human papillomavirus vaccine, nonavalent

Human papillomavirus vaccine (HPV) vaccine, nonavalent is a vaccine used to protect against diseases and cancers caused by human papillomavirus infection, a sexually transmitted disease.

HPV is a virus that only infects humans, causes warts to grow in the skin and mucous membrane, and can lead to certain types of cancers later in life. HPV vaccine works by stimulating the vaccinated individual’s acquired immune response to the virus.

HPV vaccine is an inactivated viral vaccine that is prepared from purified virus-like particles from nine subtypes of HPV virus, combined using DNA recombinant technology. The vaccine is sterile and noninfectious and is produced from L1 protein, the major protein in the protein shell (capsid) that covers the viral genetic material. HPV vaccine provides immunity against nine subtypes of the HPV virus including 6, 11, 16, 18, 31, 33, 45, 52, and 58.

The administration of the vaccine induces production of antibodies to the HPV surface protein (antigen) in the vaccinated individual. The immune system, if exposed to HPV later, recognizes the HPV antigen and fights the infection. The exact mechanism by which the HPV vaccine protects against development of HPV-related cancers is not clear, but it is believed to be because of the acquired (humoral) immune response induced by the vaccine.

HPV vaccine provides protection only against cancers and diseases caused by HPV infection, which include the following:

Males and Females:

• Anal cancer, mouth and throat (oropharyngeal) cancer, 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
• 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

Females:

• 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) grades 2 and 3
  • Vaginal intraepithelial neoplasia (VaIN) grades 2 and 3

• Do not administer human papillomavirus vaccine to individuals with hypersensitivity to yeast or any other component of the vaccine, or with a history of severe allergic reaction to a previous dose of the HPV vaccine.
• Medical facilities for appropriate management of anaphylactic reactions following the vaccination should be available at the vaccination facility.
• Vaccine administration to individuals with minor illnesses with or without fever may be acceptable, but defer the vaccine in moderate to severe febrile illnesses until the illness is resolved.
• Monitor the person for 15 minutes after vaccination for fainting (syncope), seizure with fainting (convulsive syncope) or allergic reactions. When syncope is associated with convulsions, it is usually temporary and can be resolved by restoring blood flow to the brain by maintaining a supine position, or with head at a lower level than the feet (Trendelenburg position).
• Intramuscular injections may cause hematoma in people with bleeding disorders. Exercise caution and schedule the vaccination shortly after administration of therapy for the bleeding disorder.
• Immune response to the HPV vaccine may be lower in individuals who are immunocompromised, including those on immunosuppressant or corticosteroid treatments.
• HPV vaccine may not provide protection to 100% of vaccinated individuals.

Common side effects of human papillomavirus vaccine, nonavalent include:

• Injection site reactions including:
  • Pain
  • Redness (erythema)
  • Swelling
  • Itching (pruritus)
  • Bruising
  • Mass
  • Hemorrhage
  • Blood pooling and clotting (hematoma)
  • Warmth
  • Tissue hardening (induration)
  • Hypersensitivity
• High temperature (pyrexia)
• Headache
• Nausea
• Dizziness
• Fatigue
• Diarrhea
• Upper abdominal pain
• Muscle pain (myalgia)
• Mouth and throat pain (oropharyngeal pain)
• Influenza
• Upper respiratory tract infection

Less common side effects of human papillomavirus vaccine, nonavalent include:

• Vomiting
• Inflammation of the pancreas (pancreatitis)
• Hives (urticaria)
• Cellulitis
• Blood clot block in the vein (deep vein thrombosis/DVT)
• Pulmonary embolism
• Low red blood cell count due to autoimmune destruction (autoimmune hemolytic anemia)
• Bruising from low platelet count (idiopathic thrombocytopenic purpura)
• Swelling of lymph nodes (lymphadenopathy)
• Bronchospasm
• Autoimmune diseases
• Severe allergic reactions (anaphylaxis)
• Joint pain (arthralgia)
• Muscle pain (myalgia)
• Weakness (asthenia)
• Chills
• Feeling ill (malaise)
• Guillain-Barre syndrome, a condition in which the immune system attacks the nerves
• Widespread inflammation in the brain and spinal cord (acute disseminated encephalomyelitis)
• Inflammation in sections of the spinal cord on both sides (transverse myelitis)
• Motor neuron disease
• Seizures
• Paralysis
• Death

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Suspension for intramuscular (IM) injection

• 0.5 mL/single-dose vial or syringe

Immunization to Prevent HPV Infection

• Protects against diseases/precancerous conditions caused by human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 45, 52, and 58

Adult:

• 0.5 mL IM as a 2- or 3-dose series depending on age at initial vaccination

Adults through age 26 years

• Recommended as routine vaccination for all adults through age 26 years
• Age of initial vaccination
  • 15 years or above: 3-dose series at 0, 1-2, 6 months (minimum intervals: 4 weeks between doses 1 and 2; 12 weeks between doses 2 and 3; 5 months between doses 1 and 3; repeat dose if administered too soon)
  • 9-14 years and received 1 dose or 2 doses less than 5 months apart: 1 dose
  • 9-14 years and received 2 doses at least 5 months apart: HPV vaccination complete, no additional dose needed

