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Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following vaccination with CERVARIX. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion by maintaining a supine or Trendelenburg position.
The tip caps of the prefilled syringes may contain natural rubber latex which may cause allergic reactions in latex-sensitive individuals.
Preventing And Managing Allergic Vaccine Reactions
Prior to administration, the healthcare provider should review the immunization history for possible vaccine hypersensitivity and previous vaccination-related adverse reactions to allow an assessment of benefits and risks. Appropriate medical treatment and supervision should be readily available in case of anaphylactic reactions following administration of CERVARIX.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).
Patient labeling is provided as a tear-off leaflet at the end of this Full Prescribing Information.
Provide the Vaccine Information Statements prior to immunization. These are required by the National Childhood Vaccine Injury Act of 1986 and are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines).
Inform the patient, parent, or guardian:
- Vaccination does not substitute for routine cervical cancer screening. Women who receive CERVARIX should continue to undergo cervical cancer screening per standard of care.
- CERVARIX does not protect against disease from HPV types to which a woman has previously been exposed through sexual activity.
- Since syncope has been reported following vaccination in young females, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended.
- Safety has not been established in pregnant women.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
CERVARIX has not been evaluated for its carcinogenic or mutagenic potential. Vaccination of female rats with CERVARIX, at doses shown to be significantly immunogenic in the rat, had no effect on fertility.
Use In Specific Populations
Pregnancy Category B
Reproduction studies have been performed in rats at a dose approximately 47 times the human dose (on a mg/kg basis) and revealed no evidence of impaired fertility or harm to the fetus due to CERVARIX. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
An evaluation of the effect of CERVARIX on embryo-fetal, pre- and post-natal development was conducted using rats. One group of rats was administered CERVARIX 30 days prior to gestation and during the period of organogenesis (gestation days 6, 8, 11, and 15). A second group of rats was administered saline at 30 days prior to gestation followed by CERVARIX on days 6, 8, 11, and 15 of gestation. Two additional groups of rats received either saline or adjuvant following the same dosing regimen. CERVARIX was administered at 0.1 mL/rat/occasion (approximately 47-fold excess relative to the projected human dose on a mg/kg basis) by intramuscular injection. No adverse effects on mating, fertility, pregnancy, parturition, lactation, or embryo-fetal, pre- and post-natal development were observed. There were no vaccine-related fetal malformations or other evidence of teratogenesis.
Overall Outcomes: In pre-licensure clinical studies, pregnancy testing was performed prior to each vaccine administration and vaccination was discontinued if a subject had a positive pregnancy test. In all clinical trials, subjects were instructed to take precautions to avoid pregnancy until 2 months after the last vaccination. During pre-licensure clinical development, a total of 7,276 pregnancies were reported among 3,696 females receiving CERVARIX and 3,580 females receiving a control (Hepatitis A Vaccine 360 EL.U., Hepatitis A Vaccine 720 EL.U., or 500 mcg Al(OH)3). The overall proportions of pregnancy outcomes were similar between treatment groups. The majority of women gave birth to normal infants (62.2% and 62.6% of recipients of CERVARIX and control, respectively). Other outcomes included spontaneous abortion (11.0% and 10.8% of recipients of CERVARIX and control, respectively), elective termination (5.8% and 6.1% of recipients of CERVARIX and control, respectively), abnormal infant other than congenital anomaly (2.8% and 3.2% of recipients of CERVARIX and control, respectively), and premature birth (2.0% and 1.7% of recipients of CERVARIX and control, respectively). Other outcomes (congenital anomaly, stillbirth, ectopic pregnancy, and therapeutic abortion) were reported less frequently in 0.1% to 0.8% of pregnancies in both groups.
Outcomes Around Time of Vaccination: In pre-licensure studies, sub-analyses were conducted to describe pregnancy outcomes in 761 women (N = 396 for CERVARIX and N = 365 for pooled control, HAV 360 EL.U., HAV 720 EL.U., or 500 mcg Al(OH)3) who received a dose of CERVARIX or control between 45 days prior to and 30 days after the last menstrual period (LMP) and for whom pregnancy outcome was known. The majority of women gave birth to normal infants (65.2% and 69.3% of recipients of CERVARIX and control, respectively). Spontaneous abortion was reported in a total of 11.7% of subjects (13.6% of recipients of CERVARIX and 9.6% of control recipients), and elective termination was reported in a total of 9.7% of subjects (9.9% of recipients of CERVARIX and 9.6% of control recipients). Abnormal infant other than congenital anomaly was reported in a total of 4.9% of subjects (5.1% of recipients of CERVARIX and 4.7% of control recipients), and premature birth was reported in a total of 2.5% of subjects (2.5% of both groups). Other outcomes (congenital anomaly, stillbirth, ectopic pregnancy, and therapeutic abortion) were reported in 0.3% to 1.8% of pregnancies among recipients of CERVARIX and in 0.3% to 1.4% of pregnancies among control recipients.
A post-hoc analysis was performed on a pooled database of pregnancies with known outcome among women 15 to 25 years of age enrolled in controlled clinical trials (N = 4,670 for CERVARIX and N = 4,689 for pooled control, HAV 360 EL.U., HAV 720 EL.U., or 500 mcg Al(OH)3). In an analysis of pregnancies with exposure to CERVARIX or control between 45 days prior to and 30 days after the LMP, the relative risk of spontaneous abortion was 1.54 (95% CI: 0.95, 2.54) for exposure to one dose of CERVARIX (n/N = 46/326) compared with one dose of control (n/N = 33/338) and 1.21 (95% CI: 0.27, 7.33) for exposure to 2 doses of CERVARIX (n/N = 8/71) compared with 2 doses of control (n/N = 3/38).
The association between vaccination with CERVARIX and spontaneous abortion was evaluated in a post-marketing, retrospective, observational, cohort study using primary care medical records in the United Kingdom. The study assessed the risk of spontaneous abortion during weeks 1 to 19 of gestation in two cohorts of women 15 to 25 years of age: one cohort who received one or more doses of CERVARIX between 45 days prior to and 30 days after the LMP (close exposure) and another cohort who received the last dose of CERVARIX between 18 months and 120 days prior to the LMP (remote exposure). The hazard ratio for spontaneous abortion was 1.26 (95% CI: 0.77, 2.09) for the close-exposure cohort (n/N = 23/207) compared with the remote-exposure cohort (n/N = 56/632). In sensitivity analyses for the close-exposure cohort, the hazard ratio compared with the remote-exposure cohort was 1.07 (95% CI: 0.61, 1.86) for women who received only one dose of CERVARIX (n/N = 17/178) and 2.59 (95% CI: 1.11, 6.04) for women who received 2 doses of CERVARIX (n/N = 6/29).
In non-clinical studies in rats, serological data suggest a transfer of anti-HPV-16 and anti-HPV-18 antibodies via milk during lactation in rats. Excretion of vaccine-induced antibodies in human milk has not been studied for CERVARIX. Because many drugs are excreted in human milk, caution should be exercised when CERVARIX is administered to a nursing woman.
Safety and effectiveness in pediatric patients younger than 9 years of age have not been established. The safety and effectiveness of CERVARIX have been evaluated in 1,275 subjects 9 through 14 years of age and 6,362 subjects 15 through 17 years of age. [See ADVERSE REACTIONS and Clinical Studies]
Clinical studies of CERVARIX did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects. CERVARIX is not approved for use in subjects 65 years of age and older.
Last reviewed on RxList: 10/19/2015
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