FluMist Trivalent Adverse Reactions

The most common solicited adverse reactions (≥10% in vaccine recipients and at least 5% greater than in placebo recipients) reported after FluMist Trivalent were runny nose or nasal congestion (ages 2 years through 49 years), fever over 100°F (children ages 2 years through 6 years), and sore throat (adults ages 18 years through 49 years).
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.
A total of 9537 children and adolescents 1 through 17 years of age and 3041 adults 18 through 64 years of age received FluMist Trivalent 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 as follows. In addition, 4179 children 6 through 59 months of age received FluMist Trivalent in Study MI-CP111, a randomized, active-controlled trial. Among pediatric FluMist Trivalent 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.
FluMist Trivalent in Children and Adolescents: The safety of FluMist Trivalent 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 Trivalent = 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 Trivalent 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 Trivalent 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 Trivalent compared to those who received inactivated Influenza Virus Vaccine, as shown in Table 6. (See Table 6.)

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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 Trivalent recipients and 2.6% (18/683) in inactivated Influenza Virus Vaccine recipients.
Table 7 shows pooled solicited adverse reactions occurring in at least 1% of FluMist Trivalent 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 Trivalent, placebo, or control vaccine. In these studies, solicited reactions were documented for 10 days post vaccination. Solicited reactions following the second dose of FluMist Trivalent were similar to those following the first dose and were generally observed at a lower frequency. (See Table 7.)

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In clinical studies D153-P501 and AV006, unsolicited adverse reactions in children occurring in at least 1% of FluMist Trivalent recipients and at a higher rate (≥1% rate difference after rounding) compared to placebo were abdominal pain (2% FluMist Trivalent vs. 0% placebo) and otitis media (3% FluMist Trivalent vs. 1% placebo). An additional adverse reaction identified in the active-controlled trial MI-CP111 occurring in at least 1% of FluMist Trivalent recipients and at a higher rate (≥1% rate difference after rounding) compared to active control was sneezing (2% FluMist Trivalent 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 Trivalent, the solicited adverse reactions as well as unsolicited adverse reactions reported were generally consistent with observations from the trials in Table 7. Abdominal pain was reported in 12% of FluMist Trivalent recipients compared to 4% of placebo recipients and decreased activity was reported in 6% of FluMist Trivalent recipients compared to 0% of placebo recipients.
In Study AV018, in which FluMist Trivalent 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 Trivalent.
FluMist Trivalent in Adults: In adults 18 through 49 years of age in Study AV009, solicited adverse reactions occurring in at least 1% of FluMist Trivalent recipients and at a higher rate (≥1% rate difference after rounding) compared to AF-SPG placebo include runny nose (44% FluMist Trivalent vs. 27% placebo), headache (40% FluMist Trivalent vs. 38% placebo), sore throat (28% FluMist Trivalent vs. 17% placebo), tiredness/weakness (26% FluMist Trivalent vs. 22% placebo), muscle aches (17% FluMist Trivalent vs. 15% placebo), cough (14% FluMist Trivalent vs. 11% placebo), and chills (9% FluMist Trivalent vs. 6% placebo).
In Study AV009, unsolicited adverse reactions occurring in at least 1% of FluMist Trivalent recipients and at a higher rate (≥1% rate difference after rounding) compared to placebo were nasal congestion (9% FluMist Trivalent vs. 2% placebo) and sinusitis (4% FluMist Trivalent vs. 2% placebo).
Postmarketing Experience: The following events have been spontaneously reported during post approval use of FluMist Trivalent or FluMist Quadrivalent. Data for FluMist Quadrivalent are relevant to FluMist Trivalent because both vaccines are manufactured using the same process and have overlapping compositions. 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, syncope.
Respiratory, thoracic, and mediastinal disorders: Epistaxis.
Skin and subcutaneous tissue disorders: Rash.