Human papillomavirus bivalent vaccine: Pediatric drug information

Copyright 1978-2015 Lexicomp, Inc. All rights reserved.

(For additional information see "Human papillomavirus bivalent vaccine: Drug information" and see
"Human papillomavirus bivalent vaccine: Patient drug information")
For abbreviations and symbols that may be used in Lexicomp (show table)

Brand Names: US

Cervarix

Brand Names: Canada

Cervarix

Therapeutic Category

Vaccine;

Vaccine, Inactivated (Viral)

Dosing: Usual
(For additional information see "Human papillomavirus bivalent vaccine: Drug information")
Pediatric:
Primary immunization:
CDC (ACIP) recommendations: Female only: Children 9 years and Adolescents: IM: 0.5
mL per dose for a total of 3 doses administered as follows: Initial dose followed by a
second dose at 1 to 2 months after initial and third dose at 6 months after the initial
dose. Administer first dose to females at age 11 to 12 years although series may be
initiated as early as 9 years of age. Minimum interval between the first and second
dose is 4 weeks; minimum interval between the second and third dose of vaccine is
12 weeks (16 weeks preferred); minimum interval between first and third dose is 24
weeks. If the dose is given in an interval shorter than recommended, the dose
should be repeated. The HPV vaccine series should be completed with the same
product whenever possible (CDC/ACIP [Markowitz 2014]; CDC/ACIP [Strikas
2015]).
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 (Strikas 2015): Note: Do not restart
the series. If doses have been given, begin the below schedule at the applicable dose

number. IM: 0.5 mL per dose for a total of 3 doses in females ages 13 to 18 years who
are incompletely vaccinated or were not previously vaccinated, administered as follows:
First dose given on the elected date
Second dose given at least 4 weeks after the first dose
Third dose given at 16 weeks after the second dose (minimum interval: 12 weeks) and at
least 24 weeks after the first dose
Adult: Immunization:
CDC (ACIP) recommendations: 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. Administer the second and
third doses at 1 to 2 months and 6 months after the first dose. Minimum interval between
first and second doses is 4 weeks; the minimum interval between the second and third
dose is 12 weeks (16 weeks preferred); the minimum interval between first and third
doses is 24 weeks. 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 (CDC/ACIP [Kim 2015]; CDC/ACIP
[Markowitz 2014]).
Manufacturer's labeling: Females 25 years: 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.
Dosing adjustment in renal impairment: There are no dosage adjustments provided in the
manufacturer's labeling.
Dosing adjustment in hepatic impairment: There are no dosage adjustments provided in the
manufacturer's labeling.

Dosage Forms: US
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)]

Generic Equivalent Available: US

No

Medication Guide and/or Vaccine Information Statement (VIS)

In the U.S, the appropriate CDC-approved Vaccine Information Statement (VIS) must be provided to
the patient prior to administering each dose of this vaccine; VIS is available
at http://www.cdc.gov/vaccines/hcp/vis/vis-statements/hpv-cervarix.html.

Administration
IM: Shake suspension well prior to use; do not use suspension if it is discolored or contains
particulate matter; should be a homogenous, turbid, white suspension. Do not dilute or mix with
other vaccines. Administer IM into the deltoid region of the upper arm; not for IV, intradermal, or
SubQ administration. To prevent syncope related injuries, adolescents and adults should be
vaccinated while seated or lying down (NCIRD/ACIP 2011). US law requires that the date of
administration, the vaccine manufacturer, lot number of vaccine, and the administering persons
name, title and address be entered into the patients 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) should be used for the
vaccination and firm pressure on 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/Stability
U.S. labeling: Store under refrigeration at 2C to 8C (36F to 46F); 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 2C to 8C (36F to 46F); do not freeze; discard if
frozen. Vaccine can be administered if stored between 8C and 25C (46F to 77F) for up to 3
days or stored between 25C and 37C (77F to 98.6F) for up to 1 day. Discard vaccine if
exposed to temperatures >37C (98.6F). Protect from light.

Use
Prevention of cervical cancer and cervical intraepithelial neoplasia with or without cervical
adenocarcinoma in situ caused by Human Papillomavirus (HPV) types 16 and 18 (FDA
approved in girls 9 years and women 25 years of age)
The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for
females 11 to 12 years of age; may be started at 9 years of age; catch-up vaccination is
recommended for females 13 to 26 years of age (CDC/ACIP [Markowitz 2014]; CDC/ACIP
[Strikas 2015])

Medication Safety Issues

Sound-alike/look-alike issues:

Papillomavirus vaccine types 16, 18 (Cervarix) may be confused with Papillomavirus vaccine
types 6, 11, 16, 18 (Gardasil)
Cervarix may be confused with Cerebyx, CeleBREX

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).

