Kenneth McCall, BSPharm, PharmD, CGP Associate Professor | UNE

Objectives Discuss the gap between current rates and Healthy People 2020 goals for vaccinations. Categorize each of the CDC recommended flu vaccines based upon live/inactivated, route, prep., and storage. Discuss the influenza vaccines for 2016 including the new quadrivalent and mammalian cell vaccines. Identify vaccine contraindications and recommend vaccines based upon age and medical history. Apply ACIP recommendations and FDA approved indications for the CDC recommended vaccines. Recognize federal and state laws that regulate vaccine administration.

CDC ACIP 2016 Recommended Adult Immunization Schedule

Maine Pharmacist-Administered Immunization Regulations No Rx RequiredRx Required a Rx or ProtocolNot permitted Adult (≥18 years) with PCP b Influenza ✓ - RPh or Intern Other Vaccines c ✓ -RPh or Intern Adult (≥18 years) without PCP Influenza ✓ - RPh or Intern Other Vaccines c ✓ - RPh or Intern Child < 18 years Other Vaccines c ✗ Child 7-17 years Influenza ✓ -RPh only Child <7 years Influenza ✗ Intern administration permitted as indicated under direct supervision of licensed pharmacist a Verbal/phone authorization acceptable b Primary care physician or existing relationship with a nurse practitioner or an authorized practitioner in Maine c All vaccines licensed by the US FDA recommended by the CDC ACIP

Influenza versus Common Cold

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Vaccine Coverage & Age Group Distribution of Influenza Positive Specimens 9 Trivalent  A/California/7/2009 (H1N1)-like virus  A/Switzerland/ /2013 (H3N2)-like virus  B/Phuket/3073/2013-like virus (Yamagata) Quadrivalent  A/California/7/2009 (H1N1)-like virus  A/Switzerland/ /2013 (H3N2)-like virus  B/Phuket/3073/2013-like virus (Yamagata)  B/Brisbane/60/2008-like virus (Victoria)

A (H1N1) B (Yamagata) B (Victoria) A (H3)

Egg Allergy Recommendation 11 Persons with egg allergy may tolerate egg in baked products (e.g., bread or cake). Tolerance to egg-containing foods does not exclude the possibility of egg allergy. Abbreviations: IIV = inactivated influenza vaccine, trivalent or quadrivalent; RIV3 = recombinant influenza vaccine, trivalent.

ACIP Recommendations Influenza Season For 2016–17, U.S.-licensed trivalent influenza vaccines contain: A/California/7/2009 (H1N1)-like virus A/Hong Kong/4801/2014 (H3N2)- like virus B/Brisbane/60/2008-like (B/Victoria lineage) virus. This represents changes in the influenza A (H3N2) virus and the influenza B virus as compared with the 2015–16 season. Quadrivalent influenza vaccines will contain these vaccine viruses, and a B/Phuket/3073/2013-like (B/Yamagata lineage) virus. All persons aged ≥6 months should receive influenza vaccine annually. In light of concerns regarding low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013–14 and 2015–16 seasons, for the 2016–17 season, ACIP makes the interim recommendation that live attenuated influenza vaccine (LAIV4) should not be used. Persons who report having had reactions to egg involving such symptoms as angio- edema, respiratory distress, lightheadedness, or recurrent emesis; or who required epinephrine or another emergency medical intervention, may receive Flublok if they are aged 18 years or older and there are no other contraindications.

Age Indication for Influenza Vaccines: United States, Vaccine years 2 years 3 years 4-8 years 9-17 years years years 65+ years Fluzone / Fluzone Quad ✓✓✓✓✓✓✓✓ Flumist Quad ✓✓✓✓✓ Fluarix Quad ✓✓✓✓✓✓ FluLaval Quad ✓✓✓✓✓✓ Fluvirin ✓✓✓✓✓ Afluria 1 +- ✓✓ Flucelvax Quad ✓✓✓✓✓ Flublok 2 ✓✓✓ Fluzone Intradermal Quad ✓✓ Fluzone High-Dose ✓ Fluad Adjuvated Trivalent ✓ 1.Age indication via needle/syringe is >5 years and by Pharmjet needle-free injection is years. 2.FDA labeled age indication expanded in 2015 to 18 years and older (now including adults 65+). 13 “A licensed, age-appropriate vaccine should be used.”

