Quadrivalent Human Papillomavirus

Girls And Women

GARDASIL® is a vaccine indicated in girls and women 9 through 26 years of age for the prevention of the following diseases caused by Human Papillomavirus (HPV) types included in the vaccine:

• Cervical, vulvar, vaginal, and anal cancer caused by HPV types 16 and 18
• Genital warts (condyloma acuminata) caused by HPV types 6 and 11

And the following precancerous or dysplastic lesions caused by HPV types 6, 11, 16, and 18:

• Cervical intraepithelial neoplasia (CIN) grade 2/3 and Cervical adenocarcinoma in situ (AIS)
• Cervical intraepithelial neoplasia (CIN) grade 1
• Vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3
• Vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3
• Anal intraepithelial neoplasia (AIN) grades 1, 2, and 3

Boys And Men

GARDASIL is indicated in boys and men 9 through 26 years of age for the prevention of the following diseases caused by HPV types included in the vaccine:

• Anal cancer caused by HPV types 16 and 18
• Genital warts (condyloma acuminata) caused by HPV types 6 and 11

And the following precancerous or dysplastic lesions caused by HPV types 6, 11, 16, and 18:

• Anal intraepithelial neoplasia (AIN) grades 1, 2, and 3

Limitations Of GARDASIL Use And Effectiveness

The health care provider should inform the patient, parent, or guardian that vaccination does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening.  Women who receive GARDASIL should continue to undergo cervical cancer screening per standard of care. [See PATIENT INFORMATION]

Recipients of GARDASIL should not discontinue anal cancer screening if it has been recommended by a health care provider. [See PATIENT INFORMATION]

GARDASIL has not been demonstrated to provide protection against disease from vaccine and nonvaccine HPV types to which a person has previously been exposed through sexual activity. [See Clinical Studies]

GARDASIL is not intended to be used for treatment of active external genital lesions; cervical, vulvar, vaginal, and anal cancers; CIN; VIN; VaIN; or AIN.

GARDASIL has not been demonstrated to protect against diseases due to HPV types not contained in the vaccine. [See Clinical Studies]

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL protects only against those vulvar, vaginal, and anal cancers caused by HPV 16 and 18.

GARDASIL does not protect against genital diseases not caused by HPV.

Vaccination with GARDASIL may not result in protection in all vaccine recipients.

GARDASIL has not been demonstrated to prevent HPV-related CIN 2/3 or worse in women older than 26 years of age. [See Clinical Studies]

Overall Summary Of Adverse Reactions

Headache, fever, nausea, and dizziness; and local injection site reactions (pain, swelling, erythema, pruritus, and bruising) occurred after administration with GARDASIL.

Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following vaccination with GARDASIL and may result in falling with injury; observation for 15 minutes after administration is recommended. [See WARNINGS AND PRECAUTIONS]

Anaphylaxis has been reported following vaccination with GARDASIL.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

Studies in Girls and Women (9 Through 45 Years of Age) and Boys and Men (9 Through 26 Years of Age)

In 7 clinical trials (5 Amorphous Aluminum Hydroxyphosphate Sulfate [AAHS]-controlled, 1 saline placebo-controlled, and 1 uncontrolled), 18,083 individuals were administered GARDASIL or AAHS control or saline placebo on the day of enrollment, and approximately 2 and 6 months thereafter, and safety was evaluated using vaccination report cards (VRC)-aided surveillance for 14 days after each injection of GARDASIL or AAHS control or saline placebo in these individuals. The individuals who were monitored using VRC-aided surveillance included 10,088 individuals 9 through 45 years of age at enrollment who received GARDASIL and 7,995 individuals who received AAHS control or saline placebo. Few individuals (0.2%) discontinued due to adverse reactions. The race distribution of the 9- through 26- year-old girls and women in the safety population was as follows: 62.3% White; 17.6% Hispanic (Black and White); 6.8% Asian; 6.7% Other; 6.4% Black; and 0.3% American Indian. The race distribution of the 24- through 45-year-old women in the safety population of Study 6 was as follows: 20.6% White; 43.2% Hispanic (Black and White); 0.2% Other; 4.8% Black; 31.2% Asian; and 0.1% American Indian. The race distribution of the 9- through 26-year-old boys and men in the safety population was as follows: 42.0% White; 19.7% Hispanic (Black and White); 11.0% Asian; 11.2% Other; 15.9% Black; and 0.1% American Indian.

