Indications
Cervarix® is indicated for the prevention of the following diseases caused by oncogenic human papillomavirus (HPV) types 16 and 18 [see Clinical Studies (14)]:
- cervical cancer,
- cervical intraepithelial neoplasia (CIN) grade 2 or worse and adenocarcinoma in situ, and
- cervical intraepithelial neoplasia (CIN) grade 1.
Cervarix is approved for use in females 10 through 25 years of age.
Limitations of Use and Effectiveness
Cervarix does not provide protection against disease due to all HPV types [see Clinical Studies (14.3)].
Cervarix 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)].
Females should continue to adhere to recommended cervical cancer screening procedures [see Patient Counseling Information (17)].
Vaccination with Cervarix may not result in protection in all vaccine recipients.
Cervarix Dosage and Administration
Preparation for Administration
Shake vial or syringe well before withdrawal and use. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered. With thorough agitation, Cervarix is a homogeneous, turbid, white suspension. Do not administer if it appears otherwise.
Dose and Schedule
Immunization with Cervarix consists of 3 doses of 0.5-mL each, by intramuscular injection according to the following schedule: 0, 1, and 6 months. The preferred site of administration is the deltoid region of the upper arm.
Do not administer this product intravenously, intradermally, or subcutaneously.
Dosage Forms and Strengths
Cervarix is a suspension for intramuscular injection available in 0.5-mL single-dose vials and prefilled TIP-LOK® syringes.
Contraindications
Severe allergic reactions (e.g., anaphylaxis) to any component of Cervarix [see Description (11)].
Warnings and Precautions
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 Cervarix. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion by maintaining a supine or Trendelenburg position.
Latex
The tip cap and the rubber plunger of the needleless prefilled syringes contain dry natural latex rubber that may cause allergic reactions in latex sensitive individuals. The vial stopper does not contain latex.
Preventing and Managing Allergic Vaccine Reactions
Prior to administration, the healthcare provider should review the immunization history for possible vaccine hypersensitivity and previous vaccination-related adverse reactions to allow an assessment of benefits and risks. Appropriate medical treatment and supervision should be readily available in case of anaphylactic reactions following administration of Cervarix.
Adverse Reactions
The most common local adverse reactions (≥20% of subjects) were pain, redness, and swelling at the injection site.
The most common general adverse events (≥20% of subjects) were fatigue, headache, myalgia, gastrointestinal symptoms, and arthralgia.
Clinical Studies 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 with rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. There is the possibility that broad use of Cervarix could reveal adverse reactions not observed in clinical trials.
Studies in Females 10 Through 25 Years of Age: The safety of Cervarix was evaluated by pooling data from controlled and uncontrolled clinical trials involving 23,713 females 10 through 25 years of age in the pre-licensure clinical development program. In these studies, 12,785 females (10 through 25 years of age) received at least one dose of Cervarix and 10,928 females received at least one dose of a control [Hepatitis A Vaccine containing 360 EL.U. (10 through 14 years of age), Hepatitis A Vaccine containing 720 EL.U. (15 through 25 years of age), or Al(OH)3 (500 mcg, 15 through 25 years of age)].
Data on solicited local and general adverse events were collected by subjects or parents using standardized diary cards for 7 consecutive days following each vaccine dose (i.e., day of vaccination and the next 6 days). Unsolicited adverse events were recorded with diary cards for 30 days following each vaccination (day of vaccination and 29 subsequent days). Parents and/or subjects were also asked at each study visit about the occurrence of any adverse events and instructed to immediately report serious adverse events throughout the study period. These studies were conducted in North America, Latin America, Europe, Asia, and Australia. Overall, the majority of subjects were white (59%), followed by Asian (26%), Hispanic (9%), black (3%), and other racial/ethnic groups (3%).
Solicited Adverse Events: The reported frequencies of solicited local injection site reactions (pain, redness, and swelling) and general adverse events (fatigue, fever, gastrointestinal symptoms, headache, arthralgia, myalgia, and urticaria) within 7 days after vaccination in females 10 through 25 years of age are presented in Table 1. An analysis of solicited local injection site reactions by dose is presented in Table 2. Local reactions were reported more frequently with Cervarix when compared with the control groups; in ≥84% of recipients of Cervarix, these local reactions were mild to moderate in intensity. Compared with dose 1, pain was reported less frequently after doses 2 and 3 of Cervarix, in contrast to redness and swelling where there was a small increased incidence. There was no increase in the frequency of general adverse events with successive doses.
