The Government of Rwanda, together with QIAGEN N.V. (NASDAQ:
QGEN, F:QIA) and Merck (NYSE: MRK), known as MSD outside the United
States and Canada, today announced the launch, in Kigali, Rwanda,
of a comprehensive national cervical cancer prevention program that
includes vaccination with GARDASIL [Human Papillomavirus
Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] for
appropriate girls 12 to 15 years of age and modern molecular
diagnostic screening for women between the ages of 35 and 45.
Rwanda is the first nation in Africa to offer a comprehensive
prevention program that incorporates both HPV vaccination and HPV
testing. Rwanda has a population of 2.72 million women ages 15
years and older. Cervical cancer ranks as the most frequent cancer
in women of all ages in Rwanda.
"It is our goal to create a comprehensive, coordinated program
that includes HPV vaccination, cancer screening with HPV DNA
testing, and treatment in order to address the nation's unmet needs
for cervical cancer-related health services," said Dr. Richard
Sezibera, Rwanda’s Minister of Health. "This vaccination and
screening program brings us one step closer to reaching our goal of
protecting the girls and women in our country. We are pleased to
have the support of Merck and QIAGEN on this important government
initiative."
During the first three years of the national prevention program
the Ministry of Health, with the support of Merck, will offer
GARDASIL to appropriate girls 12 to 15 years of age, while QIAGEN's
DNA-based molecular diagnostic HPV tests – the digene HC2 HPV DNA
Test and the careHPV Test – will be offered to women between the
ages of 35 and 45. QIAGEN’s careHPV test has been designed to reach
women where access to medical care is more challenging – the
portable testing system can be performed in any health clinic
setting by healthcare workers with minimal lab training.
Merck will provide more than two million doses of GARDASIL to
the Government of Rwanda at no cost, while QIAGEN will provide
250,000 HPV screening tests at no cost along with all necessary
equipment and training to successfully perform the tests.
Thereafter, the Government of Rwanda will continue routine
vaccination of appropriate 12 year old girls, and Merck will
provide GARDASIL at a discounted access price that is made
available for national vaccination programs in GAVI-eligible
countries. Similarly, QIAGEN will make its HPV tests accessible
under a tiered-market pricing structure designed to enable
developing countries to establish and maintain the use of HPV
testing within national cervical cancer screening and treatment
programs.
"Over eighty-five percent of cervical cancer cases occur in the
world's poorest countries, having an impact on the women affected,
their families and their communities," said Dr. Mark Feinberg,
chief public health and science officer, Merck Vaccines. "Reducing
the incidence of cervical cancer is a very important public health
goal. Through this collaboration with the Government of Rwanda,
QIAGEN and numerous global public health organizations working in
the country to introduce HPV vaccination and HPV DNA testing, women
and girls in Rwanda will have greater access to a comprehensive
cervical cancer prevention program. We hope this initiative by the
Government of Rwanda provides a helpful model for other
resource-limited countries to consider as they work to develop
their own programs."
GARDASIL is approved in the United States for use in girls and
young women 9 through 26 years of age for the prevention of
cervical, vulvar, vaginal and anal 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. GARDASIL is also approved in the United States for use in
boys and men ages 9 through 26 years of age for the prevention of
anal cancer caused by HPV types 16 and 18, for the prevention of
anal dysplasias and precancerous lesions caused by HPV types 6, 11,
16 and 18, and the prevention of genital warts caused by HPV types
6 and 11.
Merck and QIAGEN announced plans to launch a collaborative HPV
vaccination and HPV screening program in September 2009 to help
prevent cervical cancer. In addition to their own separate
initiatives, the two companies committed to jointly provide up to
five million doses of GARDASIL and 500,000 HPV tests to developing
countries at no charge. As the first recipient of this
collaborative effort, Rwanda will become the first GAVI-eligible
country to implement a comprehensive program involving both HPV
vaccination and HPV DNA-based molecular testing to improve access
to cervical cancer prevention programs. QIAGEN and Merck continue
to reach out to select GAVI-eligible countries to explore the
feasibility of implementing cervical cancer reduction programs.
"Expanding access to HPV testing, regardless of where a woman
lives, is a commitment of QIAGEN to help reduce the tremendous
burden of cervical cancer, particularly in the developing world.
Women in Rwanda, and in other countries where our DNA-based
molecular diagnostic tests are available, are being screened for
prevention of this potentially life-threatening disease with the
most modern diagnostic detection technology available,” said Peer
Schatz, chief executive officer of QIAGEN N.V. “In many countries
women are the cornerstone of families and their communities. It is
unfortunate that cervical cancer, which effective measures can help
to prevent, often strikes women in their prime years of
productivity. We are pleased to partner with the Republic of Rwanda
and Merck to introduce this comprehensive program that will greatly
expand access to HPV testing and vaccination, which together can
help reduce the burden of this disease. We believe this program
will demonstrate the positive impact that these types of
collaborations can have in terms of improving healthcare.”
