Indication for GARDASIL 9

GARDASIL 9 is a vaccine indicated in females 9 through 26 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 26 years of age for the prevention of anal cancer caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant) does not eliminate the necessity for womengirls to continue to undergo recommended cervical cancer screening later in life. Recipients of GARDASIL 9 should not discontinue anal cancer screening if it has been recommended by a health care professional.

GARDASIL 9 has not been demonstrated to provide protection against diseases from vaccine HPV types to which a person has previously been exposed through sexual activity.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, and anal cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, and anal cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58.

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

Select Safety Information for GARDASIL®9 9 (Human Papillomavirus 9-valent Vaccine, Recombinant)

GARDASIL 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. 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.

Safety and effectiveness of GARDASIL 9 have not been established in pregnant women.

The most common (≥10%) local and systemic adverse reactions in females were injection-site pain, swelling, erythema, and headache. The most common (≥10%) local and systemic reactions in males were injection-site pain, swelling, and erythema.

The duration of immunity of GARDASIL 9 has not been established.

There was an increase in injection-site swelling reported at the injection site for GARDASIL 9 when administered concomitantly with Menactra and Adacel. The majority of injection-site swelling adverse experiences were reported as being mild to moderate in intensity.


Dosage and Administration for GARDASIL 9

GARDASIL 9 should be administered intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh.

  • For individuals 9 through 14 years of age, GARDASIL 9 can be administered using a 2-dose or 3-dose schedule. For the 2-dose schedule, the second dose should be administered 6–12 months after the first dose. If the second dose is administered less than 5 months after the first dose, a third dose should be given at least 4 months after the second dose. For the 3-dose schedule, GARDASIL 9 should be administered at 0, 2 months, and 6 months.
  • For individuals 15 through 26 years of age, GARDASIL 9 is administered using a 3-dose schedule at 0, 2 months, and 6 months.

Before administering GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant), please read the Prescribing Information. The Patient Information also is available.