Table 1. Rates of Solicited Local Adverse Reactions and General Adverse Events in Females 10 Through 25 Years of Age Within 7 Days of Vaccination (Total Vaccinated Cohorta)
| Adverse Reaction/Event |
Cervarix
(10-25 yrs)
% |
HAV 720b
(15-25 yrs)
% |
HAV 360c
(10-14 yrs)
% |
Al(OH)3
Controld
(15-25 yrs)
% |
| Local Adverse Reaction |
N = 6,431 |
N = 3,079 |
N = 1,027 |
N = 549 |
| Pain |
91.8 |
78.0 |
64.2 |
87.2 |
| Redness |
48.0 |
27.6 |
25.2 |
24.4 |
| Swelling |
44.1 |
19.8 |
17.3 |
21.3 |
| General Adverse Event |
N = 6,432 |
N = 3,079 |
N = 1,027 |
N = 549 |
| Fatigue |
55.0 |
53.7 |
42.3 |
53.6 |
| Headache |
53.4 |
51.3 |
45.2 |
61.4 |
| GIe |
27.8 |
27.3 |
24.6 |
32.8 |
| Fever (≥99.5°F) |
12.8 |
10.9 |
16.0 |
13.5 |
| Rash |
9.6 |
8.4 |
6.7 |
10.0 |
|
N = 5,881 |
N = 3,079 |
N = 1,027 |
— |
| Myalgiaf |
49.1 |
44.9 |
33.1 |
— |
| Arthralgiaf |
20.8 |
17.9 |
19.9 |
— |
| Urticariaf |
7.4 |
7.9 |
5.4 |
— |
aTotal vaccinated cohort included subjects with at least one documented dose (N).
bHAV 720 = Hepatitis A Vaccine control group [720 EL.U. of antigen and 500 mcg Al(OH)3].
cHAV 360 = Hepatitis A Vaccine control group [360 EL.U. of antigen and 250 mcg of Al(OH)3].
dAl(OH)3 Control = control containing 500 mcg Al(OH)3.
eGI = Gastrointestinal symptoms, including nausea, vomiting, diarrhea, and/or abdominal pain.
fAdverse events solicited in a subset of subjects.
Table 2. Rates of Solicited Local Adverse Reactions in Females 10 Through 25 Years of Age by Dose Within 7 Days of Vaccination (Total Vaccinated Cohorta)
| Adverse Reaction |
Cervarix
(10-25 yrs)
% |
HAV 720b
(15-25 yrs)
% |
HAV 360c
(10-14 yrs)
% |
Al(OH)3
Controld
(15-25 yrs)
% |
|
Post-Dose |
Post-Dose |
Post-Dose |
Post-Dose |
|
1 |
2 |
3 |
1 |
2 |
3 |
1 |
2 |
3 |
1 |
2 |
3 |
| N |
6,415 |
6,197 |
5,936 |
3,070 |
2,919 |
2,758 |
1,027 |
1,021 |
1,011 |
546 |
521 |
500 |
| Pain |
86.9 |
76.2 |
78.7 |
65.6 |
54.4 |
56.1 |
48.5 |
38.5 |
36.9 |
79.1 |
66.8 |
72.4 |
| Pain, Grade 3e |
7.5 |
5.7 |
7.7 |
2.0 |
1.4 |
2.0 |
0.8 |
0.2 |
1.6 |
9.0 |
6.0 |
8.6 |
| Redness |
27.8 |
29.6 |
35.6 |
16.6 |
15.2 |
16.1 |
15.6 |
13.3 |
12.1 |
11.5 |
11.5 |
15.6 |
| Redness, >50 mm |
0.2 |
0.5 |
1.0 |
0.1 |
0.1 |
0.0 |
0.1 |
0.2 |
0.1 |
0.2 |
0.0 |
0.0 |
| Swelling |
22.7 |
25.2 |
32.7 |
10.5 |
9.4 |
10.5 |
9.4 |
8.6 |
7.6 |
10.3 |
10.4 |
12.0 |
| Swelling, >50 mm |
1.2 |
1.0 |
1.3 |
0.2 |
0.2 |
0.2 |
0.4 |
0.3 |
0.0 |
0.0 |
0.0 |
0.0 |
aTotal vaccinated cohort included subjects with at least one documented dose (N).
bHAV 720 = Hepatitis A Vaccine control group [720 EL.U. of antigen and 500 mcg Al(OH)3].
cHAV 360 = Hepatitis A Vaccine control group [360 EL.U. of antigen and 250 mcg of Al(OH)3].
dAl(OH)3 Control = control containing 500 mcg Al(OH)3.
eDefined as spontaneously painful or pain that prevented normal daily activities.
