Gardasil0.5 ml

Gardasil is a non-infectious, recombinant vaccine indicated for the prevention of disease caused by human papillomavirus (HPV) types 6, 11, 16, and 18, in the approved age range per national and manufacturer guidance (typically 9 through 45 years, per product labeling and WHO/CDC guidance).

Established / approved uses (girls and women)

• Prevention of cervical cancer and cervical intraepithelial neoplasia (CIN grades 1-3) caused by HPV types 16 and 18.
• Prevention of vulvar and vaginal cancer and related intraepithelial neoplasia (VIN, VaIN) caused by HPV types 16 and 18.
• Prevention of anal cancer and anal intraepithelial neoplasia (AIN) caused by HPV types 16 and 18.
• Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11.

Established / approved uses (boys and men)

• Prevention of anal cancer and anal intraepithelial neoplasia caused by HPV types 16 and 18.
• Prevention of genital warts caused by HPV types 6 and 11.

Guideline-supported use

• National immunization programs and WHO guidance support routine vaccination with Gardasil for adolescents (typically age 9-14 years) as primary cervical cancer and HPV-disease prevention, and catch-up vaccination up to age 26 (and, per individualized clinical decision, up to age 45) where locally approved.

Gardasil does not treat existing HPV infection, genital warts, or cervical dysplasia, and does not eliminate the need for women to continue recommended cervical cancer screening.

Each 0.5 mL dose of Human Papillomavirus Quadrivalent contains approximately:

• 20 mcg HPV type 6 L1 protein (virus-like particle, VLP)
• 40 mcg HPV type 11 L1 protein (VLP)
• 40 mcg HPV type 16 L1 protein (VLP)
• 20 mcg HPV type 18 L1 protein (VLP)

These VLPs are produced by recombinant DNA technology in yeast (Saccharomyces cerevisiae) and adsorbed onto amorphous aluminum hydroxyphosphate sulfate adjuvant. Each dose also contains sodium chloride, L-histidine, polysorbate 80, sodium borate, residual yeast protein, and water for injection. Human Papillomavirus Quadrivalent contains no preservatives and no antibiotics, and is non-infectious as it contains no live virus or viral DNA.

Gardasil is a prophylactic, non-infectious, recombinant vaccine composed of virus-like particles (VLPs) of the major capsid (L1) protein of human papillomavirus types 6, 11, 16, and 18. It is supplied as a sterile suspension for intramuscular injection and is used to prevent HPV-related cancers, precancerous lesions, and genital warts before exposure to these HPV types occurs.

Gardasil belongs to the therapeutic class of viral vaccines, specifically recombinant, non-infectious human papillomavirus (HPV) vaccines.

Human Papillomavirus Quadrivalent works by inducing an active, protective immune response. The vaccine contains non-infectious virus-like particles (VLPs) that resemble the outer shell of HPV types 6, 11, 16, and 18 but contain no viral genetic material, so they cannot cause infection or replicate.

Mechanism

• Following intramuscular administration of Human Papillomavirus Quadrivalent, the immune system recognizes the L1 VLPs as foreign antigens.
• This triggers production of type-specific neutralizing antibodies against HPV 6, 11, 16, and 18.
• Antibody and memory B-cell responses induced by Human Papillomavirus Quadrivalent confer protection so that, on future exposure to these HPV types, the virus is neutralized before it can establish infection of the cervical, vulvar, vaginal, anal, or genital epithelium.

Efficacy of Human Papillomavirus Quadrivalent has been demonstrated through prevention of persistent infection, precancerous lesions (CIN, VIN, VaIN, AIN), and genital warts attributable to the covered HPV types in clinical trials.

Gardasil should be administered only by a qualified healthcare professional, with the following precautions:

• Shake the suspension well before use to maintain a uniform suspension.
• Inspect visually for particulate matter or discoloration before administration.
• Administer by intramuscular injection only; do not give intravenously, subcutaneously, or intradermally.
• Do not mix Gardasil with any other vaccine or product in the same syringe.
• Have appropriate medical treatment available to manage possible anaphylactic reactions following administration of Gardasil.
• Observe the vaccinated individual for approximately 15 minutes after injection because of the risk of syncope (fainting).

Gardasil has not been shown to have clinically significant interactions with commonly used medicines. Relevant points:

• Gardasil may be administered concomitantly with other age-appropriate vaccines (e.g., meningococcal, tetanus-diphtheria-pertussis vaccines), using separate syringes and separate injection sites.
• Immunosuppressive therapies (e.g., high-dose corticosteroids, chemotherapy, biologic immunosuppressants) may reduce the immune response to Gardasil; vaccination timing should be individualized in immunocompromised patients.
• Gardasil is not known to interact with hormonal contraceptives.

Side effects reported with Gardasil are usually mild and self-limited.

