OREGON HEALTH AUTHORITY IMMUNIZATION PROTOCOL FOR PHARMACISTS Human Papilloma Virus Vaccines (HPV) Revisions as of 01-01-2016 Vaccination age changed to clients 7 years of age Removal of adolescent well visit flyer I. OREGON IMMUNIZATION PHARMACY PROTOCOL: 1. Check the ALERT Immunization Information System (IIS) to determine whether the patient needs this vaccine and any other vaccines. 2. Screen clients 7 years for contraindications. 3. Provide a current Vaccine Information Sheet (VIS) answering any questions. 4. Record all required data elements in the client s permanent health record. 5. Give HPV vaccine 0.5 ml intramuscularly (deltoid preferred) as appropriate for the age and sex of the patient. 6. Simultaneous vaccination may be given with all routine adolescent or adult vaccines. 7. Observe client for 15 minutes after vaccination to decrease the risk for injury should they faint. Immunizing Pharmacist Signature Date For multiple signatures see: http://1.usa.gov/pharmacyimmunizationprotocols
II. LICENSED HUMAN PAPILLOMAVIRUS (HPV) VACCINE H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 2 of 14 Product Name Vaccine Components Acceptable Age Range Recommended Age Thimerosal Gardasil 9 * (HPV 9) Gardasil * (HPV 4) Protein of HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58 Protein of HPV types 6, 11, 16, and 18 Female 9 26 ** years 11 12 yrs Male 9 26 years ** 11 12 yrs Female 9 26 years ** 11 12 yrs Male 9 26 years ** 11 12 yrs None None Cervarix (HPV 2) Protein of HPV types 16 and 18 Female only 9 26 ** 11 12 yrs None * HPV 4 is designed to prevent HPV 6 & 11 type genital warts and HPV 16, 18. HPV 9 is designed to prevent an additional five strains: 31, 33, 45, 52, and 58 which are related to cervical cancer, cervical dysplasias, vulvar or vaginal dysplasias, and anal cancers. 1 ACIP recommends routine HPV vaccination for all males 9 21 years and for some males 22 26 years of age. See section III.4 recommendations for special populations. 1 HPV vaccine can be given simultaneously with all scheduled vaccines. 8 Designed to prevent HPV 16 and 18 related to cervical cancers, cervical intraepithelial neoplasia grade 2 or worse and adenocarcinoma in situ and cervical intraepithelial neoplasia grade 1. 5 ** If persons reach age 27 years before the HPV vaccination series is complete, the second and or third doses of vaccine can be administered. 2
H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 3 of 14 III. RECOMMENDATIONS FOR USE 1. Routine vaccination of females and males 11 12 years of age with 3 doses of sexappropriate HPV vaccine. The vaccine series can begin at age 9 years.* 2. HPV vaccination is also routinely recommended for females 13 26 years of age not previously vaccinated or who have not completed the full HPV series.* a. Vaccinate with HPV2, HPV4, or HPV9 for prevention of cervical cancers and precancerous lesions. b. Vaccinate with the HPV4 or HPV9 vaccine for prevention of cervical cancer, cervical dysplasias, vulvar or vaginal dysplasias, and anal cancers. ** 3. HPV4 and HPV9 vaccination is routinely recommended for males 13 21 years of age not previously vaccinated or who have not completed the full HPV series. ** 4. Immunosuppressed males and men who have sex with men (MSM) 22 26 years of age should be vaccinated. Other males 22 26 years of age may be vaccinated at their request. ** 5. If persons reach age 27 years before the HPV vaccination series is complete, the second and or third doses of vaccine can be administered. * *HPV vaccines are not recommended for use in pregnancy. If a woman is found to be pregnant after initiation of HPV vaccination series, the remainder of the 3 dose series should be delayed until completion of the pregnancy. 1 Persons who are immunocompromised either from disease or medication can receive HPV4 vaccine. However, the immune response and vaccine effectiveness might be less than in those who are immunocompetent. 2 ACIP states that the HPV series doses 2 and 3 may be completed if the series was started at 26 years of age. 2 HPV4 is indicated for use against vulvar and vaginal cancers and pre-cancers. 3 ** HPV4 has also been demonstrated to protect against anal cancers and anal intraepithelial neoplasias. 3
