Pharmacology
Mechanism of Action
Contains inactive human papillomavirus (HPV) proteins HPV 6 L1, HPV 11 L1, HPV 16 L1, and HPV 18 L1 which produce neutralizing antibodies to prevent cervical cancer, cervical adenocarcinoma, cervical, vaginal and vulvar neoplasia, and genital warts caused by HPV. The vaccine has not been shown to provide cross-protective efficacy to HPV types not contained in the vaccine. Immunogenicity has been measured by the percentage of persons who became seropositive for antibodies contained in the vaccine; the minimum anti-HPV antibody concentration needed to protect against disease has not been determined. The population benefit to vaccination is influenced by the prevalence of HPV within the geographic area and subject characteristics (eg, lifetime sexual partners).
Efficacy: In females 16 to 26 years of age, HPV4 has shown to be ~100% effective against HPV types 16- and 18-related cervical disease and 95% to 99% effective against external genital lesions related to HPV types 6, 11, 16, or 18. In males 16 to 26 years of age, HPV4 vaccine has shown to be 84% to 100% effective against external genital lesions related to HPV types 6, 11, 16, or 18. In females 24 to 45 years of age, the vaccine was shown to be 91% effective against HPV 6, 11, 16, and 18 persistent infection and cervical or external genital disease and 83% effective against HPV types 16 and 18 only. 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 1 month following the last dose of vaccine
Duration of Action
Duration unknown. Clinical studies followed HPV4 vaccinated participants for 10 years and found no evidence of waning protection (NACI 2017).
Use: Labeled Indications
Prevention of human papillomavirus infection:
Females ≥9 years of age and ≤26 years of age: Prevention of anal cancer caused by HPV types 16 and 18; anal intraepithelial neoplasia caused by HPV types 6, 11, 16, and 18
Females ≥9 years of age and ≤45 years of age: Prevention of cervical, vulvar, and vaginal cancer caused by HPV types 16 and 18; genital warts caused by HPV types 6 and 11; cervical adenocarcinoma in situ, vulvar, vaginal, or cervical intraepithelial neoplasia caused by HPV types 6, 11, 16, and 18
Males ≥9 years of age and ≤26 years of age: Prevention of anal cancer caused by HPV types 16 and 18; anal intraepithelial neoplasia caused by HPV types 6, 11, 16, and 18; genital warts caused by HPV types 6 and 11
The Canadian National Advisory Committee on Immunization (NACI) recommends routine vaccination for females and males between 9 and 26 years of age. It should not be administered in patients <9 years of age but may be administered to patients >26 years of age who are at ongoing risk of exposure (NACI 2017).
Contraindications
Hypersensitivity to any component of the vaccine or to a previous dose of the vaccine
Dosage and Administration
Dosing: Adult
Prevention of human papillomavirus infection: IM: Adults: Females ≤45 years of age and males ≤26 years of age: Three-dose series: 0.5 mL at 0, 2, and 6 months. Administer the second dose ≥1 month after the first dose and the third dose ≥3 months after the second dose; administer all 3 doses within 12 months.
NACI recommendations: Recommended for females and males ≤26 years of age; may be given to those ≥27 years of age who are at ongoing risk (NACI 2017).
Dosing: Pediatric
Note: Quadrivalent HPV vaccine has been discontinued from the US market; other HPV vaccines should be used for immunization. Consult CDC/ACIP annual immunization schedules for additional information including specific detailed recommendations for catch-up scenarios and/or care of patients with high-risk conditions. 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) recommended immunization schedule: In a 2-dose series, 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 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: 2-dose series: IM: 0.5 mL at 0, and 6 to 12 months. Administer first dose at age 11 to 12 years; patients with any history of sexual abuse or assault, vaccination should be started at 9 years of age.
Adolescents ≥15 years: 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: 3-dose series: IM: 0.5 mL at 0, 1 to 2, and 6 months
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 a 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 suspension well before use. Inject the entire dose IM into the deltoid region of the upper arm or higher anterolateral thigh area. 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. 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. 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 (NACI 2017).
Storage
Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect from light. Administer as soon as possible after removing it from refrigeration; can be out of refrigeration (at temperatures at or below 25°C [77°F]) for a total time of not more than 72 hours.
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: Headache (8% to 21%)
Local: Pain at injection site (females: 82%; males: 61%), swelling at injection site (females: 24%; males: 14%), erythema at injection site (17% to 22%)
Miscellaneous: Fever (6% to 13%)
1% to 10%:
Central nervous system: Dizziness (≤1%)
Dermatologic: Injection site pruritus (females: 3%)
Gastrointestinal: Nausea (2% to 4%), diarrhea (males: 3%), toothache (females: 2%), vomiting (≤1%)
Local: Hematoma at injection site (females: 3%)
Neuromuscular & skeletal: Limb pain (females: 2% to 3%), arthralgia (≤1%), myalgia (≤1%)
Respiratory: Oropharyngeal pain (males: 3%), upper respiratory tract infection (males: 2%)
<1%, postmarketing, and/or case reports: Acute disseminated encephalomyelitis, anaphylactoid reaction, anaphylaxis, arthropathy (impaired joint movement at injection site), asthma, autoimmune disease, autoimmune hemolytic anemia, bronchospasm, cellulitis, chills, fatigue, Guillain-Barré syndrome, hypersensitivity reaction, immune thrombocytopenia, lymphadenopathy, malaise, neuromuscular disease, pancreatitis, paralysis, pulmonary embolism, syncope (may result in falls or be associated with tonic-clonic movements), transverse myelitis, urticaria, weakness seizure, sepsis, syncope (may result in falls with injury or be associated with tonic-clonic movements), transverse myelitis, urticaria, weakness
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 infected with HPV will be protected; those already infected with 1 or more HPV types were protected from disease in the remaining HPV types. Not for the treatment of active disease; will not protect against diseases not caused by HPV vaccine types 6, 11, 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. (Note: The HPV2 vaccine only protects again HPV types 16 and 18 and is not approved for use in males.) (NACI 2017).
Special populations:
- Altered immunocompetence: May be administered to those who are immunosuppressed. 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).
Dosage form specific issues:
- Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
- Yeast: Product may contain yeast.
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).
- Maximum efficacy: The entire 3-dose regimen should be completed for maximum efficacy.
Monitoring Parameters
Screening for HPV is not required prior to 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.
Females: Gynecologic screening exam, papillomavirus test; screening for cervical cancer should continue per current guidelines following vaccination
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 recommend pregnancy be avoided during the vaccination series.
Exposures to quadrivalent human papillomavirus vaccine during pregnancy should be reported to the manufacturer (800-567-2594) or Vaccine Safety Section at Public Health Agency of Canada (866-844-0018 or http://www.phac-aspc.gc.ca/im/vssv/index-eng.php).
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 headache, nausea, stuffy nose, sore throat, or injection site redness, swelling, pain or irritation. Have patient report immediately to prescriber severe dizziness, passing out, seizures, or abnormal movements (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.
