Kenneth McCall, BSPharm, PharmD Associate Professor UNE President Maine Pharmacy Association

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 2014 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.

Outline Background & Principles of Vaccination Influenza Vaccines Quadrivalent inactivated Quadrivalent live Mammalian High Dose Intradermal

Classification of Vaccines Live attenuated Weakened form of the wild virus or bacteria Inactivated Whole viruses or bacteria Fractions of viruses or bacteria *Epidemiology and Prevention of Vaccine-Preventable Diseases, 12th Edition

Classification of Vaccines Live attenuated: Measles, mumps, rubella, varicella, zoster, intranasal influenza Inactivated: hepatitis A, hepatitis B, influenza, pneumonia, diphtheria, tetanus, pertussis, HPV, meningicoccal *Epidemiology and Prevention of Vaccine-Preventable Diseases, 12th Edition

2014 Recommended Adult Immunization Schedule, by vaccine and age group www.cdc.gov/vaccines/schedules/hcp/adult.html

Vaccines that might be indicated for adults based on medical and other indications www.cdc.gov/vaccines/schedules/hcp/adult.html

2014 Influenza Vaccination Recommendations Annual vaccination against influenza is recommended for all persons aged 6 months or older. Adults aged 18 to 49 years can receive the recombinant or mammalian vaccine. Healthy, nonpregnant persons aged 2 to 49 years without high-risk medical conditions can receive either intranasal, live vaccine or inactivated vaccine. Health care personnel who care for severely immunocompromised persons should receive inactivated vaccine. Adults 18 to 64 years can receive either the intramuscular or intraderm. Adults 65+ years can receive either the standard-dose or the high-dose. www.cdc.gov/vaccines/schedules/hcp/adult.html

What is the Healthy People 2020 goal for annual flu vaccination for adults 65 and older? 25% 1. 100% 25% 25% 25% 2. 90% 3. 70% 4. 50%

Influenza Virus Strains Influenza A virus Moderate to severe illness All age groups Humans and other animals Influenza B virus Milder disease Primarily affects children Humans only Influenza C virus Rarely reported in humans No epidemics 15

2013-14 Influenza Surveillance CDC has antigenically characterized 2,110 influenza viruses Influenza A 2009 H1N1 [1,657]: 99.9% of the 2009 H1N1 viruses tested were characterized as A/California/7/2009-like, the influenza A (H1N1) component of the 2013-2014 Northern Hemisphere influenza vaccine. Influenza A (H3N2) [269]: 98.1% of the influenza A (H3N2) viruses tested have been characterized as A/Texas/50/2012-like, the influenza A (H3N2) component of the 2013-2014 Northern Hemisphere influenza vaccine. Influenza B [184]: 124 (67%) of the 184influenza B viruses tested belong to B/Yamagata/16/88-lineage and the remaining 60 (33%) influenza B viruses tested belong to B/Victoria/02/87 lineage. Yamagata Lineage [124]: 124 influenza B/Yamagata-lineage viruses were characterized as B/ Massachusetts/2/1012-like, which is included as an influenza B component of the 2013-2014 Northern Hemisphere trivalent and quadrivalent influenza vaccines. Victoria Lineage [60]: 60 influenza B/Victoria-lineage viruses were characterized as B/Brisbane/60/2008-like, which is included as an influenza B component of the 2013-2014 Northern Hemisphere quadrivalent influenza vaccine.

US Influenza Vaccines: 2014 Vaccine Age Group Dosage Schedule Route Inactivated, Trivalent Standard Dose Inactivated, Quadrivalent Standard Dose Inactivated, Mammalian Trivalent Standard Dose Inactivated, Recombinant Trivalent Standard Dose Inactivated, Trivalent High Dose Inactivated, Trivalent Intra-dermal Live, Quadrivalent Intranasal 6-35 mos 0.25 ml 1 or 2 shots IM 3-8 years 0.5 ml 1 or 2 shots IM >9 years 0.5 ml 1 shot IM 3-8 years 0.5 ml 1 or 2 shots IM >9 years 0.5 ml 1 shot IM >18 years 0.5 ml 1 shot IM 18-49 years 0.5 ml 1 shot IM >65 years 0.5 ml 1 shot IM 18-64 years 0.1 ml 1 shot ID 2-8 years 0.2 ml 1 or 2 Nasal 9-49 years 0.2 ml 1 dose Nasal

New Influenza Vaccines: 2013-14 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 Flumist Quadrivalent (MedImmune) live, attenuated, quadrivalent vaccine FDA approved March, 2012 People ages 2 through 49 years Flucelvax (Novartis) trivalent inactivated vaccine grown in mammalian cells. FDA approved November, 2012 Adults 18 years and older Doesn t list severe allergic reaction to egg protein in the contraindications Flublok (Protein Sciences Corp.) inactivated, trivalent, recombinant vaccine. FDA approved March 2013 People ages 6 months and older Doesn t list severe allergic reaction to egg protein in the contraindications

Which of the following was the predominant flu strain of 2013-14? 25% 1. Type B strain in trivalent vaccine 25% 25% 25% 2. Type B strain not in trivalent vaccine 3. Type A H1N1 strain 4. Type A H3N2 strain

New Influenza Vaccines: 2013-14 Fluarix (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 (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 Local Side Effect Fluarix Quadrivalent N=3,015 Trivalent Influenza Vaccine (TIV) TIV-1 (B Victoria) N=1,003 TIV-2 (B Yamagata) N=607 Pain 36 37 31 Redness 2 2 2 Swelling 2 2 1 Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline Inc; 2013.

