1. Kenneth McCall, BSPharm, PharmD Associate Professor | UNE

2. 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.

3. Outline Background & Principles of Vaccination Influenza Surveillance and Vaccines Pneumococcal Vaccine Recommendations MMR Activity HPV9 Vaccine

5. 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

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7. 2015 Recommended Adult Immunization Schedule, by vaccine and age group www.cdc.gov/vaccines/schedules/hcp/adult.html

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

9. ACIP Recommendations 2014-15 Influenza Season For 2014–15, U.S.-licensed influenza vaccines will contain the same vaccine virus strains as those in the 2013–14 vaccine. All persons aged ≥6 months should receive influenza vaccine annually. When immediately available, LAIV should be used for healthy children aged 2 through 8 years who have no contraindications or precautions. If LAIV is not immediately available, IIV should be used. Persons who care for severely immunosuppressed persons who require a protective environment should not receive LAIV, or should avoid contact with such persons for 7 days after receipt, given the theoretical risk for transmission of the live attenuated vaccine virus. Persons who report having had reactions to egg involving such symptoms as angioedema, respiratory distress, lightheadedness, or recurrent emesis; or who required epinephrine or another emergency medical intervention, may receive RIV3 if they are aged 18 through 49 years and there are no other contraindications. MMWR August 15, 2014 / 63(32);691-697

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

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16. US Influenza Vaccines: 2014 VaccineAge GroupDosageScheduleRoute Inactivated, Trivalent Standard Dose 6-35 mos0.25 ml1 or 2 shotsIM 3-8 years0.5 ml1 or 2 shotsIM >9 years0.5 ml1 shotIM Inactivated, Quadrivalent Standard Dose 3-8 years0.5 ml1 or 2 shotsIM >9 years0.5 ml1 shotIM Inactivated, Mammalian Trivalent Standard Dose >18 years0.5 ml1 shotIM Inactivated, Recombinant Trivalent Standard Dose 18-49 years0.5 ml1 shotIM Inactivated, Trivalent High Dose >65 years0.5 ml1 shotIM Inactivated, Trivalent Intra-dermal 18-64 years0.1 ml1 shotID Live, Quadrivalent Intranasal 2-8 years0.2 ml1 or 2Nasal 9-49 years0.2 ml1 doseNasal

17. 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

18. Which of the following was the predominant flu strain of 2013-14? 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

19. Which of the following is the predominant flu strain of 2014-15? 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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21. 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

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

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

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

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

26. 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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28. 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

33. 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!

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

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

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

37. Which of the following influenza vaccine(s) is/are preferred for a healthy 7-year-old boy. 1. Fluzone 2. Fluzone ID 3. Flumist 4. Flucelvax 5. 1 and 2

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39. 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. 39 N Engl J Med 2014;371:635-45

40. Occurrence of laboratory-confirmed influenza following administration of HD and SD influenza vaccines 40 Number of cases N Engl J Med 2014;371:635-45

41. Efficacy of HD Vaccine vs. Standard Dose against Laboratory Confirmed Influenza of Any Type Number (%) of cases IV3-HD: 228/15,990 (1.4%) IV3-SD: 301/15,993 (1.9%) Relative Efficacy (95% CI) 24.2% (9.7% – 36.5%) Absolute Efficacy 0.5% Number Needed to Treat 200

42. Administration Fluzone HD®: 0.5-mL dose IM - deltoid 1 inch, 25 gauge needle 42

43. Which of the following statements is FALSE when comparing the efficacy of Fluzone HD to Fluzone in adults 65 years or older? 1. The relative efficacy of Fluzone HD is 24% > than Fluzone 2. The absolute efficacy of Fluzone HD is 0.5% > than Fluzone 3. These results apply to nursing home patients 4. The NNT is 200 to avoid one additional case of influenza

45. Influenza Vaccines and Age Indications Indicated for those meeting age requirements and without contraindications Preferred: Healthy 2-8 yrs

46. Influenza Vaccine Indications 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.

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

51. ACIP Recommendations on Pneumococcal Vaccinations in Adults

52. 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.

