Cervarix® (Cervarix ®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceThe human papillomavirus vaccine is a recurrent (pancreatic) type (types 6, 11, 16, 18)The human papillomavirus vaccine is a recurrent (pancreatic) type (types 6, 11, 16, 18)
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  • Gardasil®
    suspension w / m 
    Merck Sharp and Doum B.V.     Netherlands
  • Cervarix®
    suspension w / m 
    GlaxoSmithKline Trading, ZAO     Russia
    • Dosage form: & nbspsuspension for intramuscular injection.
    Composition:

    For 1 inoculation dose (0.5 ml):

    Name

    components

    amount

    Active substances

    L1 protein of human papillomavirus type 16 (HPV-16Y)

    20 μg

    L1 a human papillomavirus type 18 protein (HPV-18Y)

    20 μg

    Excipients

    Z-O-desacil-4'-monophosphoryl lipid A

    50 μg

    Aluminum hydroxide

    0.5 mg

    Sodium chloride

    4.4 mg

    Sodium dihydrogen phosphate dihydrate

    0.624 mg

    Water for injections

    q.s. up to 0.5 ml
    Pharmacotherapeutic group:vaccine against human papillomavirus
    ATX: & nbsp

    J.07.B   Vaccines for the prevention of viral infections

    J.07   Vaccines

    Pharmacodynamics:

    IMMUNOLOGICAL PROPERTIES

    In almost all cases, cervical cancer is caused by the nonsystactis of oncogenic human papillomaviruses. Human papillomaviruses of 16 and 18 types are responsible for the occurrence of more than 70% of cases of cervical cancer and 70% of cases of low-diffused intraepithelial neoplasia of the vulva (VIN 2/3) and the vagina (VaIN 2/3). The four most common HPV types of high oncogenic risk are VG1CH-16, -18,-45 and-31 are responsible for approximately 76% of cases of squamous cell carcinoma of the cervix and 91% of cases of adenocarcinoma.

