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Influenza Virus Vaccine (Live/Attenuated)

Pronunciation

(in floo EN za VYE rus vak SEEN live ah TEN yoo aye ted)

Index Terms

  • H1N1 Influenza Vaccine
  • Influenza Vaccine
  • LAIV
  • LAIV4
  • Live Attenuated Influenza Vaccine
  • Live Attenuated Influenza Vaccine (Quadrivalent)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Liquid, Nasal [preservative free]:

FluMist: (1 ea [DSC]) [contains egg white (egg protein), gelatin (pork)]

Suspension, Nasal [preservative free]:

FluMist Quadrivalent: (1 ea) [latex free; contains egg white (egg protein), gelatin (pork)]

FluMist Quadrivalent: (1 ea [DSC]) [contains egg white (egg protein), gelatin (pork)]

Brand Names: U.S.

  • FluMist Quadrivalent
  • FluMist [DSC]

Pharmacologic Category

  • Vaccine
  • Vaccine, Live (Viral)

Pharmacology

The vaccine contains live attenuated viruses which infect and replicate within the cells lining the nasopharynx. Promotes immunity to seasonal influenza virus by inducing specific antibody production. Each year the formulation is standardized according to the US Public Health Service. Preparations from previous seasons must not be used.

Distribution

Following nasal administration, vaccine is distributed in the nasal cavity (~90%), stomach (~3%), brain (~2%), and lung (0.4%)

Onset of Action

Most adults have antibody protection within 2 weeks of vaccination (CDC/ACIP [Grohskopf 2016])

Duration of Action

≥6 to 8 months when vaccine is antigenically similar to circulating virus (CDC/ACIP [Grohskopf 2016]); response may be diminished in persons ≥65 years and limited evidence suggests titers may decline significantly 6 months following vaccination in this population (CDC/ACIP [Grohskopf 2016])

Use: Labeled Indications

Influenza disease prevention:

US labeling: Active immunization of individuals 2 to 49 years of age against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.

The Advisory Committee on Immunization Practices (ACIP) recommends routine annual vaccination with seasonal influenza vaccine for all persons ≥6 months who do not otherwise have contraindications to vaccination. Although live attenuated influenza vaccine (LAIV4) is FDA approved for healthy nonpregnant persons aged 2 to 49 years, the ACIP has made the interim recommendation that LAIV4 should not be used for any population for the 2016-17 season due to concerns regarding low effectiveness during the 2013-14 and 2015-16 seasons. Alternative products are available for certain patient populations: Persons ≥6 months may receive the trivalent inactivated influenza vaccine (IIV3) or the quadrivalent inactivated influenza vaccine (IIV4) and persons 18 years and older may receive vaccination with the recombinant influenza vaccine (RIV) (CDC/ACIP [Grohskopf 2016]).

Canadian labeling: Active immunization of individuals 2 to 59 years of age against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.

The Canadian National Advisory Committee on Immunization (NACI) recommends annual vaccination with seasonal influenza vaccine for all persons ≥6 months who do not otherwise have contraindications to the vaccine. Healthy, nonpregnant persons aged 2 to 59 years may receive vaccination with the seasonal live, attenuated influenza vaccine (LAIV) (nasal spray). When readily available and no contraindications exist, NACI prefers use of LAIV (nasal spray) in healthy persons 2 to 17 years of age. LAIV is not recommended in patients with severe asthma or wheezing requiring medical attention in the 7 days prior to vaccination, adults with chronic health conditions, and children and adults who are immunocompromised. Where LAIV is not recommended, use of quadrivalent inactivated influenza vaccine (QIV), or trivalent inactivated influenza vaccine (TIV) if QIV is not available, is recommended (NACI 2016).

Contraindications

Severe allergic reaction (eg, anaphylaxis) to any component of the vaccine, including egg protein, or to previous influenza vaccination; children and adolescents (2 to 17 years of age) receiving aspirin therapy or aspirin-containing therapy because of the association of Reye syndrome with aspirin and wild-type influenza infection.

Note: The ACIP does not consider an egg allergy to be a contraindication to influenza vaccination (CDC/ACIP [Grohskopf 2016]).

Dosing: Adult

It is important to note that influenza seasons vary in their timing and duration from year to year. In general, vaccination should begin soon after the vaccine becomes available (and, if possible, by the end of October) and prior to onset of influenza activity in the community. However, vaccination should continue throughout the influenza season as long as vaccine is available (CDC/ACIP [Grohskopf 2016]).

Immunization: Intranasal:

US labeling: Adults ≤49 years: 0.2 mL/dose (0.1 mL per nostril) (1 dose per season)

Canadian labeling: Adults ≤59 years: 0.2 mL/dose (0.1 mL per nostril) (1 dose per season)

Not indicated for use in patients ≥50 years (US labeling) or ≥60 years (Canadian labeling).

