMist is excreted in breast milk.

The most common side effects of FluMist are:

• cough,
• runny nose,
• nasal congestion,
• sore throat,
• headache,
• restlessness,
• muscle aches,
• tiredness or weakness,
• chills, and
• fever,

 Other important side effects includes:

• decreased appetite,
• abdominal pain,
• and sneezing.

Hypersensitivity reactions also have been reported.

FluMist should not be administered to individuals with asthma because it may increase wheezing.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

• This safety experience with FluMist is relevant to FluMist Quadrivalent because both vaccines are manufactured using the same process and have overlapping compositions.
• A total of 9537 children and adolescents 1 through 17 years of age and 3041 adults 18 through 64 years of age received FluMist in randomized, placebo-controlled Studies D153-P501, AV006, D153-P526, AV019, and AV009 [3 used Allantoic Fluid containing Sucrose-Phosphate-Glutamate (AF-SPG) placebo, and 2 used saline placebo] described below.
• In addition, 4179 children 6 through 59 months of age received FluMist in Study MI-CP111, a randomized, active-controlled trial.
• Among pediatric FluMist recipients 6 months through 17 years of age, 50% were female; in the study of adults, 55% were female.
• In MI-CP111, AV006, D153-P526, AV019, and AV009, subjects were
  • White (71%),
  • Hispanic (11%),
  • Asian (7%),
  • Black (6%), and
  • Other (5%), while in D153-P501, 99% of subjects were Asian.
• A total of 1382 children and adolescents 2 through 17 years of age and 1198 adults 18 through 49 years of age received FluMist Quadrivalent in randomized, active-controlled Studies MI-CP208 and MI-CP185.
• Among pediatric FluMist Quadrivalent recipients 2 through 17 years of age, 51% were female; in the study of adults, 55% were female.
• In Studies MI-CP208 and MI-CP185, subjects were
  • White (73%),
  • Asian (1%),
  • Black or African-American (19%), and
  • Other (7%); overall,
  • 22% were Hispanic or Latino.

FluMist In Children And Adolescents

• The safety of FluMist was evaluated in an AF-SPG placebo-controlled study (AV019) conducted in a Health Maintenance Organization (HMO) in children 1 through 17 years of age (FluMist = 6473, placebo = 3216).
• An increase in asthma events, captured by review of diagnostic codes, was observed in children younger than 5 years of age who received FluMist compared to those who received placebo (Relative Risk 3.53, 90% CI: 1.1, 15.7).
• In Study MI-CP111, children 6 through 59 months of age were randomized to receive FluMist or inactivated Influenza Virus Vaccine manufactured by Sanofi Pasteur Inc.
• Wheezing requiring bronchodilator therapy or accompanied by respiratory distress or hypoxia was prospectively monitored from randomization through 42 days post last vaccination.
• Hospitalization due to all causes was prospectively monitored from randomization through 180 days post last vaccination.
• Increases in wheezing and hospitalization (for any cause) were observed in children 6 months through 23 months of age who received FluMist compared to those who received inactivated Influenza Virus Vaccine, as shown in Table 1.

Table 1: Percentages of Children with Hospitalizations and Wheezing from Study MI-CP111^a

• Most hospitalizations observed were due to gastrointestinal and respiratory tract infections and occurred more than 6 weeks post vaccination.
• In post-hoc analysis, rates of hospitalization in children 6 through 11 months of age were 6.1% (42/684) in FluMist recipients and 2.6% (18/683) in inactivated Influenza Virus Vaccine recipients.
• Table 2 shows pooled solicited adverse reactions occurring in at least 1% of FluMist recipients and at a higher rate ( ≥ 1% rate difference after rounding) compared to placebo post Dose 1 for Studies D153-P501 and AV006, and solicited adverse reactions post Dose 1 for Study MI-CP111.
• Solicited adverse reactions were those about which parents/guardians were specifically queried after receipt of FluMist, placebo, or control vaccine. In these studies, solicited reactions were documented for 10 days post vaccination.
• Solicited reactions following the second dose of FluMist were similar to those following the first dose and were generally observed at a lower frequency.

Table 2: Summary of Solicited Adverse Reactions Observed Within 10 Days after Dose 1 for FluMist and Either Placebo or Active Control Recipients in Children 2 through 6 Years of Age

• In clinical studies D153-P501 and AV006, unsolicited adverse reactions in children occurring in at least 1% of FluMist recipients and at a higher rate ( ≥ 1% rate difference after rounding) compared to placebo were abdominal pain (2% FluMist vs. 0% placebo) and otitis media (3% FluMist vs. 1% placebo).
• An additional adverse reaction identified in the active-controlled trial MI-CP111 occurring in at least 1% of FluMist recipients and at a higher rate ( ≥ 1% rate difference after rounding) compared to active control was sneezing (2% FluMist vs. 1% active control).
• In a separate saline placebo-controlled trial (D153-P526) in a subset of older children and adolescents 9 through 17 years of age who received one dose of FluMist, the solicited adverse reactions as well as unsolicited adverse reactions reported were generally consistent with observations from the trials in Table 2.
• Abdominal pain was reported in 12% of FluMist recipients compared to 4% of placebo recipients and decreased activity was reported in 6% of FluMist recipients compared to 0% of placebo recipients.
• In Study AV018, in which FluMist was concomitantly administered with Measles, Mumps, and Rubella Virus Vaccine Live (MMR, manufactured by Merck & Co., Inc.) and Varicella Virus Vaccine Live (manufactured by Merck & Co., Inc.) to children 12 through 15 months of age, adverse reactions were similar to those seen in other clinical trials of FluMist.