New Influenza Vaccines: Fluarix ® (GlaxoSmithKline) – inactivated, quadrivalent vaccine FDA approved December 2012 People ages 3 years and older Fluzone® (Sanofi Pasteur) – inactivated, quadrivalent vaccine. FDA approved March 2013 People ages 6 months and older Fluad ® (Seqirus) Adjuvanted trivalent inactivated vaccine FDA approved November, 2015 People ages 65 and older Flumist® Quadrivalent (MedImmune)– live, attenuated, quadrivalent vaccine FDA approved March, 2012 People ages 2 through 49 years Flucelvax® (Novartis)– quadrivalent inactivated vaccine grown in mammalian cells. FDA approved May, 2016| Adults 4 years and older Flublok® (Protein Sciences Corp.) – inactivated, trivalent, recombinant vaccine. FDA approved March 2013 People ages 18 years and older Doesn’t list “severe allergic reaction to egg protein” in the contraindications

Which of the following was the predominant flu strain of ? 1. Type B strain in trivalent vaccine 2. Type B strain not in trivalent vaccine 3. Type A H1N1 strain 4. Type A H3N2 strain

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New Influenza Vaccines: Fluad ® (Seqirus) – Adjuvanted, inactivated, trivalent vaccine FLUAD also contains MF59C.1 adjuvant (MF59®), a squalene based oil-in-water emulsion. FDA approved November 2015 People ages 65 years and older

% of adults >65 years with local adverse reactions in days 1-7

% of adults >65 years with systemic adverse reactions in days 1-7

Seroconversion Rates at Day 22

Difference in seroconversion rate (95% CI) at day 22

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New Influenza Vaccines: Fluarix Quadrivalent® (GlaxoSmithKline) – inactivated, quadrivalent vaccine which contains two type A and two type B strains FDA approved December 2012 People ages 3 years and older Fluzone Quadrivalent® (Sanofi Pasteur) – inactivated, quadrivalent vaccine which contains two type A and two type B strains FDA approved March 2013 People ages 6 months and older

Quadrivalent vs. Trivalent: Local Side Effects Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline Inc; 2013.

Quadrivalent vs. Trivalent: Systemic Side effects Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline Inc; 2013.

Quadrivalent vs. Placebo: Vaccine Efficacy Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline Inc; 2013.

Vaccine Coverage: Trivalent versus Quadrivalent 27 Trivalent  A/California/7/2009 (H1N1)-like virus  A/Switzerland/ /2013 (H3N2)- like virus  B/Phuket/3073/2013-like virus (Yamagata) Quadrivalent  A/California/7/2009 (H1N1)-like virus  A/Switzerland/ /2013 (H3N2)- like virus  B/Phuket/3073/2013-like virus (Yamagata)  B/Brisbane/60/2008-like virus (Victoria) Conclusion: quadrivalent does not provide significantly better coverage this flu season

Administration Fluarix Quadrivalent®: 0.5-mL dose IM - deltoid 1 inch, 25 gauge needle 28

Quadrivalent Influenza Vaccines contain which of the following? 1. Four type A strains 2. Two type A strains, 1 type B, & 1 type C 3. Two type A strains & 2 type B strains 4. Four type B strains

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New Influenza Vaccines: Flumist® Quadrivalent (MedImmune)– live attenuated vaccine which contains two type A and two type B strains FDA approved March, 2012 People ages 2 through 49 years

ACIP votes down use of LAIV for flu season CDC’s Advisory Committee on Immunization Practices (ACIP) today voted that live attenuated influenza vaccine (LAIV), also known as the “nasal spray” flu vaccine, should not be used during the flu season. ACIP continues to recommend annual flu vaccination, with either the inactivated influenza vaccine (IIV) or recombinant influenza vaccine (RIV), for everyone 6 months and older.

Live Attenuated Influenza Vaccine Indication Healthy people 2 through 49 years of age Contraindications Pregnant women People who have long-term health problems with: heart disease kidney or liver disease lung disease metabolic disease, such as diabetes asthma anemia, and other blood disorders Anyone with a weakened immune system Severe egg allergy 33 I pick my nose!