Dosing: Geriatric

Not indicated for use in patients ≥50 years (US labeling) or ≥60 years (Canadian labeling).

Dosing: Pediatric

It is important to note that influenza seasons vary in their timing and duration from year to year. In general, vaccination should begin soon after the vaccine becomes available (and, if possible, by the end of October) and prior to onset of influenza activity in the community. However, vaccination should continue throughout the influenza season as long as vaccine is available (CDC/ACIP [Grohskopf 2016]).

Immunization: Intranasal:

US labeling:

Children 2 to 8 years: 0.2 mL/dose (0.1 mL per nostril) (1 or 2 doses per season; see "Note")

Children ≥9 years and Adolescents: Refer to adult dosing.

Note: Infants and children 6 months to <9 years who received at least 2 doses of trivalent or quadrivalent influenza vaccine prior to July 1, 2016, need only 1 dose of the 2016 to 2017 seasonal influenza vaccine. The two doses need not have been received during the same season or consecutive seasons. All other children <9 years (including those whose vaccination status cannot be determined) should receive 2 doses separated by ≥4 weeks, in order to achieve satisfactory antibody response (CDC/ACIP [Grohskopf 2016]).

Canadian labeling:

Children 2 to 8 years: 0.2 mL/dose (0.1 mL per nostril) (1 dose per season); a second dose should be administered 4 weeks after the first in previously unvaccinated patients.

Children ≥9 years and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Administration

For intranasal administration only; do not inject. Half the dose (0.1 mL) is administered to each nostril; patient should be in upright position. A dose divider clip is provided to allow administration of 0.1 mL into each nostril. Place the tip of the sprayer inside the nostril and depress plunger as rapidly as possible to deliver the dose. Remove dose divider clip and repeat into opposite nostril. The patient does not need to inhale during administration (may breath normally). If recipient sneezes following administration, the dose should not be repeated (CDC/ACIP [Grohskopf 2016]). Defer immunization if nasal congestion is present which may impede delivery of vaccine (CDC/ACIP [Grohskopf 2013]).

US law requires that the date of administration, name of the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address and documentation of the vaccine information statement (VIS; date on VIS, and date given to patient) be entered into the patient's permanent medical record.

Storage

Store in refrigerator at 2°C to 8°C (35°F to 46°F). Do not freeze; protect from light. The cold chain (2°C to 8°C [35°F to 46°F]) must be maintained when transporting intranasal influenza vaccine. The vaccine may be exposed to temperatures of up to 25°C for up to 12 hours without adverse impact; return to refrigerator as soon as possible; only a single excursion outside of the recommended storage conditions is permitted. Once intranasal influenza vaccine has been administered, the sprayer should be disposed of according to the standard procedures for medical waste (eg, sharps or biohazard container).

Drug Interactions

Antiviral Agents (Influenza A and B): May diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated). Management: Avoid anti-influenza antivirals during the period beginning 48 hours prior to and ending 2 weeks after vaccine administration. Persons receiving these agents within 2 weeks of the live intranasal spray vaccine should receive a repeat vaccine dose. Consider therapy modification

AzaTHIOprine: May enhance the adverse/toxic effect of Vaccines (Live). AzaTHIOprine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose azathioprine (3 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of azathioprine should be avoided. Consider therapy modification

Belimumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification

Daclizumab: May enhance the adverse/toxic effect of Vaccines (Live). Daclizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Dimethyl Fumarate: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Canadian labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. U.S. labeling does not mention this. Consider therapy modification

Fingolimod: May enhance the adverse/toxic effect of Vaccines (Live). Vaccinal infections may develop. Fingolimod may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Immunosuppressants: May enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: AzaTHIOprine; Beclomethasone (Oral Inhalation); Betamethasone (Systemic); Budesonide (Systemic); Corticotropin; Cortisone; Cytarabine (Liposomal); Deflazacort; Dexamethasone (Systemic); Fludrocortisone; Fluticasone (Oral Inhalation); Hydrocortisone (Systemic); Leflunomide; Mercaptopurine; Methotrexate; MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE; Triamcinolone (Systemic). Avoid combination

Leflunomide: May enhance the adverse/toxic effect of Vaccines (Live). Leflunomide may diminish the therapeutic effect of Vaccines (Live). Management: The ACIP guidelines state that live-attenuated vaccines should generally be avoided for at least 3 months after cessation of immunosuppressant therapy. However, the ACR does not recommend avoiding live vaccines in patients being treated with leflunomide. Consider therapy modification

