Merck and QIAGEN Collaborate to Accelerate Access to Cervical Cancer Vaccination and Screening in Developing Countries

Merck & Co., Inc. and QIAGEN N.V. today announced their intent to collaborate on a new program to increase access to HPV vaccination and HPV DNA testing in some of the most resource-poor areas of the world. This initiative is the first time a vaccine manufacturer and a molecular diagnostics company are collaborating to address the burden of cervical cancer with a comprehensive approach. Representing a combined value of approximately $600 million based on current U.S. prices, the commitments of Merck and QIAGEN were highlighted today among a select group of corporate initiatives announced at the annual meeting of the Clinton Global Initiative.

"My dream of helping to reduce the burden of cervical cancer for women is increasingly within reach. I commend Merck and QIAGEN for their contribution to advancing women's health," said Graça Machel, founder and president of the Foundation for Community Development (FDC), Mozambique, and a passionate advocate for women's health. "This program is a fine example of how vaccination and screening can be used together in a comprehensive fashion. I hope that this will pave the way for new partnerships, involving the public and private sectors, donor organizations and global health leaders to address cervical cancer in developing countries."

This collaboration will integrate two breakthrough and complementary advances in healthcare, Merck's cervical cancer vaccine, GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine Recombinant], and QIAGEN's HPV tests, the digene HC2 HPV DNA Test (called the digene HPV Test) and a new HPV DNA test that is currently in development for use specifically in the developing world.

Merck intends to provide, for free, up to five (5) million doses of GARDASIL and QIAGEN intends to add to its existing one million test donation program by providing HPV DNA tests to screen an additional 500,000 women. Merck and QIAGEN plan to seek other public and private partners to design and implement national public sector cervical cancer programs, provide treatment as needed, and support improvements in laboratory and vaccine delivery infrastructure, training of healthcare workers, education and advocacy. The two companies also plan to work with cervical cancer experts to support the development and implementation of sustainable best practice models for cervical cancer reduction in low-income, high disease burden countries.

“Nearly every minute of every day a woman is diagnosed with cervical cancer, and many of these women live in developing countries where the burden of the disease is disproportionately high and healthcare infrastructure is limited," said Margaret G. McGlynn, president, Merck Vaccines and Infectious Diseases. "We see this collaboration between the two companies as innovative and fundamental to reaching our shared goal of reducing the global burden of cervical cancer."

“With broadened access to both vaccines and testing through this initiative, we hope to ensure that girls and women - regardless of where they live – will benefit from these advances in healthcare," said Peer Schatz, CEO of QIAGEN. "Our complementary tools can demonstrate the unique impact that collaborations between pharmaceutical and diagnostic companies can have on global public health.”

Merck and QIAGEN plan to reach out to select GAVI-eligible countries to explore the feasibility of implementing cervical cancer reduction programs. These programs are expected to be national in scope - all girls within a defined age range in the selected countries would be offered vaccination, and the program would work towards implementation of screening - and treatment as needed - for all women of a defined age group. The participating countries will be announced once program details and implementation strategies have been finalized. While both companies are willing to work with countries on an individual basis, Merck and QIAGEN strongly believe that working together to develop country-wide programs that include cervical cancer vaccination and screening would bring unique benefits to global public health.

GARDASIL has received WHO prequalification and is approved for use in 112 countries, 23 of which are GAVI-eligible. In the U.S., the vaccine is indicated for use in girls and young women 9 through 26 years of age for the prevention of cervical, vulvar and vaginal cancers caused by HPV types 16 and 18; genital warts caused by HPV types 6 and 11; and precancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause approximately 70 percent of cervical cancer cases.