Immune Response Studies of FluMist Quadrivalent in Children and Adults A multicenter, randomized, double-blind study was performed to assess the immunogenicity of FluMist Quadrivalent compared to FluMist Trivalent in 2,312 children and adolescents 2 through 17 years of age. A multicenter, randomized, double-blind study was performed to assess the immunogenicity of FluMist Quadrivalent compared to FluMist Trivalent in 1,800 adults 18 through 49 years of age. Conclusion: In both studies, the addition of the second B strain did not result in immune interference to other strains included in the vaccine. FluMist Quadrivalent [package insert]. Gaithersburg, MD: MedImmune Inc; 2012.

Summary of solicited adverse reactions observed within 14 days after FluMist in Children 2-17 years FluMist Quadrivalent [package insert]. Gaithersburg, MD: MedImmune Inc; 2012.

Summary of solicited adverse reactions observed within 14 days after FluMist in Adults years FluMist Quadrivalent [package insert]. Gaithersburg, MD: MedImmune Inc; 2012.

Administration Flumist®: 0.1-mL dose in each nostril Intranasal 37

Intranasal Administration Active inhalation (sniffing) by the patient is not required

Which of the following patients is a candidate for the live influenza vaccine? yo man with severe egg allergy yo healthy woman yo man with diabetes yo healthy man yo pregnant woman

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The surveys revealed that most patients were satisfied with their PharmaJet Needle-Free flu shot experience and were likely to choose the option again. Specifically: 96% were satisfied 92% preferred the PharmaJet Needle-Free flu shot 92% would recommend a PharmaJet Needle-Free flu shot to family and friends According to Pharmajet ®…

McAllister et al_2014_Lancet* Lancet 2014;384:

McAllister et al_2014_Lancet* Methods: Randomized (1:1), open-label trial. Healthy adults aged years (N = 1250) Afluria (trivalent inactivated influenza vaccine) IM needle-free jet injector IM with needle and syringe Outcomes: Antibody titers Seroconversion rates Adverse events Lancet 2014;384:

McAllister et al_2014_Lancet* Lancet 2014;384:

McAllister et al_2014_Lancet* Lancet 2014;384: Seroconversion rates of participants in the immunogenicity population by study group

Lancet 2014;384:

Which of the following local side effects is more common when Afluria is administered via Pharmajet versus syringe/needle? 1. Pain 2. Itching 3. Swelling 4. Redness 5. Bruising

Intradermal Influenza Vaccine Indicated for persons 18 through 64 years of age Contraindications Severe egg allergy Associated with higher rates of injection site reactions (erythema, induration, swelling, and pruritus, but not pain) than the IM inactivated influenza vaccines Erythema (>75%) Induration (>50%) Swelling (>50%) Pain (>50%) Pruritus (>40%) 49

Intradermal vs Traditional IM needle Length

30 Gauge Needle and Less Volume

Methods: Multicenter, randomized, double-blind controlled study ID vaccine (9 mcg of hemagglutinin per strain) N=1,803 IM vaccine (15 mcg of hemagglutinin per strain): N=452 in adults 18 to 60 years of age. Human Vaccines. 2010;6:

Comparison of local side effects to ID and IM influenza vaccine 53 Percent Human Vaccines. 2010;6:

Intradermal Injection Technique 1. Remove needle cap 2. Hold microinjection system between thumb and middle finger  Do not place fingers on the windows 3. Insert needle rapidly perpendicular to the skin 4. Inject using the index finger 5. Remove needle from the skin and activate the needle shield by pushing firmly on the plunger

Which side effect is more common with the intradermal influenza vaccine than the IM influenza vaccine? 1. Injection site pain 2. Headache 3. Fever 4. Injection site swelling 5. Malaise

The mother of a 12-year-old child requests the least painful influenza vaccination. What would you recommend? 1. Afluria via Pharmajet 2. Flumist Nasal Spray 3. Fluzone Intradermal 4. Fluzone Intramuscular

Tips for a Ouch-Free Flu Shot Do not prepare the vaccine in front of the patient. Use a prefilled syringe or change the needle. Make sure the alcohol is dry before injecting. Ensure the patient’s arm is relaxed. Inject into the deltoid at least 3 finger widths below the crest of the shoulder. Distract kids; ask them to pretend they are blowing out candles on a birthday cake or blow on a pinwheel. Keep calm and carry on.