H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 4 of 14 IV. RECOMMENDED BLENDED VACCINE SCHEDULE FOR Gardasil 4 or 9 * ** and Cervarix (HPV2) ** Dose and Route: 0.5mL IM Dose Recommended Age Minimum Age 1 11 12 years *** 9 years 2 Recommended Spacing 1 2 months after 1 st dose 3 6 months after 1 st dose Minimum Spacing 4 weeks after 1 st dose 12 weeks after 2 nd dose and 24 weeks after 1 st dose * If vaccine history or specific HPV product is unknown, any available HPV vaccine product may be used to continue or complete the series for females for protection against HPV 16 and 18. 1 HPV4 or HPV9 may be used to continue or complete the series for males. 1 There are no data on efficacy of fewer than 3 doses of HPV9. 1 Cervarix is approved for use in females only. ** Approved for use in persons 9 26 years of age. 2 Ideally, vaccine should be administered before potential exposure to HPV through sexual contact. 2 Any HPV series with <3 doses of HPV might provide less protection than a complete 3-dose series of HPV. 2 Approved for use in females 9 26 years of age and for males 9 21 years, and for some males 22 26 years of age. See section III.4. 1, 2 *** ACIP recommended age for vaccination is 11 12 years of age. Providers should take advantage of any opportunity to vaccinate persons as young as 9 years of age. 2 For retrospective evaluation only, the third (3) dose can be considered to be valid if it was separated from the first (1) dose by at least 16 weeks and from the second (2) dose by at least 12 weeks. 2
H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 5 of 14 Note: If the vaccination schedule is interrupted, the vaccine series does not need to be restarted. 1, 2 V. CONTRAINDICATIONS: For persons with a history of immediate hypersensitivity to any vaccine component 1 For GARDASIL ; a history of immediate hypersensitivity to yeast 1 For CERVARIX ; do not use prefilled syringes for individuals who have had anaphylactic reactions to latex 1 Pregnancy 1 : HPV vaccines are not to be given during pregnancy. Pregnancy registries for HPV4 and HPV2 have been closed. A new pregnancy registry has been established for HPV9. Exposure during pregnancy can be reported to the respective manufacturer: o HPV9 report to Merck Pregnancy Registry at 1-800-986-8999. o HPV4 report to Merck at 1-877-888-4231. o HPV2 to GlaxoSmithKlein at 1-888-825-5249 All clinics and pharmacies enrolled with the VFC program must report exposure during pregnancy to VAERS (see section X). VI. PRECAUTIONS: HPV vaccine can be administered to persons with minor acute illnesses (e.g.,) diarrhea or mild upper respiratory tract infections, with or without fever). 2 Vaccination of people with moderate or severe acute illnesses should be deferred until after the illness improves. 2 Observe client for 15 minutes in case of syncope. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following HPV vaccination. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion by maintaining a supine or Trendelenburg position. 2
H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 6 of 14 VII. SIDE EFFECTS AND ADVERSE REACTIONS Table 1: Injection site and systemic adverse reactions occurring within five days of each vaccination with Gardasil 9 and Gardasil 4 in girls and women. Gardasil 9 Gardasil 4 After any dose After any dose Number followed for Safety N=7071 N=7078 % % Age in Years 16 26 Injection Site Adverse Reactions Pain (any) 89.9 83.5 Redness (any) 34.0 25.6 Swelling (any) 40.0 28.8 Systemic Adverse Reactions N=7022 N=7024 Temperature >100 6.0 5.9 Temperature >102 1.0 0.8 Age in Years 9 15 N =299 N=300 Injection Site Adverse Reactions Pain (any) 89.3 88.3 Redness (any) 34.1 29.3 Swelling (any) 47.8 36.0 Systemic Adverse Reactions N=299 N=300 Temperature >101 6.7 3.3 Temperature >102 1.3 0.7 Gardasil 9 package insert table 1 page 5 3
VII. SIDE EFFECTS AND ADVERSE REACTIONS Cont. H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 7 of 14 Table 2: Rates (%) of solicited and unsolicited injection-site and systemic adverse reactions among boys 9 through 15 years of age who received Gardasil 9 Gardasil 9 Study Number: NCT00943722 Number followed for Safety N =639 Adverse Reaction % Age in Years: 9 through 15 Solicited Local Reaction, Injection site 1 5 days post-vaccination, any dose Pain 71.5 Redness 24.9 Swelling 26.9 Solicited Systemic Adverse Reaction Oral Temp 100.0 F (n= 637) 10.4 Unsolicited Local Reaction, Injection site 1 5 days post-vaccination, any dose Injection-Site Hematoma 1.3 Injection-Site Induration 1.1 Unsolicited Systemic Adverse Reactions 1 15 days post-vaccination, any dose Headache 9.4 Pyrexia * 8.9 Nausea 1.3 * Report of feeling febrile Gardasil 9 package insert table 3 page 6 3