Quadrivalent vs. Trivalent: Systemic Side effects Systemic Side Effect Fluarix Quadrivalent N=3,015 Trivalent Influenza Vaccine (TIV) TIV-1 (B Victoria) N=1,003 Muscle Aches 16 19 16 Headache 16 16 13 Fatigue 16 18 15 Arthralgia 8 10 9 GI Symptoms 7 7 6 Shivering 4 5 4 Fever 99.5 F 2 1 2 TIV-2 (B Yamagata) N=607 Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline Inc; 2013.

Quadrivalent vs. Placebo: Vaccine Efficacy Attack Rates (n/n) Vaccine Efficacy N N % % LL UL Antigenically Matched Strains FLUARIX 5,103 49 1.0 66.9 51.9 77.4 placebo 2,549 74 2.9 - - - All Cultured-Confirmed Influenza (Matched, Unmatched, and Untyped) FLUARIX 5,103 63 1.2 61.6 46.0 72.8 placebo 2,549 82 3.2 - - - Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline Inc; 2013.

Administration Fluarix : 0.5-mL dose IM - deltoid 1 inch, 25 gauge needle 26

Quadrivalent Influenza Vaccines contain which of the following? 25% 1. Four type A strains 25% 25% 25% 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

New Influenza Vaccines: 2013-14 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

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 I pick my nose! 30

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 18-49 years FluMist Quadrivalent [package insert]. Gaithersburg, MD: MedImmune Inc; 2012.

Administration Flumist : 0.1-mL dose in each nostril Intranasal 34

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

Which of the following patients is a candidate for the live influenza vaccine? 20% 1. 45 yo man with severe egg allergy 20% 20% 20% 20% 2. 27 yo healthy woman 3. 38 yo man with diabetes 4. 54 yo healthy man 5. 19 yo pregnant woman

New Influenza Vaccines: 2013-14 Flucelvax (Novartis) trivalent inactivated vaccine grown in mammalian cells rather than chicken embryo cells. FDA approved November, 2012 Adults 18 years and older Doesn t list severe allergic reaction to egg protein in the contraindications

Head-to-Head Comparison: 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 **Agriflu Flucelvax [package insert]. Cambridge, MA: Novartis Vaccines & Diagnostics Inc; 2012.

Flucelvax Compared to Agriflu Systemic Adverse Reactions **Agriflu

Administration Flucelvax : 0.5-mL dose IM - deltoid 1 inch, 25 gauge needle 43

Which of the following influenza vaccines does not include severe egg allergy as a contraindication? 20% 1. Inactivated quadrivalent 20% 20% 20% 20% 2. Live quadrivalent 3. Inactivated trivalent intradermal 4. Inactivated trivalent high dose 5. Inactivated trivalent mammalian

New Influenza Vaccines: 2013-14 Flublock (Protein Sciences Corporation) trivalent inactivated vaccine grown in insect cells rather than chicken embryo cells. FDA approved November, 2013 Adults 18 through 49 years of age. Doesn t list severe allergic reaction to egg protein in the contraindications

Vaccine Efficacy against Culture-Confirmed Influenza in Healthy Adults 18-49 years

Frequency of Local and Systemic Reactions within 7 days of Flublok or Placebo in Adults 18-49 years

Administration Flucelvax : 0.5-mL dose IM - deltoid 1 inch, 25 gauge needle 49

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

Select an influenza vaccine for a healthy 37- year-old woman with severe egg allergy. 25% 1. Flublok 25% 25% 25% 2. Flumist 3. Fluzone 4. Fluarix

Methods: Multicenter, randomized, double-blind controlled study HD vaccine (60 mcg of hemagglutinin per strain): N=2,575 SD vaccine (15 mcg of hemagglutinin per strain): N=1,262 in adults 65 years of age and older. J Infect Dis. 2009;200(2):172-80 53

antibody titer level Comparison of responses to high-dose (HD) and standard-dose (SD) influenza vaccine 140 120 100 700 600 500 80 60 400 300 SD HD 40 200 20 100 0 A/H1N1 B J Infect Dis. 2009;200(2):172-80 0 A/H3N2 54

Percent Comparison of systemic side effects to HD and SD influenza vaccine 25 20 15 10 SD HD 5 0 Fever Headache Malaise Myalgia J Infect Dis. 2009;200(2):172-80 55

Administration Fluzone HD : 0.5-mL dose IM - deltoid 1 inch, 25 gauge needle 56

Intradermal Influenza Vaccine Indication Persons 18 through 64 years of age Contraindications Severe egg allergy 58

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;6:346-54.

