Drug Class Description
Viral Vaccine

Generic Name
Papillomavirus

Drug Description
1 dose (0.5 ml) contains:Human Papillomavirus1 type 16 L1 protein2,3,4 20 microgramsHuman Papillomavirus1 type 18 L1 protein2,3,4 20 micrograms1Human Papillomavirus = HPV2adjuvanted by AS04 containing:3-O-desacyl-4'- monophosphoryl lipid A (MPL)3 50 micrograms3adsorbed on aluminium hydroxide, hydrated (Al(OH)3) 0.5 milligrams Al3+ in total4L1 protein in the form of non-infectious virus-like particles (VLPs) produced by recombinant DNA technology using a Baculovirus expression system which uses Hi-5 Rix4446 cells derived from Trichoplusia ni.Suspension for injection in pre-filled syringe.Turbid white suspension. Upon storage, a fine white deposit with a clear colourless supernatant may be observed.

Presentation
Cervarix suspension for injection in pre-filled syringeHuman Papillomavirus vaccine [Types 16, 18] (Recombinant, adjuvanted, adsorbed)

Indications
CERVARIX is indicated for the prevention of high-grade cervical intraepithelial neoplasia (CIN grades 2 and 3) and cervical cancer causally related to Human Papillomavirus (HPV) types 16 and 18. The indication is based on demonstration of efficacy in women aged 15-25 years following vaccination with Cervarix and on the immunogenicity of the vaccine in girls and women aged 10-25 years. The use of Cervarix should be in accordance with official recommendations.

Adult Dosage
The recommended vaccination schedule is 0, 1, 6 months.The need for a booster dose has not been established.It is recommended that subjects who receive a first dose of Cervarix complete the 3-dose vaccination course with Cervarix.Girls aged less than 10 years: Cervarix is not recommended for use in girls below 10 years of age due to lack of data on safety and immunogenicity in this age-group.Cervarix is for intramuscular injection in the deltoid region.

Child Dosage
Girls aged less than 10 years: Cervarix is not recommended for use in girls below 10 years of age due to lack of data on safety and immunogenicity in this age-group.

Contra Indications
Hypersensitivity to the active substances or to any of the excipients.Administration of Cervarix should be postponed in subjects suffering from an acute severe febrile illness. However, the presence of a minor infection, such as a cold, is not a contraindication for immunisation.

Special Precautions
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.Cervarix should under no circumstances be administered intravascularly or intradermally.No data are available on subcutaneous administration of Cervarix.As with other vaccines administered intramuscularly, Cervarix should be given with caution to individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following an intramuscular administration to these subjects.Vaccination is not a substitute for regular cervical screening or for precautions against exposure to HPV and sexually transmitted diseases.As with any vaccine, a protective immune response may not be elicited in all vaccinees.Cervarix protects against disease caused by HPV types 16 and 18. Other oncogenic HPV types can also cause cervical cancer and therefore routine cervical screening remains critically important and should follow local recommendations.Cervarix has not been shown to have a therapeutic effect. The vaccine is therefore not indicated for treatment of cervical cancer, cervical intraepithelial neoplasia (CIN) or any other established HPV-related lesions.Cervarix does not prevent HPV-related lesions in women who are infected with HPV-16 or HPV-18 at the time of vaccination.Duration of protection has not fully been established. Timing and need of booster dose(s) has not been investigated.There are no data on the use of Cervarix in subjects with impaired immune responsiveness such as HIV infected patients or patients receiving immunosuppressive treatment. As with other vaccines, an adequate immune response may not be elicited in these individuals.There are no safety, immunogenicity or efficacy data to support interchangeability of Cervarix with other HPV vaccines.

Interactions
In all clinical trials individuals who had received immunoglobulin or blood products within 3 months prior to the first vaccine dose were excluded.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 significance of this observation is not known.Cervarix may be administered concomitantly with a combined hepatitis A (inactivated) and hepatitis B (rDNA) vaccine (HAB vaccine).Administration of Cervarix at the same time as Twinrix (HAB vaccine) has shown no clinically relevant interference in the antibody response to the HPV and hepatitis A antigens. Anti-HBs geometric mean antibody titers were lower on co-administration, but the clinical significance 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 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 efficacy 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 productsAs with other vaccines it may be expected that, in patients receiving immunosuppressive treatment, an adequate response may not be elicited.

Adverse Reactions
Clinical trialsIn 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 subjects whilst 13,811 subjects 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.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.Adverse 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)Nervous system disorders:Very common: headacheUncommon: dizzinessGastrointestinal disorders:Common: gastrointestinal symptoms including nausea, vomiting, diarrhoea and abdominal painSkin and subcutaneous tissue disorders:Common: itching/pruritus, rash, urticariaMusculoskeletal and connective tissue disorders:Very common: myalgiaCommon: arthralgiaInfections and infestations:Uncommon: upper respiratory tract infectionGeneral disorders and administration site conditions:Very common: injection site reactions including pain, redness, swelling; fatigueCommon: fever (38°C)Uncommon: other injection site reactions such as induration, local paraesthesiaA similar safety profile has been observed in subjects with prior or current HPV infection as compared to subjects negative for oncogenic HPV DNA or seronegative for HPV-16 and HPV-18 antibodies.Post marketing surveillanceBecause these events were reported spontaneously, it is not possible to reliably estimate their frequency.Blood and lymphatic system disordersLymphadenopathyImmune system disordersAllergic reactions (including anaphylactic and anaphylactoid reactions), angioedemaNervous system disordersSyncope or vasovagal responses to injection, sometimes accompanied by tonic-clonic movements

Manufacturer
GlaxoSmithKline

Drug Availability
(POM)

Updated
04 March 2010