Common Injection-Site Adverse Reactions in Girls and Women 9 Through 26 Years of Age

The injection site adverse reactions that were observed among recipients of GARDASIL at a frequency of at least 1.0% and also at a greater frequency than that observed among AAHS control or saline placebo recipients are shown in Table 1.

Table 1: Injection-Site Adverse Reactions in Girls and Women 9 Through 26 Years of Age*

Adverse Reaction (1 to 5 Days Postvaccination)	GARDASIL (N = 5088) %	AAHS Control† (N = 3470) %	Saline Placebo (N = 320) %
Injection Site
Pain	83.9	75.4	48.6
Swelling	25.4	15.8	7.3
Erythema	24.7	18.4	12.1
Pruritus	3.2	2.8	0.6
Bruising	2.8	3.2	1.6
*The injection-site adverse reactions 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 AAHS control or saline placebo recipients. †AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate

Common Injection-Site Adverse Reactions in Boys and Men 9 Through 26 Years of Age

The injection site adverse reactions that were observed among recipients of GARDASIL at a frequency of at least 1.0% and also at a greater frequency than that observed among AAHS control or saline placebo recipients are shown in Table 2.

Table 2: Injection-Site Adverse Reactions in Boys and Men 9 Through 26 Years of Age*

Adverse Reaction (1 to 5 Days Postvaccination)	GARDASIL (N = 3093) %	AAHS Control† (N = 2029) %	Saline Placebo (N = 274) %
Injection Site
Pain	61.4	50.8	41.6
Erythema	16.7	14.1	14.5
Swelling	13.9	9.6	8.2
Hematoma	1.0	0.3	3.3
*The injection-site adverse reactions 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 AAHS control or saline placebo recipients. †AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate

Evaluation of Injection-Site Adverse Reactions by Dose in Girls and Women 9 Through 26 Years of Age

An analysis of injection-site adverse reactions in girls and women by dose is shown in Table 3. Of those girls and women who reported an injection-site reaction, 94.3% judged their injection-site adverse reaction to be mild or moderate in intensity.

Table 3: Post dose Evaluation of Injection-Site Adverse Reactions in Girls and Women 9 Through 26 Years of Age (1 to 5 Days Postvaccination)

Adverse Reaction	GARDASIL (% occurrence)			AAHS Control* (% occurrence)			Saline Placebo (% occurrence)
	Post- dose 1 N† = 5011	Post- dose2 N = 4924	Post- dose3 N = 4818	Post- dose1 N = 3410	Post- dose2 N = 3351	Post- dose3 N = 3295	Post- dose1 N = 315	Post- dose2 N = 301	Post- dose3 N = 300
Pain	63.4	60.7	62.7	57.0	47.8	49.6	33.7	20.3	27.3
Mild/Moderate	62.5	59.7	61.2	56.6	47.3	48.9	33.3	20.3	27.0
Severe	0.9	1.0	1.5	0.4	0.5	0.6	0.3	0.0	0.3
Swelling‡	10.2	12.8	15.1	8.2	7.5	7.6	4.4	3.0	3.3
Mild/Moderate	9.6	11.9	14.2	8.1	7.2	7.3	4.4	3.0	3.3
Severe	0.6	0.8	0.9	0.2	0.2	0.2	0.0	0.0	0.0
Erythema‡	9.2	12.1	14.7	9.8	8.4	8.9	7.3	5.3	5.7
Mild/Moderate	9.0	11.7	14.3	9.5	8.4	8.8	7.3	5.3	5.7
Severe	0.2	0.3	0.4	0.3	0.1	0.1	0.0	0.0	0.0
*AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate †N = Number of individuals with follow-up ‡Intensity of swelling and erythema was measured by size (inches): Mild = 0 to ≤ 1; Moderate = > 1 to ≤ 2; Severe = > 2.