    After completion of the course of primary vaccination, immunological memory is formed to HPV-16 and -18, which is confirmed by a secondary response, which is recorded after 6.8 years. Anamnestic immune response was also recorded for related types of HPV-45 and -31.
    Effective protection was documented for at least 9.4 years after the introduction of the first dose of the vaccine. Studies on the duration of protective immunity are continuing.
    Prophylactic efficacy in women aged 15 to 25 years.
    Conclusions about the clinical effectiveness of the Cervarix® vaccine are based on the results of clinical trials in 19 778 women aged 15 to 25 years.
    In clinical trials, the effectiveness of the vaccine was evaluated for the prevention of precancerous lesions of CIN1 + (cervical intraepithelial neoplasia of the first degree and higher), CIN2 + (cervical intraepithelial neoplasia of the second degree and higher), CIN3 + (cervical intraepithelial neoplasia of the third degree and higher), ASC-US (atypical cells of unknown values); psrsistiruyuschey within 6 and 12 months of HPV-infraction; V1N1 + (intraepithelial neoplasia of the vulva of the first degree and above),VaINl + (vaginal intraepithelial neoplasia of the first degree and above).
    In a population of initially uninfected women (study HPV-001/007/023), the Cervarix® vaccine effectively prevented:
    • persisting for 6 and 12 months of HPV infection caused by HPV-16/18, in more than 98% and 97% of cases, respectively;
    • CIN1 + lesions due to HPV-16, -18, in 100% of cases;
    • CIN2 + lesions due to HPV-16. -18, in 100% of cases.
    At the same time, effective protection against the above virological and / or cytological conditions in initially uninfected women persisted for 9.4 years from the moment of the first dose.
    According to the results of the study (HPV-008, analysis at the end of the study) in a population of initially uninfected women, the Cervarix® vaccine effectively prevented:
    • CIN3 + lesions, caused by HPV-16, -18, in 100% of cases;
    • VIN1 + or VaINl + lesions due to HPV-16, -18, in more than 75% of cases (final analysis of the HPV-008 study).
    In a mixed population (26% of initially infected women: a current HPV infection or a history of HPV infection), the Cervarix® vaccine effectively prevented:
    • persistent within 6 months of an HPV infection caused by HPV-16, -18, more than 94% of cases;
    • defeat CIN1 +, conditional HPV-16, -18, in 98% of cases;
    • defeat CIN2 +, conditional HPV-16, -18, more than 98% of cases. The Cervarix® vaccine did not protect against HPV genotype-related diseases, in which women were DNA-positive at the time of inclusion in the study. but those women who were already infected with one type of HPV prior to vaccination were protected from diseases, caused by another vaccine type.
    The Csrvarix® vaccine provided an effective defense against
    infection and precancerous conditions caused by genotypes of HPV that are not included in the vaccine (HPV-31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, - 68):
    • 54% protection against C1N2 + in 12 oncogenic types (excluding HPV-16 and -18) in the population of initially uninfected women;
    • the preventive efficacy of the Cervarix® vaccine against CIN2 + and CIN3 + in women with initially negative PCR for 14 oncogenic HPV types, regardless of the type of DNA in the lesion and
    • regardless of serological status, was 65% and more than 93%, respectively.
    Prophylactic efficacy in women 26 years of age and older
    The efficacy of the Cervarix® vaccine was evaluated in a double-blind, randomized clinical trial that included 5,777 women aged 26 years and older.The prophylactic efficacy against persistent infection of HPV-16, -18 for 6 months in combination with CIN1 + lesion was more than 81% in vaccinated patients.
      Immunogenicity of the vaccine
        The immunogenicity of the Cervarix® vaccine was evaluated in more than 5,000 women aged 9 to 55 years.
          A full course of vaccination (according to the scheme of 0-1-6 months) leads to the formation of specific antibodies against HPV-16 and HPV-18 in more than 99% of initially delayed women.
          Induced by the vaccine Cervarix® average the geometric titres of IgG were higher than after the transferred natural HPV infection. Women, both seropositive and seronegative, at the time of the first dose, developed a similar immune response to vaccination.
          Immunogenicity in women from 15 to 25 years old
          The immunogenicity of the Cervarix® vaccine in for 76 months after the first dose in the study HPV-001/007 in women aged 15-25 years.
          In the HPV-023 study the duration of the study of the immune response was approximately 113 months (9.4 years) after the administration of the first dose of the vaccine. The results of this study showed that 100% of women were over-positive for 9.4 years after the course of primary vaccination.
          The tiger of antibodies reached a maximum by the 7th month of observation, then decreased somewhat, reaching a plateau by 18 months, and remained 10 times higher than the level of antibodies with natural HPV infection in throughout the observation period (113 months). Similar results were obtained in the HPV-008 study, where the follow-up period was 48 months.
          Immunogenicity in other age cohorts
          According to the combined analysis (HPV -029, -030, -048), girls at the age of 9 years had a 99.7% and 100% seroconversion to HPV types 16 and 18, respectively, by the 7th month of follow-up ( all three doses of the vaccine are administered). The average geometric titre of antibodies was at least 2 times higher than that of girls aged 10-14 and 15-25 years old.
          In two clinical studies (IIPV-012, -013), a 100% seroconversion was observed in girls aged 10-14 years, by both 16 and 18 types of HPV by the 7th month of observation (all three doses of the vaccine were administered). The average geometric antibody titres were at least 2 times higher in this age cohort compared to the cohort of 15-25 years.
          In a continuing clinical study (HPV-070) of girls 9-14 years old, vaccinated in a 2-dose regimen (0-6 months or 0-12 months), all vaccinated patients experienced seroconversion to viruses of types such as HPV-16 and -18 1 month after the second dose of the vaccine.The immune response in girls 9-14 years after the introduction of two doses of the vaccine was no less effective than the immune response in girls 15-25 years after the introduction of three doses of the vaccine.
          The conclusion about the efficacy of the 2-dose regimen for the administration of the Cervarix® vaccine was based on immunogenicity data from girls,
          vaccinated at the age of 9 to 14 years.
          Immunogenicity in women 26 years of age and older
          In the Phase III clinical trial (HPV-015), women aged 26 and over are 48 months old, i.e. 42 months after the completion of the full vaccination schedule, in initially seronegative women in 100% and 99.4%, high concentrations of antibodies to HPV-16 and HPV-18, respectively, remained. The antibody titer peaked at month 7, and then gradually decreased to 18 months and stabilized, reaching a plateau by 48 months.
          In another clinical study (MRU-014) conducted among women aged 26-55 years (N = 362), all women were seropositive for HPV-16 and -18 after the third dose of the vaccine (up to 7 months). The average geometric tigers of antibodies were lower in this population, but compared with a cohort of vaccinated age 15-25 years. However, all women remained seropositive for HPV-16, and virtually all women remained seropositive for HPV-18 during follow-up (up to 48 months),while the level of antibodies was significantly higher than with natural HPV infection.
          Immunogenicity in HIV-infected women
          In a clinical study conducted in 120 HIV-positive individuals without clinical manifestation of the disease at the age of 18 to 25 years (60 participants received the Cervarix® vaccine, all women vaccinated with Cervarix® were seropositive for HPV-16 and -18 after the third dose (up to 7 months), and seropositivity for types 16 and 18 persisted to 12 months.The average geometric titers were lower in this group than the group of HIV-negative individuals, but 15 times higher than the levels of antibodies recorded with natural HPV -infection.
          At the same time, HIV-positive people aged 18-25 years were well tolerated with Cervarix®, and the vaccination did not affect the level of CD4 + T-lymphocytes, the viral load and the progression of HIV infection.
          Indications:

          Prevention of persistent infection, precancerous lesions cervix,

          vulva and vagina, cervical cancer,vulva, vagina (squamous and

          adenocarcinomas) in girls and women from 9 up to 45 years of age due to viruses

          human papillomavirus high oncogenic risk.
          Contraindications:
          • hypersensitivity to any of the components of the vaccine;
          • hypersensitivity reactions to the previous administration of Cervarix ®
          The introduction of Cervarix® should be delayed in persons with acute fever, caused, among other things, exacerbation of chronic diseases.
          Carefully:

          Cervarix® should be used with caution in thrombocytopenia or disorders of the blood coagulation system, since during intramuscular injection bleeding may occur.

          Currently, there is no evidence of the possibility of subcutaneous administration of Cervarix ®.

          It is unlikely that Cervarix® can cause regression of lesions, as well as prevent the progression of a disease caused by HPV-16 and / or HPV-18 before vaccination, in this connection, the use of the vaccine for this purpose is not shown. Clinical evidence suggests that Cervarix® is safe and immunogenic for persons who are seropositive for HPV-16 and / or HPV-18 types who have no evidence of an intraepithelial lesion in cytological examination or only atypical flat cells of an ambiguous meaning (ASC-US).

          Vaccination does not prevent infection and diseases caused by certain types of HPV.

          Vaccination is a method of primary prevention and does not negate the need for regular examinations at the doctor (secondary prevention).

          In connection with the possibility of developing an anaphylactic reaction in rare cases, the vaccinated should be under medical supervision for 30 minutes, and procedural rooms should be provided with antishock therapy.

          In patients with immunodeficiency states, for example, in HIV infection, an adequate immune response may not be achieved.

          Pregnancy and lactation:

          Pregnancy

          The effect of the Cervarix® vaccine on intrauterine, perinatal and postnatal survival and development has been studied in animal models (rats). Similar studies in animals do not confirm the presence of direct or indirect adverse effects on fertility, pregnancy, intrauterine development, childbirth or postnatal development.

          Data on pregnant women collected from clinical trials from the registries of pregnant women, during epidemiological studies, do not suggest that the risk of pathology among Newborns, including malformations, will change. To conclude whether or not the Cervarix® vaccine is influenced by the risk of spontaneous abortion, data are insufficient.

          Pregnant women and women planning pregnancy, it is recommended to postpone the vaccination until the end of pregnancy.

          Breastfeeding period

          The impact on children who are breastfeeding at the time of their mothers' vaccination with Cervarix® has not been evaluated in clinical trials.

          Data from serological studies have shown that it is possible to isolate antibodies to vaccine antigens with milk during the lactation period in rats. It is not known whether similar excretion of postvaccinal antibodies occurs with human milk. The use of the Cervarix® vaccine during breastfeeding is only possible if the expected benefit over the risk is exceeded.
          Dosing and Administration:

          Cervarix® vaccine is introduced intramuscularly, into the deltoid muscle region.

          Cervarix® vaccine should never be administered intravenously or intradermally. There is no data on subcutaneous injection.

          Before use, the vaccine should be visually inspected for absence of foreign matter and shake the syringe or vial well to get an opaque white suspension. During storage, a white precipitate is formed with a clear, colorless supernatant, which is not a deterioration in quality, after shaking, the precipitate must completely break up. If the vaccine does not correspond to the above description or contains foreign matter, all should be destroyed.

          The vaccine should be used immediately after removal from the refrigerator.

          Instructions for use of the vaccine in a syringe

          1. Unscrew the protective cap of the syringe by turning it counter-clockwise (while holding the syringe by the cylinder, avoiding contact with the plunger of the syringe).

          2. Twisting the movement clockwise connect the needle with the syringe until you feel them snap on each other (see Figure 1).

          3. Remove the protective cap from the needle (in some cases it can be tightly attached to the needle).

          4. Enter the vaccine.

          Unused preparation and waste from its use must be destroyed in accordance with the requirements adopted in the Russian Federation.

          Vaccination schedules

          A single dose for all ages is 0.5 ml.

          The choice of the vaccination scheme depends on the age of the vaccinated at the time the introduction of the first dose of the vaccine.

