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).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Human papillomavirus quadrivalent vaccine (4vHPV) (United States: Not available): Pediatric drug information")
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 2021]).
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
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, suspension [preservative free]:
Gardasil: HPV 6 L1 protein 20 mcg, HPV 11 L1 protein 40 mcg, HPV 16 L1 protein 40 mcg, and HPV 18 L1 protein 20 mcg per 0.5 mL (0.5 mL) [contains aluminum, polysorbate 80; manufactured using S. cerevisiae (yeast)]
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).
IM: Shake suspension well prior to use; do not use suspension if it is discolored or contains particulate matter; do not dilute or mix with other vaccines. Administer IM into the deltoid region of the upper arm or in the higher anterolateral area of the thigh; not for IV, intradermal, or SubQ administration. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (ACIP [Kroger 2021]). To prevent syncope related injuries, adolescents should be vaccinated while seated or lying down (ACIP [Kroger 2021]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person’s name, title, and address be entered into the patient’s permanent medical record.
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 at least 2 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 (ACIP [Kroger 2021]).
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).
Papillomavirus vaccine types 6, 11, 16, 18 (Gardasil) may be confused with Papillomavirus vaccine types 16, 18 (Cervarix)
Papillomavirus vaccine types 6, 11, 16, 18 (Gardasil) may be confused with Papillomavirus vaccine 9-valent (Gardasil 9)
HPV (human papilloma virus vaccine) may be confused with IPV (inactivated poliovirus vaccine)
HPV (human papilloma virus vaccine) may be confused with HBV (previously used for hepatitis B vaccine; HepB is correct abbreviation)
HPV (human papilloma virus vaccine) may be confused with Hib (Haemophilus b conjugate vaccine)
HPV4 (human papillomavirus vaccine [quadrivalent]) may be confused with HepA (hepatitis A vaccine)
HPV4 (human papillomavirus vaccine [quadrivalent]) may be confused with HepB (hepatitis B vaccine)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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
Hypersensitivity to any component of the vaccine or to a previous dose of the vaccine
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).
• Shoulder injury related to vaccine administration: Vaccine administration that is too high on the upper arm may cause shoulder injury (eg, shoulder bursitis, tendinitis) resulting in shoulder pain and reduced range of motion following injection. Use proper injection technique for vaccines administered in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013).
• 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 2021]; 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 2021]; 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 2021]).
• 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 2021]; 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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetaminophen: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification
Cladribine: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of cladribine when possible. Patients vaccinated less than 14 days before initiating or during cladribine should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Corticosteroids (Systemic): May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Administer vaccines at least 2 weeks prior to immunosuppressive corticosteroids if possible. If patients are vaccinated less than 14 days prior to or during such therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. Risk D: Consider therapy modification
Elivaldogene Autotemcel: May enhance the adverse/toxic effect of Vaccines. Specifically, there may be a greater risk for contracting an infection from any live vaccine. Elivaldogene Autotemcel may diminish the therapeutic effect of Vaccines. Management: Administration of vaccines is not recommended in the 6 weeks before myeloablative conditioning, and until hematologic recovery after elivaldogene autotemcel treatment. Risk X: Avoid combination
Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). 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. Risk D: Consider therapy modification
Immunosuppressants (Cytotoxic Chemotherapy): May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Immunosuppressants (Miscellaneous Oncologic Agents): May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Immunosuppressants (Therapeutic Immunosuppressant Agents): May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Methotrexate: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Administer vaccines at least 2 weeks prior to methotrexate initiation, if possible. If patients are vaccinated less than 14 days prior to or during methotrexate therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. Risk D: Consider therapy modification
Propacetamol: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of propacetamol before or during vaccine administration when possible. Propacetamol is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification
RiTUXimab: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of rituximab when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 6 months after therapy is complete. Risk D: Consider therapy modification
Siponimod: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Avoid administration of vaccines (inactivated) during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy. Risk D: Consider therapy modification
Teplizumab: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Vaccination with inactivated or non-replicating vaccines is not recommended in the 2 weeks prior to teplizumab therapy, during treatment, or for 6 weeks following completion of therapy. Risk D: Consider therapy modification
The manufacturer recommends pregnancy be avoided during the vaccination series.
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).
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).
It is not known if this vaccine is present in breast milk.
Breastfeeding women may receive the human papillomavirus vaccine if otherwise indicated. Administration does not affect the safety of breastfeeding for the mother or the infant. Breastfeeding infants should be vaccinated according to the recommended schedules (NACI 2017).
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
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).
Onset: Seroconversion was observed 1 month following the last dose of vaccine
Duration: Duration unknown. Clinical studies followed HPV4 vaccinated participants for 10 years and found no evidence of waning protection (NACI 2017).