The pattern of solicited local adverse reactions and general adverse events following administration of Cervarix was similar between the age cohorts (10 through 14 years and 15 through 25 years).
Unsolicited Adverse Events: The frequency of unsolicited adverse events that occurred within 30 days of vaccination (≥1% for Cervarix and greater than any of the control groups) in females 10 through 25 years of age are presented in Table 3.
Table 3. Rates of Unsolicited Adverse Events in Females 10 Through 25 Years of Age Within 30 Days of Vaccination (≥1% For Cervarix and Greater Than HAV 720, HAV 360, or Al(OH)3 Control) (Total Vaccinated Cohorta)
| Adverse Event |
Cervarix
%
(N = 6,654) |
HAV 720b
%
(N = 3,186) |
HAV 360c
%
(N = 1,032) |
Al(OH)3 Controld
%
(N = 581) |
| Headache |
5.3 |
7.6 |
3.3 |
9.3 |
| Nasopharyngitis |
3.6 |
3.4 |
5.9 |
3.3 |
| Influenza |
3.2 |
5.6 |
1.3 |
1.9 |
| Pharyngolaryngeal pain |
2.9 |
2.7 |
2.2 |
2.2 |
| Dizziness |
2.2 |
2.6 |
1.5 |
3.1 |
| Upper respiratory infection |
2.0 |
1.3 |
6.7 |
1.5 |
| Chlamydia infection |
2.0 |
4.4 |
0.0 |
0.0 |
| Dysmenorrhea |
2.0 |
2.3 |
1.9 |
4.0 |
| Pharyngitis |
1.5 |
1.8 |
2.2 |
0.5 |
| Injection site bruising |
1.4 |
1.8 |
0.7 |
1.5 |
| Vaginal infection |
1.4 |
2.2 |
0.1 |
0.9 |
| Injection site pruritus |
1.3 |
0.5 |
0.6 |
0.2 |
| Back pain |
1.1 |
1.3 |
0.7 |
3.1 |
| Urinary tract infection |
1.0 |
1.4 |
0.3 |
1.2 |
aTotal vaccinated cohort included subjects with at least one dose administered (N).
bHAV 720 = Hepatitis A Vaccine control group [720 EL.U. of antigen and 500 mcg Al(OH)3].
cHAV 360 = Hepatitis A Vaccine control group [360 EL.U. of antigen and 250 mcg of Al(OH)3].
dAl(OH)3 Control = control containing 500 mcg Al(OH)3.
New Onset Autoimmune Diseases (NOADs): The pooled safety database, which included controlled and uncontrolled trials which enrolled females 10 through 25 years of age, was searched for new medical conditions indicative of potential new onset autoimmune diseases. Overall, the incidence of potential NOADs, as well as NOADs, in the group receiving Cervarix was 0.8% (95/12,533) and comparable to the pooled control group (0.8%, 87/10,730) during the 4.3 years of follow-up (mean 3.0 years) (Table 4).
In the largest randomized, controlled trial (Study 2) which enrolled females 15 through 25 years of age and which included active surveillance for potential NOADs, the incidence of potential NOADs and NOADs was 0.8% among subjects who received Cervarix (78/9,319) and 0.8% among subjects who received Hepatitis A Vaccine [720 EL.U. of antigen and 500 mcg Al(OH)3] control (77/9,325).