HPV testing identifies women with high-risk HPV infections that can cause cervical cancer, enabling diagnosis and treatment to be put in place before cervical cancer develops. The digene HPV Test is approved in the U.S. and Europe where it is used as a screening test. In the U.S., it is approved to be used together with a Pap test in women 30 years and older. In Europe it is approved as an initial general population screening test either alone or together with a Pap test. It is also used as a follow-up to inconclusive Pap test results and as a post-cervical cancer treatment follow-up. To ensure that HPV testing can reach women in all regions of the world, QIAGEN is developing a new HPV DNA test for public-health programs in low-resource countries. The cervical cancer collaboration with Merck will include the digene HPV Test as well as the new HPV DNA test in development, when commercially available.

Cervical cancer affects approximately 500,000 women worldwide and about 85 percent of these women live in the developing world. By affecting women in their most productive years, cervical cancer strikes at the heart of families and deprives developing world economies of the many important contributions women make.

Important information about GARDASIL

GARDASIL does not substitute for routine cervical cancer screening, and women who receive GARDASIL should continue to undergo screening.

GARDASIL has not been demonstrated to provide protection against diseases from vaccine and non-vaccine HPV types to which a woman has previously been exposed through sexual activity. GARDASIL is not intended to be used for treatment of active genital warts; cervical, vulvar, and vaginal cancers; cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN) or vaginal intraepithelial neoplasia (VaIN).

GARDASIL has not been demonstrated to protect against diseases due to HPV types not contained in the vaccine. Not all vulvar and vaginal cancers are caused by HPV, and GARDASIL protects only against those vulvar and vaginal cancers caused by HPV types 16 and 18.

Select safety information

GARDASIL is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL.

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 GARDASIL. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion.

GARDASIL is not recommended for use in pregnant women.

The most common adverse reaction was headache. Common adverse reactions that were observed among recipients of GARDASIL at a frequency of at least 1.0 percent and greater than placebo were: fever, nausea, dizziness; and injection-site pain, swelling, erythema, pruritus and bruising.

Dosage and administration for GARDASIL

GARDASIL is a ready-to-use, three-dose, intramuscular vaccine. GARDASIL should be administered in three separate intramuscular injections in the deltoid region of the upper arm or in the higher anterolateral area of the thigh. The following dosage schedule is recommended: first dose at elected date, second dose two months after the first dose and the third dose six months after the first dose.

Other Merck and QIAGEN access efforts for the developing world

Merck is pursuing a systematic and thoughtful approach to accelerate access to GARDASIL in the developing world through four key pillars: innovation, partnerships, pricing and implementation. In 2007 at the Clinton Global Initiative, Merck made a pledge to donate at least three (3) million doses of GARDASIL through the GARDASIL Access Program, which enables organizations and institutions in eligible lowest income countries to gain operational experience in the design and implementation of HPV vaccination projects.

The collaboration between Merck and QIAGEN represents a new commitment and approach that is in addition to the GARDASIL Access Program.

QIAGEN is working to improve access to HPV testing through the development of its new HPV test and the QIAGENcares corporate social responsibility program. In April 2009, QIAGEN announced a donation of one million HPV tests to low-income countries over five years. This new collaboration with Merck increases QIAGEN’s HPV test donation by 50 percent bringing a total commitment of 1.5 million HPV tests to be provided to developing regions. Both the previous donation program and the Merck-QIAGEN collaboration are part of the QIAGENcares effort.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

About QIAGEN

QIAGEN N.V., (NASDAQ: QGEN; Frankfurt Prime Standard: QIA), a Netherlands holding company, is the leading global provider of sample and assay technologies. Sample technologies are used to isolate and process DNA, RNA and proteins from biological samples such as blood or tissue. Assay technologies are used to make such isolated biomolecules visible. QIAGEN has developed and markets more than 500 consumable products as well as automated solutions for such consumables. The company provides its products to molecular diagnostics laboratories, academic researchers, pharmaceutical and biotechnology companies, and applied testing customers for purposes such as forensics, animal or food testing and pharmaceutical process control. QIAGEN’s assay technologies include one of the broadest panels of molecular diagnostic tests available worldwide. This panel includes the digene HPV Test, which is regarded as the "gold standard" in testing for high-risk types of human papillomavirus (HPV), the primary cause of cervical cancer. QIAGEN employs more than 3,000 people in over 30 locations worldwide. Further information about QIAGEN can be found at http://www.qiagen.com/.