Mercaptopurine: May enhance the adverse/toxic effect of Vaccines (Live). Mercaptopurine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose 6-mercaptopurine (1.5 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of mercaptopurine should be avoided. Consider therapy modification

Methotrexate: May enhance the adverse/toxic effect of Vaccines (Live). Methotrexate may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose methotrexate (0.4 mg/kg/week or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of methotrexate should be avoided. Consider therapy modification

Salicylates: Influenza Virus Vaccine (Live/Attenuated) may enhance the adverse/toxic effect of Salicylates. Specifically, Reye's syndrome may develop. Avoid combination

Tuberculin Tests: Vaccines (Live) may diminish the diagnostic effect of Tuberculin Tests. Management: If a parenteral live vaccine has been recently administered, a scheduled PPD skin test should not be administered for at least 4-6 weeks following the administration of the vaccine. Consider therapy modification

Venetoclax: May enhance the adverse/toxic effect of Vaccines (Live). Venetoclax may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live, attenuated vaccines before, during, or after (prior to B-cell recovery) venetoclax treatment. Avoid combination

Test Interactions

Administration of the intranasal influenza virus vaccine (live, LAIV) may cause a positive result on the rapid influenza diagnostic test for the 7 days after vaccine administration; for a person with influenza-like illness during this time, the positive test could be caused by either the live attenuated vaccine or wild-type influenza virus (Ali 2004).

Adverse Reactions

Frequency of events reported within 10 days.

>10%:

Central nervous system: Headache (adults: 40%; children: 3% to 9%), irritability (children: 12% to 21%), lethargy (children: 7% to 14%)

Gastrointestinal: Sore throat (adults: 28%; children: 5% to 11%), decreased appetite (children: 13% to 21%), abdominal pain (children: 2% to 12%)

Neuromuscular & skeletal: Fatigue (adults: ≤26%), weakness (adults: ≤26%), myalgia (adults: 17%; children: 2% to 6%)

Respiratory: Cough (adults: 14%), nasal congestion (children: ≤58%; adults: ≤44%), rhinorrhea (children: ≤58%; adults: ≤44%)

1% to 10%:

Central nervous system: Chills (adults: 9%; children: 2% to 4%)

Otic: Otitis media (children: 3%)

Respiratory: Sinusitis (adults: 4%), sneezing (children: 2%), wheezing (children: 6 to 23 months - 6%; 24 to 59 months - 2%)

Miscellaneous: Fever (children: 100°F to 101°F - 6% to 9%; >101°F - 1% to 4%)

<1% (Limited to important or life-threatening): Anaphylaxis, Bell's palsy, encephalitis (vaccine-associated), epistaxis, exacerbation of asthma, Guillain-Barre syndrome, hypersensitivity reaction, meningitis (including eosinophilic meningitis), pericarditis, subacute necrotizing encephalomyelopathy (Leigh syndrome exacerbation)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (NCIRD/ACIP, 2011).

Disease-related concerns:

• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Consider deferring administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (NCIRD/ACIP, 2011).

• Asthma/wheezing: Children <24 months of age had increased wheezing and hospitalizations following administration in clinical trials; use of the nasal spray is not approved in this age group. ACIP recommends not using LAIV in patients with chronic pulmonary disorders including asthma and children 2 to 4 years of age who have had asthma or wheezing episodes within the past year (CDC/ACIP [Grohskopf 2016]). Risk of wheezing following vaccination is increased in children <5 years of age with a history of recurrent wheezing and in persons of any age with asthma. Patients with severe asthma or active wheezing were not included in clinical trials.

• Cardiovascular disorders: ACIP does not recommend the use of LAIV in patients with chronic disorders of the cardiovascular system (except isolated hypertension) (CDC/ACIP [Grohskopf 2016]).

• Medical conditions predisposing to influenza complications: Safety of LAIV in patients with medical conditions predisposing to influenza complications has not been established.

• Guillain-Barré syndrome: Use with caution in patients with history of Guillain-Barré syndrome (GBS); patients with history of GBS have a greater likelihood of developing GBS than those without. As a precaution, the ACIP recommends that patients with a history of GBS and who are at low risk for severe influenza complications, and patients known to have experienced GBS within 6 weeks following previous vaccination should generally not be vaccinated (consider influenza antiviral chemoprophylaxis in these patients). Based on limited data, the benefits of vaccinating persons with a history of GBS who are also at high risk for complications of influenza, may outweigh the risks (CDC/ACIP [Grohskopf 2016]). Recent studies of patients who received the trivalent inactivated influenza vaccine or the monovalent H1N1 influenza vaccine have shown the risk of GBS is lower with vaccination than with influenza infection (Baxter, 2013; Greene, 2013; Kwong, 2013).

