- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
|Human Papillomavirus1 type 16 L1 protein2,3,4||20 micrograms|
|Human Papillomavirus1 type 18 L1 protein2,3,4||20 micrograms|
|1Human Papillomavirus = HPV 2adjuvanted by AS04 containing:|
|3-O-desacyl-4'- monophosphoryl lipid A (MPL)3||50 micrograms|
|3adsorbed on aluminium hydroxide, hydrated (Al(OH)3)||0.5 milligrams Al3+ in total|
PosologyThe vaccination schedule depends on the age of the subject.
|Age at the time of the first injection||Immunization and schedule|
|9 to and including 14 years*||Two doses each of 0.5 ml. The second dose given between 5 and 13 months after the first dose|
|From 15 years and above||Three doses each of 0.5 ml at 0, 1, 6 months**|
Paediatric population (children < 9 years of age)Cervarix is not recommended for use in children below 9 years of age due to lack of data on safety and immunogenicity in this age-group.
Method of administrationCervarix is for intramuscular injection in the deltoid region (see also sections 4.4 and 4.5).Cervarix should under no circumstances be administered intravascularly or intradermally. No data are available on subcutaneous administration of Cervarix (see section 4.4).If Cervarix is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites (see section 4.5).
Use with other vaccinesCervarix may be administered concomitantly with a combined booster vaccine containing diphtheria (d), tetanus (T) and pertussis [acellular] (pa) with or without inactivated poliomyelitis (IPV), (dTpa, dTpa-IPV vaccines), with no clinically relevant interference with antibody response to any of the components of either vaccine. The sequential administration of combined dTpa-IPV followed by Cervarix one month later tended to elicit lower anti-HPV-16 and anti-HPV-18 GMTs as compared to Cervarix alone. The clinical relevance of this observation is not known.Cervarix may be administered concomitantly with a combined hepatitis A (inactivated) and hepatitis B (rDNA) vaccine (Twinrix) or with hepatitis B (rDNA) vaccine (Engerix B).Administration of Cervarix at the same time as Twinrix has shown no clinically relevant interference in the antibody response to the HPV and hepatitis A antigens. Anti-HBs geometric mean antibody concentrations were significantly lower on co-administration, but the clinical relevance of this observation is not known since the seroprotection rates remain unaffected. The proportion of subjects reaching anti-HBs ≥ 10mIU/ml was 98.3% for concomitant vaccination and 100% for Twinrix given alone. Similar results were observed when Cervarix was given concomitantly with Engerix B with 97.9% of subjects reaching anti-HBs ≥ 10mIU/ml compared to 100% for Engerix B given alone.If Cervarix is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.
Use with hormonal contraceptiveIn clinical studies, approximately 60% of women who received Cervarix used hormonal contraceptives. There is no evidence that the use of hormonal contraceptives has an impact on the efficacy of Cervarix.
Use with systemic immunosuppressive medicinal productsSee section 4.4.
PregnancySpecific studies of the vaccine in pregnant women were not conducted. Data in pregnant women collected as part of pregnancy registries, epidemiological studies and inadvertent exposure during clinical trials are insufficient to conclude whether or not vaccination with Cervarix affects the risk of adverse pregnancy outcomes including spontaneous abortion.However, during the clinical development program, a total of 10,476 pregnancies were reported including 5,387 in women who had received Cervarix. Overall, the proportions of pregnant subjects who experienced specific outcomes (e.g., normal infant, abnormal infants including congenital anomalies, premature birth, and spontaneous abortion) were similar between treatment groups. Animal studies do not indicate direct or indirect harmful effects with respect to fertility, pregnancy, embryonal/foetal development, parturition or post-natal development (see section 5.3).As a precautionary measure, it is preferable to avoid the use of Cervarix during pregnancy. Women who are pregnant or trying to become pregnant, are advised to postpone or interrupt vaccination until completion of pregnancy.
Breast-feedingThe effect on breast-fed infants of the administration of Cervarix to their mothers has not been evaluated in clinical studies.Cervarix should only be used during breast-feeding when the possible advantages outweigh the possible risks.
FertilityNo fertility data are available.