Forward-looking statements

Merck: This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2008, and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.

QIAGEN: Statements contained in this release that are not historical facts are forward-looking statements, including statements about QIAGEN products, markets, strategy and operating results. Such statements are based on QIAGEN’s current expectations that involve risks and uncertainties including, but not limited to, those associated with: management of growth and international operations (including currency fluctuations and logistics), variability of operating results, commercial development of markets (including applied testing, clinical and academic research, proteomics, women's health/HPV testing and molecular diagnostics), relationships with customers, suppliers and strategic partners, competition, changes in technology, fluctuations in demand, regulatory requirements, identifying, developing and producing integrated products differentiated from competitors' products, market acceptance of products, and integration of acquired technologies and businesses. For further information, refer to QIAGEN’s reports filed with or furnished to the SEC, including its latest Form 20-F. Information in this release is as of the date of the release, and QIAGEN undertakes no duty to update this information unless required by law.

Prescribing information and patient product information for GARDASIL® are attached.

GARDASIL® is a registered trademark of Merck & Co. Inc., Whitehouse Station, N.J., USA

Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=6056379&lang=en

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use GARDASIL safely and effectively. See full prescribing information for GARDASIL.

GARDASIL

[Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant]

Suspension for intramuscular injection

Initial U.S. Approval: 2006

RECENT MAJOR CHANGES

    
      
        
          Indications and Usage (1)
        
        
           
        
        
        
      
      
        
          Indications (1.1)
        
        
        
        
          09/2008
        
      
      
        
          Limitations of GARDASIL Use and Effectiveness (1.2)
        
        
        
        
          05/2009
        
      
      
        
          Contraindications (4)
        
        
        
        
          09/2008
        
      
      
        
          Warnings and Precautions (5)
        
        
        
        
        
      
      
        
          Syncope (5.1)
        
        
        
        
          06/2009
        
      
    
    

INDICATIONS AND USAGE

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, and vaginal 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

Limitations of GARDASIL Use and Effectiveness

• Women who receive GARDASIL should continue to undergo cervical cancer screening. (1.2) (17.1)
• GARDASIL has not been demonstrated to provide protection against disease from vaccine and non-vaccine HPV types to which a woman has previously been exposed through sexual activity. (1.2) (14.2)

• GARDASIL is not intended to be used for treatment of active genital warts; cervical, vulvar, and vaginal cancers; CIN; VIN; or VaIN. (1.2)
• GARDASIL has not been demonstrated to protect against diseases due to HPV types not contained in the vaccine. (1.2) (14.3)
• Not all vulvar and vaginal cancers are caused by HPV, and GARDASIL protects only against those vulvar and vaginal cancers caused by HPV 16 and 18. (1.2)
• GARDASIL does not protect against genital diseases not caused by HPV. (1.2)
• Vaccination with GARDASIL may not result in protection in all vaccine recipients. (1.2)

DOSAGE AND ADMINISTRATION

0.5-mL suspension for intramuscular injection at the following schedule: 0, 2 months, 6 months. (2.1)

DOSAGE FORMS AND STRENGTHS

• 0.5-mL suspension for injection as a single-dose vial and prefilled syringe (3) (11)

CONTRAINDICATIONS

• Hypersensitivity, including severe allergic reactions to yeast (a vaccine component), or after a previous dose of GARDASIL. (11)

WARNINGS AND PRECAUTIONS

• 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 GARDASIL. 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.

ADVERSE REACTIONS

The most common adverse reaction was headache. Common adverse reactions (frequency of at least 1.0% and greater than AAHS control or saline placebo) are fever, nausea, dizziness; and injection-site pain, swelling, erythema, pruritus, and bruising. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Merck & Co., Inc. at 1-877-888-4231 or VAERS at 1-800-822-7967 or www.vaers.hhs.gov.