Adults aged 27-45 years

• Need for vaccination based on shared decision making between patient and clinician
• 2- or 3-dose series depending on age at initial vaccination (see dosing for age through 26 years)

Pediatric:

• HPV vaccination routinely recommended at age 11-12 years (can start at age 9 years)

Routine and catch-up vaccination

• 0.5 mL IM as a 2- or 3-dose series depending on age at initial vaccination
• Age 9 through 14 years at initial vaccination: 2-dose series at 0, 6-12 months (minimum interval: 5 months; repeat dose if administered too soon)
• Age 15 years or above at initial vaccination: 3-dose series at 0, 1-2, 6 months (minimum intervals: 4 weeks between doses 1 and 2; 12 weeks between doses 2 and 3; 5 months between doses 1 and 3; repeat dose if administered too soon)
• Special situations
  • Immunocompromising conditions, including HIV infection: 3-dose series as above
  • History of sexual abuse or assault: Start at age 9 years

Adult and Pediatric:

Indications for males

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
• 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

Indications for females

• 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
• Indicated for prevention of 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) grades 2 and 3
  • Vaginal intraepithelial neoplasia (VaIN) grades 2 and 3
  • Anal intraepithelial neoplasia (AIN) grades 1, 2, and 3

Dosing Considerations

• For more vaccine information see: http://www.cdc.gov/vaccines/schedules/hcp/index.html

Limitations of use and effectiveness

• Inform the patient, parent, or guardian that vaccination does not eliminate the necessity for women to continue to undergo recommended cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancer screening
• Has not been demonstrated to provide protection against disease from vaccine HPV types to which a person has previously been exposed through sexual activity or HPV types not covered by the vaccine
• Not a treatment for external genital lesions; cervical, vulvar, vaginal, and anal cancers; CIN; VIN; VaIN; or AIN
• Not all vulvar, vaginal, anal, oropharyngeal, and other head and neck cancers are caused by HPV
• May not result in protection in all vaccine recipients

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Human papillomavirus vaccine, nonavalent has no listed severe interactions with other drugs.
• Human papillomavirus vaccine, nonavalent has serious interactions with at least 42 different drugs.
• Moderate interactions of human papillomavirus vaccine, nonavalent include:
  • cyclosporine
  • dengue vaccine
  • ibrutinib
  • ifosfamide
  • lomustine
  • mechlorethamine
  • melphalan
  • onasemnogene abeparvovec
  • oxaliplatin
  • ponesimod
  • procarbazine
  • rituximab
  • rituximab-hyaluronidase
  • satralizumab
  • tralokinumab
  • ublituximab
  • ustekinumab
  • voclosporin
• Mild interactions of human papillomavirus vaccine, nonavalent include:
  • chloroquine
  • ozanimod

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• There are no adequate and well-controlled studies on HPV vaccination in pregnant women. Available human data on HPV vaccine administration during pregnancy do not show evidence of vaccine-associated fetal harm or increase in risk of miscarriages or major birth defects.
• HPV vaccination is not recommended during pregnancy and should be delayed until after pregnancy, however, pregnancy testing before vaccination is not required.
• If a person is found to be pregnant after initiating HPV vaccine series second and/or third doses should be delayed until after pregnancy.
• There are no data on the presence of HPV vaccine in breastmilk, or its effect on milk production or the breastfed infant. Decision to breastfeed should be made after considering the developmental and health benefits of breastfeeding, along with the potential adverse effects to the infant from the vaccine or the mother’s risk for contracting HPV infection.
• There is a pregnancy exposure registry to monitor pregnancy outcomes in women exposed to HPV vaccine (GARDASIL 9) during pregnancy. To enroll in or obtain information about the registry, call Merck Sharp and Dohme Corp., a subsidiary of Merck and Co., Inc., at 1-800-986-8999.

• Human papillomavirus vaccine, nonavalent is recommended as a routine vaccination for all males and females from age 9 through 26 years, and based on the need for vaccination in individuals 27 to 45 years of age.
• Complete the full series of doses to ensure efficacy of HPV vaccination.
• The HPV nonavalent vaccine does not protect against disease caused by HPV types not included in the vaccine.
• The HPV nonavalent vaccine does not protect against disease from vaccine and non-vaccine HPV types to which a person has already been exposed before the vaccination.
• HPV vaccine is only for the prevention of disease and not for the treatment of active disease.
• HPV vaccination does not eliminate the necessity for recommended cancer screening. Cervical or anal cancer screening is still required following vaccine administration.
• More information on HPV vaccine is available at  https://www.cdc.gov/vaccines/vpd/hpv/hcp/recommendations.html