Pharmacology
Mechanism of Action
Contains inactive human papillomavirus (HPV) proteins HPV 16 L1, and HPV 18 L1 which produce neutralizing antibodies to prevent cervical cancer, cervical adenocarcinoma, and cervical neoplasia cause by HPV.
Efficacy: HPV2 has shown to be 95% to 99% effective against HPV types 16 and 18-related cervical disease in females 15 to 25 years of age. In addition, vaccination against HPV types 16 and 18 may prevent ~70% of anogenital cancers and 60% of high-risk precancerous cervical lesions (NACI 2017).
Pharmacokinetics/Pharmacodynamics
Onset of Action
Seroconversion was observed at month 7
Duration of Action
Unknown. Clinical studies followed HPV2 vaccinated participants for 10 years and found no evidence of waning protection (NACI 2017).
Use: Labeled Indications
Prevention of human papillomavirus infection: Prevention in females 9 to 45 years of age of the following diseases caused by oncogenic HPV types 16 and 18: Cervical cancer, cervical intraepithelial neoplasia (CIN) grades 1 to 3 and cervical adenocarcinoma in situ
The Canadian National Advisory Committee on Immunization (NACI) recommends routine vaccination for females between 9 and 26 years of age. It should not be administered in females <9 years but may be administered to females >26 years who are at ongoing risk of exposure (NACI 2017).
Contraindications
Hypersensitivity to any component of the formulation
Dosage and Administration
Dosing: Adult
Prevention of human papillomavirus infection: IM: Females ≤45 years: 0.5 mL at 0, 1, and 6 months. Administer the second dose 1 to 2.5 months after the first dose; administer the third dose 5 to 12 months after the first dose.
NACI recommendations: Recommended for females ≤26 years; may be given to those ≥27 years who are at ongoing risk (NACI 2017).
Dosing: Pediatric
Note: Bivalent HPV vaccine has been discontinued from the US market; other HPV vaccines should be used for immunization. According to ACIP, doses administered ≤4 days before minimum interval or age are considered valid; however, local or state mandates may supersede this timeframe (ACIP [Kroger 2017]).
Primary immunization:
CDC (ACIP) recommendations: In a 2-dose series, the minimum interval between the first and second dose is 5 months. In a 3-dose schedule, minimum interval between first and second doses is 4 weeks; the minimum interval between the second and third dose is 12 weeks; the minimum interval between first and third doses is 5 months (CDC/ACIP [Meites 2016])
Non-immunocompromised patients and certain specified medical conditions: Asplenia, asthma, chronic granulomatous disease, chronic liver disease, chronic lung disease, chronic renal disease, central nervous system anatomic barrier defects (eg, cochlear implant), complement deficiency, diabetes, heart disease, or sickle cell disease:
Children ≥9 years and Adolescents <15 years: Females: 2-dose series: IM: 0.5 mL at 0, and 6 to 12 months. Administer first dose at age 11 to 12 years; for patients with any history of sexual abuse or assault, vaccination should be started at 9 years of age
Adolescents ≥15 years: Females: 3-dose series: IM: 0.5 mL at 0, 1 to 2, and 6 months
Immunocompromised patients including those with immunocompromising conditions that might reduce cell-mediated or humoral immunity, such as B lymphocyte antibody deficiencies, T lymphocyte complete or partial defects, HIV infection, malignant neoplasms, transplantation, autoimmune disease, or immunosuppressive therapy): Children ≥9 years and Adolescents: Females: 3-dose series: IM: 0.5 mL at 0, 1 to 2, and 6 months
Manufacturer's labeling: Females: Children ≥9 years and Adolescents: IM: 0.5 mL per dose for a total of 3 doses. Administer the second and third doses at 1 and 6 months after initial dose.
Catch-up immunization: CDC (ACIP) recommendations (Meites 2016): Note: Do not restart the series. If doses have been given, begin the below schedule at the applicable dose number. Children ≥9 years and Adolescents: IM: 0.5 mL per dose for a total of 2 to 3 doses (See CDC/ACIP recommendations above for 2-dose vs 3-dose schedule criteria):
First dose given on the elected date
Second dose given at least 4 weeks after the first dose (for 3-dose schedule) or 5 months after the first dose (for a 2-dose schedule)
Third dose (for a 3-dose schedule) given at least 12 weeks after the second dose and at least 5 months after the first dose
Administration
IM: Shake well prior to use. Do not use if discolored or if containing particulate matter, or if syringe is cracked. Inject IM into the deltoid region of the upper arm. Do not administer IV, SubQ, or intradermally. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. To prevent syncope related injuries, patients should be vaccinated while seated or lying down. When given with other age appropriate vaccines, human papillomavirus vaccine should be given after other vaccines because it may cause more pain with injection (NACI 2017).
