Composition, form of production and packaging
Suspension for the / m introduction homogeneous, opaque, white, without foreign inclusions, with sedimentation divided into 2 layers: the top - a transparent colorless liquid, the bottom - a white precipitate.
0.5 ml (1 dose)
L1 proteins of human papillomavirus
type 16 20 Ојg
type 18 20 Ојg
Excipients: 3-o-deacyl-4'-monophosphoryl lipid A, aluminum hydroxide, sodium chloride, sodium dihydrogen phosphate dihydrate, water d / u.
0.5 ml - bottles (1) - plastic blisters (1) - cardboard packs.
0.5 ml - bottles (5) - plastic blisters (2) - cardboard packs.
0.5 ml - bottles (10) - plastic blisters (1) - cardboard packs.
0.5 ml - bottles (100) - packs of cardboard.
0.5 ml - syringes (1) complete with 1 or 2 needles or without them - plastic blisters (1) - cardboard packs.
0.5 ml - syringes (5) complete with 1 or 2 needles or without them - plastic blisters (2) - cardboard packs.
0.5 ml - syringes (10) complete with 1 or 2 needles or without them - plastic blisters (1) - cardboard packs.
0.5 ml - syringes (10) complete with 1 or 2 needles or without them - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
Recombinant adsorbed vaccine for the prevention of diseases caused by human papillomaviruses (HPV) containing an adjuvant AS04. It is a mixture of virus-like particles of recombinant HPV surface proteins types 16 and 18, whose action is enhanced by the adjuvant system AS04.
L1, HPV-16 and HPV-18 proteins were obtained using recombinant baculoviruses HPV-16 and HPV-18 on Trichoplusia ni cell culture (Hi-5 Rix4446). AS04 consists of aluminum hydroxide and 3-O-desacyl-4'-monophosphoryl lipid A (MPL).
According to epidemiological data, in most cases, cervical cancer is caused by oncogenic human papillomaviruses. HPV-16 and HPV-18 are responsible for the occurrence of more than 70% of cervical cancer cases, as well as about 50% of all cases of development of cervical intraepithelial lesions around the world.
The efficacy of Cervarix in relation to HPV-16 and HPV-18 and infection-related consequences was confirmed by clinical studies involving 1113 persons aged 15-25 years. Combined analysis of the results of the study and subsequent 4-year follow-up showed:
- 94.7% effectiveness in preventing infection (95% CI: 83.5; 98.9);
- 96.0% efficacy against cervical infection persisting for at least 6 months (95% CI: 75.2, 99.9);
- 100% effective against cervical infection persisting for at least 12 months (95% CI: 52.2);
- 95.7% efficacy against HPV infection detected at the stage of cytological disorders * (95% CI: 83.5, 99.5);
- 100% protection from the development of HPV infection, detected histologically, at the CIN1 + ** stage (95% CI: 42.4, 100);
- 100% protection from the development of HPV infection, detected histologically, at the CIN2 + *** stage (95% CI: -7.7, 100).
* - Cytological abnormalities include abnormal ASC-US flat squares, low squamous cell intraepithelial lesion (LSIL), high squamous intraepithelial lesion (HSIL), and the presence of atypical flat cells in which HSIL (ASC- H).
** CIN1 + - intraepithelial cervical neoplasia of 1 degree and higher.
*** CIN2 + - intraepithelial cervical neoplasia of 2 degrees and higher
The vaccine provides cross-protection in 40.6% of those vaccinated against any manifestations of HPV infection that have been cytologically detected by other oncogenic types of HPV (95% CI: 14.9, 58.8). The vaccine is effective against the development of any CIN2 lesions (regardless of the type of HPV virus DNA) in 73.3% of subjects (95% CI: -1.0, 95.2).
Immunogenicity of the vaccine
A full course of vaccination (according to the scheme 0-1-6 months) leads to the formation of specific antibodies against HPV-16 and HPV-18, determined in 100% vaccinated 18 months after the introduction of the last dose of the vaccine in the age groups from 10 to 25 years.
The maximum severity of the immune response was noted immediately after the completion of the vaccination course (7th month). Antibodies persisted for 4 years after observation after the first dose.
Additionally, the neutralizing ability of the produced antibodies has been proven.
All initially seronegative women, including the age group of 46-55 years, became seropositive after the completion of the vaccination course (7th month), the level of antibodies for 7 months was at least 3-4 times higher than observed in the efficacy studies at 18 months after vaccination. The protective level of antibodies was observed after 18 months and remained at the same level during the four-year observation period, without further reduction.
