In 5 clinical trials (4 placebo-controlled), subjects were administered GARDASIL or placebo on the day of enrollment, and approximately 2 and 6 months thereafter. Few subjects (0.1%) discontinued due to adverse experiences. In all except 1 of the clinical trials, safety was evaluated using vaccination report card (VRC)-aided surveillance for 14 days after each injection of GARDASIL or placebo. The subjects who were monitored using VRC-aided surveillance included 5088 girls and women 9 through 26 years of age at enrollment who received GARDASIL and 3790 girls and women who received placebo.

The vaccine-related adverse experiences that were observed among female recipients of GARDASIL at a frequency of at least 1.0% and also at a greater frequency than that observed among placebo recipients are shown in Table 6.

Table 6
Vaccine-related Injection-site and Systemic Adverse Experiences*

*The vaccine-related adverse experiences that were observed among recipients of GARDASIL were at a frequency of at least 1.0% and also at a greater frequency than that observed among placebo recipients.

All-cause systemic adverse experiences for female subjects that were observed at a frequency of greater than or equal to 1% where the incidence in the vaccine group was greater than or equal to the incidence in the placebo group are shown in Table 7.

Table 7
All-cause Common Systemic Adverse Experiences

Evaluation of Injection-site Adverse Experiences by Dose

An analysis of injection-site adverse experiences in female subjects by dose is shown in Table 8. Overall, 94.3% of subjects who received GARDASIL judged their injection-site adverse experience to be mild or moderate in intensity.

Table 8
Postdose Evaluation of Injection-site Adverse Experiences

Evaluation of Fever by Dose

An analysis of fever in girls and women by dose is shown in Table 9.

Table 9
Postdose Evaluation of Fever

Serious Adverse Experiences

A total of 102 subjects out of 21,464 total subjects (9- to 26-year-old girls and women and 9- to 15-year-old boys) who received both GARDASIL and placebo reported a serious adverse experience on Day 1-15 following any vaccination visit during the clinical trials for GARDASIL. The most frequently reported serious adverse experiences for GARDASIL compared to placebo and regardless of causality were:

headache                           (0.03% GARDASIL vs. 0.02% Placebo),
gastroenteritis                     (0.03% GARDASIL vs. 0.01% Placebo),
appendicitis                        (0.02% GARDASIL vs. 0.01% Placebo),
pelvic inflammatory disease (0.02% GARDASIL vs. 0.01% Placebo).

One case of bronchospasm and 2 cases of asthma were reported as serious adverse experiences that occurred during Day 1-15 of any vaccination visit.

Across the clinical studies, 17 deaths were reported in 21,464 male and female subjects. The events reported were consistent with events expected in healthy adolescent and adult populations. The most common cause of death was motor vehicle accident (4 subjects who received GARDASIL and 3 placebo subjects), followed by overdose/suicide (1 subject who received GARDASIL and 2 subjects who received placebo), and pulmonary embolus/deep vein thrombosis (1 subject who received GARDASIL and 1 placebo subject). In addition, there were 2 cases of sepsis, 1 case of pancreatic cancer, and 1 case of arrhythmia in the group that received GARDASIL, and 1 case of asphyxia in the placebo group.

In the clinical studies, subjects were evaluated for new medical conditions that occurred over the course of up to 4 years of follow up. The number of subjects who received both GARDASIL and placebo and developed a new medical condition potentially indicative of a systemic immune disorder is shown in Table 10.

Table 10
Summary of Subjects Who Reported an Incident Condition Potentially Indicative of Systemic Autoimmune Disorder After Enrollment in Clinical Trials of GARDASIL

Safety in Concomitant Use with Other Vaccines

The safety of GARDASIL when administered concomitantly with hepatitis B vaccine (recombinant) was evaluated in a placebo-controlled study. There were no statistically significant higher rates in systemic or injection-site adverse experiences among subjects who received concomitant vaccination compared with those who received GARDASIL or hepatitis B vaccine alone.

The US Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine, including but not limited to the reporting of events required by the National Childhood Vaccine Injury Act of 1986. For information or a copy of the vaccine reporting form, call the VAERS toll-free number at 1-800-822-7967 or report on line to www.vaers.hhs.gov.

Use with Other Vaccines

Results from clinical studies indicate that GARDASIL may be administered concomitantly (at a separate injection site) with hepatitis B vaccine (recombinant) (see CLINICAL PHARMACOLOGY, Studies with Other Vaccines). Co-administration of GARDASIL with other vaccines has not been studied.

In clinical studies, 13,293 subjects (vaccine = 6644; placebo = 6649) who had post-Month 7 follow-up used hormonal contraceptives for a total of 17,597 person-years (65.1% of the total follow-up time in the study for these subjects). Use of hormonal contraceptives or lack of use of hormonal contraceptives among study participants did not alter vaccine efficacy in the PPE population.

Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune responses to vaccines (see PRECAUTIONS, General).

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