1. National Foundation for Infectious Diseases (NFID). Call to action: HPV vaccination as a public health priority. http://www.nfid.org/publications/cta/hpv-call-to-action.pdf. Published August 2014. Accessed March 25, 2017.
2. de Sanjose S, Quint WGV, Alemany L, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048–1056.
3. de Sanjose S, Alemany L, Ordi J, et al. Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva. Eur J Cancer. 2013;49(16):3450–3461.
4. Alemany L, Saunier M, Tinoco L, et al. Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples. Eur J Cancer. 2014;50(16):2846–2854.
5. Alemany L, Saunier M, Alvarado-Cabrero I, et al. Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide. Int J Cancer. 2015;136(1):98–107.
6. Joura EA, Ault KA, Bosch FX, et al. Attribution of 12 high-risk human papillomavirus genotypes to infection and cervical disease. Cancer Epidemiol Biomarkers Prev. 2014;23(10):1997–2008.
7. Garland SM, Steben M, Sings HL, et al. Natural history of genital warts: analysis of the placebo arm of 2 randomised phase III trials of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine. J Infect Dis. 2009;199(6):805–814.
8. Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer. 2012;131(10):2349–2359.
9. Data available on request from Merck Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package VACC-1196399-0000.
10. Centers for Disease Control and Prevention (CDC). Storage and handling. In: Hamborsky J, Kroger A, Wolf C, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Washington, DC: Public Health Foundation; 2015:63–77.
11. Centers for Disease Control and Prevention (CDC). Vaccine administration. In: Hamborsky J, Kroger A, Wolf C, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Washington, DC: Public Health Foundation; 2015:79–106.
12. Centers for Disease Control and Prevention (CDC). National, regional, state, and selected local area vaccination coverage among adolescents aged 13–17 years—United States, 2014. https://www.cdc.gov/mmwr/
preview/mmwrhtml/mm6429a3.htm. Accessed June 22, 2017.
13. Schuchat A. Recommending HPV vaccine successfully. http://www.medscape.com/viewarticle/810030. Published September 3, 2013. Accessed May 1, 2017.
14. Petrosky E, Bocchini JA Jr, Hariri S, et al. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2015;64(11):300–304.
15. Centers for Disease Control and Prevention (CDC). Recommended immunization schedule for children and adolescents aged 18 years or younger—United States, 2017. https://www.cdc.gov/vaccines/schedules/
downloads/child/0-18yrs-child-combined-schedule.pdf. Published January 1, 2017. Accessed May 8, 2017.
16. Centers for Disease Control and Prevention (CDC). Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014;63(RR-5):1–30.
17. Finer LB, Philbin JM. Sexual initiation, contraceptive use, and pregnancy among young adolescents. Pediatrics. 2013;131(5):1–6.
18. Data available on request from Merck Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package VACC-1244939-0000.
19. Centers for Disease Control and Prevention (CDC). Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65(49):1405–1408.
20. Centers for Disease Control and Prevention (CDC). Human papillomavirus. In: Hamborsky J, Kroger A, Wolfe C, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Washington DC: Public Health Foundation; 2015: 175–186.
21. American Academy of Family Physicians (AAFP). Strong recommendation to vaccinate against HPV is key to boosting uptake. http://www.aafp.org/news/health-of-the-public/20140212hpv-vaccltr.html. Published February 12, 2014. Accessed May 7, 2017.
22. Centers for Disease Control and Prevention (CDC). Surveillance of Vaccination Coverage Among Adult Populations—United States, 2015. https://www.cdc.gov/mmwr/volumes/66/ss/ss6611a1.htm. Updated June 21, 2017. Accessed January 21, 2018.
23. McQuillan G, Kruszon-Moran D. Prevalence of HPV in Adults Aged 18–69: United States, 2011–2014. NCHS Data Brief. 2017;280:1–7.
24. Rahman S, Pierce Campbell CM, Rolisson DE, et al. Seroprevalence and associated factors of 9-valent human papillomavirus (HPV) types among men in the multinational HIM study. PLOS ONE. 2016(11):1–16.
25. Bahmanyar ER, Paavonen J, et al. Prevalence and risk factors for cervical HPV infection and abnormalities in young adult women at enrolment in the multinational PATRICIA trial. Gynecologic Oncology. 2012;(127):440–450.
26. American Cancer Society (ACS). American Cancer Society Recommendations for Human Papillomavirus (HPV) Vaccine Use. https://www.cancer.org/cancer/cancer-causes/infectious-agents/hpv/acs-recommendations-for-hpv-vaccine-use.html. Revised July 19, 2016. Accessed February 14, 2018.
27. National Center for Health Statistics.1993. Section 1. In: Vital Statistics of the United States, 1989, Volume I – Natality. Public Health Service, Washington. U.S. Government Printing Office, 1–370.
28. Barnard M, George P, Perryman ML, et al. Human papillomavirus (HPV) vaccine knowledge, attitudes, and uptake in college students: implications from the precaution adoption process model. PLOS ONE. 2017;12(8):1–9.
29. Rosenthal SL, Weiss TW, Zimet GD, et al. Predictors of HPV vaccine uptake among women aged 19–26: importance of a physician's recommendation. Vaccine. 2011;29(5):890–895.
30. Yanofsky VR, Patel RV, Goldenberg G. Genital warts: a comprehensive review. J Clin Aesthet Dermatol. 2012;5(6):25–36.
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Efficacy of GARDASIL 9

Original 4 HPV types

Established efficacy for HPV Types 6, 11, 16, and 18

Efficacy against diseases caused by HPV Types 6, 11, 16, and 18 for GARDASIL 9 was inferred from a non-inferiority comparison of geometric mean titers (GMTs) versus GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

In clinical studies of young men and women 16 to 26 years of age naïve to HPV Type 6, 11, 16, or 18, efficacy of GARDASIL wasa:

CERVICAL CANCER
HPV 16- and 18-related CIN 2/3 or AIS

98% efficacy

VULVAR/VAGINAL CANCER
HPV 16- and 18-related VIN 2/3 and VaIN 2/3

100% efficacy

ANAL CANCER
HPV 6-, 11-, 16-, and 18-related AIN 2/3

75% efficacy

GENITAL WARTS
HPV 6- and 11-related

89% efficacy in males

99% efficacy in females

Study results for data above:

  • Cervical: 2 CIN 2/3 or AIS cases in the group receiving GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] (n=8,493) vs 112 cases in the group receiving placebo (n=8,464) [95% CI, 93.5–99.8]
  • Vulvar/Vaginal: no VIN 2/3 or VaIN 2/3 cases in either group receiving GARDASIL (n=7,772) vs 10 cases in the VIN 2/3 group receiving placebo (n=7,744) [95% CI, 55.5–100.0], and 9 cases in the VaIN 2/3 group receiving placebo (n=7,744) [95% CI, 49.5–100.0]
  • Anal: 3 AIN 2/3 cases in the male group receiving GARDASIL (n=194) vs 13 cases in the male group receiving placebo (n=208) [95% CI, 8.8–95.4]
  • Genital Warts: 3 genital warts cases in the male group receiving GARDASIL (n=1,394) vs 28 cases in the male group receiving placebo (n=1,404) [95% CI, 65.3–97.9], and 2 genital warts cases in the female group receiving GARDASIL (n=6,932) vs 189 cases in the female group receiving placebo (n=6,856) [95% CI, 96.2–99.9]

aStudy Design: Efficacy of GARDASIL was assessed in 5 AAHS-controlled, double-blind, randomized clinical studies evaluated 24,596 individuals (20,541 girls and women 16 to 26 years of age and 4,055 boys and men 16 to 26 years of age at enrollment). Efficacy was evaluated in subjects who received all 3 vaccinations within 1 year of enrollment, had no major deviations from the study protocol, were naïve to the relevant HPV type(s) (Types 6, 11, 16, and 18) prior to dose 1, and remained PCR negative to the relevant HPV type(s) through 1 month postdose 3 (Month 7).

AAHS=amorphous aluminum hydroxyphosphate sulfate.
AIN=anal intraepithelial neoplasia.
AIS=adenocarcinoma in situ.

Additional 5 HPV types

Demonstrated clinical efficacy against 5 more HPV types

In a worldwide clinical study of young women 16 to 26 years of age naïve to HPV Type 31, 33, 45, 52, or 58a:

97% efficacy

CERVICAL CANCER | CIN 2/3, AIS

VULVAR CANCER | VIN 2/3

VAGINAL CANCER | VaIN 2/3

HPV 31-, 33-, 45-, 52- and 58-related

One case in the group receiving GARDASIL 9 (n=6,016) vs 30 cases in the group receiving GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] (n=6,017) [95% CI, 80.9–99.8]

aStudy Design: Efficacy of GARDASIL 9 in 16- to 26-year-old women was assessed in an active comparator-controlled, double-blind, randomized clinical study that included a total of 14,204 women (GARDASIL 9=7,099; GARDASIL=7,105). Subjects were followed up with a median duration of 40 months (range 0 to 64 months) and efficacy was measured starting after the Month 7 visit. Efficacy was evaluated in subjects who received all 3 vaccinations within 1 year of enrollment, had no major deviations from the study protocol, were naïve to the relevant HPV type(s) prior to dose 1, and remained PCR negative to the relevant HPV type(s) through 1 month postdose 3 (Month 7).

AIN=anal intraepithelial neoplasia.
AIS=adenocarcinoma in situ.
CIN=cervical intraepithelial neoplasia.
PCR=polymerase chain reaction.
VaIN=vaginal intraepithelial neoplasia.
VIN=vulvar intraepithelial neoplasia.