53. 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.

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

55. Rationale & Design of CAPITA: Community Acquired Pneumonia Immunization Trail in Adults Primary Clinical Objective: establish the efficacy of PCV13 vaccine in the prevention of a first episode of pneumococcal CAP in community dwelling adults > 65 years. Methods: Randomized, placebo controlled trial with approximately 85,000 subjects. Notable Exclusion Criteria: Previous vaccination with any pneumococcal vaccine Residence in long-term care facility Immunodeficiency Neth J Med. 2008 Oct;66(9):378-83.

58. PPSV23 (Pneumovax®) AgeWho receives the vaccine? ≥65 years old Vaccination history unclear or never received vaccine before Revaccinate: If patient received vaccine before the age of 65 and it has been ≥ 5 years since administration 2-64 years old Chronic cardiovascular disease (CHF, cardiomyopathies) Chronic pulmonary disease (COPD) Diabetes mellitus Alcoholism Chronic liver disease Cerebrospinal fluid leaks Re-vaccination after 5 years if: (see figure 1 on next slide) functional or anatomic asplenia Immunocompromising conditions Chronic kidney disease 19-64 years old Cigarette smokers Asthma ACIP: Pneumococcal. MMWR. http://www.immunize.org/acip/ Accessed 30 July 2014.http://www.immunize.org/acip/

59. Administration Pneumovax® & Prevnar®: 0.5 mL dose 1 inch, 25 gauge needle Intramuscular (IM) - deltoid CDC: Vaccines and Immunizations. Pneumococcal Disease. http://www.cdc.gov/. Accessed 30 July 2014.http://www.cdc.gov/

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

61. 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

62. 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

63. Which of the following vaccines is a live vaccine? 1. Pneumovax 2. Flumist 3. Prevnar 4. Fluarix 5. Fluzone HD

65. Pathogen (Common name) Table PathogenClassificationTransmissionComplication MeaslesVirusRespiratoryDiarrhea pneumonia MumpsVirusRespiratoryMeningitis RubellaVirusRespiratoryArthritis

68. Measles, Mumps, Rubella Vaccination All adults born in 1957 or later should have documentation of 1 or more doses of MMR vaccine unless they have a medical contraindication to the vaccine, laboratory evidence of immunity to each of the three diseases, or documentation of provider-diagnosed measles or mumps disease. A routine second dose of MMR vaccine, administered a minimum of 28 days after the first dose, is recommended for adults who are students in postsecondary educational institutions; work in a health-care facility; or plan to travel internationally.

69. MMR Vaccine Contraindications AIDS or other clinical manifestations of HIV, including persons with CD4+ T-lymphocyte values <200 per mm 3 Malignant neoplasms affecting the bone marrow Chemotherapy or radiation within the last 3 months Persons on immunosuppressive therapy, including high-dose corticosteroids (>20 mg/day of prednisone or equivalent) lasting two or more weeks

70. Administration MMR: 0.65-mL dose (reconstituted) SQ – upper, outer tricep 5/8 inch, 25 gauge needle 70

71. Which of the following vaccine- preventable pathogens is a bacteria? 1. Measles 2. Mumps 3. Rubella 4. Pneumococcus 5. Influenza 6. Varicella

76. http://www.cancer.gov/clinicaltrials/results/summary/2015/gardasil9-0215

78. Human papillomavirus (HPV) vaccination Two vaccines are licensed for use in females, bivalent HPV vaccine (HPV2 – types 16,18) and quadrivalent HPV vaccine (HPV9 – types 6,11,16,18,31,33,45,52,58). Only one HPV vaccine is licensed for use in males (HPV9). For females, either HPV9 or HPV2 is recommended in a 3- dose series for routine vaccination at 9 to 12 years of age, and for those 13 through 26 years of age, if not previously vaccinated. For males, HPV9 is recommended in a 3-dose series for routine vaccination at 9 to 12 years of age, and for those 13 through 15 years of age, if not previously vaccinated.