For patients at risk of hemorrhage following intramuscular injection, the vaccine should be administered intramuscularly if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, intramuscular vaccination can be scheduled shortly after such therapy is administered (ACIP [Kroger 2017]). A fine needle (23 gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for 5 to 10 minutes (NACI 2017). The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2017]; NACI 2017).
Storage
Store under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze. Store in original package to protect from light. Administer as soon as possible after removing from refrigeration. Stable for up to 3 days when stored between 8°C and 25°C (46°F to 77°F) or for up to 1 day when stored at 25°C to 37°C (77°F to 99°F). Discard if exposed to >37°C (99°F). May develop a fine, white deposit with a clear, colorless supernatant during storage (not a sign of deterioration).
Drug Interactions
Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting fingolimod. If vaccinated during fingolimod therapy, revaccinate 2 to 3 months after fingolimod discontinuation. Consider therapy modification
Immunosuppressants: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Exceptions: Cytarabine (Liposomal). Consider therapy modification
Siponimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Avoid administration of vaccines (inactivated) during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy. Consider therapy modification
Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy
Adverse Reactions
>10%:
Central nervous system: Fatigue (55%)
Local: Pain at injection site (92%), erythema at injection site (48%), swelling at injection site (44%)
Neuromuscular & skeletal: Myalgia (49%), arthralgia (21%)
1% to 10%:
Dermatologic: Urticaria (7%), injection site pruritus (1%)
Genitourinary: Vaginal infection (1%)
Infection: Influenza (3%), infection (chlamydia: 2%)
Respiratory: Nasopharyngitis (4%), pharyngolaryngeal pain (3%), pharyngitis (2%)
<1%, postmarketing, and/or case reports: Anaphylactoid reaction, anaphylaxis, angioedema, erythema multiforme, hypersensitivity reaction, induration at injection site, lymphadenopathy, paresthesia (local), syncope (may be associated with tonic-clonic movements), vasodepressor syncope
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (NACI 2017).
- Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2017]; NACI 2017).
Disease-related concerns:
- Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Defer administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (NACI 2017).
- Bleeding disorders: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia); bleeding/hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (ACIP [Kroger 2017]; NACI 2017).
- Human papillomavirus (HPV) infection: There is no evidence that individuals already exposed to or infected with HPV will be protected; those already infected with 1 or more HPV types were protected from disease in the remaining HPV types. Will not provide therapeutic benefit for active HPV disease or abnormal Pap test; will not protect against diseases not caused by HPV vaccine types 16 and 18.
Concurrent drug therapy issues:
- Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2017]).
- Vaccines: In order to maximize vaccination rates, simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) is recommended of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The NACI prefers each dose in a HPV vaccine series be the same vaccine when possible; however, if the previous vaccine is not known then any of the HPV vaccines licensed for use in Canada may be used (NACI 2017).
Special populations:
- Altered immunocompetence: Consider deferring immunization during periods of severe immunosuppression (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination (NACI 2017). In general, household and close contacts of persons with altered immunocompetence may receive all age appropriate vaccines. Inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; inactivated vaccines administered during chemotherapy should be readministered after immune competence is regained (ACIP [Kroger 2017]; IDSA [Rubin 2014]; NACI 2017).
- Males: Not approved for use in males.
Other warnings/precautions:
- Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (NACI 2017).
Monitoring Parameters
Gynecologic screening exam, papillomavirus test as per current guidelines; screening for HPV is not required prior to vaccination and screening for cervical cancer should continue as recommended following vaccination. Monitor for anaphylaxis and syncope for 15 minutes following administration (NACI 2017). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.
Pregnancy
Pregnancy Considerations
Administration of the human papillomavirus vaccine during pregnancy is not recommended. Although exposure to human papillomavirus vaccine has not been causally associated with adverse pregnancy outcomes, until additional information is available the vaccine series (or completion of the series) should be delayed until pregnancy is completed (NACI 2017).
The manufacturer recommends pregnancy be avoided for 2 months following vaccination. Exposures to bivalent human papillomavirus vaccine during pregnancy should be reported to the manufacturer (800-387-7374).
Patient Education
- Discuss specific use of vaccine and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience loss of strength and energy, headache, muscle pain, joint pain, nausea, vomiting, diarrhea, abdominal pain, or injection site pain or irritation. Have patient report immediately to prescriber severe dizziness, passing out, abnormal movements, or seizures (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