Summary of safety profileIn clinical studies that enrolled girls and women aged from 10 up to 72 years (of which 79.2% were aged 10-25 years at the time of enrolment), Cervarix was administered to 16,142 females whilst 13,811 females received control. These subjects were followed for serious adverse events over the entire study period. In a pre-defined subset of subjects (Cervarix = 8,130 versus control = 5,786), adverse events were followed for 30 days after each injection. In two clinical studies that enrolled males aged 10 to 18 years, 2,617 males received Cervarix and were followed-up with active safety surveillance.The most common adverse reaction observed after vaccine administration was injection site pain which occurred after 78% of all doses. The majority of these reactions were of mild to moderate severity and were not long lasting.
Tabulated list of adverse reactionsAdverse reactions considered as being at least possibly related to vaccination have been categorised by frequency.Frequencies are reported as:Very common (≥1/10)Common (≥1/100 to <1/10)Uncommon (≥1/1,000 to <1/100)
|System Organ Class||Frequency||Adverse reactions|
|Infections and infestations||Uncommon||Upper respiratory tract infection|
|Nervous system disorders||Very common||Headache|
|Gastrointestinal disorders||Common||Gastrointestinal symptoms including nausea, vomiting, diarrhoea and abdominal pain|
|Skin and subcutaneous tissue disorders||Common||Itching/pruritus, rash, urticaria|
|Musculoskeletal and connective tissue disorders||Very common||Myalgia|
|General disorders and administration site conditions||Very common||Injection site reactions including pain, redness, swelling; fatigue|
|Uncommon||Other injection site reactions such as induration, local paraesthesia|
|Blood and lymphatic system disorders||Not known*||Lymphadenopathy|
|Immune system disorders||Not known*||Allergic reactions (including anaphylactic and anaphylactoid reactions), angioedema|
|Nervous system disorders||Not known*||Syncope or vasovagal responses to injection, sometimes accompanied by tonic-clonic movements (see section 4.4)|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via
IrelandHPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; e-mail: email@example.com
United Kingdomthe Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Mechanism of actionCervarix is an adjuvanted non-infectious recombinant vaccine prepared from the highly purified virus-like particles (VLPs) of the major capsid L1 protein of oncogenic HPV types 16 and 18. Since the VLPs contain no viral DNA, they cannot infect cells, reproduce or cause disease. Animal studies have shown that the efficacy of L1 VLP vaccines is largely mediated by the development of a humoral immune response.HPV-16 and HPV-18 are estimated to be responsible for approximately 70% of cervical cancers, 90% of anal cancers, 70% of HPV-related high grade vulvar and vaginal intraepithelial neoplasia and 78% of HPV related high-grade anal (AIN 2/3) intraepithelial neoplasia.Other oncogenic HPV types can also cause ano-genital cancers (approximately 30%). HPV 45, -31 and -33 are the 3 most common non-vaccine HPV types identified in squamous cervical carcinoma (12.1%) and adenocarcinoma (8.5%).The term premalignant ano-genital lesions in section 4.1 corresponds to high-grade Cervical Intraepithelial Neoplasia (CIN2/3), high-grade vulvar intraepithelial neoplasia (VIN2/3), high-grade vaginal intraepithelial neoplasia (VaIN2/3) and high-grade anal intraepithelial neoplasia (AIN 2/3).
Clinical efficacy in women aged 15 to 25 yearsThe efficacy of Cervarix was assessed in two controlled, double-blind, randomised Phase II and III clinical trials that included a total of 19,778 women aged 15 to 25 years.The phase II trial (study 001/007) enrolled only women who:- Were tested negative for oncogenic HPV DNA of types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68- Were seronegative for HPV-16 and HPV-18 and - Had normal cytologyThe primary efficacy endpoint was incident infection with HPV-16 and/or HPV-18. Twelve-month persistent infection was evaluated as additional efficacy endpoint.The phase III trial (study 008) enrolled women without pre-screening for the presence of HPV infection, i.e. regardless of baseline cytology and HPV serological and DNA status.The primary efficacy endpoint was CIN2+ associated with HPV-16 and/or HPV-18 (HPV-16/18). Cervical Intraepithelial Neoplasia (CIN) grade 2 and 3 (CIN2/3) and cervical adenocarcinoma in situ (AIS) were used in the clinical trials as surrogate markers for cervical cancer.The secondary endpoints included 6- and 12-month persistent infection.Persistent infection that lasts for at least 6 months has also been shown to be a relevant surrogate marker for cervical cancer.