Evaluation of Injection-Site Adverse Reactions by Dose in Boys and Men 9 Through 26 Years of Age

An analysis of injection-site adverse reactions in boys and men by dose is shown in Table 4. Of those boys and men who reported an injection-site reaction, 96.4% judged their injection-site adverse reaction to be mild or moderate in intensity.

Table 4: Post dose Evaluation of Injection-Site Adverse Reactions in Boys and Men 9 Through 26 Years of Age (1 to 5 Days Postvaccination)

Adverse Reaction	GARDASIL (% occurrence)			AAHS Control* (% occurrence)			Saline Placebo (% occurrence)
	Post-dose N†=3003	Post-dose2 N = 2898	Post-dose3 N = 2826	Post-dose1 N = 1950	Post-dose2 N = 1854	Post-dose3 N = 1799	Post-dose1 N = 269	Post-dose2 N = 263	Post-dose3 N = 259
Pain	44.7	36.9	34.4	38.4	28.2	25.8	27.5	20.5	16.2
Mild/Moderate	44.5	36.4	34.1	37.9	28.2	25.5	27.5	20.2	16.2
Severe	0.2	0.5	0.3	0.4	0.1	0.3	0.0	0.4	0.0
Swelling‡	5.6	6.6	7.7	5.6	4.5	4.1	4.8	1.5	3.5
Mild/Moderate	5.3	6.2	7.1	5.4	4.5	4.0	4.8	1.5	3.1
Severe	0.2	0.3	0.5	0.2	0.0	0.1	0.0	0.0	0.4
Erythema‡	7.2	8.0	8.7	8.3	6.3	5.7	7.1	5.7	5.0
Mild/Moderate	6.8	7.7	8.3	8.0	6.2	5.6	7.1	5.7	5.0
Severe	0.3	0.2	0.3	0.2	0.1	0.1	0.0	0.0	0.0
*AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate †N = Number of individuals with follow-up ‡Intensity of swelling and erythema was measured by size (inches): Mild = 0 to ≤ 1; Moderate = > 1 to ≤ 2; Severe = > 2.

Common Systemic Adverse Reactions in Girls and Women 9 Through 26 Years of Age

Headache was the most commonly reported systemic adverse reaction in both treatment groups (GARDASIL = 28.2% and AAHS control or saline placebo = 28.4%). Fever was the next most commonly reported systemic adverse reaction in both treatment groups (GARDASIL = 13.0% and AAHS control or saline placebo = 11.2%).

Adverse reactions that were observed among recipients of GARDASIL, at a frequency of greater than or equal to 1.0% where the incidence in the GARDASIL group was greater than or equal to the incidence in the AAHS control or saline placebo group, are shown in Table 5.

Table 5: Common Systemic Adverse Reactions in Girls and Women 9 Through 26 Years of Age (GARDASIL ≥ Control)*

Adverse Reactions (1 to 15 Days Post vaccination)	GARDASIL (N = 5088) %	AAHS Control† or Saline Placebo (N = 3790) %
Pyrexia	13.0	11.2
Nausea	6.7	6.5
Dizziness	4.0	3.7
Diarrhea	3.6	3.5
Vomiting	2.4	1.9
Cough	2.0	1.5
Toothache	1.5	1.4
Upper respiratory tract infection	1.5	1.5
Malaise	1.4	1.2
Arthralgia	1.2	0.9
Insomnia	1.2	0.9
Nasal congestion	1.1	0.9
*The adverse reactions in this table are those that were observed among recipients of GARDASIL at a frequency of at least 1.0% and greater than or equal to those observed among AAHS control or saline placebo recipients. †AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate

Common Systemic Adverse Reactions in Boys and Men 9 Through 26 Years of Age

Headache was the most commonly reported systemic adverse reaction in both treatment groups (GARDASIL = 12.3% and AAHS control or saline placebo = 11.2%). Fever was the next most commonly reported systemic adverse reaction in both treatment groups (GARDASIL = 8.3% and AAHS control or saline placebo = 6.5%).