DRUG INTERACTIONS

GARDASIL may be administered concomitantly with RECOMBIVAX HB. (7.1)

USE IN SPECIFIC POPULATIONS

Safety and effectiveness of GARDASIL have not been established in the following populations:

• Pregnant women. Physicians are encouraged to register pregnant women exposed to GARDASIL by calling 1-800-986-8999 so that Merck can monitor maternal and fetal outcomes (8.1).

• Children below the age of 9 years and pediatric males of any age. (8.4)
• Immunocompromised individuals. Response to GARDASIL may be diminished. (8.6)

• Women 27 years of age and older. (14.4).

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 06/2009

FULL PRESCRIBING INFORMATION:

CONTENTS* 1 INDICATIONS AND USAGE

1.1 Indications

1.2 Limitations of GARDASIL Use and Effectiveness

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

2.2 Method of Administration

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Syncope

5.2 Managing Allergic Reactions

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Post-Marketing Experience

7 DRUG INTERACTIONS

7.1 Use with RECOMBIVAX HB

7.2 Use with Hormonal Contraceptives

7.3 Use with Systemic Immunosuppressive Medications

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Immunocompromised Individuals

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Prophylactic Efficacy – HPV Types 6, 11, 16, and 18 in Women 16 Through 26 Years of Age

14.2 Effectiveness of GARDASIL in Prevention of HPV Types 6-, 11-, 16-, or 18-Related Disease in Women 16 Through 26 Years of Age, Regardless of Current or Prior Exposure to Vaccine HPV Types

14.3 Effectiveness of GARDASIL in Prevention of Any HPV Type Related Genital Disease in Women 16 Through 26 Years of Age, Regardless of Current or Prior Infection with Vaccine or Non-Vaccine HPV Types

14.4 Other Studies

14.5 Immunogenicity

14.6 Studies with RECOMBIVAX HB

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

17.1 Information for the Patient, Parent, or Guardian 17.2 FDA-Approved Patient Labeling

*Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGE

1.1 Indications

GARDASIL®1 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, and vaginal 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

1.2 Limitations of GARDASIL Use and Effectiveness

The health care provider should inform the patient, parent, or guardian that vaccination does not substitute for routine cervical cancer screening. Women who receive GARDASIL should continue to undergo cervical cancer screening per standard of care. [See Patient Counseling Information (17.1).]

GARDASIL has not been demonstrated to provide protection against disease from vaccine and non-vaccine HPV types to which a woman has previously been exposed through sexual activity. [See Clinical Studies (14.2).]

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

GARDASIL has not been demonstrated to protect against diseases due to HPV types not contained in the vaccine. [See Clinical Studies (14.3).]

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

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

GARDASIL should be administered intramuscularly as a 0.5-mL dose at the following schedule: 0, 2 months, 6 months. [See Clinical Studies (14.5).]

2.2 Method of Administration

Shake well before use. Thorough agitation immediately before administration is necessary to maintain suspension of the vaccine. GARDASIL should not be diluted or mixed with other vaccines. After thorough agitation, GARDASIL is a white, cloudy liquid. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use the product if particulates are present or if it appears discolored.

GARDASIL should be administered intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh.

Do not administer GARDASIL intravenously, intradermally, or subcutaneously.

Syncope 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 (5.1).]

Single-Dose Vial Use

Withdraw the 0.5-mL dose of vaccine from the single-dose vial using a sterile needle and syringe and use promptly.Prefilled Syringe Use With and Without Needle Guard (Safety) Device

Prefilled Syringe With Needle Guard (Safety) Device

Instructions for using the prefilled single-dose syringes preassembled with needle guard (safety) device

(Graphic Omitted)

NOTE: Please use the enclosed needle for administration. If a different needle is chosen, it should fit securely on the syringe and be no longer than 1 inch to ensure proper functioning of the needle guard device. Two detachable labels are provided which can be removed after the needle is guarded.