          Age from 9 to 14 years inclusive

          Enter 2 doses of the vaccine. The second dose is administered 5-13 months after the first dose.

          If the girls in this age group received a second dose earlier than 5 months after the first dose, the third dose must be entered necessarily. In this case, a vaccination scheme is recommended for this age group, including the administration of 3 doses of the vaccine.

          Age 15 years and over

          Since the age of 15 years and over, only a vaccination scheme has been recommended, including the administration of 3 doses of the vaccine.

          The scheme of vaccination, including the introduction of 3 doses of the vaccine: 0-1-6 months. If it is necessary to change the vaccination schedule, the second dose can be administered 1-2.5 months after the first dose, and the third dose after 5-12 months after the first dose. The need for revaccination has not been established to date. The presence of an anamnestic response to the administration of a provocative dose

          Side effects:

          In controlled vaccine trials Cervarix® most often recorded pain at the injection site.

          The undesirable reactions listed below are grouped according to organ systems and frequency of occurrence: very often ≥10%, often from ≥1% to <_ 10%, sometimes from ≥0.1% to <_1%, rarely from ≥0.01% to <0.1%, very rarely, including individual reports <0.01%.

          From the nervous system: Often - headache, sometimes dizziness.

          From the gastrointestinal tract: often - nausea, vomiting, diarrhea, abdominal pain.

          From the skin and its appendages: often - itching, rash, hives.

          From the osteomuscular system and connective tissue: highly often - myalgia, often - arthralgia, rarely - Muscular weakness.

          Infectious complications: sometimes - infections of the upper respiratory tract.

          On the part of the body as a whole and related to the place of administration: Often - a sense of fatigue, local reactions, including pain, redness, swelling; often - fever (> 38 ° C); sometimes - other reactions at the site of administration, including compaction, decreased local sensitivity, pruritus.

          Overdose:So far, no cases of overdose have been reported.
          Interaction:

          Data on the interaction of Cervarix ® with other vaccines with their simultaneous application are not available.

          Clinical studies have found that approximately 60% of women who received the Cervarix® vaccine used oral contraceptives (POC). Data on the adverse effects of POC on the efficacy of Cervarix® vaccine are not available.

          It is assumed that in patients receiving immunosuppressants, an adequate immune response may not be achieved.

          Effect on the ability to drive transp. cf. and fur:

          Special studies on the effect of the vaccine on the ability to drive or work with machinery have not been carried out. However, the clinical status of patients and the profile of adverse reactions should be considered.

          Form release / dosage:Suspension for intramuscular injection.
          Packaging:

          For 0.5 ml in a bottle of neutral glass type I (Hev.F.), sealed with a plug of synthetic butyl rubber (Heph. F) and an aluminum cap for running in, equipped with a protective plastic lid.

          For 0.5 ml in a syringe made of neutral glass type I (Hept. F.), The nozzle of the syringe is closed with a protective cap.

          Completeness

          For 1 bottle in a cardboard pack together with instructions for use.

          For 1 syringe in a blister of polyvinyl chloride (PVC), closed with a film of polyethylene terephthalate (PET). For 1 blister in a cardboard pack together with instructions for use.

          1 syringe with 1 needle in a plastic container with a cannula closed with a plastic cap, in a PVC blister, covered with a PET film. For 1 blister in a cardboard pack together with instructions for use.

          1 syringe with 2 needles in plastic containers with cannula, closed plastic caps, in a PVC blister, closed with a PET film. For 1 blister in a cardboard pack together with instructions for use. Packaging for medical institutions

          Bottles

          For 10 bottles in a cardboard pack together with instructions for use.

          For 100 bottles in a cardboard pack together with instructions for use.

          Syringes

          For 5 syringes in a PVC blister, closed with a PET film. 2 blisters per cardboard pack together with instructions for use.

          For 10 syringes in a PVC blister, closed with a PET film. For 1 blister in a cardboard pack together with instructions for use.

          For 10 syringes in a cardboard bundle with a built-in cardboard tray with protective perforation against unauthorized opening together with instructions for use.

          Syringes can be supplied without needles or complete with 1 or 2 needles in plastic containers with cannulas closed with a plastic cap.

          Storage conditions:
          Store at a temperature of 2 to 8 ° C. Do not freeze.

          Keep in a dark place.

          Keep out of the reach of children.
          Shelf life:

          3 years.

          Do not use after the expiration date printed on the package.
          Terms of leave from pharmacies:On prescription
          Registration number:LSR-006423/08
          Date of registration:11.08.2008
          The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia
          Manufacturer: & nbsp
          Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO
          Information update date: & nbsp25.10.15
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