Important information about GARDASIL
GARDASIL does not eliminate the necessity for women to continue
to undergo recommended cervical cancer screening.
Recipients of GARDASIL should not discontinue anal cancer
screening if it has been recommended by a health care provider.
GARDASIL has not been demonstrated to provide protection against
diseases from vaccine and non-vaccine HPV types to which a person
has previously been exposed through sexual activity.
GARDASIL is not intended to be used for treatment of active
external genital lesions; cervical, vulvar, vaginal and anal
cancers; cervical intraepithelial neoplasia, vulvar intraepithelial
neoplasia, vaginal intraepithelial neoplasia, or anal
intraepithelial neoplasia.
GARDASIL has not been demonstrated to protect against disease
due to HPV types not contained in the vaccine.
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 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.
HPV testing
HPV testing can identify women with high-risk HPV infections
that can cause cervical cancer. These tests enable diagnosis and
treatment to be under taken before cervical cancer develops. The
digene HPV Test is approved in Europe and FDA approved in the
United States where it is used as a screening test. In the United
States, it is approved to be used together with a Pap test in women
30 years and older. In Europe, it is CE marked and 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 help ensure that HPV testing can reach women in all regions
of the world, QIAGEN has developed the careHPV Test, a portable HPV
DNA test for public-health programs in low-resource countries that
can be run in settings with no main electricity or running water
and can provide same-day test results. The careHPV test is
CE-marked and pending WHO prequalification. The cervical cancer
prevention collaboration with Merck will include donations of both
the digene HPV Test and the careHPV Test.
HPV and cervical cancer
HPV is a widespread virus that is transmitted through sexual
contact. For most, HPV will clear on its own. However, for those
who don't clear certain types, HPV can cause cervical, vaginal and
vulvar cancers in women and anal cancer and genital warts in men
and women. There is no way to predict who will or will not clear
the virus.
Cervical cancer is estimated to develop in approximately 500,000
women annually around the world. After breast cancer, cervical
cancer is considered the second most common malignancy found in
women. The World Health Organization estimates that only about five
percent of women in the developing world have been screened for
cervical disease in the previous five years compared to 75 percent
in the developed world.
Other Merck and QIAGEN access efforts in the developing
world
Merck is pursuing a systematic and thoughtful approach to
improve 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 million doses of GARDASIL through the
GARDASIL® Access Program, which is enabling organizations and
institutions in eligible lowest income countries to gain
operational experience designing and implementing HPV vaccination
projects.
The collaboration between Merck and QIAGEN represents a new
commitment and approach that is in addition to, and distinct from,
the charitable GARDASIL® Access Program.
QIAGEN is working to improve access to cervical cancer screening
through its QIAGENcares corporate social responsibility program.
Through the QIAGENcares program, QIAGEN is developing the rapid,
portable careHPV Test for low-resource settings and health clinics
in the developing world and has committed to donating 1.5 million
HPV tests to developing countries with the aim of expanding access
to cervical cancer screening in areas with the highest disease
burden. In addition to its donation to Rwanda, QIAGEN currently
provides HPV tests to programs in China and India.
About the Government of Rwanda
Visit www.moh.gov.rw
About Merck
Today's Merck is a global healthcare leader working to help the
world be well. Merck is known as MSD outside the United States and
Canada. Through our prescription medicines, vaccines, biologic
therapies, and consumer care and animal health products, we work
with customers and operate in more than 140 countries to deliver
innovative health solutions. We also demonstrate our commitment to
increasing access to healthcare through far-reaching policies,
programs and partnerships. For more information, visit
www.merck.com.
About QIAGEN
QIAGEN N.V., 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 bio-molecules visible. QIAGEN has
developed and markets more than 500 sample and assay 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 a "gold standard" in testing
for high-risk types of human papillomavirus (HPV), the primary
cause of cervical cancer, as well as a broad suite of solutions for
infectious disease testing and companion diagnostics. QIAGEN
employs nearly 3,600 people in over 30 locations worldwide. Further
information about QIAGEN can be found at www.QIAGEN.com.