VII. SIDE EFFECTS AND ADVERSE REACTIONS Cont. H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 8 of 14 Table 3: GARDASIL 4 : Adverse reactions in males and females 9 26 years of age 1 5 days post vaccination. 4 Gardasil AAHS Control * Saline Placebo Number followed for Safety N =5088 N=3470 N=320 % % % Age in Years 9 26 Females Local Reaction, Injection site 1 5 days post-vaccination Pain 83.9 75.4 48.6 Redness 24.7 18.4 12.1 Swelling 25.4 15.8 7.3 Itching 3.2 2.8 0.6 Bruising 2.8 3.2 1.6 Systemic Reaction 1 5 days post-vaccination Pyrexia ** 13.0 11.2 Headache 28.2 28.4 28.4 Number followed for Safety N=3093 N=2029 N=274 Age in Years 9 26 Males Local Reaction, Injection site 1 5 days post-vaccination Pain 61.4 50.8 41.6 Redness 16.7 14.1 14.5 Swelling 13.9 9.6 8.2 Hematoma 1.0 0.3 3.3 Systemic Reaction 1 5 days post-vaccination Pyrexia ** 8.3 6.5 Headache 12.3 11.2 * AHHS Control: Amorphous Aluminum Hydroxyphosphate Sulfate Gardasil 4 package insert table 1 page 4 4 Gardasil 4 package insert table 2 page 4 4 Gardasil 4 package insert table 5 page 6 4 ** Report of feeling febrile
VII. SIDE EFFECTS AND ADVERSE REACTIONS Cont. H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 9 of 14 Post-dose evaluation of fever in girls and women 9 26 years of age (1 5 days postvaccination) Temperature (F ) After dose 1 N=4945 Gardasil 4 % occurrence After dose 2 N=4804 After dose 3 N=4671 AHHS Control * or Saline Placebo % occurrence After dose 1 N=3681 After dose 2 N = 3564 After dose 3 N=3467 100 to <102 3.7 4.1 4.4 3.1 3.8 3.6 102 0.3 0.5 0.5 0.2 0.4 0.5 Gardasil 4 package insert page 7 4 * AHHS Control: Amorphous Aluminum Hydroxyphosphate Sulfate: adjuvant Post-dose evaluation of fever in boys and men 9 26 years of age (1 5 days postvaccination) Temperature (F ) After dose 1 N=2972 Gardasil 4 % occurrence After dose 2 N=2849 After dose 3 N=2792 AHHS Control * or Saline Placebo % occurrence After dose 1 N=2194 After dose 2 N = 2079 After dose 3 N=2046 100 to <102 2.4 2.5 2.3 2.1 2.2 1.6 102 0.6 0.5 0.5 0.5 0.3 0.3 Gardasil 4 package insert page 7 4 * AHHS Control: Amorphous Aluminum Hydroxyphosphate Sulfate
H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 10 of 14 VII. SIDE EFFECTS AND ADVERSE REACTIONS Cont. Table 4: CERVARIX : Adverse reactions in females 9 25 years of age 7 days postvaccination.* 5 Cervarix AI(0H) 3 Control Number followed for N=6669 N=549 Safety % % Age in Years 9 25 15 25 Local Reaction, Injection site Pain 91.9 87.2 Redness 48.4 24.4 Swelling 44.3 21.3 Systemic Reaction N=6670 N=549 Rash 9.5 10.0 Fever (<99.5 F) 12.9 13.5 Headache 53.4 61.4 Tiredness 54.6 53.6 Gastro-intestinal 27.9 32.8 N=6119 Joint Pain 20.7 Muscle pain 48.8 Hives 7.2 *Package insert table 1 page 5. 5 Al(OH) 3 Control: Aluminum hydroxide, 500 mcg. 5 A general term for any eruption that appears on the skin. Not permanent. 8 Multiple swollen raised areas on the skin that are migratory, intensely itchy, and last up to 24 hours. 8
H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 11 of 14 VIII. OTHER CONSIDERATIONS A. Cervical cancer screening is recommended beginning at age 21 years and continuing through age 65 years for both vaccinated and unvaccinated women. 1 B. Pap test: HPV screenings are approved for use with Papanicolaou (Pap) test for routine screening in women >30 years of age or for following up certain abnormal Pap test results. One HPV screening has been approved for primary cervical cancer screening but is not currently part of national recommendations. There are no other approved indications for clinical HPV testing. Screening is not necessary prior to receiving HPV vaccine. 2 C. Abnormal Pap test: This vaccine can be given to females who have an equivocal or abnormal Pap test, a positive Hybrid Capture II high-risk test, or genital warts. However, vaccine recipients should be advised that the vaccine will not have any therapeutic effect on existing Pap test abnormalities, HPV infection or genital warts. Vaccination of these females would provide protection against infection with vaccine HPV types not already acquired. 2 D. Lactating women can receive HPV vaccine. 2 E. HPV vaccine is recommended through age 26 years for men who have sex with men and for immunocompromised persons (including those who have had transplants or HIV infection), who have not been vaccinated previously or have not completed the 3 dose series. These individuals are more likely to develop HPV-associated disease and cancer. 1,2 F. It is unclear whether there will be any difference in response to vaccination between immunocompromised and immunocompetent persons. 2 G. There are no data on efficacy of fewer than 3 doses of HPV vaccine. 1
