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Papillomavirus (Types 16, 18) Vaccine (Human, Recombinant)

Pronunciation

(pap ih LO ma VYE rus typs SIX teen AYE teen vak SEEN YU man ree KOM be nant)

Index Terms

  • 2-Valent HPV
  • 2vHPV
  • Bivalent Human Papillomavirus Vaccine
  • GSK-580299
  • HPV 16/18 L1 VLP/AS04 VAC
  • HPV Vaccine (Bivalent)
  • HPV2
  • Human Papillomavirus Vaccine (Bivalent)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, suspension [preservative free]:

Cervarix: HPV 16 L1 protein 20 mcg and HPV 18 L1 protein 20 mcg per 0.5 mL (0.5 mL) [contains aluminum, natural rubber/natural latex in prefilled syringe; manufactured using Trichoplusia ni (insect cells)]

Brand Names: U.S.

  • Cervarix

Pharmacologic Category

  • Vaccine
  • Vaccine, Inactivated (Viral)

Pharmacology

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: Moderate- to high-grade cervical intraepithelial neoplasia (CIN 2/3) and adenocarcinoma in situ (AIS) are the immediate and necessary precursors of squamous cell carcinoma and adenocarcinoma of the cervix, respectively. Vaccination with 2vHPV reduced the incidence of CIN 2/3 and AIS by 87% to 98% in several randomized clinical trials. (CDC/ACIP [Markowitz, 2014]).

Onset of Action

Peak seroconversion was observed 1 month following the last dose of vaccine (CDC/ACIP [Markowitz, 2014])

Duration of Action

Not well defined; >8 to 10 years (CDC/ACIP [Markowitz, 2014])

Use: Labeled Indications

Prevention of human papillomavirus infection:

US labeling: Prevention in females 9 to 25 years of age of the following diseases caused by oncogenic HPV types 16 and 18: Cervical cancer, cervical intraepithelial neoplasia (CIN) grade 2 or higher and adenocarcinoma in situ, and CIN grade 1.

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for females 11 to 12 years of age; for patients with any history of sexual abuse or assault, vaccination should be started at 9 years of age. Catch-up vaccination is recommended for females 13 to 26 years of age (CDC/ACIP [Markowitz, 2014]; ACIP [Robinson 2016]).

Canadian labeling: Females 9 through 45 years of age: Prevention of cervical cancer, cervical adenocarcinoma in situ, and cervical intraepithelial neoplasia caused by human papillomavirus (HPV) types 16, 18

The 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 [CCDR, 2012]).

Contraindications

Severe hypersensitivity (eg, anaphylaxis) to papillomavirus recombinant vaccine or any component of the formulation

Dosing: Adult

Immunization: IM:

US labeling: Females ≤25 years: 0.5 mL at 0, 1, and 6 months

CDC/ACIP recommended immunization schedule: 0.5 mL per dose for a total of 3 doses; administer the second and third doses at 1 to 2 and 6 months after initial dose. There should be a 4-week minimum interval between the first and second dose; a 12-weeks minimum interval (16 weeks preferred) between the second and third dose; a 24-week minimum interval between the first and third dose. Begin series in females ≤26 years if not previously vaccinated or who have not completed the 3 dose series (typically administer first dose at age 11 to 12 years). If a female reaches 27 years of age before the vaccination series is complete, the remaining doses can be administered after age 26 years. Inadequate doses or doses received following a shorter than recommended dosing interval should be repeated. The HPV vaccine series should be completed with the same product whenever possible (ACIP [Kim 2016]; CDC/ACIP [Markowitz, 2014]).

Canadian labeling: Females ≤45 years: 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; if necessary, may administer the second and third doses at 1 to 2.5 months and 5 to 12 months respectively after the initial dose.

Dosing: Pediatric

Immunization: IM:

US labeling: Children ≥9 years and Adolescents: Females: 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

CDC/ACIP recommended immunization schedule: 0.5 mL per dose for a total of 3 doses; administer the second and third doses at 1 to 2 and 6 months after initial dose. There should be a 4-week minimum interval between the first and second dose; a 12-weeks minimum interval (16 weeks preferred) between the second and third dose; a 24-week minimum interval between the first and third dose. Typically administer first dose to females at age 11 to 12 years; for patients with any history of sexual abuse or assault, vaccination should be started at 9 years; begin series in female adolescents (≥13 years) if not previously vaccinated or who have not completed the 3-dose series. Inadequate doses or doses received following a shorter than recommended dosing interval should be repeated. The HPV vaccine series should be completed with the same product whenever possible (ACIP [Robinson 2016]; CDC/ACIP [Markowitz, 2014]).