Adverse reactions that were observed among recipients of GARDASIL, at a frequency of greater than or equal to 1.0% where the incidence in the group that received GARDASIL was greater than or equal to the incidence in the AAHS control or saline placebo group, are shown in Table 6.

Table 6: Common Systemic Adverse Reactions in Boys and Men 9 Through 26 Years of Age (GARDASIL ≥ Control)*

Adverse Reactions (1 to 15 Days Post vaccination)	GARDASIL (N = 3093) %	AAHS Control† or Saline Placebo (N = 2303) %
Headache	12.3	11.2
Pyrexia	8.3	6.5
Oropharyngeal pain	2.8	2.1
Diarrhea	2.7	2.2
Nasopharyngitis	2.6	2.6
Nausea	2.0	1.0
Upper respiratory tract infection	1.5	1.0
Abdominal pain upper	1.4	1.4
Myalgia	1.3	0.7
Dizziness	1.2	0.9
Vomiting	1.0	0.8
*The adverse reactions in this table are those that were observed among recipients of GARDASIL at a frequency of at least 1.0% and greater than or equal to those observed among AAHS control or saline placebo recipients. †AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate

Evaluation of Fever by Dose in Girls and Women 9 Through 26 Years of Age

An analysis of fever in girls and women by dose is shown in Table 7.

Table 7: Post dose Evaluation of Fever in Girls and Women 9 Through 26 Years of Age (1 to 5 Days Postvaccination)

Temperature(°F)	GARDASIL (% occurrence)			AAHS Control* or Saline Placebo (% occurrence)
	Post dose 1 N†= 4945	Post dose 2 N = 4804	Post dose 3 N = 4671	Post dose 1 N = 3681	Post dose 2 N = 3564	Post dose 3 N = 3467
≥ 100 to < 102	3.7	4.1	4.4	3.1	3.8	3.6
≥ 102	0.3	0.5	0.5	0.2	0.4	0.5
*AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate †N = Number of individuals with follow-up

Evaluation of Fever by Dose in Boys and Men 9 Through 26 Years of Age

An analysis of fever in boys and men by dose is shown in Table 8.

Table 8: Post dose Evaluation of Fever in Boys and Men 9 Through 26 Years of Age (1 to 5 Days Postvaccination)

Temperature (°F)	GARDASIL (% occurrence)			AAHS Control* or Saline Placebo (% occurrence)
	Post dose 1 N†= 2972	Post dose 2 N = 2849	Post dose 3 N = 2792	Post dose 1 N = 2194	Post dose 2 N = 2079	Post dose 3 N = 2046
≥ 100 to < 102	2.4	2.5	2.3	2.1	2.2	1.6
≥ 102	0.6	0.5	0.5	0.5	0.3	0.3
*AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate †N = Number of individuals with follow-up

Serious Adverse Reactions in the Entire Study Population

Across the clinical studies, 258 individuals (GARDASIL N = 128 or 0.8%; placebo N = 130 or 1.0%) out of 29,323 (GARDASIL N = 15,706; AAHS control N = 13,023; or saline placebo N = 594) individuals (9- through 45-year-old girls and women; and 9- through 26-year-old boys and men) reported a serious systemic adverse reaction.

Of the entire study population (29,323 individuals), 0.04% of the reported serious systemic adverse reactions were judged to be vaccine related by the study investigator. The most frequently (frequency of 4 cases or greater with either GARDASIL, AAHS control, saline placebo, or the total of all three) reported serious systemic adverse reactions, regardless of causality, were:

Headache [0.02% GARDASIL (3 cases) vs. 0.02% AAHS control (2 cases)],

Gastroenteritis [0.02% GARDASIL (3 cases) vs. 0.02% AAHS control (2 cases)],

Appendicitis [0.03% GARDASIL (5 cases) vs. 0.01% AAHS control (1 case)],

Pelvic inflammatory disease [0.02% GARDASIL (3 cases) vs. 0.03% AAHS control (4 cases)],

Urinary tract infection [0.01% GARDASIL (2 cases) vs. 0.02% AAHS control (2 cases)],

Pneumonia [0.01% GARDASIL (2 cases) vs. 0.02% AAHS control (2 cases)],

Pyelonephritis [0.01% GARDASIL (2 cases) vs. 0.02% AAHS control (3 cases)],

Pulmonary embolism [0.01% GARDASIL (2 cases) vs. 0.02% AAHS control (2 cases)].