79. Human papillomavirus (HPV) vaccination HPV vaccines are not live vaccines and can be administered to persons who are immuno- compromised as a result of infection (including HIV infection), disease, or medications. HPV vaccine can be administered to persons with a history of genital warts, abnormal Papanicolaou test, or positive HPV DNA test.

80. Administration Gardasil®/Cervarix® IM - deltoid 1 inch, 25 gauge needle 80

81. The mother of a 12-year-old boy requests the HPV vaccination. Select the correct vaccine and series. Gardasil®: 3 dose series Cervarix®: 3 dose series Gardasil®: 2 dose series Cervarix®: 2 dose series

83. Pathogen (Common name) Table PathogenClassificationTransmissionComplication Influenza (flu) virusRespiratoryPneumonia PneumococcusGram + BacteriaRespiratoryMeningitis/Bacteremia Varicella (chicken pox) virusRespiratoryBacterial infection Zoster (shingles) virusLatent varicellaNeuralgia HPV (genital warts) virusSexual contactCervical cancer MeningococcusGram - BacteriaRespiratoryInvasive disease Tetanus (lockjaw) Gram + Bacteria-toxinwoundRespiratory failure DiphtheriaGram + Bacteria-toxinRespiratoryMyocarditis/Neuritis Pertussis (whooping cough) Gram - BacteriaRespiratoryPneumonia MeaslesvirusRespiratoryDiarrhea, pneumonia MumpsvirusRespiratoryMeningitis RubellavirusRespiratoryArthritis Hepatitis AvirusFecal-oralAcute/chronic hepatitis Hepatitis BvirusBlood-serous fluidsAcute hepatitis

84. Adult Vaccine Table VaccineVaccine Type Route / Reconstitute SeriesStorage Influenza IIVInactivatedIM / No1x annuallyFridge FlumistLiveIntranasal / No1x annuallyFridge PneumovaxInactivatedIM or SQ / No1-2 dosesFridge ZostavaxLiveSQ / Yes1 doseFreezer Gardasil (HPV4) Cervarix (HPV2) InactivatedIM / No3 dosesFridge TdInactivatedIM / No1 q 10 yearsFridge TdapInactivatedIM / No1x, then TdFridge VarivaxLiveSQ / Yes2 dosesFreezer MMRLiveSQ / Yes1-2 doses Fridge or Freezer Menactra, Menveo Menomune (MPSV4) InactivatedIM / No1-2+ dosesFridge Havrix, VaqtaInactivatedIM / No2 dosesFridge Recombivax-HB Engerix-B InactivatedIM / No3 dosesFridge

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88. Clinical Presentation of Herpes Zoster 1–3 Abnormal Skin Sensations Headache Photophobia Malaise Unilateral Dermatomal Rash Maculopapules/Vesicles Altered Sensitivity to Touch Unbearable Itching Cessation of New Vesicles Pustulation Scabbing Cutaneous Healing Neurologic Cutaneous Ophthalmic Visceral (rare) Prodrome Acute HZ RashEvolution of RashComplications? Pain (varying severity) “Aching”, “burning”, “stabbing”, “shock-like” 1.Oxman MN. In: Arvin AM et al, eds. Varicella-Zoster Virus: Virology and Clinical Management. Cambridge, UK: Cambridge University Press; 2000:246–275. 2.Weaver BA. J Am Osteopath Assoc. 2007;107(suppl 1):S2–S7. 3. Harpaz R et al. MMWR Morb Mortal Wkly Rep. 2008;57(RR-5):1–30. © Phototake. © Dr. P. Marazzi / Photo Researchers, Inc. Herpes Zoster Rash Follows a Dermatomal Distribution © Phototake.