3, 4, 5 H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 12 of 14 IX. STORAGE AND HANDLING All clinics and pharmacies enrolled with the VFC program must immediately report any storage and handling deviations to their health educator. A map of the Health Educator assignments is available at: http://bit.ly/he_map. GARDASIL 9 is supplied in vials and syringes: Store refrigerated at 2 to 8 C (36 to 46 F). Do not freeze Protect from light GARDASIL9 should be administered as soon as possible after being removed from refrigeration GARDASIL 9 can be administered provided total (cumulative multiple excursion) time out of refrigeration (at temperatures between 8 C and 25 C) does not exceed 72 hours. Cumulative multiple excursions between 0 C and 2 C are also permitted as long as the total time between 0 C and 2 C does not exceed 72 hours. These are not, however, recommendations for storage. GARDASIL is supplied in vials and syringes: Store refrigerated at 2 to 8 C (36 to 46 F). Do not freeze Protect from light GARDASIL should be administered as soon as possible after being removed from refrigeration GARDASIL can be out of refrigeration at temperatures at or below 25 C/77 F for a total time of not more than 72 hours CERVARIX is available in 0.5-mL single-dose disposable prefilled TIP-LOK syringes (packaged without needles): Store refrigerated between 2º and 8ºC (36º and 46ºF) Do not freeze Discard if the vaccine has been frozen Upon storage, a fine, white deposit with a clear, colorless supernatant may be observed. This does not constitute a sign of deterioration
H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 13 of 14 X. ADVERSE EVENTS REPORTING Adverse events following immunization must be reported to the Vaccine Adverse Events Reporting System (VAERS). The VAERS online report form is available at https://vaers.hhs.gov/esub/step1. A pharmacist who administers any vaccine must report the following elements to the OHA ALERT Immunization Information System in a manner prescribed by OHA within 15 days of administration. This replaces the former requirement to notify the primary health care provider. A pharmacist is not required to notify the primary health care provider. Oregon Administrative Rule 855-019-0290-(2). 9 To request this material in an alternative format (e.g., Braille) or to clarify any part of the above order, contact the Oregon Health Authority Immunization Program at 971.673.0300 and 711 for TTY. For other questions, consult with the vaccine recipient s primary health care provider or a consulting physician. Electronic copy of this protocol available at: 1.usa.gov/PharmacyImmunizationProtocols
H u m a n P a p i l l o m a V i r u s V a c c i n e P a g e 14 of 14 REFERENCES 1. CDC. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015. MMWR 2015; 64; 300 304. Available at: www.cdc.gov/mmwr/pdf/wk/mm6411.pdf. Accessed 27 March 2015. 2. CDC. Human papillomavirus vaccination: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2014. MMWR 2014; 63(RR05); 1 30. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/rr6305a1.htm?s_cid=rr6305a1_e Accessed 31 March 2015. 3. Gardasil 9 package insert (p5). Available at: www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm426 457.pdf. Accessed 31 March 2015. 4. Gardasil package insert. Available at: www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm111 263.pdf. Accessed 31 March 2015. 5. Cervarix package insert. Available at: www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm186 981. pdf. Accessed 31 March 2015. 6. Human Papillomavirus. In: Epidemiology and Prevention of Vaccine-Preventable Diseases ( Pink Book ). Atkinson W, Hamborsky J, Wolfe S, eds. 12 th ed. Washington, DC: Public health foundation, May, 2012 139 49. Available at: www.cdc.gov/vaccines/pubs/pinkbopok/index.html. Accessed 18 December 2014 7. CDC. General Recommendations on Immunizations. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2011; 60 (RR-2). Available at: www.cdc.gov/mmwr/pdf/rr/rr6002.pdf. 8. Merck Manual. Available at: http://www.merckmanuals.com/professional/dermatologic_disorders/approach_to_t he_dermatologic_patient/urticaria.html Accessed 15 December 2014. 9. Oregon Administrative Rule. Board of Pharmacy. Division 19. Licensing of pharmacists: 855 019 0290 (2). Available at: http://arcweb.sos.state.or.us/pages/rules/oars_800/oar_855/855_019.html Accessed 12 May 2015.