One case (0.006% GARDASIL; 0.0% AAHS control or saline placebo) of bronchospasm; and 2 cases (0.01% GARDASIL; 0.0% AAHS control or saline placebo) of asthma were reported as serious systemic adverse reactions that occurred following any vaccination visit.

In addition, there was 1 individual in the clinical trials, in the group that received GARDASIL, who reported two injection-site serious adverse reactions (injection-site pain and injection-site joint movement impairment).

Deaths in the Entire Study Population

Across the clinical studies, 40 deaths (GARDASIL N = 21 or 0.1%; placebo N = 19 or 0.1%) were reported in 29,323 (GARDASIL N = 15,706; AAHS control N = 13,023, saline placebo N = 594) individuals (9- through 45-year-old girls and women; and 9- through 26-year-old boys and men). The events reported were consistent with events expected in healthy adolescent and adult populations. The most common cause of death was motor vehicle accident (5 individuals who received GARDASIL and 4 individuals who received AAHS control), followed by drug overdose/suicide (2 individuals who received GARDASIL and 6 individuals who received AAHS control), gunshot wound (1 individual who received GARDASIL and 3 individuals who received AAHS control), and pulmonary embolus/deep vein thrombosis (1 individual who received GARDASIL and 1 individual who received AAHS control). In addition, there were 2 cases of sepsis, 1 case of pancreatic cancer, 1 case of arrhythmia, 1 case of pulmonary tuberculosis, 1 case of hyperthyroidism, 1 case of post-operative pulmonary embolism and acute renal failure, 1 case of traumatic brain injury/cardiac arrest, 1 case of systemic lupus erythematosus, 1 case of cerebrovascular accident, 1 case of breast cancer, and 1 case of nasopharyngeal cancer in the group that received GARDASIL; 1 case of asphyxia, 1 case of acute lymphocytic leukemia, 1 case of chemical poisoning, and 1 case of myocardial ischemia in the AAHS control group; and 1 case of medulloblastoma in the saline placebo group.

Systemic Autoimmune Disorders in Girls and Women 9 Through 26 Years of Age

In the clinical studies, 9- through 26-year-old girls and women were evaluated for new medical conditions that occurred over the course of follow-up. New medical conditions potentially indicative of a systemic autoimmune disorder seen in the group that received GARDASIL or AAHS control or saline placebo are shown in Table 9. This population includes all girls and women who received at least one dose of GARDASIL or AAHS control or saline placebo, and had safety data available.

Table 9: Summary of Girls and Women 9 Through 26 Years of Age Who Reported an Incident Condition Potentially Indicative of a Systemic Autoimmune Disorder After Enrollment in Clinical Trials of GARDASIL, Regardless of Causality