Prophylactic efficacy against HPV-16/18 infection in a population naïve to oncogenic HPV typesWomen (N=1,113) were vaccinated in study 001 and evaluated for efficacy up to month 27. A subset of women (N=776) vaccinated in study 001 was followed in study 007 up to 6.4 years (approximately 77 months) after the first dose (mean follow-up of 5.9 years). There were five cases of 12-month persistent HPV-16/18 infection (4 HPV-16; 1 HPV-18) in the control group and one HPV-16 case in the vaccine group in study 001. In study 007 the efficacy of Cervarix against 12-month persistent HPV-16/18 infection was 100% (95% CI: 80.5; 100). There were sixteen cases of persistent HPV-16 infection, and five cases of persistent HPV-18 infection, all in the control group.In study HPV-023, subjects from the Brazilian cohort (N=437) of study 001/007 were followed up to a mean of 8.9 years (standard deviation 0.4 years) after the first dose. At study completion, there were no cases of infection or histopathological lesions associated with HPV-16 or HPV-18 in the vaccine group in study HPV-023. In the placebo group, there were 4 cases of 6-month persistent infection and 1 case of 12-month persistent infection. The study was not powered to demonstrate a difference between the vaccine and the placebo group for these endpoints.
Prophylactic efficacy against HPV-16/18 in women naïve to HPV-16 and/or HPV-18In study HPV-008, the primary analyses of efficacy were performed on the According to Protocol cohort (ATP cohort: including women who received 3 vaccine doses and were DNA negative and seronegative at month 0 and DNA negative at month 6 for the HPV type considered in the analysis) This cohort included women with normal or low-grade cytology at baseline and excluded only women with high-grade cytology (0.5% of the total population). Case counting for the ATP cohort started on day 1 after the third dose of vaccine.Overall, 74% of women enrolled were naïve to both HPV-16 and HPV-18 (i.e. DNA negative and seronegative at study entry).Two analyses of study HPV-008 have been performed: an event-triggered analysis performed once at least 36 CIN2+ cases associated with HPV-16/18 were accrued in the ATP cohort and an end-of study analysis.Vaccine efficacy against the primary endpoint CIN2+ is presented in Table 1. In a supplemental analysis, the efficacy of Cervarix was evaluated against HPV-16/18-related CIN3+.
Table 1: Vaccine efficacy against high grade cervical lesions associated with HPV-16/18 (ATP cohort)
|HPV-16/18 endpoint||ATP cohort(1)|
|End of study analysis(3)|
|Cervarix(N = 7338)||Control(N = 7305)||% Efficacy (95% CI)|
|N = number of subjects included in each group n = number of cases (1) ATP: includes women who received 3 doses of vaccine, were DNA negative and seronegative at month 0 and DNA negative at month 6 to the relevant HPV type (HPV-16 or HPV-18) (2) including 4 cases of CIN2+ and 2 cases of CIN3+ in which another oncogenic HPV type was identified in the lesion, concomitantly with HPV-16 or HPV-18. These cases are excluded in the HPV type assignment analysis (see under Table). (3) mean follow-up of 40 months post dose 3|
Table 2: Vaccine efficacy against virological endpoints associated with HPV-16/18 (ATP cohort)
|HPV-16/18 endpoint||ATP cohort(1)|
|End of study analysis(2)|
|Cervarix(N = 7338)||Control(N = 7305)||% Efficacy (95% CI)|
|6-month persistent infection||35/7182||588/7137||94.3% (92.0;96.1)|
|12-month persistent infection||26/7082||354/7038||92.9% (89.4;95.4)|
|N = number of subjects included in each group n = number of cases (1) ATP: includes women who received 3 doses of vaccine, were DNA negative and seronegative at month 0 and DNA negative at month 6 to the relevant HPV type (HPV-16 or HPV-18) (2) mean follow-up of 40 months post dose 3|
Efficacy against HPV-16/18 in women with evidence of HPV-16 or HPV-18 infection at study entry.There was no evidence of protection from disease caused by the HPV types for which subjects were HPV DNA positive at study entry. However, individuals already infected (HPV DNA positive) with one of the vaccine-related HPV types prior to vaccination were protected from clinical disease caused by the other vaccine HPV type.