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New Influenza Vaccines: Flucelvax® (Novartis)– quadrivalent inactivated vaccine grown in mammalian cells rather than chicken embryo cells. FDA approved May, 2016 Adults 4 years and older

Randomized, Controlled Trial: Flucelvax vs. Placebo Barrett PN, et al. Lancet 2011;377:751-59

Flucelvax vs. Placebo Local & Systemic Adverse Reactions Flucelvax [package insert]. Cambridge, MA: Novartis Vaccines & Diagnostics Inc; 2012.

Flucelvax Compared to Agriflu Local Adverse Reactions Flucelvax [package insert]. Cambridge, MA: Novartis Vaccines & Diagnostics Inc; **Agriflu

Flucelvax Compared to Agriflu Systemic Adverse Reactions **Agriflu

Administration Flucelvax®: 0.5-mL dose IM - deltoid 1 inch, 25 gauge needle 64

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New Influenza Vaccines: Flublok® (Protein Sciences Corporation)– trivalent inactivated vaccine grown in insect cells rather than chicken embryo cells. FDA approved November, 2013 Adults 18 years and older (new indication as of April 2015; previously years). Doesn’t list “severe allergic reaction to egg protein” in the contraindications* *Flublok contains no egg proteins, antibiotics, or preservatives. The stoppers used for the single-dose vials are not made with natural rubber latex.

Vaccine Efficacy against Culture-Confirmed Influenza in Healthy Adults years

Frequency of Local and Systemic Reactions within 7 days of Flublok or Placebo in Adults years

ACIP Recommendations for flu vaccination of person who report egg allergy.

Administration Flublok®: 0.5-mL dose IM - deltoid 1 inch, 25 gauge needle 70

Select an influenza vaccine for a healthy 37- year-old woman with severe egg allergy. 1. Flublok 2. Flumist 3. Fluzone 4. Fluarix

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Methods: Multicenter, randomized, double-blind controlled study HD vaccine (60 mcg of hemagglutinin per strain): N=15,991 SD vaccine (15 mcg of hemagglutinin per strain): N=15,998 Adults 65 years and older. Nursing home residents and immunocompromised persons were excluded. 73 N Engl J Med 2014;371:635-45

Occurrence of laboratory-confirmed influenza following administration of HD and SD influenza vaccines 74 Number of cases N Engl J Med 2014;371:635-45

75 Methods: Retrospective cohort study HD vaccine (60 mcg of hemagglutinin per strain): N= 929,730 SD vaccine (15 mcg of hemagglutinin per strain): : N= 1,615,545 US Medicare beneficiaries 65 years and older who received influenza vaccine in a community pharmacy Primary outcome: probable episode of influenza-related illness defined by a community medical encounter with the provision of a rapid influenza test followed by dispensing of oseltamivir within a 2-day period

Efficacy of HD Vaccine versus SD Vaccine Against Influenza-Related Illness Similar results to Diazgranados et al. Those who received IIV-HD 22% less likely to have influenza- associated illness and 22% less likely to be admitted to the hospital for influenza 76 Lancet Infect Dis 2015;15:

Administration Fluzone HD®: 0.5-mL dose IM - deltoid 1 inch, 25 gauge needle 77

Age Indication for Influenza Vaccines: United States, Vaccine years 2 years 3 years 4-8 years 9-17 years years years 65+ years Fluzone / Fluzone Quad ✓✓✓✓✓✓✓✓ Flumist Quad ✓✓✓✓✓ Fluarix Quad ✓✓✓✓✓✓ FluLaval Quad ✓✓✓✓✓✓ Fluvirin ✓✓✓✓✓ Afluria 1 +- ✓✓ Flucelvax Quad ✓✓✓✓✓ Flublok 2 ✓✓✓ Fluzone Intradermal Quad ✓✓ Fluzone High-Dose ✓ Fluad Adjuvated Trivalent ✓ 1.Age indication via needle/syringe is >5 years and by Pharmjet needle-free injection is years. 2.FDA labeled age indication expanded in 2015 to 18 years and older (now including adults 65+). 79 “A licensed, age-appropriate vaccine should be used.”