Conditions	GARDASIL (N = 10,706) n (%)	AAHS Control* or Saline Placebo (N = 9412) n (%)
Arthralgia/Arthritis/Arthropathy†	120 (1.1)	98 (1.0)
Autoimmune Thyroiditis	4 (0.0)	1 (0.0)
Celiac Disease	10 (0.1)	6 (0.1)
Diabetes Mellitus Insulin-dependent	2 (0.0)	2 (0.0)
Erythema Nodosum	2 (0.0)	4 (0.0)
Hyperthyroidism‡	27 (0.3)	21 (0.2)
Hypothyroidism§	35 (0.3)	38 (0.4)
Inflammatory Bowel Disease¶	7 (0.1)	10 (0.1)
Multiple 55 clerosis	2 (0.0)	4 (0.0)
Nephritis#	2 (0.0)	5 (0.1)
Optic Neuritis	2 (0.0)	0 (0.0)
Pigmentation DisorderÞ	4 (0.0)	3 (0.0)
Psoriasisβ	13 (0.1)	15 (0.2)
Raynaud's Phenomenon	3 (0.0)	4 (0.0)
Rheumatoid Arthritisà	6 (0.1)	2 (0.0)
Scleroderma/Morphea	2 (0.0)	1 (0.0)
Stevens-Johnson Syndrome	1 (0.0)	0 (0.0)
Systemic Lupus Erythematosus	1 (0.0)	3 (0.0)
Uveitis	3 (0.0)	1 (0.0)
All Conditions	245 (2.3)	218 (2.3)
*AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate †Arthralgia/Arthritis/Arthropathy includes the following terms: Arthralgia, Arthritis, Arthritis reactive, and Arthropathy ‡Hyperthyroidism includes the following terms: Basedow's disease, Goiter, Toxic nodular goiter, and Hyperthyroidism §Hypothyroidism includes the following terms: Hypothyroidism and thyroiditis ¶Inflammatory bowel disease includes the following terms: Colitis ulcerative, Crohn's disease, and Inflammatory bowel disease #Nephritis includes the following terms: Nephritis, Glomerulonephritis minimal lesion, Glomerulonephritis proliferative ÞPigmentation disorder includes the following terms: Pigmentation disorder, Skin depigmentation, and Vitiligo βPsoriasis includes the following terms: Psoriasis, Pustular psoriasis, and Psoriatic arthropathy àRheumatoid arthritis includes juvenile rheumatoid arthritis. One woman counted in the rheumatoid arthritis group reported rheumatoid arthritis as an adverse experience at Day 130. N = Number of individuals enrolled n = Number of individuals with specific new Medical Conditions NOTE: Although an individual may have had two or more new Medical Conditions, the individual is counted only once within a category. The same individual may appear in different categories.

Systemic Autoimmune Disorders in Boys and Men 9 Through 26 Years of Age

In the clinical studies, 9- through 26-year-old boys and men were evaluated for new medical conditions that occurred over the course of follow-up. New medical conditions potentially indicative of a systemic autoimmune disorder seen in the group that received GARDASIL or AAHS control or saline placebo are shown in Table 10. This population includes all boys and men who received at least one dose of GARDASIL or AAHS control or saline placebo, and had safety data available.

Table 10: Summary of Boys and Men 9 Through 26 Years of Age Who Reported an Incident Condition Potentially Indicative of a Systemic Autoimmune Disorder After Enrollment in Clinical Trials of GARDASIL, Regardless of Causality

Conditions	GARDASIL (N = 3093) n (%)	AAHS Control* or Saline Placebo (N = 2303) n (%)
Alopecia Areata	2 (0.1)	0 (0.0)
Ankylosing Spondylitis	1 (0.0)	2 (0.1)
Arthralgia/Arthritis/Reactive Arthritis	30 (1.0)	17 (0.7)
Autoimmune Thrombocytopenia	1 (0.0)	0 (0.0)
Diabetes Mellitus Type 1	3 (0.1)	2 (0.1)
Hyperthyroidism	0 (0.0)	1 (0.0)
Hypothyroidism†	3 (0.1)	0 (0.0)
Inflammatory Bowel Disease‡	1 (0.0)	2 (0.1)
Myocarditis	1 (0.0)	1 (0.0)
Proteinuria	1 (0.0)	0 (0.0)
Psoriasis	0 (0.0)	4 (0.2)
Skin Depigmentation	1 (0.0)	0 (0.0)
Vitiligo	2 (0.1)	5 (0.2)
All Conditions	46 (1.5)	34 (1.5)
*AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate †Hypothyroidism includes the following terms: Hypothyroidism and Autoimmune thyroiditis ‡Inflammatory bowel disease includes the following terms: Colitis ulcerative and Crohn's disease N = Number of individuals who received at least one dose of either vaccine or placebo n = Number of individuals with specific new Medical Conditions NOTE: Although an individual may have had two or more new Medical Conditions, the individual is counted only once within a category. The same individual may appear in different categories.