Table 4. Incidence of New Medical Conditions Indicative of Potential New Onset Autoimmune Disease and New Onset Autoimmune Disease Throughout the Follow-up Period Regardless of Causality in Females 10 Through 25 Years of Age (Total Vaccinated Cohorta)
|
Cervarix
(N = 12,533) |
Pooled Control Groupb
(N = 10,730) |
|
n (%)c |
n (%)c |
| Total Number of Subjects With at Least One Medical Condition |
95 (0.8) |
87 (0.8) |
| Arthritisd |
9 (0.1) |
4 (0.0) |
| Celiac disease |
2 (0.0) |
5 (0.0) |
| Dermatomyositis |
0 (0.0) |
1 (0.0) |
| Diabetes mellitus insulin-dependent (Type 1 or unspecified) |
5 (0.0) |
5 (0.0) |
| Erythema nodosum |
3 (0.0) |
0 (0.0) |
| Hyperthyroidisme |
14 (0.1) |
15 (0.1) |
| Hypothyroidismf |
30 (0.2) |
28 (0.3) |
| Inflammatory bowel diseaseg |
8 (0.1) |
4 (0.0) |
| Multiple sclerosis |
4 (0.0) |
1 (0.0) |
| Myelitis transverse |
1 (0.0) |
0 (0.0) |
| Optic neuritis/Optic neuritis retrobulbar |
3 (0.0) |
1 (0.0) |
| Psoriasish |
8 (0.1) |
11 (0.1) |
| Raynaud’s phenomenon |
0 (0.0) |
1 (0.0) |
| Rheumatoid arthritis |
4 (0.0) |
3 (0.0) |
| Systemic lupus erythematosusi |
2 (0.0) |
3 (0.0) |
| Thrombocytopeniaj |
1 (0.0) |
1 (0.0) |
| Vasculitisk |
1 (0.0) |
3 (0.0) |
| Vitiligo |
2 (0.0) |
2 (0.0) |
aTotal vaccinated cohort included subjects with at least one documented dose (N).
bPooled Control Group = Hepatitis A Vaccine control group [720 EL.U. of antigen and 500 mcg Al(OH)3], Hepatitis A Vaccine control group [360 EL.U. of antigen and 250 mcg of Al(OH)3], and a control containing 500 mcg Al(OH)3.
cn (%): number and percentage of subjects with medical condition.
dTerm includes reactive arthritis and arthritis.
eTerm includes Basedow's disease, goiter, and hyperthyroidism.
fTerm includes thyroiditis, autoimmune thyroiditis, and hypothyroidism.
gTerm includes colitis ulcerative, Crohn's disease, proctitis ulcerative, and inflammatory bowel disease.
hTerm includes psoriatic arthropathy, nail psoriasis, guttate psoriasis, and psoriasis.
iTerm includes systemic lupus erythematosus and cutaneous lupus erythematosus.
jTerm includes idiopathic thrombocytopenic purpura and thrombocytopenia.
kTerm includes leukocytoclastic vasculitis and vasculitis.
Serious Adverse Events: In the pooled safety database, inclusive of controlled and uncontrolled studies, which enrolled females 10 through 72 years of age, 5.3% (862/16,142) of subjects who received Cervarix and 5.9% (814/13,811) of subjects who received control reported at least one serious adverse event, without regard to causality, during the entire follow-up period (up to 7.4 years).
Among females 10 through 25 years of age enrolled in these clinical studies, 6.4% of subjects who received Cervarix and 7.2% of subjects who received the control reported at least one serious adverse event during the entire follow-up period (up to 7.4 years).
Deaths: In completed and ongoing studies which enrolled 57,323 females 9 through 72 years of age, 37 deaths were reported during the 7.4 years of follow-up: 20 in subjects who received Cervarix (0.06%, 20/33,623) and 17 in subjects who received control (0.07%, 17/23,700). Causes of death among subjects were consistent with those reported in adolescent and adult female populations. The most common causes of death were motor vehicle accident (5 subjects who received Cervarix; 5 subjects who received control) and suicide (2 subjects who received Cervarix; 5 subjects who received control), followed by neoplasm (3 subjects who received Cervarix; 2 subjects who received control), autoimmune disease (3 subjects who received Cervarix; 1 subject who received control), infectious disease (3 subjects who received Cervarix; 1 subject who received control), homicide (2 subjects who received Cervarix; 1 subject who received control), cardiovascular disorders (2 subjects who received Cervarix), and death of unknown cause (2 subjects who received control). Among females 10 through 25 years of age, 31 deaths were reported (0.05%, 16/29,467 of subjects who received Cervarix and 0.07%, 15/20,192 of subjects who received control.