In women initially seropositive for HPV-16 and / or HPV-18, CervarixВ® caused the production of the same level of antibodies as in the initially seronegative women, with the antibody titer being significantly higher than that produced after the infection
The AS04 adjuvant system causes a longer immune response, which is superior to that of aluminum salts as an adjuvant. The antibody titre when AS04 was used was at least twice as high within 4 years after the first dose, and the number of B-lymphocytes in memory exceeded approximately twice during 2 years after the administration of the first dose.
- prevention of cervical cancer in women from 10 to 25 years;
- prevention of acute and chronic infections caused by HPV, cell disorders including development of atypical flat cells of unclear value (ASC-US), intraepithelial cervical neoplasias (CIN), precancerous lesions (CIN2 +) caused by oncogenic human papillomavirus (HPV) viruses in women 10 to 25 years.
Cervarix В® is administered in / m, in the deltoid region of the muscle. Cervarix В® under no circumstances should be administered intravenously or intradermally.
Before use, the vaccine should be visually inspected for absence of foreign particles and shake the syringe or vial well to get a non-transparent suspension of whitish color. If the vaccine does not comply with the above description or contains foreign matter, it should be destroyed.
The recommended single dose for girls over 10 years and women is 0.5 ml.
The scheme of primary immunization includes the introduction of three doses of the vaccine according to the scheme of 0-1-6 months.
The need for revaccination has not been established to date.
In controlled studies of the Cervarix В® vaccine, pain at the injection site was most often recorded.
The undesirable reactions listed below are grouped according to organ systems and frequency of occurrence: very often (? 10%), often (? 1%, but <10%), sometimes (? 0.1%, but <1%), rarely (? 0.01 %, but <0.1%), very rarely (<0.01%), including individual messages.
From the side of the central nervous system: very often - headache; sometimes - dizziness .
On the part of the digestive system: often - nausea, vomiting, diarrhea, abdominal pain.
From the skin and its appendages: often - itching, rash, hives.
From the osteomuscular system and connective tissue: very often - myalgia; often - arthralgia; rarely - muscle 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: very often - a feeling of fatigue, local reactions, including pain, redness, swelling; often - fever (? 38 В° C); sometimes - other reactions at the site of administration, including compaction, decreased local sensitivity, itching.
- hypersensitivity to any of the components of the vaccine;
- reactions of hypersensitivity to the previous administration of Cervarix.
The introduction of Cervarix should be delayed in persons with acute fever, caused by t.ch. aggravation of chronic diseases.
PREGNANCY AND LACTATION
Controlled studies on the use of the Cervarix В® vaccine during pregnancy and during lactation were not conducted.
In experimental studies, there was no evidence of a possible adverse effect of the vaccine on fetal development or postnatal development. Nevertheless, it is recommended that Zervarix vaccination be postponed and carried out after childbirth.
In experimental animal studies, it has been shown that antibodies to vaccine antigens with milk can be isolated.
Cervarix В® should be used with caution in thrombocytopenia or violations of the blood coagulation system, since during the / m introduction, bleeding may occur.
Currently, there is no evidence of the possibility of c / c introduction of Cervarix.
It is unlikely that Cervarix В® can cause regression of lesions, and also prevent the progression of a disease caused by HPV-16 and / or HPV-18 before vaccination, and therefore the use of the vaccine is not shown for this purpose. Clinical evidence suggests that Cervarix В® is safe and immunogenic when administered to persons seropositive for HPV-16 and / or HPV-18 types who have no evidence of intraepithelial involvement in cytological research or only atypical, flat cells of uncertain significance (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).
Due to 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 anti-shock therapy.
In patients with immunodeficiency states, for example, in HIV infection, an adequate immune response may not be achieved.
Impact on the ability to drive vehicles and manage mechanisms
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.
So far, no cases of overdose have been reported.
Data on the interaction of Cervarix with other vaccines with their simultaneous application are absent.
Clinical studies have found that approximately 60% of women who received the Cervarix В® vaccine used oral contraceptives. Data on the adverse effects of contraceptives on the efficacy of the Cervarix В® vaccine are not available.
It is assumed that in patients receiving immunosuppressants, an adequate immune response may not be achieved.
TERMS OF RELEASE FROM PHARMACY
Packaging containing 1 syringe or vial is dispensed by prescription.
Packaging containing 10 or 100 syringes or vials is intended for treatment and prevention facilities.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored and transported at a temperature of 2 В° to 8 В° C; Do not freeze. Keep out of the reach of children. Shelf life - 3 years.