Central nervous system: Fatigue

Dermatologic: Urticaria
Local: Injection site reactions: Pain, pruritus, redness, swelling
Neuromuscular & skeletal: Arthralgia, myalgia
Respiratory: Nasopharyngitis, pharyngitis, pharyngolaryngeal pain, upper respiratory tract infection
Miscellaneous: Chlamydia infection, influenza, vaginal infection
Rare but important or life-threatening: Allergic reactions, anaphylactic/anaphylactoid reactions,
angioedema, erythema multiforme, lymphadenopathy, syncope (may be associated with tonicclonic movements), vasovagal response

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

Warnings/Precautions
Concerns related to adverse effects:
Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1:1000)
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 ageappropriate 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 (CDC/ACIP [Kim, 2015]).
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).

Metabolism/Transport Effects
None known.

Drug Interactions
(For additional information: Launch Lexi-Interact Drug Interactions Program)
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. Risk D:
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. Risk D: 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). Risk D: Consider therapy modification

Pregnancy Risk Factor

B (show table)

Pregnancy Implications
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]).

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

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: 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 HPV2 reduced the incidence of CIN
2/3 and AIS by 87% to 98% in several randomized clinical trials. (CDC/ACIP [Markowitz, 2014]).

Pharmacodynamics
Onset of action: Peak seroconversion was observed 1 month following the last dose of vaccine
Duration: Not well defined; >5 years

Additional Information
Comparison of HPV vaccines: Cervarix and Gardasil are both vaccines formulated to protect
against infection with the human papillomavirus. Both are inactive vaccines which contain proteins
HPV16 L1 and HPV 18 L1, the cause of >70% of invasive cervical cancer. The vaccines differ in
that Gardasil also contains HPV 6 L1 and HPV 11 L1 proteins which protect against 75% to 90% of
genital warts. The vaccines also differ in their preparation and adjuvants used. The viral proteins in
Cervarix are prepared using Trichoplusia ni (insect cells) which are adsorbed onto an aluminum salt
which is also combined with a monophosphoryl lipid. The viral proteins in Gardasil are prepared
using S. cerevisiae (baker's yeast) which are then adsorbed onto an aluminum salt. Results from a
short-term study (measurements obtained 1 month following the third vaccination in the series)
have shown that the immune response to HPV 16 and HPV 18 may be greater with Cervarix;
although the clinical significance of these differences is not known, local adverse events may also
occur more frequently with this preparation. Both vaccines are effective and results from long-term
studies are pending (Einstein 2009).
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REFERENCES
1.

Einstein MH, Baron M, Levin MJ, et al. Comparison of the immunogenicity and safety of
Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women
aged 18-45 years. Hum Vaccin. 2009;5(10):507-519. [PubMed 19684472]

2.

Kim DK, Bridges CB, Harriman KH; Advisory Committee on Immunization Practices (ACIP);
ACIP Adult Immunization Work Group; Centers for Disease Control and Prevention (CDC). Advisory
committee on Immunization Practices recommended immunization schedule for adults aged 19
years or older - United States, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(4):9192. http://www.cdc.gov/vaccines/schedules/downloads/adult/adult-combined-schedule.pdf [PubMed
25654609]

3.

Markowitz LE, Dunne EF, Saraiya M, et.al; Centers for Disease Control and Prevention
(CDC). Human papillomavirus vaccination: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Recomm Rep. 2014;63(RR-05):1-30. [PubMed 25167164]

4.

National Centers for Immunization and Respiratory Diseases (NCIRD). General

recommendations on immunizationrecommendations of the Advisory Committee on Immunization
Practices (ACIP) [published correction appears in MMWR Recomm Rep. 2011;60:993]. MMWR
Recomm Rep. 2011;60(2):1-64. [PubMed21293327]

5.

Petrosky E, Bocchini JA, Hariri S, et.al. Use of 9-valent human papillomavirus (HPV)
vaccine: Updated HPV vaccination recommendations of the Advisory Committee on Immunization
Practices. MMWR Morb Mortal Wkly Rep. 2015;64(11):300-304. [PubMed 25811679]

6.

Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination
of the immunocompromised host. Clin Infect Dis. 2014;58(3):e44-e100.[PubMed 24311479]

7.

Strikas RA; Advisory Committee on Immunization Practices (ACIP); ACIP Child/Adolescent

Immunization Work Group; Centers for Disease Control and Prevention (CDC). Advisory Committee
on Immunization Practices recommended immunization schedule for persons aged 0 through 18
yearsUnited States, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(4):9394. http://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf. [
PubMed25654610]
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