Efficacy against HPV types 16 and 18 in women with and without prior infection or disease.The Total Vaccinated Cohort (TVC) included all subjects who received at least one dose of the vaccine, irrespective of their HPV DNA status, cytology and serostatus at baseline. This cohort included women with or without current and/or prior HPV infection. Case counting for the TVC started on day 1 after the first dose.The efficacy estimates are lower in the TVC as this cohort includes women with pre-existing infections/lesions, which are not expected to be impacted by Cervarix.The TVC may approximate to the general population of women in the age range of 15-25 years.Vaccine efficacy against high grade cervical lesions associated with HPV-16/18 observed in TVC at end of study is presented in Table 3.
Table 3: Vaccine efficacy against high grade cervical lesions associated with HPV-16/18 (TVC)
|End of study analysis(2)|
|Cervarix(N = 8694)||Control(N = 8708)||% Efficacy (95% CI)|
|N = number of subjects included in each group n = number of cases (1) TVC: includes all vaccinated subjects (who received at least one dose of vaccine) irrespective of HPV DNA status, cytology and serostatus at baseline. This cohort includes women with pre-existing infections/lesions (2) mean follow-up of 44 months post dose 1|
|End of study analysis(2)|
|Cervarix||Control||% Efficacy (95% CI)|
|6-month persistent infection||504/8863||1227/8870||60.9% (56.6;64.8)|
|12-month persistent infection||335/8648||767/8671||57.5% (51.7;62.8)|
|N = number of subjects included in each group n = number of cases (1) TVC: includes all vaccinated subjects (who received at least one dose of vaccine) irrespective of HPV DNA status, cytology and serostatus at baseline. (2) mean follow-up of 44 months post dose 1|
Overall impact of the vaccine on cervical HPV disease burdenIn study HPV-008, the incidence of high grade cervical lesions was compared between the placebo and vaccine group irrespective of the HPV DNA type in the lesion. In the TVC and TVC-naïve cohorts, the vaccine's efficacy was demonstrated against high-grade cervical lesions at end of study (Table 5).The TVC-naïve is a subset of the TVC that includes women with normal cytology, and who were HPV DNA negative for 14 oncogenic HPV types and seronegative for HPV-16 and HPV-18 at baseline.
Table 5: Vaccine efficacy against high-grade cervical lesions irrespective of the HPV DNA type in the lesion
|End of study analysis(3)|
|Cervarix||Control||% Efficacy (95% CI)|
|N = number of subjects included in each group (1) TVC naïve: includes all vaccinated subjects (who received at least one dose of vaccine) who had normal cytology, were HPV DNA negative for 14 oncogenic HPV types and seronegative for HPV-16 and HPV-18 at baseline. (2) TVC: includes all vaccinated subjects (who received at least one dose of vaccine) irrespective of HPV DNA status, cytology and serostatus at baseline. (3) mean follow-up of 44 months post dose 1|
Cross-protective efficacyThe cross-protective efficacy of Cervarix against histopathological and virological endpoints (persistent infection) has been evaluated in study HPV-008 for 12 non-vaccine oncogenic HPV types. The study was not powered to assess efficacy against disease caused by individual HPV types. The analysis against the primary endpoint was confounded by multiple co-infections in the CIN2+ lesions. Unlike histopathological endpoints, virological endpoints are less confounded by multiple infections.HPV-31, 33 and 45 showed consistent cross-protection for 6-month persistent infection and CIN2+ endpoints in all study cohorts. End of study vaccine efficacy against 6-month persistent infection and CIN2+ associated with individual non-vaccine oncogenic HPV types is presented in Table 6 (ATP cohort).