At any of the following steps, avoid contact with the Trigger Fingers to keep from activating the safety device prematurely.

Remove Syringe Tip Cap and Needle Cap. Attach Luer Needle by pressing both Anti-Rotation Tabs to secure syringe and by twisting the Luer Needle in a clockwise direction until secured to the syringe. Remove Needle Sheath. Administer injection per standard protocol as stated above under DOSAGE AND ADMINISTRATION. Depress the Plunger while grasping the Finger Flange until the entire dose has been given. The Needle Guard Device will NOT activate to cover and protect the needle unless the ENTIRE dose has been given. While the Plunger is still depressed, remove needle from the vaccine recipient. Slowly release the Plunger and allow syringe to move up until the entire needle is guarded. For documentation of vaccination, remove detachable labels by pulling slowly on them. Dispose in approved sharps container.

Prefilled Syringe Without Needle Guard (Safety) Device

This package does not contain a needle guard (safety device) or a needle. Shake well before use. Attach the needle by twisting in a clockwise direction until the needle fits securely on the syringe. Administer the entire dose as per standard protocol.

3 DOSAGE FORMS AND STRENGTHS

GARDASIL is a suspension for intramuscular administration available in 0.5-mL single dose vials and prefilled syringes. See Description (11) for the complete listing of ingredients.

4 CONTRAINDICATIONS Hypersensitivity, including severe allergic reactions to yeast (a vaccine component), or after a previous dose of GARDASIL. [See Description (11).]

5 WARNINGS AND PRECAUTIONS

5.1 Syncope

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 GARDASIL. 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.

5.2 Managing Allergic Reactions

Appropriate medical treatment and supervision must be readily available in case of anaphylactic reactions following the administration of GARDASIL.

6 ADVERSE REACTIONS

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 (5.1).]

Anaphylaxis has been reported following vaccination with GARDASIL.

6.1 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 26 Years of Age

In 5 clinical trials (3 Amorphous Aluminum Hydroxyphosphate Sulfate [AAHS]-controlled, 1 saline placebo-controlled, and 1 uncontrolled), 8878 subjects 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 subjects. 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 AAHS control or saline placebo. Few subjects (0.1%) discontinued due to adverse reactions. The race distribution of the study subjects 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.

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*

 

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

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 2. Overall, 94.3% of girls and women who received GARDASIL judged their injection-site adverse reaction to be mild or moderate in intensity.

Table 2

Postdose Evaluation of Injection-Site Adverse Reactions

(1 to 5 Days Postvaccination)

GARDASIL

(% occurrence)

AAHS Control*

(% occurrence)

Saline Placebo

(% occurrence)

Adverse

Reaction

        
        
          Post-

          

dose

1

N** = 5011

        
        
          Post-

          

dose

2

N = 4924

        
        
          Post-

          

dose

3

N = 4818

        
        
          Post-

          

dose

1

N = 3410

        
        
          Post-

          

dose

2

N = 3351

        
        
          Post-

          

dose

3

N = 3295

        
        
          Post-

          

dose

1

N = 315

        
        
          Post-

          

dose

2

N = 301

        
        
          Post-

          

dose

3

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 subjects 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 3.

Table 3

Common Systemic Adverse Reactions (GARDASIL ≥ Control)*

Adverse Reactions

(1 to 15 Days Postvaccination)

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

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 4.

Table 4

Postdose Evaluation of Fever

(1 to 5 Days Postvaccination)

GARDASIL

(% occurrence)

AAHS Control* or Saline Placebo

(% occurrence)

Temperature

(°F)

 

        
        
          Postdose 1

          

N** = 4945

        
        
          Postdose 2

          

N = 4804

        
        
          Postdose 3

          

N = 4671

        
        
          Postdose 1

          

N = 3681

        
        
          Postdose 2

          

N = 3564

        
        
          Postdose 3

          

N = 3467

        
      
      
        
          ≥100 to