Safety in Concomitant Use with RECOMBIVAX HB® [hepatitis B vaccine (recombinant)] in Girls and Women 16 Through 23 Years of Age

The safety of GARDASIL when administered concomitantly with RECOMBIVAX HB® [hepatitis B vaccine (recombinant)] was evaluated in an AAHS-controlled study of 1871 girls and women with a mean age of 20.4 years [see Clinical Studies]. The race distribution of the study individuals was as follows: 61.6% White; 23.8% Other; 11.9% Black; 1.6% Hispanic (Black and White); 0.8% Asian; and 0.3% American Indian. The rates of systemic and injection-site adverse reactions were similar among girls and women who received concomitant vaccination as compared with those who received GARDASIL or RECOMBIVAX HB [hepatitis B vaccine (recombinant)].

Safety in Concomitant Use with Menactra [Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine] and Adacel [Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)]

The safety of GARDASIL when administered concomitantly with Menactra [Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine] and Adacel [Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap)] was evaluated in a randomized study of 1040 boys and girls with a mean age of 12.6 years [see Clinical Studies]. The race distribution of the study subjects was as follows: 77.7% White; 1.4% Multi-racial; 12.3% Black; 6.8% Hispanic (Black and White); 1.2% Asian; 0.4% American Indian, and 0.2% Indian.

There was an increase in injection-site swelling reported at the injection site for GARDASIL (concomitant = 10.9%, non-concomitant = 6.9%) when GARDASIL was administered concomitantly with Menactra and Adacel as compared to non-concomitant (separated by 1 month) vaccination. The majority of injection-site swelling adverse experiences were reported as being mild to moderate in intensity.

Safety in Women 27 Through 45 Years of Age

The adverse reaction profile in women 27 through 45 years of age was comparable to the profile seen in girls and women 9 through 26 years of age.

Postmarketing Experience

The following adverse events have been spontaneously reported during post-approval use of GARDASIL. Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or to establish a causal relationship to vaccine exposure.

Blood and lymphatic system disorders: Autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, lymphadenopathy.

Respiratory, thoracic and mediastinal disorders: Pulmonary embolus.

Gastrointestinal disorders: Nausea, pancreatitis, vomiting.

General disorders and administration site conditions: Asthenia, chills, death, fatigue, malaise.

Immune system disorders: Autoimmune diseases, hypersensitivity reactions including anaphylactic/anaphylactoid reactions, bronchospasm, and urticaria.

Musculoskeletal and connective tissue disorders: Arthralgia, myalgia.

Nervous system disorders: Acute disseminated encephalomyelitis, dizziness, Guillain-Barré syndrome, headache, motor neuron disease, paralysis, seizures, syncope (including syncope associated with tonic-clonic movements and other seizure-like activity) sometimes resulting in falling with injury, transverse myelitis.

Infections and infestations: cellulitis.

Vascular disorders: Deep venous thrombosis.

Included as part of the PRECAUTIONS section.

No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.

Before receiving this vaccine, tell your doctor if you have:

• high fever, or signs of infection;
• a weak immune system;
• a bleeding or blood-clotting disorder, such as hemophilia; or
• if you are taking a blood thinner such as warfarin (Coumadin).

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. However, you should not receive HPV vaccine without telling your doctor if you are pregnant or plan to become pregnant before you have received all doses of this vaccine.

It is not known whether HPV vaccine passes into breast milk or if it could harm a nursing baby. Do not receive this vaccine without telling your doctor if you are breast-feeding a baby.

HPV vaccine will not protect against sexually transmitted diseases such as chlamydia, gonorrhea, herpes, HIV, syphilis, and trichomoniasis.

HPV quadrivalent vaccine will not prevent diseases caused by HPV types other than types 6, 11, 16, and 18. There are over 100 different types of HPV.

Contact your doctor if you will miss an HPV vaccine booster dose or if you get behind schedule. The next dose should be given as soon as possible. There is no need to start over.

Be sure you receive all recommended doses of this vaccine. If you do not receive the full series of vaccines, you may not be fully protected against the disease.