90. Zoster Vaccination Rates are Low 1–3 1. Centers for Disease Control and Prevention (CDC). cdc.gov/vaccines/stats-surv/nhis/2009-nhis.htm. Accessed January 19, 2011. 2. Centers for Disease Control and Prevention (CDC). Morbid Mortal Wkly Rep. 2012;61(4):66–72. 3. Centers for Disease Control and Prevention (CDC). MMWR. 2013;62(4):61–76. 4. Harpaz R et al. Morbid Mortal Wkly Rep. 2008;57(RR-5):1–30.  More than 99.5% of US adults ≥40 years of age have serologic evidence of previous infection of varicella zoster virus; therefore, all older adults are at risk of zoster infection 4 % Vaccinated (cumulative) in Individuals Aged ≥60 Years Year 7% 10% 14% 2008 20092010 0 5 10 15 20 25 30 35 40 45 50 15.8% 2011 20102009 2008

91. Zoster Vaccine Indication ACIP recommends routine vaccination of all persons aged >60 years with 1 dose of zoster vaccine. NEW FDA LABELING: “ZOSTAVAX is a live attenuated virus vaccine indicated for prevention of herpes zoster (shingles) in individuals 50 years of age and older.” Persons who report a previous episode of zoster and persons with chronic medical conditions can be vaccinated unless those conditions are contraindications or precautions. Zoster vaccination is not indicated to treat acute zoster. 91 Recommendations of the Advisory Committee on Immunization Practices (ACIP) http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5705a1.htm?s_cid=rr5705a1_e Zostavax ® [package insert]. Whitehouse Station, NJ: Merck; April 2011.

92. Vaccine Contraindications Allergy to neomycin or any vaccine component Pregnancy Immunocompromised status AIDS or other clinical manifestations of HIV, including persons with CD4+ T-lymphocyte values <200 per mm 3 malignant neoplasms affecting the bone marrow chemotherapy or radiation within the last 3 months Persons on immunosuppressive therapy, including high- dose corticosteroids (>20 mg/day of prednisone or equivalent) lasting two or more weeks 92

93. Efficacy of ZOSTAVAX ® (Zoster Vaccine Live) on Incidence of Herpes Zoster in Adults Aged  60 Years Based on the results of the Shingles Prevention Study (SPS) a RESULTS BY AGE GROUPS (YEARS) Placebo (n=10,356) ZOSTAVAX (n=10,370) Number of Zoster Cases 64 % in subjects 60–69 [95% CI: 56–71] Placebo (n=7,559) ZOSTAVAX (n=7,621) Number of Zoster Cases 41 % in subjects 70–79 [95% CI: 28–52] Placebo (n=1,332) ZOSTAVAX (n=1,263) Number of Zoster Cases 18 % in subjects  80 [95% CI: –29–48; NS] 334 122 261 156 47 37 Placebo (n=19,247) ZOSTAVAX (n=19,254) Number of Zoster Cases 51 % in subjects  60 [95% CI: 44–58] OVERALL LOWER INCIDENCE OF ZOSTER a 642 315 CI=confidence interval; NS=not significant. a In the Shingles Prevention Study, efficacy was evaluated in a placebo-controlled, double-blind clinical trial of ZOSTAVAX. 38,546 subjects 60 years of age or older were randomized to receive a single dose of either ZOSTAVAX (n=19,270) or placebo (n=19,276) and were monitored for the development of zoster for a median of 3.1 years (range, 31 days to 4.90 years).