Postmarketing Experience
In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for Cervarix since market introduction (2007) are listed below. This list includes serious events or events which have suspected causal association to Cervarix. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccination.
Blood and Lymphatic System Disorders: Lymphadenopathy.
Immune System Disorders: Allergic reactions (including anaphylactic and anaphylactoid reactions), angioedema, erythema multiforme.
Nervous System Disorders: Syncope or vasovagal responses to injection (sometimes accompanied by tonic-clonic movements).
Drug Interactions
Concomitant Vaccine Administration
There are no data to assess the concomitant use of Cervarix with other vaccines.
Do not mix Cervarix with any other vaccine in the same syringe or vial.
Hormonal Contraceptives
Among 7,693 subjects 15 through 25 years of age in Study 2 (Cervarix, N = 3,821 or Hepatitis A Vaccine 720 EL.U., N = 3,872) who used hormonal contraceptives for a mean of 2.8 years, the observed efficacy of Cervarix was similar to that observed among subjects who did not report use of hormonal contraceptives.
Immunosuppressive Therapies
Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to Cervarix [see Use in Specific Populations (8.6)].
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category B
Reproduction studies have been performed in rats at a dose approximately 47 times the human dose (on a mg/kg basis) and revealed no evidence of impaired fertility or harm to the fetus due to Cervarix. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Non-Clinical Studies: An evaluation of the effect of Cervarix on embryo-fetal, pre- and post-natal development was conducted using rats. One group of rats was administered Cervarix 30 days prior to gestation and during the period of organogenesis (gestation days 6, 8, 11, and 15). A second group of rats was administered saline at 30 days prior to gestation followed by Cervarix on days 6, 8, 11, and 15 of gestation. Two additional groups of rats received either saline or adjuvant following the same dosing regimen. Cervarix was administered at 0.1 mL/rat/occasion (approximately 47-fold excess relative to the projected human dose on a mg/kg basis) by intramuscular injection. No adverse effects on mating, fertility, pregnancy, parturition, lactation, or embryo-fetal, pre- and post-natal development were observed. There were no vaccine-related fetal malformations or other evidence of teratogenesis.
Clinical Studies: Overall Outcomes: In clinical studies, pregnancy testing was performed prior to each vaccine administration and vaccination was discontinued if a subject had a positive pregnancy test. In all clinical trials, subjects were instructed to take precautions to avoid pregnancy until 2 months after the last vaccination. During pre-licensure clinical development, a total of 7,276 pregnancies were reported among 3,696 females receiving Cervarix and 3,580 females receiving a control (Hepatitis A Vaccine 360 EL.U., Hepatitis A Vaccine 720 EL.U., or 500 mcg Al(OH)3). The overall proportions of pregnancy outcomes were similar between treatment groups. The majority of women gave birth to normal infants (62.2% and 62.6% of recipients of Cervarix and control, respectively). Other outcomes included spontaneous abortion (11.0% and 10.8% of recipients of Cervarix and control, respectively), elective termination (5.8% and 6.1% of recipients of Cervarix and control, respectively), abnormal infant other than congenital anomaly (2.8% and 3.2% of recipients of Cervarix and control, respectively), and premature birth (2.0% and 1.7% of recipients of Cervarix and control, respectively). Other outcomes (congenital anomaly, stillbirth, ectopic pregnancy, and therapeutic abortion) were reported less frequently in 0.1% to 0.8% of pregnancies in both groups.
Outcomes Around Time of Vaccination: Sub-analyses were conducted to describe pregnancy outcomes in 761 women [N = 396 for Cervarix and N = 365 pooled control, HAV 360 EL.U., HAV 720 EL.U., and 500 mcg Al(OH)3] who had their last menstrual period within 30 days prior to, or 45 days after a vaccine dose and for whom pregnancy outcome was known. The majority of women gave birth to normal infants (65.2% and 69.3% of recipients of Cervarix and control, respectively). Spontaneous abortion was reported in a total of 11.7% of subjects (13.6% of recipients of Cervarix and 9.6% of control recipients) and elective termination was reported in a total of 9.7% of subjects (9.9% of recipients of Cervarix and 9.6% of control recipients). Abnormal infant other than congenital anomaly was reported in a total of 4.9% of subjects (5.1% of recipients of Cervarix and 4.7% of control recipients) and premature birth was reported in a total of 2.5% of subjects (2.5% of both groups). Other outcomes (congenital anomaly, stillbirth, ectopic pregnancy, and therapeutic abortion) were reported in 0.3% to 1.8% of pregnancies among recipients of Cervarix and in 0.3% to 1.4% of pregnancies among control recipients.