Merck's Forward-Looking Statement
This news release includes “forward-looking statements” within
the meaning of the safe harbor provisions of the United States
Private Securities Litigation Reform Act of 1995. Such statements
may include, but are not limited to, statements about the benefits
of the merger between Merck and Schering-Plough, including future
financial and operating results, the combined company’s plans,
objectives, expectations and intentions and other statements that
are not historical facts. Such statements are based upon the
current beliefs and expectations of Merck’s management and are
subject to significant risks and uncertainties. Actual results may
differ from those set forth in the forward-looking statements.
The following factors, among others, could cause actual results
to differ from those set forth in the forward-looking statements:
the possibility that the expected synergies from the merger of
Merck and Schering-Plough will not be realized, or will not be
realized within the expected time period; the impact of
pharmaceutical industry regulation and health care legislation; the
risk that the businesses will not be integrated successfully;
disruption from the merger making it more difficult to maintain
business and operational relationships; Merck’s ability to
accurately predict future market conditions; dependence on the
effectiveness of Merck’s patents and other protections for
innovative products; the risk of new and changing regulation and
health policies in the United States and internationally and the
exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause
results to differ materially from those described in the
forward-looking statements can be found in Merck’s 2010 Annual
Report on Form 10-K and the company’s other filings with the
Securities and Exchange Commission (SEC) available at the SEC’s
Internet site (www.sec.gov).
Prescribing Information and Patient Product Information for
GARDASIL® are attached and available at
http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf
and
http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_ppi.pdf
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9883616
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese 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 injectionInitial U.S. Approval: 2006
RECENT MAJOR CHANGES
Indications and Usage (1) Girls and Women (1.1)
12/2010 Boys and Men (1.2) 12/2010 Limitations of GARDASIL Use and
Effectiveness (1.3) 04/2011
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, 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
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. (1)
Limitations of GARDASIL Use and Effectiveness:
- GARDASIL does not eliminate the
necessity for women to continue to undergo recommended cervical
cancer screening. (1.3) (17)
- Recipients of GARDASIL should not
discontinue anal cancer screening if it has been recommended by a
health care provider. (1.3) (17)
- GARDASIL has not been demonstrated to
provide protection against disease from vaccine and non-vaccine HPV
types to which a person has previously been exposed through sexual
activity. (1.3) (14.4) (14.5)
- 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. (1.3)
- GARDASIL has not been demonstrated to
protect against diseases due to HPV types not contained in the
vaccine. (1.3) (14.4) (14.5)
- 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.
(1.3)
- GARDASIL does not protect against
genital diseases not caused by HPV. (1.3)
- Vaccination with GARDASIL may not
result in protection in all vaccine recipients. (1.3)
- GARDASIL has not been demonstrated to
prevent HPV-related CIN 2/3 or worse in women older than 26 years
of age. (14.7)
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. (4) (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. (5.1)
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 Sharp
& Dohme Corp., a subsidiary of 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) or with Menactra and Adacel. (7.2)
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 Sharp & Dohme Corp., a
subsidiary of Merck & Co., Inc., can monitor maternal and fetal
outcomes. (8.1)
- Children below the age of 9 years.
(8.4)
- Immunocompromised individuals. Response
to GARDASIL may be diminished. (8.6)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved
patient labeling.
Revised: 04/2011
FULL PRESCRIBING INFORMATION:
CONTENTS*
1
INDICATIONS AND USAGE
1.1 Girls and Women 1.2 Boys and Men 1.3 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 Postmarketing Experience
7
DRUG INTERACTIONS
7.1 Use with RECOMBIVAX HB 7.2 Use with Menactra and Adacel 7.3 Use
with Hormonal Contraceptives 7.4 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 Girls
and Women 16 Through 26 Years of Age 14.2 Prophylactic Efficacy –
HPV Types 6, 11, 16, and 18 in Boys and Men 16 Through 26 Years of
Age
14.3 Prophylactic Efficacy – Anal Disease
Caused by HPV Types 6, 11,
16, and 18 in Boys and Men 16 Through 26 Years of Age in the MSM
Sub-study
14.4 Population Impact in Girls and Women 16 Through 26 Years of
Age 14.5 Population Impact in Boys and Men 16 Through 26 Years of
Age 14.6 Overall Population Impact 14.7 Studies in Women 27 Through
45 Years of Age 14.8 Immunogenicity 14.9 Studies with RECOMBIVAX HB
[hepatitis B vaccine (recombinant)]
14.10 Studies 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)]
16
HOW SUPPLIED/STORAGE AND
HANDLING
17
PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing
information are not listed.
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Girls and Women
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, 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
1.2 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
1.3 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 Counseling
Information (17).]
Recipients of GARDASIL should not discontinue anal cancer
screening if it has been recommended by a health care provider.
[See Patient Counseling Information (17).]