Other Clinical End Points

Data for other clinical end pointsa

In a worldwide clinical study of young women 16 to 26 years of age naïve to HPV Type 31, 33, 45, 52, or 58a:

93% efficacy

against HPV 31-, 33-, 45-, 52-, and 58-related ASC-US HR-HPV positive or worse Pap abnormality

Thirty-five cases in the group receiving GARDASIL 9 (n=5,881) vs 462 cases in the group receiving GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] (n=5,882) [95% CI, 89.7–94.8]

97% efficacy

against HPV 31-, 33-, 45-, 52-, and 58-related biopsy

Seven cases in the group receiving GARDASIL 9 (n=6,016) vs 222 cases in the group receiving GARDASIL (n=6,017) [95% CI, 93.6–98.6]

88% efficacy

against HPV 31-, 33-, 45-, 52-, and 58-related definitive therapyb

Four cases in the group receiving GARDASIL 9 (n=6,012) vs 32 cases in the group receiving GARDASIL (n=6,014) [95% CI, 65.7–96.0]

aStudy Design: Efficacy of GARDASIL 9 in 16- to 26-year-old women was assessed in an active comparator-controlled, double-blind, randomized clinical study that included a total of 14,204 women (GARDASIL 9=7,099; GARDASIL=7,105). Subjects were followed up with a median duration of 40 months (range 0 to 64 months) and efficacy was measured starting after the Month 7 visit. Efficacy was evaluated in subjects who received all 3 vaccinations within 1 year of enrollment, had no major deviations from the study protocol, were naïve to the relevant HPV type(s) prior to dose 1, and remained PCR negative to the relevant HPV type(s) through 1 month postdose 3 (Month 7).

bIncluding loop electrosurgical excision procedure (LEEP) and conization.

ASC-US=atypical squamous cells of undetermined significance.
HR=high-risk.

Indication for GARDASIL 9

GARDASIL 9 is a vaccine indicated in females 9 through 26 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 26 years of age for the prevention of anal cancer caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant) does not eliminate the necessity for womengirls to continue to undergo recommended cervical cancer screening later in life. Recipients of GARDASIL 9 should not discontinue anal cancer screening if it has been recommended by a health care professional.

GARDASIL 9 has not been demonstrated to provide protection against diseases from vaccine HPV types to which a person has previously been exposed through sexual activity.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, and anal cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, and anal cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58.

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

Select Safety Information for GARDASIL®9 9 (Human Papillomavirus 9-valent Vaccine, Recombinant)

GARDASIL 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. 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.

Safety and effectiveness of GARDASIL 9 have not been established in pregnant women.

The most common (≥10%) local and systemic adverse reactions in females were injection-site pain, swelling, erythema, and headache. The most common (≥10%) local and systemic reactions in males were injection-site pain, swelling, and erythema.

The duration of immunity of GARDASIL 9 has not been established.

There was an increase in injection-site swelling reported at the injection site for GARDASIL 9 when administered concomitantly with Menactra and Adacel. The majority of injection-site swelling adverse experiences were reported as being mild to moderate in intensity.


Dosage and Administration for GARDASIL 9

GARDASIL 9 should be administered intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh.

  • For individuals 9 through 14 years of age, GARDASIL 9 can be administered using a 2-dose or 3-dose schedule. For the 2-dose schedule, the second dose should be administered 6–12 months after the first dose. If the second dose is administered less than 5 months after the first dose, a third dose should be given at least 4 months after the second dose. For the 3-dose schedule, GARDASIL 9 should be administered at 0, 2 months, and 6 months.
  • For individuals 15 through 26 years of age, GARDASIL 9 is administered using a 3-dose schedule at 0, 2 months, and 6 months.

Before administering GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant), please read the Prescribing Information. The Patient Information also is available.

VACC-1246170-0000 05/18