Seroprotection Rate Comparison of responses to Intradermal (ID) and Intramuscular (IM) influenza vaccine 100 100 90 90 80 80 70 70 60 50 40 60 50 40 IM 15 mcg ID 9 mcg 30 30 20 20 10 10 0 A/H1N1 B Human Vaccines. 2010;6:346-54. 0 A/H3N2 62

Percent Comparison of systemic side effects to ID and IM influenza vaccine 35 30 25 20 15 IM 15 mcg ID 9 mcg 10 5 0 Fever Headache Malaise Myalgia Human Vaccines. 2010;6:346-54. 63

Percent Comparison of local side effects to ID and IM influenza vaccine 90 80 70 60 50 40 30 20 10 0 Erythema Swelling Induration Pain Human Vaccines. 2010;6:346-54. IM 15 mcg ID 9 mcg 64

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? 0% 1. Injection site pain 0% 0% 0% 0% 2. Headache 3. Fever 4. Injection site swelling 5. Malaise

Influenza Vaccines and Age Indications Vaccine Age Indications 6-23m 2-3y 3-17y 18-49y 50-64y 65+y Inactivated Trivalent (Fluzone, Afluria, Fluvirin ) Inactivated Quadrivalent (Fluarix, FluLaval, Fluzone ) Inactivated Mammalian Trivalent (Flucelvax ) Recombinant Influeza Vaccine, Trivalent (FluBlok ) Live Quadrivalent (Flumist ) Intradermal Trivalent (Fluzone ID ) High Dose Trivalent (Fluzone HD ) Indicated for those meeting age requirements and without contraindications

Influenza Vaccine Indications Vaccine Indication Inactivated Trivalent (Fluzone, Afluria, Fluvirin ) Inactivated Quadrivalent (Fluarix ) Inactivated Mammalian & Recombinant Trivalent (FluBlok, Flucelvax ) Live Quadrivalent (Flumist ) Pregnant Severe Egg Allergy Patients with high risk medical conditions** Intradermal Trivalent (Fluzone ID ) High Dose Trivalent (Fluzone HD ) Indicated for individuals meeting age requirements. contraindicated **Patients with high risk medical conditions: including immunocompromised, chronic cardiovascular disease, Diabetes Mellitus, pulmonary disease, or metabolic disease.

Which of the following influenza vaccine(s) is/are appropriate for a healthy 16-year-old boy. 20% 1. Fluzone 20% 20% 20% 20% 2. Fluzone ID 3. Fluzone HD 4. Flucelvax 5. 1 and 2

Which of the following influenza vaccines is NOT indicated for a 72-year old woman? 25% 1. Inactivated trivalent IM vaccine 25% 25% 25% 2. Inactivated quadrivalent vaccine 3. Inactivated high dose vaccine 4. Inactivated trivalent intradermal vaccine

A 35-year-old woman requests an annual flu shot. She has ulcerative colitis and is taking Prednisone 40 mg QD. Which flu vaccine(s) is/are appropriate? 14% 1. Influenza intradermal vaccine 14% 14% 14% 14% 14% 14% 2. Influenza intramuscular vaccine 3. Influenza high dose vaccine 4. Flumist nasal spray 0.2 ml nasal 5. Either 1 or 2 6. Either 2 or 3 7. Either 2 or 4

Pathogen (Common name) Table Pathogen Classification Transmission Complication Influenza (flu) virus Respiratory Pneumonia Pneumococcus Gram + Bacteria Respiratory Meningitis/Bacteremia Varicella (chicken pox) virus Respiratory Bacterial infection Zoster (shingles) virus Latent varicella Neuralgia HPV (genital warts) virus Sexual contact Cervical cancer Meningococcus Gram - Bacteria Respiratory Invasive disease Tetanus (lockjaw) Gram + Bacteria-toxin wound Respiratory failure Diphtheria Gram + Bacteria-toxin Respiratory Myocarditis/Neuritis Pertussis (whooping cough) Gram - Bacteria Respiratory Pneumonia Measles virus Respiratory Diarrhea, pneumonia Mumps virus Respiratory Meningitis Rubella virus Respiratory Arthritis Hepatitis A virus Fecal-oral Acute/chronic hepatitis Hepatitis B virus Blood-serous fluids Acute hepatitis

Vaccine Adult Vaccine Table Vaccine Type Route / Reconstitute Series Influenza IIV Inactivated IM / No 1x annually Fridge Flumist Live Intranasal / No 1x annually Fridge Pneumovax Inactivated IM or SQ / No 1-2 doses Fridge Storage Zostavax Live SQ / Yes 1 dose Freezer Gardasil (HPV4) Cervarix (HPV2) Inactivated IM / No 3 doses Fridge Td Inactivated IM / No 1 q 10 years Fridge Tdap Inactivated IM / No 1x, then Td Fridge Varivax Live SQ / Yes 2 doses Freezer MMR Live SQ / Yes 1-2 doses Fridge or Freezer Menactra, Menveo Menomune (MPSV4) Inactivated IM / No 1-2+ doses Fridge Havrix, Vaqta Inactivated IM / No 2 doses Fridge Recombivax-HB Engerix-B Inactivated IM / No 3 doses Fridge