Vaccine against human papillomavirus (Vaccine against human papillomavirus)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Vaccines, serums, phages and toxoids

Included in the formulation
Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

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

J.07   Vaccines

Pharmacodynamics:

Recombinant adsorbed vaccine for the prevention of diseases caused by human papillomaviruses, containing an adjuvant AS04. It is a mixture of virus-like particles of recombinant surface proteins human papillomavirus 16th and 18th types, the action of which is enhanced with the help of the adjuvant system AS04.

L1 proteins human papillomavirus On the 16th and The 18th type was obtained using recombinant baculoviruses human papillomavirus On the 16th and 18 types on the culture of Trichoplusia ni cells (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. ATHuman papillomaviruses On the 16th and 18 types are responsible for the occurrence of more than 70% of cases of cervical cancer, as well as about 50% of all cases of development of cervical intraepithelial lesions around the world.

Clinical efficacy

The effectiveness of the drug in relation to human papillomavirus On the 16th and 18 types and infections associated with infection was confirmed by clinical studies, including 1113 people 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 infection human papillomaviruses detected at the stage of cytological disorders * (95% CI: 83.5, 99.5);

- 100% protection from the development of human papilloma virus infection, detectable histologically, at the CIN1 + ** stage (95% CI: 42.4, 100);

- 100% protection against infection human papillomavirus detected histologically, at the CIN2 + *** stage (95% CI: -7.7, 100).

* - Cytological abnormalities include abnormal ASC-US flat cells, low squamous intraepithelial lesion (LSIL), high squamous intraepithelial lesion (HSIL), and the presence of atypical flatcells, in which HSIL (ASC-H) can not be excluded.

** CIN1 + - intraepithelial cervical neoplasia of the 1 st degree and higher.

*** CIN2 + - intraepithelial cervical neoplasia of the 2nd degree and higher.

The vaccine provides cross-protection in 40.6% of those vaccinated against any manifestations of infection of human papillomaviruses detected cytologically, caused by other oncogenic types of human papillomavirus (95% CI: 14.9, 58.8). The vaccine is effective against the development of any CIN2 lesions (regardless of type deoxyribonucleic acid human papillomaviruses) in 73.3% of subjects (95% CI: -1.0, 95.2).

Pharmacokinetics:

The full course of vaccination (according to the scheme of 0-1-6 months) leads to the formation of specific antibodies against human papillomavirus 16 and 18 types, 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 expression 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 at the 7th month was at least 3-4 times higher than observed in the studies evaluating the effectiveness on the 18th month 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 human papillomavirus 16 and / or 18 types, the drug 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.

Indications:

Preventive maintenance of a cancer of a neck of a uterus at women from 10 till 25 years; prevention of acute and chronic infections caused by human papillomavirus(CIN), precancerous lesions (CIN2 +) caused by oncogenic human papillomaviruses in women from 10 to 25 years of age, including cell disorders, including the development of atypical flat cells of unknown significance (ASC-US), intraepithelial cervical neoplasias (CIN).

ICD-10

I.B95-B97.B97.7   Papillomaviruses as a cause of diseases classified elsewhere

II.C51-C58.C53   Malignant neoplasm of cervix

Contraindications:

Pincreased sensitivity to any of the components of the vaccine; reactions of hypersensitivity to the previous administration of the drug.

The administration of the drug should be delayed in persons with an acute febrile condition caused by t.ch. aggravation of chronic diseases.

Carefully:

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

Pregnancy and lactation:

Controlled studies on the use of the vaccine during pregnancy and during lactation was not carried out.

AT experimental research There was no evidence of a possible adverse effect of the vaccine on fetal development or postnatal development. However, vaccination with the drug during pregnancy is recommended to postpone and hold it after childbirth.

AT experimental research on animals it was shown that it is possible to isolate antibodies to antigens of the vaccine with milk.

Dosing and Administration:

A drug injected intramuscularly, into the deltoid muscle region. A drug under no circumstances should not be administered intravenously or subcutaneously.

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.

Vaccination schedules

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.

Side effects:

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

The adverse 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 reports.

From the central nervous system: very often - headache; sometimes - dizziness.

From 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 ° C); sometimes - other reactions at the site of administration, including compaction, decreased local sensitivity, itching.

Overdose:

So far, no cases of overdose have been reported.

Interaction:

Data on the interaction of the drug with other vaccines with their simultaneous application are absent.

Clinical studies have found that approximately 60% of women who received the vaccine used oral contraceptives. There is no evidence of a negative effect of contraceptives on the effectiveness of the vaccine.

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

Special instructions:

At present, there is no data on the possibility of subcutaneous administration.

It is unlikely that the drug can cause regression of lesions, as well as prevent the progression of the disease caused by human papillomaviruses 16th and / or 18th types that existed before the vaccination, and therefore the use of the vaccine for this purpose is not shown. Clinical evidence suggests that the drug is safe and immunogenic when administered to persons seropositive for human papillomavirus 16th and / or 18th types, who have no signs of intraepithelial lesion in cytological examination or only atypical flat cells of ambiguous significance (ASC-US).

Vaccination does not prevent infection and diseases caused by certain types human papillomavirus.

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 immunodeficient conditions, for example, with infection human immunodeficiency virus, 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.

Instructions
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