It is not known whether the observed numerical imbalance in spontaneous abortions in pregnancies which occurred around the time of vaccination is due to a vaccine-related effect.
Pregnancy Registry: GlaxoSmithKline maintains a surveillance registry to collect data on pregnancy outcomes and newborn health status outcomes following vaccination with Cervarix during pregnancy. Women who receive Cervarix during pregnancy should be encouraged to contact GlaxoSmithKline directly or their healthcare provider should contact GlaxoSmithKline by calling 1-888-452-9622.
Nursing Mothers
In non-clinical studies in rats, serological data suggest a transfer of anti-HPV-16 and anti-HPV-18 antibodies via milk during lactation in rats. Excretion of vaccine-induced antibodies in human milk has not been studied for Cervarix. Because many drugs are excreted in human milk, caution should be exercised when Cervarix is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients younger than 10 years of age have not been established. The safety and effectiveness of Cervarix have been evaluated in 1,193 subjects 10 through 14 years of age and 6,316 subjects 15 through 17 years of age. [See Adverse Reactions (6.1) and Clinical Studies (14.5).]
Geriatric Use
Clinical studies of Cervarix did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects. Cervarix is not approved for use in subjects 65 years of age and older.
Immunocompromised Individuals
The immune response to Cervarix may be diminished in immunocompromised individuals [see Drug Interactions (7.3)].
Cervarix Description
Cervarix [Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant] is a non-infectious recombinant, AS04-adjuvanted vaccine that contains recombinant L1 protein, the major antigenic protein of the capsid, of oncogenic HPV types 16 and 18. The L1 proteins are produced in separate bioreactors using the recombinant Baculovirus expression vector system in a serum-free culture media composed of chemically-defined lipids, vitamins, amino acids, and mineral salts. Following replication of the L1 encoding recombinant Baculovirus in Trichoplusia ni insect cells, the L1 protein accumulates in the cytoplasm of the cells. The L1 proteins are released by cell disruption and purified by a series of chromatographic and filtration methods. Assembly of the L1 proteins into virus-like particles (VLPs) occurs at the end of the purification process. The purified, non-infectious VLPs are then adsorbed on to aluminum (as hydroxide salt). The adjuvant system, AS04, is composed of 3-O-desacyl-4’-monophosphoryl lipid A (MPL) adsorbed on to aluminum (as hydroxide salt).
Cervarix is prepared by combining the adsorbed VLPs of each HPV type together with the AS04 adjuvant system in sodium chloride, sodium dihydrogen phosphate dihydrate, and Water for Injection.
Cervarix is a sterile suspension for intramuscular injection. Each 0.5-mL dose is formulated to contain 20 mcg of HPV type 16 L1 protein, 20 mcg of HPV type 18 L1 protein, 50 mcg of the 3-O-desacyl-4’-monophosphoryl lipid A (MPL), and 0.5 mg of aluminum hydroxide. Each dose also contains 4.4 mg of sodium chloride and 0.624 mg of sodium dihydrogen phosphate dihydrate. Each dose may also contain residual amounts of insect cell and viral protein (<40 ng) and bacterial cell protein (<150 ng) from the manufacturing process. Cervarix does not contain a preservative.
Cervarix - Clinical Pharmacology
Mechanism of Action
Animal studies suggest that the efficacy of L1 VLP vaccines may be mediated by the development of IgG neutralizing antibodies directed against HPV-L1 capsid proteins generated as a result of vaccination.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Cervarix has not been evaluated for its carcinogenic or mutagenic potential. Vaccination of female rats with Cervarix, at doses shown to be significantly immunogenic in the rat, had no effect on fertility.
Clinical Studies
Cervical intraepithelial neoplasia (CIN) grade 2 and 3 lesions or cervical adenocarcinoma in situ (AIS) are the immediate and necessary precur