Canadian labeling: Children ≥9 years and Adolescents: Females: 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; if necessary, may administer the second and third doses at 1 to 2.5 months and 5 to 12 months respectively after the initial dose.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Administration

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. To prevent syncope related injuries, adolescents and adults should be vaccinated while seated or lying down (NCIRD/ACIP, 2011). Observe for syncope for 15 minutes following administration. 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 (NCIRD/ACIP, 2011).

Compatibility

Do not mix with other vaccines or injections. Separate needles and syringes should be used for each injection.

Storage

U.S. labeling: Store under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze; discard if frozen. May develop a fine, white deposit with a clear, colorless supernatant during storage (not a sign of deterioration).

Canadian labeling: Store under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze; discard if frozen. Vaccine can be administered if stored between 8°C and 25°C (46°F to 77°F) for up to 3 days or stored between 25°C and 37°C (77°F to 98.6°F) for up to 1 day. Discard vaccine if exposed to temperatures >37°C (98.6°F). Protect from light.

Drug Interactions

Belimumab: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Patients should receive inactivated vaccines prior to initiation of belimumab therapy whenever possible, due to the risk for an impaired response to the vaccine during belimumab therapy. Consider therapy modification

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

Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy

Adverse Reactions

All serious adverse reactions must be reported to the U.S. Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS) 1-800-822-7967 or online at https://vaers.hhs.gov/esub/index. In Canada, adverse reactions may be reported to local provincial/territorial health agencies or to the Vaccine Safety Section at Public Health Agency of Canada (1-866-844-0018).

>10%:

Central nervous system: Fatigue (55%)

Local: Injection site reactions: Pain (92%), redness (48%), swelling (44%)

Neuromuscular & skeletal: Myalgia (49%), arthralgia (21%)

1% to 10%:

Dermatologic: Urticaria (7%)

Local: Injection site: Pruritus (1%)

Respiratory: Nasopharyngitis (4%), pharyngolaryngeal pain (3%), upper respiratory tract infection (2%), pharyngitis (1%)

Miscellaneous: Influenza (3%), chlamydia infection (2%), vaginal infection (1%)

<1%, postmarketing, and/or case reports: Allergic reactions, anaphylactic/anaphylactoid reactions, angioedema, erythema multiforme, lymphadenopathy, syncope (may be associated with tonic-clonic movements), vasovagal response

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 (NCIRD/ACIP, 2011).

• 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 (NCIRD/ACIP, 2011).

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. Consider deferring 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) (NCIRD/ACIP, 2011).

• Bleeding disorders: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia) and/or patients on anticoagulant therapy; 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 (NCIRD/ACIP, 2011).

• 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:

• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible (NCIRD/ACIP, 2011).

Special populations:

• Altered immunocompetence: Use with caution in severely immunocompromised patients (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination. In general, household and close contacts of persons with altered immunocompetence may receive all age appropriate vaccines (IDSA [Rubin, 2014]; NCIRD/ACIP, 2011); inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible (IDSA [Rubin, 2014]).

• Males: Safety and efficacy have not been established in males.

Dosage form specific issues:

• Latex: Packaging may contain natural rubber/natural latex.

Other warnings/precautions:

• Appropriate use: Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the ACIP Adult Recommended Immunization Schedule (ACIP [Kim 2016]). Specific recommendations for vaccination in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions as well as contacts of immunocompromised patients are available from the IDSA (Rubin, 2014).

• 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 (NCIRD/ACIP, 2011).

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 syncope for 15 minutes following administration (NCIRD/ACIP, 2011). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. In clinical trials, pregnancy testing was conducted prior to each vaccine administration and vaccination was discontinued if the woman was found to be pregnant; women were also instructed to avoid pregnancy for 2 months after receiving the vaccine. Pregnancies with vaccination within 1 month of their last menstrual period (LMP) had a higher rate of spontaneous abortions. The association between vaccination and spontaneous abortion occurring between gestation weeks 1 to 19 was evaluated in a postmarketing study. Women who were vaccinated within 1 month of their LMP were compared to women vaccinated 18 months prior to and 120 days after their LMP. The rate of spontaneous abortion was not statistically significant (HR 1.26, 95% CI 0.77 to 2.09). Based on available registry data, the rate of major birth defects is within the reported background rates (CDC/ACIP [Markowitz, 2014]).

Administration of the vaccine in pregnancy is not recommended; until additional information is available, the vaccine series (or completion of the series) should be delayed until pregnancy is completed. Pregnancy testing is not required prior to administration of the vaccine (CDC/ACIP [Petrosky, 2015]).

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, difficulty with motor activity, seizures, or enlarged lymph nodes (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.

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