GARDASIL has not been demonstrated to provide protection against
disease from vaccine and non-vaccine HPV types to which a person
has previously been exposed through sexual activity. [See Clinical
Studies (14.4, 14.5).]
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 (14.4, 14.5).]
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 (14.7).]
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 (14.8).]
2.2 Method of Administration
For intramuscular use only.
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.
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
This package does not contain 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 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 1Injection-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)%
SalinePlacebo(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 2Injection-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)%
SalinePlacebo(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 3Postdose Evaluation of
Injection-Site Adverse Reactions in Girls and Women 9 Through 26
Years of Age(1 to 5 Days Postvaccination)
GARDASIL(% occurrence)
AAHS Control*(% occurrence)
Saline Placebo(% occurrence)
AdverseReaction
Post-dose1N** =5011
Post-dose2N = 4924
Post-dose3N = 4818
Post-dose1N = 3410
Post-dose2N = 3351
Post-dose3N = 3295
Post-dose1N = 315
Post-dose2N = 301
Post-dose3N = 300
PainMild/ModerateSevere
63.462.50.9
60.759.71.0
62.761.21.5
57.056.60.4
47.847.30.5
49.648.90.6
33.733.30.3
20.320.30.0
27.327.00.3
Swelling***Mild/ModerateSevere
10.29.60.6
12.811.90.8
15.114.20.9
8.28.10.2
7.57.20.2
7.67.30.2
4.44.40.0
3.03.00.0
3.33.30.0
Erythema***Mild/ModerateSevere
9.29.00.2
12.111.70.3
14.714.30.4
9.89.50.3
8.48.40.1
8.98.80.1
7.37.30.0
5.35.30.0
5.75.70.0
*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 4Postdose Evaluation of
Injection-Site Adverse Reactions in Boys and Men 9 Through 26 Years
of Age(1 to 5 Days Postvaccination)
GARDASIL(% occurrence)
AAHS Control*(% occurrence)
Saline Placebo(% occurrence)
AdverseReaction
Post-dose1N** =3003
Post-dose2N = 2898
Post-dose3N = 2826
Post-dose1N = 1950
Post-dose2N = 1854
Post-dose3N = 1799
Post-dose1N = 269
Post-dose2N = 263
Post-dose3N = 259
PainMild/ModerateSevere
44.744.50.2
36.936.40.5
34.434.10.3
38.437.90.4
28.228.20.1
25.825.50.3
27.527.50.0
20.520.20.4
16.216.20.0
Swelling***Mild/ModerateSevere
5.65.30.2
6.66.20.3
7.77.10.5
5.65.40.2
4.54.50.0
4.14.00.1
4.84.80.0
1.51.50.0
3.53.10.4
Erythema***Mild/ModerateSevere
7.26.80.3
8.07.70.2
8.78.30.3
8.38.00.2
6.36.20.1
5.75.60.1
7.17.10.0
5.75.70.0
5.05.00.0
*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 5Common Systemic Adverse
Reactions in Girls and Women 9 Through 26 Years of
Age(GARDASIL ≥Control)*
Adverse Reactions(1 to 15 Days
Postvaccination)
GARDASIL(N = 5088)%
AAHS Control** or
SalinePlacebo(N = 3790)%
PyrexiaNauseaDizzinessDiarrheaVomitingCoughToothacheUpper
respiratory tract infectionMalaiseArthralgiaInsomniaNasal
congestion
13.06.74.03.62.42.01.51.51.41.21.21.1
11.26.53.73.51.91.51.41.51.20.90.90.9
* 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 6Common Systemic Adverse
Reactions in Boys and Men 9 Through 26 Years of Age(GARDASIL
≥Control)*
Adverse Reactions(1 to 15 Days
Postvaccination)
GARDASIL(N = 3093)%
AAHS Control** or
SalinePlacebo(N = 2303)%
HeadachePyrexiaOropharyngeal
painDiarrheaNasopharyngitisNauseaUpper respiratory tract
infectionAbdominal pain upperMyalgiaDizzinessVomiting
12.38.32.82.72.62.01.51.41.31.21.0
11.26.52.12.22.61.01.01.40.70.90.8
*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 7Postdose Evaluation of
Fever in Girls and Women 9 Through 26 Years of Age(1 to 5
Days Postvaccination)
GARDASIL(% occurrence)
AAHS Control* or Saline Placebo(%
occurrence)
Temperature(°F)
Postdose 1N** = 4945
Postdose 2N = 4804
Postdose 3N = 4671
Postdose 1N = 3681
Postdose 2N = 3564
Postdose 3N = 3467
≥100 to
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