Vaccine Information: FluMist Quadrivalent (Page 2 of 5)

6.2 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

7 DRUG INTERACTIONS

7.1 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 [see Contraindications (4.2)]. Avoid aspirin-containing therapy in these age groups during the first 4 weeks after vaccination with FluMist Quadrivalent unless clearly needed.

7.2 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.

7.3 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.

7.4 Concomitant Administration with Other Live Vaccines

Concomitant administration of the trivalent formulation of FluMist with Measles, Mumps, and Rubella Virus Vaccine Live (MMR, manufactured by Merck & Co., Inc.) and the Varicella Vaccine Live (manufactured by Merck & Co., Inc.) was studied in children 12 through 15 months of age [see Clinical Studies (14.5)]. Concomitant administration of the MMR and the varicella vaccine with the trivalent or quadrivalent FluMist formulations has not been studied in children older than 15 months of age.

7.5 Intranasal Products

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

FluMist Quadrivalent is not absorbed systemically following intranasal administration and maternal use is not expected to result in fetal exposure to the drug.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk: Pregnant women infected with seasonal influenza are at increased risk of severe illness associated with influenza infection compared with non-pregnant women. Pregnant women with influenza may be at increased risk for adverse pregnancy outcomes, including preterm labor and delivery.

Data

Animal Data: In a developmental and reproductive toxicity study, female rats were administered FluMist Quadrivalent either three times (during the period of organogenesis) or six times (prior to gestation and during the period of organogenesis), 200 microliter/rat/occasion (approximately 150 human dose equivalents), by intranasal instillation revealing no evidence of impaired fertility or harm to the fetus due to FluMist Quadrivalent.

8.2 Lactation

Risk Summary

FluMist is not absorbed systemically by the mother following intranasal administration and breastfeeding is not expected to result in exposure of the child to FluMist.

8.4 Pediatric Use

Safety and effectiveness of FluMist Quadrivalent in children 24 months of age and older is based on data from FluMist clinical studies and a comparison of post-vaccination antibody titers between persons who received FluMist Quadrivalent and those who received FluMist [see Clinical Studies (14.1, 14.2)]. FluMist Quadrivalent is not approved for use in children younger than 24 months of age because use of FluMist in children 6 through 23 months has been associated with increased risks of hospitalization and wheezing in clinical trials [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

8.5 Geriatric Use

FluMist Quadrivalent is not approved for use in persons 65 years of age and older because in a clinical study (AV009), effectiveness of FluMist to prevent febrile illness was not demonstrated in adults 50 through 64 years of age [see Clinical Studies (14.3)]. In this study, solicited events among individuals 50 through 64 years of age were similar in type and frequency to those reported in younger adults. In a clinical study of FluMist in persons 65 years of age and older, subjects with underlying high-risk medical conditions (N = 200) were studied for safety. Compared to controls, FluMist recipients had a higher rate of sore throat.

11 DESCRIPTION

FluMist Quadrivalent (Influenza Vaccine Live, Intranasal) is a live quadrivalent vaccine for administration by intranasal spray. FluMist Quadrivalent contains four vaccine virus strains: an A/H1N1 strain, an A/H3N2 strain and two B strains. FluMist Quadrivalent contains B strains from both the B/Yamagata/16/88 and the B/Victoria/2/87 lineages. FluMist Quadrivalent is manufactured according to the same process as FluMist.

The influenza virus strains in FluMist Quadrivalent 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) (i.e., they do not produce classic influenza-like illness in the ferret model of human influenza infection).

No evidence of reversion has been observed in the recovered vaccine strains that have been tested (135 of possible 250 recovered isolates) using FluMist [see Clinical Pharmacology (12.2)]. For each of the four reassortant strains in FluMist Quadrivalent, 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. Thus, the four viruses contained in FluMist Quadrivalent maintain the replication characteristics and phenotypic properties of the MDV and express the HA and NA of wild-type viruses. 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.

Each of the reassortant strains in FluMist Quadrivalent express the HA and NA of wild- type viruses that are related to strains expected to circulate during the 2019-2020 influenza season. Three of the viruses (A/H1N1, A/H3N2 and one B strain) have been recommended by the United States Public Health Service (USPHS) for inclusion in the annual trivalent and quadrivalent influenza vaccine formulations. An additional B strain has been recommended by the USPHS for inclusion in the quadrivalent influenza vaccine formulation.

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. 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 four strains are subsequently blended and diluted as required to attain the desired potency with stabilizing buffers to produce the quadrivalent bulk vaccine. The bulk vaccine is then filled directly into individual sprayers for nasal administration.

Each pre-filled refrigerated FluMist Quadrivalent sprayer contains a single 0.2 mL dose. Each 0.2 mL dose contains 106.5-7.5 FFU (fluorescent focus units) of live attenuated influenza virus reassortants of each of the four strains: A/Switzerland/3330/2017 (H1N1) (an A/Brisbane/02/2018 (H1N1)pdm09 — like virus), A/Kansas/14/2017 (H3N2), B/Phuket/3073/2013 (B/Yamagata/16/88 lineage), and B/Colorado/06/2017 (B/Victoria/2/87 lineage). 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, and 0.96 mg/dose monobasic potassium phosphate. Each dose contains residual amounts of ovalbumin (< 0.024 mcg/dose), and may also contain residual amounts of gentamicin sulfate (< 0.015 mcg/mL), and ethylenediaminetetraacetic acid (EDTA) (< 2.3 mcg/dose). FluMist Quadrivalent 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 Quadrivalent is a colorless to pale yellow suspension and is clear to slightly cloudy.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Immune mechanisms conferring protection against influenza following receipt of FluMist Quadrivalent vaccine are not fully understood; serum antibodies, mucosal antibodies, and influenza-specific T cells may play a role.

FluMist and FluMist Quadrivalent contain live attenuated influenza viruses that must infect and replicate in cells lining the nasopharynx of the recipient to induce immunity. Vaccine viruses capable of infection and replication can be cultured from nasal secretions obtained from vaccine recipients (shedding) [see Pharmacodynamics (12.2)].

VxLabels.com provides trustworthy package insert and label information about marketed drugs and vaccines as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by VxLabels.com. Every individual vaccine label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

Vaccine Sections

Vaccine Information by RSS

As the leading independent provider of trustworthy vaccine information, our database comes directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. VxLabels.com provides the full vaccine subset of the FDA's repository. Vaccine information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2019. All Rights Reserved.