Table 6: Vaccine efficacy for non-vaccine oncogenic HPV types
|HPV type||6-month persistent infection||CIN2+|
|Cervarix||Control||% Efficacy (95% CI)||Cervarix||Control||% Efficacy (95% CI)|
|HPV-16 related types (A9 species)|
|HPV-31||58||247||76.8% (69.0;82.9)||5||40||87.5% (68.3;96.1)|
|HPV-33||65||117||44.8% (24.6;59.9)||13||41||68.3% (39.7;84.4)|
|HPV-35||67||56||-19.8% (<0;17.2)||3||8||62.5% (<0;93.6)|
|HPV-52||346||374||8.3% (<0;21.0)||24||33||27.6% (<0;59.1)|
|HPV-58||144||122||-18.3% (<0;7.7)||15||21||28.5% (<0;65.7)|
|HPV-18 related types (A7 species)|
|HPV-39||175||184||4.8% (<0;23.1)||4||16||74.9% (22.3;93.9)|
|HPV-45||24||90||73.6% (58.1;83.9)||2||11||81.9% (17.0;98.1)|
|HPV-59||73||68||-7.5% (<0;23.8)||1||5||80.0% (<0;99.6)|
|HPV-68||165||169||2.6% (<0;21.9)||11||15||26.8% (<0;69.6)|
|HPV-51||349||416||16.6% (3.6;27.9)||21||46||54.4% (22.0;74.2)|
|HPV-56||226||215||-5.3% (<0;13.1)||7||13||46.1% (<0;81.8)|
|HPV-66||211||215||2.3% (<0;19.6)||7||16||56.4% (<0;84.8)|
|n= number of cases (1) ATP: includes women who received 3 doses of vaccine, were DNA negative at month 0 and at month 6 to the relevant HPV type. The limits of the confidence interval around the vaccine efficacy were calculated. When the value zero is included, i.e. when the lower limit of the CI is <0, the efficacy is not considered statistically significant. The efficacy against CIN3 was only demonstrated for HPV-31 and there was no evidence of protection against AIS for any of the HPV types.|
Clinical efficacy in women aged 26 years and olderThe efficacy of Cervarix was assessed in a double-blind, randomised Phase III clinical trial (HPV-015) that included a total of 5777 women aged 26 years and older. The study was conducted in North America, Latin America, Asia Pacific and Europe, and allowed women with previous history of HPV disease/infection to be enrolled. An interim analysis was performed when all subjects had completed the month 48 study visit. The primary analyses of efficacy were performed on the ATP cohort for efficacy and the TVC.Vaccine efficacy against 6 month persistent infection with HPV-16/18 (relevant surrogate marker for cervical cancer) is summarised in the following table.
Table 7: Vaccine efficacy against 6M PI with HPV 16/18 in ATP and TVC
|Cervarix||Control||% Efficacy (97.7% CI)||Cervarix||Control||% Efficacy (97.7% CI)|
|6M PI||6/1859||34/1822||82.9% (53.8; 95.1)||71/2767||132/2776||47% (25.4; 62.7)|
|N= number of subject in each group n= number of subjects reporting at least one event in each group 6M PI = 6-month persistent infection CI = Confidence Interval (1) 3 doses of vaccine, DNA negative and seronegative at month 0 and DNA negative at month 6 for the relevant HPV type (HPV-16 and/or HPV-18) (2) at least one dose of vaccine, irrespective of HPV DNA and serostatus at month 0. Includes 15% of subjects with previous history of HPV disease/infection|
Immune response to Cervarix after the primary vaccination courseNo minimal antibody level associated with protection against CIN of grade 2 or 3 or against persistent infection associated with vaccine HPV types has been identified for HPV vaccines.The antibody response to HPV-16 and HPV-18 was measured using a type-specific direct ELISA (version 2, MedImmune methodology, modified by GSK) which was shown to correlate with the pseudovirion-based neutralisation assay (PBNA). The immunogenicity induced by three doses of Cervarix has been evaluated in 5,465 female subjects from 9 to 55 years of age and over 800 male subjects aged 10 to 18 years.In clinical trials, more than 99% of initially seronegative subjects had seroconverted to both HPV types 16 and 18 one month after the third dose. Vaccine-induced IgG Geometric Mean Titres (GMT) were well above titres observed in women previously infected but who cleared HPV infection (natural infection). Initially seropositive and seronegative subjects reached similar titres after vaccination.
Persistence of Immune Response to CervarixStudy 001/007, which included women from 15 to 25 years of age at the time of vaccination, evaluated the immune response against HPV-16 and HPV-18 up to 76 months after administration of the first vaccine dose. In study 023 (a subset of study 001/007), the immune response continued to be evaluated up to 113 months. 92 subjects in the vaccine group had immunogenicity data at the [M107-M113] interval after the first vaccine dose with a median follow-up of 8.9 years. Of these subjects, 100% (95% CI: 96.1;100) remained seropositive for HPV-16 and HPV-18 in the ELISA assay.Vaccine-induced IgG GMTs for both HPV-16 and HPV-18 peaked at month 7 and then declined to reach a plateau from month 18 up to the [M107-M113] interval with ELISA GMTs for both HPV-16 and HPV-18 at least still 10-fold higher than the ELISA GMTs observed in women who cleared a natural HPV infection.In study 008, immunogenicity up to month 48 was similar to the response observed in study 001. A similar kinetic profile was observed with the neutralising antibodies.In another clinical trial (study 014) performed in women aged 15 to 55 years, all subjects seroconverted to both HPV types 16 and 18 after the third dose (at month 7). The GMTs were, however, lower in women above 25 years. Nevertheless, all subjects remained seropositive for both types throughout the follow-up phase (up to month 18) maintaining antibody levels at an order of magnitude above those encountered after natural infection.