Characteristics of Influenza Vaccines: United States, VaccineLiveMercuryEgg Protein Latex Fluzone / Fluzone Quad ✓1✓1 ✓ Flumist Quad ✓✓ Fluarix Quad ✓ FluLaval Quad ✓✓ Fluvirin ✓1✓1 ✓✓3✓3 Afluria ✓1✓1 ✓ Flucelvax Quad ✓2✓2 ✓3✓3 Flublok Fluzone Intradermal Quad ✓ Fluzone High-Dose ✓ 1.Multi-dose vials contain mercury. Single-dose prefilled syringes are mercury-free. 2.Estimated to contain <50 femtograms (5x10 -8 mcg) of total egg protein per 0.5 ml dose. 3.Syringe tip may contain natural rubber latex.

Route of Admin. for Influenza Vaccines: United States, VaccineYoung Children* Older Children Adults Fluzone / Fluzone Quad IM ThighIM Deltoid Flumist Quad Intranasal Fluarix Quad IM ThighIM Deltoid FluLaval Quad IM ThighIM Deltoid Fluvirin IM ThighIM Deltoid Afluria IM Deltoid Flucelvax Quad IM Deltoid Flublok IM Deltoid Fluzone Intradermal Quad ID Deltoid Fluzone High-Dose IM Deltoid *Generally, less than 7 years old.

Which of the following influenza vaccine(s) is/are appropriate for a healthy 16-year-old boy. 1. Fluzone 2. Fluzone ID 3. Fluzone HD 4. Flucelvax 5. 1 and 4

Which of the following influenza vaccines is NOT indicated for a 72-year old woman? 1. Inactivated trivalent IM vaccine 2. Inactivated quadrivalent vaccine 3. Inactivated high dose vaccine 4. Inactivated trivalent intradermal vaccine

Pneumococcal Disease Pneumococcal disease is caused the bacterium Streptococcus pneumoniae Clinical Features Pneumonia Otitis media Sinus infections Bacteremia Meningitis Risk Factors Asplenia Chronic heart, pulmonary, liver, or renal disease Cigarette smoking Cerebrospinal fluid leak Age less than 2 years, or 65 years and older Complex immunization recommendation for adults 85

90 serotypes identified The 10 most common serotypes are estimated to account for about 62% of invasive disease worldwide Up to 36% of adult CAP Up to 50% of HAP 13-19% of all cases of meningitis CDC: Vaccines and Immunizations. Pneumococcal Disease. Accessed 30 July Streptococcus Pneumoniae

Pneumococcal Vaccines Pneumovax 23® (PPSV23, pneumococcal polysaccharide vaccine) Prevnar 13® (PCV13, pneumococcal conjugate vaccine)

ACIP Recommendations on Pneumococcal Vaccinations in Adults

Pneumococcal vaccine-naïve persons aged > 65 years *minimum interval between sequential administration of PCV13 and PPSV23 is 8 weeks; PPSV23 can be given later than 6-12 months after PCV13 if this window is missed.

Persons who previously received PPSV23 at age > 65 years *minimum interval between sequential administration of PCV13 and PPSV23 is 8 weeks; PPSV23 can be given later than 6-12 months after PCV13 if this window is missed.

Persons who previously received PPSV23 before age 65 years who are now aged > 65 years

A 65-year-old man who is pneumonia vaccine naïve. What pneumonia vaccine(s) is/are recommended? 1. Pneumovax only 2. Prevnar only 3. Both; Pneumovax prior to Prevnar 4. Both; Prevnar prior to Pneumovax

Which of the following statements about the administration of influenza and pneumonia vaccines is true? 1. Same day, opposite arm, separate syringe 2. Same day, same arm, mixed in 1 syringe 3. Must be separated by at least 7 days 4. Must be separated by at least 4 weeks