GARDASIL- human papillomavirus type 6 l1 capsid protein antigen, human papillomavirus type 11 l1 capsid protein antigen, human papillomavirus type 16 l1 capsid protein antigen and human papillomavirus type 18 l1 capsid protein antigen injection, suspension
Merck Sharp & Dohme Corp.
1 INDICATIONS AND USAGE
1.1 Girls and Women
GARDASIL� 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
1.2 Boys and Men
GARDASIL is indicated in boys and men 9 through 26 years of age for the prevention of the following diseases caused by HPV types included in the vaccine:
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:
Anal intraepithelial neoplasia (AIN) grades 1, 2, and 3
1.3 Limitations of GARDASIL Use and Effectiveness
The health care provider should inform the patient, parent, or guardian that vaccination does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening. Women who receive GARDASIL should continue to undergo cervical cancer screening per standard of care. [See Patient Counseling Information (17).]
Recipients of GARDASIL should not discontinue anal cancer screening if it has been recommended by a health care provider. [See Patient Counseling Information (17).]
GARDASIL has not been demonstrated to provide protection against disease from vaccine and non-vaccine HPV types to which a person has previously been exposed through sexual activity. [See Clinical Studies (14.4, 14.5).]
GARDASIL is not intended to be used for treatment of active external genital lesions; cervical, vulvar, vaginal, and anal cancers; CIN; VIN; VaIN; or AIN.
GARDASIL has not been demonstrated to protect against diseases due to HPV types not contained in the vaccine. [See Clinical Studies (14.4, 14.5).]
Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL protects only against those vulvar, vaginal, and anal cancers caused by HPV 16 and 18.
GARDASIL does not protect against genital diseases not caused by HPV.
Vaccination with GARDASIL may not result in protection in all vaccine recipients.
GARDASIL has not been demonstrated to prevent HPV-related CIN 2/3 or worse in women older than 26 years of age.
DOSAGE AND ADMINISTRATION
2.1 Dosage
GARDASIL should be administered intramuscularly as a 0.5-mL dose at the following schedule: 0, 2 months, 6 months
Method of Administration
For intramuscular use only.
Shake well before use. Thorough agitation immediately before administration is necessary to maintain suspension of the vaccine. GARDASIL should not be diluted or mixed with other vaccines. After thorough agitation, GARDASIL 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.
GARDASIL 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 GARDASIL and may result in falling with injury; observation for 15 minutes after administration is recommended. [See Warnings and Precautions (5.1).]
Single-Dose Vial Use
Withdraw the 0.5-mL dose of vaccine from the single-dose vial using a sterile needle and syringe and use promptly.
Prefilled Syringe Use
This package does not contain a needle. Shake well before use. Attach the needle by twisting in a clockwise direction until the needle fits securely on the syringe. Administer the entire dose as per standard protocol.
3 DOSAGE FORMS AND STRENGTHS
GARDASIL is a suspension for intramuscular administration available in 0.5-mL single dose vials and prefilled syringes. See Description (11) for the complete listing of ingredients.
DESCRIPTION
GARDASIL, Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant, is a non-infectious recombinant quadrivalent vaccine prepared from the purified virus-like particles (VLPs) of the major capsid (L1) protein of HPV Types 6, 11, 16, and 18. The L1 proteins are produced by separate fermentations in recombinant Saccharomyces cerevisiae and self-assembled into VLPs. The fermentation process involves growth of S. cerevisiae on chemically-defined fermentation media which include vitamins, amino acids, mineral salts, and carbohydrates. The VLPs are released from the yeast cells by cell disruption and purified by a series of chemical and physical methods. The purified VLPs are adsorbed on preformed aluminum-containing adjuvant (Amorphous Aluminum Hydroxyphosphate Sulfate). The quadrivalent HPV VLP vaccine is a sterile liquid suspension that is prepared by combining the adsorbed VLPs of each HPV type and additional amounts of the aluminum-containing adjuvant and the final purification buffer.
GARDASIL is a sterile suspension for intramuscular administration. Each 0.5-mL dose contains approximately 20 mcg of HPV 6 L1 protein, 40 mcg of HPV 11 L1 protein, 40 mcg of HPV 16 L1 protein, and 20 mcg of HPV 18 L1 protein
Each 0.5-mL dose of the vaccine contains approximately 225 mcg of aluminum (as Amorphous Aluminum Hydroxyphosphate Sulfate adjuvant), 9.56 mg of sodium chloride, 0.78 mg of L-histidine, 50 mcg of polysorbate 80, 35 mcg of sodium borate, <7 mcg yeast protein/dose, and water for injection. The product does not contain a preservative or antibiotics.
After thorough agitation, GARDASIL is a white, cloudy liquid.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
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.
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Inform the patient, parent, or guardian:
Vaccination does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening. Women who receive GARDASIL should continue to undergo cervical cancer screening per standard of care.
Recipients of GARDASIL should not discontinue anal cancer screening if it has been recommended by a health care provider.
GARDASIL has not been demonstrated to provide protection against disease from vaccine and non-vaccine HPV types to which a person has previously been exposed through sexual activity.
Since syncope has been reported following vaccination sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended.
Vaccine information is required to be given with each vaccination to the patient, parent, or guardian.
Information regarding benefits and risks associated with vaccination.
GARDASIL is not recommended for use in pregnant women.
Importance of completing the immunization series unless contraindicated.
Report any adverse reactions to their health care provider.