FluMist Quadrivalent In Children And Adolescents

• In the randomized, active-controlled Study MI-CP208 that compared FluMist Quadrivalent and FluMist in children and adolescents 2 through 17 years of age, the rates of solicited adverse reactions reported were similar between subjects who received FluMist Quadrivalent and FluMist. Table 3 includes solicited adverse reactions post Dose 1 from Study MI-CP208 that either occurred at a higher rate ( ≥ 1% rate difference after rounding) in FluMist Quadrivalent recipients compared to FluMist recipients or were identified in previous FluMist clinical studies (see Table 2).
• In this study, solicited adverse reactions were documented for 14 days post vaccination. Solicited adverse reactions post Dose 2 were observed at a lower frequency compared to those post Dose 1 for FluMist Quadrivalent and were similar between subjects who received FluMist Quadrivalent and FluMist.

Table 3: Summary of Solicited Adverse Reactionsa Observed Within 14 Days after Dose 1 for FluMist Quadrivalent and FluMist Recipients in Study MI-CP208b in Children and Adolescents 2 through 17 Years of Age

• In Study MI-CP208, no unsolicited adverse reactions occurred at a higher rate (1% or greater) in FluMist Quadrivalent recipients compared to FluMist recipients.

FluMist In Adults

• In adults 18 through 49 years of age in Study AV009, solicited adverse reactions occurring in at least 1% of FluMist recipients and at a higher rate ( ≥ 1% rate difference after rounding) compared to AF-SPG placebo include
  • runny nose (44% FluMist vs. 27% placebo),
  • headache (40% FluMist vs. 38% placebo),
  • sore throat (28% FluMist vs. 17% placebo),
  • tiredness/weakness (26% FluMist vs. 22% placebo),
  • muscle aches (17% FluMist vs. 15% placebo),
  • cough (14% FluMist vs. 11% placebo), and
  • chills (9% FluMist vs. 6% placebo).
• In Study AV009, unsolicited adverse reactions occurring in at least 1% of FluMist recipients and at a higher rate ( ≥ 1% rate difference after rounding) compared to placebo were
  • nasal congestion (9% FluMist vs. 2% placebo) and
  • sinusitis (4% FluMist vs. 2% placebo).

FluMist Quadrivalent In Adults

• In the randomized, active-controlled Study MI-CP185 that compared FluMist Quadrivalent and FluMist in adults 18 through 49 years of age, the rates of solicited adverse reactions reported were generally similar between subjects who received FluMist Quadrivalent and FluMist.
• Table 4 presents solicited adverse reactions that either occurred at a higher rate ( ≥ 1% rate difference after rounding) in FluMist Quadrivalent recipients compared to FluMist recipients or were identified in Study AV009.

Table 4: Summary of Solicited Adverse Reactions^a Observed Within 14 Days after Dose 1 for FluMist Quadrivalent and FluMist Recipients in Study MI-CP185^b in Adults 18 through 49 Years of Age

• In Study MI-CP185, no unsolicited adverse reactions occurred at a higher rate (1% or greater) in FluMist Quadrivalent recipients compared to FluMist recipients.

Postmarketing Experience

The following events have been spontaneously reported during post approval use of FluMist. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.

• Cardiac disorders: Pericarditis
• Congenital, familial, and genetic disorders: Exacerbation of symptoms of mitochondrial encephalomyopathy (Leigh syndrome)
• Gastrointestinal disorders: Nausea, vomiting, diarrhea
• Immune system disorders: Hypersensitivity reactions (including anaphylactic reaction, facial edema, and urticaria)
• Nervous system disorders: Guillain-Barré syndrome, Bell's Palsy, meningitis, eosinophilic meningitis, vaccine-associated encephalitis
• Respiratory, thoracic, and mediastinal disorders: Epistaxis
• Skin and subcutaneous tissue disorders: Rash

Aspirin Therapy

• Do not administer FluMist Quadrivalent to children and adolescents through 17 years of age who are receiving aspirin therapy or aspirin-containing therapy because of the association of Reye's syndrome with aspirin and wild-type influenza.
• Avoid aspirin-containing therapy in these age groups during the first 4 weeks after vaccination with FluMist Quadrivalent unless clearly needed.

Antiviral Agents Against Influenza A and/or B

• Antiviral drugs that are active against influenza A and/or B viruses may reduce the effectiveness of FluMist Quadrivalent if administered within 48 hours before, or within 2 weeks after vaccination.
• The concurrent use of FluMist Quadrivalent with antiviral agents that are active against influenza A and/or B viruses has not been evaluated.
• If antiviral agents and FluMist Quadrivalent are administered concomitantly, revaccination should be considered when appropriate.

Concomitant Administration With Inactivated Vaccines

• The safety and immunogenicity of FluMist Quadrivalent when administered concomitantly with inactivated vaccines have not been determined.
• Studies of FluMist and FluMist Quadrivalent excluded subjects who received any inactivated or subunit vaccine within two weeks of enrollment.

Concomitant Administration With Other Live Vaccines

• Concomitant administration of FluMist Quadrivalent with Measles, Mumps, and Rubella Virus Vaccine Live (MMR, manufactured by Merck & Co., Inc.) or the Varicella Virus Vaccine Live (manufactured by Merck & Co., Inc.) has not been studied. Concomitant administration of FluMist with MMR and the varicella vaccine was studied in children 12 through 15 months of age.
• Concomitant administration of FluMist with the MMR and the varicella vaccine in children older than 15 months of age has not been studied.

Intranasal Products

• There are no data regarding co-administration of FluMist Quadrivalent with other intranasal preparations.