• HIV: ACIP does not recommend the use of LAIV in patients with HIV (CDC/ACIP, [Grohskopf 2016]).

• Nasal congestion: Defer immunization if nasal congestion is present which may impede delivery of vaccine (CDC/ACIP [Grohskopf, 2013]).

Concurrent drug therapy issues:

• Oral influenza antiviral medications: Live influenza virus vaccine (LAIV) should not be given until 48 hours after the completion of influenza antiviral therapy (influenza A and B). Influenza antiviral therapy (influenza A and B) should not be administered for 2 weeks after receiving LAIV. If influenza antiviral therapy (influenza A and B) and LAIV are administered concomitantly, revaccination should be considered.

• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible (NCIRD/ACIP, 2011).

Special populations:

• Adults: The safety and efficacy of the nasal spray have not been established in adults ≥50 years of age (US labeling) or ≥60 years of age (Canadian labeling).

• Pediatric: Due to association of Reye syndrome with aspirin, use of LAIV is contraindicated in pediatric patients on concurrent aspirin therapy; aspirin-containing products should be avoided for 4 weeks following vaccination in children and adolescents ≤17 years of age.

• Altered immunocompetence: Data on the use of LAIV in immunocompromised patients is limited. Avoid contact with severely immunocompromised individuals for at least 7 days following vaccination (at least 14 days per Canadian labeling). ACIP does not recommend the use of LAIV in immunosuppressed patients (CDC/ACIP [Grohskopf 2016]). ACIP does not recommend the use of LAIV for persons who care for severely immunocompromised individuals who require a protective environment due to the theoretical risk of transmitting the live virus from the vaccine. Persons who care for the severely immunocompromised should receive either IIV or RIV (CDC/ACIP [Grohskopf 2016]). In general, live vaccines should be administered ≥4 weeks prior to planned immunosuppression and avoided within 2 weeks of immunosuppression when feasible (IDSA [Rubin, 2014]).

• Pregnant women: ACIP and NACI do not recommend the use of LAIV in pregnant women (CDC/ACIP [Grohskopf 2016]; NACI 2016).

Dosage form specific issues:

• Arginine: Manufactured using arginine.

• Chicken egg protein: Manufactured with chicken egg protein. Allergy to eggs must be distinguished from allergy to the vaccine. Recommendations are available from the ACIP and NACI regarding influenza vaccination to persons who report egg allergies; however, ACIP states a prior severe allergic reaction to influenza vaccine, regardless of the component suspected, is a contraindication to vaccination. Per ACIP, patients with a history of egg allergy who have experienced only hives following egg exposure should receive influenza vaccine if otherwise appropriate. Patients with a history of egg allergy other than hives (eg, angioedema, respiratory distress) should receive influenza vaccine if otherwise appropriate and administered in an inpatient or outpatient medical setting with health care supervision able to recognize and manage severe allergic conditions (CDC/ACIP [Grohskopf 2016]). NACI recommend use of IIV in persons reporting an egg allergy (due to lack of data of LAIV use in this setting) (NACI 2016).

• Gelatin: Manufactured using gelatin.

• Gentamicin: Manufactured with gentamicin.

Other warnings/precautions:

• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (NCIRD/ACIP, 2011). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula, 2009).

• Appropriate use: The safety of LAIV has not been established in individuals with underlying medical conditions that may predispose them to complications following wild-type influenza infection. Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the ACIP Recommended Adult Immunization Schedule (ACIP [Kim 2016]). Specific recommendations for use of this vaccine in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions as well as contacts of immunocompromised patients are available from the IDSA (Rubin, 2014).

• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (NCIRD/ACIP, 2011).

• Previous season vaccines: Influenza vaccines from previous seasons must not be used (CDC/ACIP [Grohskopf 2016]).

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. LAIV is not recommended for use during pregnancy. Influenza vaccination with the inactivated influenza vaccine (IIV) is recommended for all women who are or will become pregnant during the influenza season and who do not otherwise have contraindications to the vaccine (CDC/ACIP [Grohskopf 2016]).

Healthy pregnant women do not need to avoid contact with persons vaccinated with LAIV (CDC/ACIP 62[07] 2013). The nasal vaccine contains the same strains of influenza A and B found in the injection. Information specific to the use of LAIV in pregnancy is limited.

Health care providers are encouraged to refer women exposed to the influenza vaccine during pregnancy to the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) by contacting The Organization of Teratology Information Specialists (OTIS) at (877) 311-8972.

Patient Education

• Discuss specific use of vaccine and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience rhinitis, rhinorrhea, headache, muscle pain, loss of strength and energy, lack of appetite, pharyngitis, cough, or irritability (children) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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