Evidence of Anamnestic (Immune Memory) ResponseIn study 024 (a subset of study 001/007), a challenge dose of Cervarix was administered to 65 subjects at a mean interval of 6.8 years after the administration of the first vaccine dose. An anamnestic immune response to HPV-16 and HPV-18 (by ELISA) was observed one week and one month after the challenge dose, GMTs one month after the challenge dose exceeded those observed one month after the primary 3-dose vaccination.
Bridging the efficacy of Cervarix from young adult women to adolescentsIn a pooled analysis (HPV-029,-30 & -48), 99.7% and 100% of females aged 9 years seroconverted to HPV types 16 and 18, respectively after the third dose (at month 7) with GMTs at least 1.4-fold and 2.4-fold higher as compared to females aged 10-14 years and 15 to 25 years, respectively.In two clinical trials (HPV-012 & -013) performed in girls aged 10 to 14 years, all subjects seroconverted to both HPV types 16 and 18 after the third dose (at month 7) with GMTs at least 2-fold higher as compared to women aged 15 to 25 years.In clinical trials (HPV-070 and HPV-048) performed in girls aged 9 to 14 years receiving a 2-dose schedule (0, 6 months or 0, 12 months) and young women aged 15-25 years receiving Cervarix according to the standard 0, 1, 6 months schedule, all subjects seroconverted to both HPV types 16 and 18 one month after the second dose. The immune response after 2 doses in females aged 9 to 14 years was non-inferior to the response after 3 doses in women aged 15 to 25 years.On the basis of these immunogenicity data, the efficacy of Cervarix is inferred from 9 to 14 years of age.
Immunogenicity in women aged 26 years and olderIn the Phase III study (HPV-015) in women 26 years and older, at the 48-month time point, i.e. 42 months after completion of the full vaccination course, 100% and 99.4% of initially seronegative women remained seropositive for anti-HPV-16 and anti-HPV-18 antibodies, respectively. All initially seropositive women remained seropositive for both anti-HPV-16 and anti-HPV-18 antibodies. Antibody titers peaked at month 7 then gradually declined up to month 18 and stabilized to reach a plateau up to month 48.
Immunogenicity in males aged 10 to 18 yearsImmunogenicity in males was assessed in 2 clinical trials HPV-011 (N=173) and HPV-040 (N=556). The data showed comparable immunogenicity in males and females. In study HPV-011, all subjects seroconverted to both HPV-16 and 18 and GMT levels were non inferior to those observed in females aged 15 to 25 years in study HPV-012.
Bridging of clinical efficacy against anal lesions and cancersNo efficacy study against anal premalignant lesions has been conducted with Cervarix. However, studies conducted in girls aged 9 to 14 years (study HPV-071) and in women aged 18 to 45 years (study HPV-010) have consistently shown a higher immune response with Cervarix than with the comparator for which efficacy data against anal premalignant lesions are conclusive and have shown protection.
Immunogenicity in HIV infected womenIn study HPV-020, conducted in South Africa, 22 HIV uninfected and 42 HIV infected subjects (WHO clinical stage 1; ATP cohort for immunogenicity) received Cervarix. All subjects were seropositive in the ELISA assay to both HPV 16 and 18 one month after the third dose (at Month 7) and the seropositivity for HPV 16 and 18 was maintained up to Month 12. The GMTs appeared to be lower in the HIV infected group (non overlapping 95% confidence interval). The clinical relevance of this observation is unknown. Functional antibodies were not determined. No information exists about protection against persistent infection or precancerous lesions among HIV infected women.
Instructions for administration of the vaccine presented in pre-filled syringe
|1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap by twisting it anticlockwise.|
|2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock. 3. Remove the needle protector, which on occasion can be a little stiff. 4. Administer the vaccine.|
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