Very common / common

• Injection-site reactions: pain, swelling, redness (erythema), itching, bruising.
• Headache
• Fever
• Nausea
• Dizziness

Uncommon / rare but important

• Syncope (fainting), sometimes with brief seizure-like activity, shortly after injection of Gardasil (see Precautions).
• Hypersensitivity reactions, including anaphylaxis.
• Postmarketing reports of Guillain-Barré syndrome, venous thromboembolism, and autoimmune conditions have been described temporally after receipt of Gardasil, without an established causal relationship.

Pregnancy: Gardasil is not recommended during pregnancy. Vaccination with Gardasil should be deferred until after completion of the pregnancy. If a dose of Gardasil is inadvertently given during pregnancy, no specific intervention is required, but the exposure should be discussed with a physician; available data have not shown clear evidence of harm to the fetus, but data remain limited, so Gardasil should be used in pregnancy only if clearly needed and after consulting a physician.

Lactation: It is not known whether components of Gardasil are excreted in human breast milk. Gardasil may be considered for use in breastfeeding women when the potential benefit justifies the potential risk; a physician should be consulted before administering Gardasil while breastfeeding.

• Syncope: Fainting (with occasional seizure-like activity) can occur after injection of Gardasil; the vaccinated person should be observed for about 15 minutes after each dose.
• Acute illness: Vaccination with Gardasil should be deferred in individuals with moderate or severe acute illness until they have recovered.
• Not for treatment: Gardasil does not treat existing HPV infection, genital warts, or cervical/vulvar/vaginal/anal dysplasia already present at the time of vaccination.
• Reduced protection in immunocompromised individuals: Individuals with impaired immune responsiveness may have a diminished antibody response to Gardasil.
• Screening still required: Gardasil does not eliminate the need for women to continue routine cervical cancer screening as recommended by their physician.
• Bleeding disorders: Gardasil should be given with caution, using a fine needle and firm pressure at the injection site, in individuals with thrombocytopenia or a bleeding disorder.

There is limited experience with overdosage of Gardasil. Reported cases of administration of a higher-than-recommended dose of Gardasil have shown an adverse-event profile broadly similar to that seen with the standard 0.5 mL dose. There is no specific antidote for Gardasil. If an overdose of Gardasil is suspected or an individual develops severe or worsening symptoms after vaccination, they should seek immediate medical attention, and supportive care and monitoring should be provided; contacting emergency services or a poison control center is advised if symptoms are severe.

Store Gardasil refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze; discard the vaccine if it has been frozen. Protect from light. Keep out of reach of children. Do not use after the expiry date printed on the pack.

• Pediatric use (below 9 years): Safety and efficacy of Gardasil have not been established in children younger than 9 years; Gardasil is not indicated in this age group.
• Adolescents and adults (9-45 years): Gardasil is indicated per the age-based 2-dose or 3-dose schedule described under Dosage and Administration.
• Geriatric use: Gardasil has not been specifically evaluated in individuals 65 years of age and older.
• Immunocompromised individuals (e.g., HIV infection, transplant recipients, those on immunosuppressive therapy): Gardasil may be given, but may produce a diminished immune response; the standard 3-dose schedule is generally used regardless of age at first dose.
• Renal/hepatic impairment: No dose adjustment of Gardasil is established or generally required for renal or hepatic impairment, as Gardasil is not metabolized by these organs.

Protection with Gardasil requires completion of the full age-appropriate vaccination series (2 doses for those who start between 9 and 14 years of age, or 3 doses for those who start at 15 years of age or older, or who are immunocompromised). Gardasil is not a treatment course but a preventive immunization series; there is currently no routine booster dose recommendation for Gardasil beyond completion of the primary series, based on available long-term efficacy data.

Human Papillomavirus Quadrivalent is classified under: Vaccines > Viral vaccines > Recombinant subunit vaccines > Human papillomavirus (HPV) vaccines.

Human Papillomavirus Quadrivalent contains non-infectious virus-like particles (VLPs) made of the L1 capsid protein of HPV types 6, 11, 16, and 18, produced by recombinant DNA technology. These VLPs closely mimic the natural virus structure but contain no viral DNA, so they cannot cause infection. Administration of Human Papillomavirus Quadrivalent stimulates the immune system to produce type-specific neutralizing antibodies against HPV 6, 11, 16, and 18. On subsequent natural exposure, these antibodies bind to and neutralize the corresponding HPV types at the site of entry, preventing establishment of infection and the resulting precancerous and cancerous changes or genital warts that these HPV types can otherwise cause.

B (FDA legacy pregnancy category, as classified in the original product labeling)

Gardasil is approved for use beginning at 9 years of age. It is not recommended, and safety and efficacy have not been established, in children younger than 9 years. For children and adolescents who begin the series between 9 and 14 years of age, a 2-dose schedule of Gardasil (0 and 6-12 months) is used per current WHO/CDC guidance. Adolescents who are immunocompromised should receive the standard 3-dose schedule of Gardasil regardless of age at the first dose. As with adults, individuals in this age group should be observed for approximately 15 minutes after each dose of Gardasil because of the risk of syncope.