94. Efficacy of ZOSTAVAX ® (Zoster Vaccine Live) on Incidence of PHN in Adults Aged  60 Years Who Developed Zoster Post-Vaccination The benefit of ZOSTAVAX in the prevention of PHN can be primarily attributed to the effect of the vaccine on the prevention of herpes zoster. 0 Overall Number of PHN Cases 8027 8.6 12.5 10 20 30 % of Zoster Cases With PHN 39% b Number of HZ Cases 642315 (95% CI: 7–59) ZOSTAVAX Placebo HZ=herpes zoster; PHN=postherpetic neuralgia. a PHN was defined as herpes zoster-associated pain rated as ≥3 on a 10-point scale and occurring or persisting at least 90 days after rash onset. b Age-adjusted estimate based on the age strata (60–69 and ≥70 years of age) at randomization. Based on the results of the Shingles Prevention Study (SPS) a

95. Efficacy of ZOSTAVAX ® (Zoster Vaccine Live) on Incidence of Herpes Zoster in Adults Aged 50–59 Years Based on the results of the ZOSTAVAX Efficacy and Safety Trial (ZEST) 1,a a Study Design for ZEST: In the ZOSTAVAX Efficacy and Safety Trial, efficacy was evaluated in a placebo- controlled, double-blind study of ZOSTAVAX. 22,439 subjects 50 to 59 years of age were randomized to receive a single dose of either ZOSTAVAX (n=11,211) or placebo (n=11,228) and were monitored for the occurrence of shingles for a median of 1.3 years postvaccination (range, 0 to 2 years). 1. Schmader KE et al. Clin Infect Dis. 2012;54:922–928. 99 30 Placebo (n=11,228) ZOSTAVAX (n=11,211) Number of Zoster Cases 70 % in subjects 50–59 [95% CI: 54–81]

96. Storage and Handling zoster vaccine must be stored frozen The vaccine must be discarded if not used within 30 minutes after reconstitution. New labeling: Zostavax may be stored and/or transported at fridge temp for up to 72 hours prior to reconstitution. Any unused vaccine at fridge temp should be discarded. 96 Zostavax ® [package insert]. Whitehouse Station, NJ: Merck; April 2011.

98. Administration Zostavax: 0.65-mL dose (reconstituted) SQ – upper, outer tricep 5/8 inch, 25 gauge needle 98

99. Which of the following statements about the administration of influenza and zoster 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.

101. Pathogen (Common name) Table PathogenClassificationTransmissionComplication Influenza (flu) virusRespiratoryPneumonia PneumococcusGram + BacteriaRespiratoryMeningitis/Bacteremia Varicella (chicken pox) virusRespiratoryBacterial infection Zoster (shingles) virusLatent varicellaNeuralgia HPV (genital warts) virusSexual contactCervical cancer MeningococcusGram - BacteriaRespiratoryInvasive disease Tetanus (lockjaw) Gram + Bacteria-toxinwoundRespiratory failure DiphtheriaGram + Bacteria-toxinRespiratoryMyocarditis/Neuritis Pertussis (whooping cough) Gram - BacteriaRespiratoryPneumonia MeaslesvirusRespiratoryDiarrhea, pneumonia MumpsvirusRespiratoryMeningitis RubellavirusRespiratoryArthritis Hepatitis AvirusFecal-oralAcute/chronic hepatitis Hepatitis BvirusBlood-serous fluidsAcute hepatitis

102. Adult Vaccine Table VaccineVaccine Type Route / Reconstitute SeriesStorage Influenza IIVInactivatedIM / No1x annuallyFridge FlumistLiveIntranasal / No1x annuallyFridge PneumovaxInactivatedIM or SQ / No1-2 dosesFridge ZostavaxLiveSQ / Yes1 doseFreezer Gardasil (HPV4) Cervarix (HPV2) InactivatedIM / No3 dosesFridge TdInactivatedIM / No1 q 10 yearsFridge TdapInactivatedIM / No1x, then TdFridge VarivaxLiveSQ / Yes2 dosesFreezer MMRLiveSQ / Yes1-2 doses Fridge or Freezer Menactra, Menveo Menomune (MPSV4) InactivatedIM / No1-2+ dosesFridge Havrix, VaqtaInactivatedIM / No2 dosesFridge Recombivax-HB Engerix-B InactivatedIM / No3 dosesFridge