HPV only infects human beings. Animal studies with analogous animal papillomaviruses suggest that the efficacy of L1 VLP vaccines may involve the development of humoral immune responses. Human beings develop a humoral immune response to the vaccine, although the exact mechanism of protection is unknown.

Human Papillomavirus Quadrivalent is a vaccine indicated in girls and women 9 through 26 years of age for the prevention of the following diseases caused by Human Papillomavirus (HPV) types included in the vaccine:

• Cervical, vulvar, vaginal, and anal cancer caused by HPV types 16 and 18.
• Genital warts (condyloma acuminata) caused by HPV types 6 and 11.

And the following precancerous or dysplastic lesions caused by HPV types 6, 11, 16, and 18:

• Cervical intraepithelial neoplasia (CIN) grade 2/3 and Cervical adenocarcinoma in situ (AIS).
• Cervical intraepithelial neoplasia (CIN) grade 1.
• Vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3.
• Vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3.
• Anal intraepithelial neoplasia (AIN) grades 1, 2, and 3.

0.5 ml suspension for intramuscular injection at the following schedule: 0, 2 months, 6 months.

Administration

For intramuscular use only. Shake well before use. Thorough agitation immediately before administration is necessary to maintain suspension of the vaccine. Human Papillomavirus Quadrivalent should not be diluted or mixed with other vaccines. After thorough agitation, Human Papillomavirus Quadrivalent is a white, cloudy liquid. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use the product if particulates are present or if it appears discolored. Human Papillomavirus Quadrivalent should be administered intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh. Syncope has been reported following vaccination with Human Papillomavirus Quadrivalent and may result in falling with injury; observation for 15 minutes after administration is recommended.

Hypersensitivity, including severe allergic reactions to yeast (a vaccine component), or after a previous dose of Human Papillomavirus Quadrivalent.

The most common adverse reaction was headache. Common adverse reactions (frequency of at least 1.0% and greater than AAHS control or saline placebo) are fever, nausea, dizziness; and injection-site pain, swelling, erythema, pruritus, and bruising.

Overdose Effects

There have been reports of administration of higher than recommended doses of Human Papillomavirus Quadrivalent. In general, the adverse event profile reported with overdose was comparable to recommended single doses of Human Papillomavirus Quadrivalent.

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 vaccination with Human Papillomavirus Quadrivalent. 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.

Use in Special Populations

Pediatric Use: Safety and effectiveness have not been established in pediatric patients below 9 years of age.

Geriatric Use: The safety and effectiveness of Human Papillomavirus Quadrivalent have not been evaluated in a geriatric population, defined

as individuals aged 65 years and over.

Pregnancy & Lactation

Pregnancy Category B. Reproduction studies have been performed in female rats at doses equivalent to the recommended human dose and have revealed no evidence of impaired female fertility or harm to the fetus due to Human Papillomavirus Quadrivalent. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, Human Papillomavirus Quadrivalent should be used during pregnancy only if clearly needed. It is not known whether Human Papillomavirus Quadrivalent is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Human Papillomavirus Quadrivalent is administered to a nursing woman.