Pharmaceutical Name

Trade (marketing or proprietary) name: GARDASIL®9

Generic (nonproprietary or active ingredient) name: Human Papillomavirus 9-valent Vaccine, Recombinant Suspension for intramuscular injection.

Indication and Usage

Reason the product has been approved for sale on the market.

The FDA has approved this vaccine:

Girls and Women GARDASIL®9 is a vaccine indicated in girls and women 9 through 45 years of age for the prevention of the following diseases:

• Cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by Human Papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58
• 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, 18, 31, 33, 45, 52, and 58:
  • 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

Boys and Men
GARDASIL 9 is indicated in boys and men 9 through 45 years of age for the prevention of the following diseases:

• Anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• 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, 18, 31, 33, 45, 52, and 58:
  • Anal intraepithelial neoplasia (AIN) grades 1, 2, and 3

Manufacturer Insert

Limitations of Use and Effectiveness

Vaccination with GARDASIL 9 does not eliminate the necessity for vaccine recipients to undergo screening for cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers as recommended by a health care provider.

• GARDASIL 9 has not been demonstrated to provide protection against disease caused by:
  • HPV types not covered by the vaccine,
  • HPV types to which a person has previously been exposed through sexual activity.
• Not all vulvar, vaginal, anal, oropharyngeal and other head and neck cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV 16, 18, 31, 33, 45, 52, and 58.
• GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers; CIN; VIN; VaIN; or AIN.
• Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

Ingredients

Also known as “excipients” for vaccines.

GARDASIL 9, Human Papillomavirus 9-valent Vaccine, Recombinant, is a non-infectious recombinant 9-valent vaccine prepared from the purified virus-like particles (VLPs) of the major capsid (L1) protein of HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Each 0.5-mL dose of the vaccine also contains approximately 500 mcg of aluminum (provided as AAHS), 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, and water for injection. The product does not contain a preservative or antibiotics.

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

Hypersensitivity, including severe allergic reactions to yeast (a vaccine component), or after a previous dose of GARDASIL 9 or GARDASIL.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

Syncope: 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 by maintaining a supine or Trendelenburg position.

Managing Allergic Reactions: Appropriate medical treatment and supervision must be readily available in case of anaphylactic reactions following the administration of GARDASIL 9.

Use with Systemic Immunosuppressive Medications: Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune responses to vaccines.

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

Vomiting, Urticaria (hives), Autoimmune hemolytic anemia, Idiopathic thrombocytopenic purpura, Lymphadenopathy, Pulmonary embolus, Pancreatitis, Asthenia (weakness), Chills, Death, Malaise (discomfort), Autoimmune diseases, Hypersensitivity reactions including anaphylactic/anaphylactoid reactions, Bronchospasm, Arthralgia (joint pain), Myalgia (muscle pain), Acute disseminated encephalomyelitis, Guillain-Barré syndrome, Motor neuron disease, Paralysis, Seizures, Transverse myelitis, Cellulitis, Deep venous thrombosis.

Specific Populations

Pregnancy

There are no adequate and well-controlled studies of GARDASIL 9 in pregnant women.

Breastfeeding

Available data are not sufficient to assess the effects of GARDASIL 9 on the breastfed infant or on milk production/excretion.

Fertility

GARDASIL 9 has not been evaluated for the potential to cause carcinogenicity, genotoxicity or impairment of male fertility.

Pediatric

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

Immunocompromised Individuals

The immunologic response to GARDASIL 9 may be diminished in immunocompromised individuals.

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

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. Efficacy of GARDASIL 9 against anogenital diseases related to the vaccine HPV types in human beings is thought to be mediated by humoral immune responses induced by the vaccine, although the exact mechanism of protection is unknown.

Analytical Deep Dive

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