Hexaxim suspension for injection 1 dose syringe 0.5 ml with one or two needles No. 1

Instructions Hexaxim suspension for injection 1 dose syringe 0.5 ml with one or two needles No. 1

Composition

active ingredients:

Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) (DTaP-IPV-HB-Hib);

One dose of vaccine1 (0.5 ml) contains:

diphtheria toxoid ≥ 20 IU2

tetanus toxoid ≥ 40 IU2,3

Bordetella pertussis antigens:

pertussis toxoid 25 mcg

filamentous hemagglutinin 25 mcg

inactivated poliovirus4:

type 1 (Mahoney strain) 40 D-units5

type 2 (MEF-1 strain) 8 D-units5

type 3 (Saukett strain) 32 D-units5

Hepatitis B6 virus surface antigen 10 μg

Haemophilus influenzae type b polysaccharide 12 mcg

(polyribosylribitol phosphate),

conjugated with tetanus protein 22–36 mcg

1 Adsorbed on hydrated aluminum hydroxide (corresponding to 0.6 mg Al3+).

2 International units.

3 Or equivalent activity as determined by immunogenicity assessment.

4 Obtained on Vero cells.

5 Or equivalent amount of antigen determined by an appropriate immunochemical method.

6 Obtained in Hansenula polymorpha yeast cells using recombinant DNA technology.

excipients:

disodium hydrogen phosphate, potassium dihydrogen phosphate, trometamol, sucrose, essential amino acids, including L-phenylalanine, sodium hydroxide and/or acetic acid and/or hydrochloric acid (for pH adjustment), and water for injections.

The vaccine may contain trace amounts of substances used in the manufacturing process: glutaraldehyde, formaldehyde, neomycin, streptomycin and polymyxin B (see section "Contraindications").

Excipient with known properties:

phenylalanine – 85 mcg (see section “Special instructions for use”).

Dosage form

Suspension for injection, 0.5 ml (1 dose).

Main physicochemical properties: sterile, cloudy suspension with a whitish tint.

Pharmacotherapeutic group

Combined antibacterial and antiviral vaccines.

ATX code J07CA09.

Immunological and biological properties

Pharmacodynamics

The immunogenicity of the Hexaxim® vaccine in children over 24 months of age has not been studied in clinical trials.

Immune response after primary vaccination

The immunogenicity of Hexaxim® vaccine was evaluated in clinical studies in children from 6 weeks of age. Infants were vaccinated with two doses (at 3-5 months of age without hepatitis B vaccination immediately after birth) or with a three-dose primary vaccination course (at 6-10-14 weeks with or without hepatitis B vaccination; 2-3-4 months without hepatitis B vaccination immediately after birth; 2-4-6 months without hepatitis B vaccination immediately after birth and with hepatitis B vaccination immediately after birth).

In immunogenicity studies, seroprotective antibody levels (≥ 0.01 IU/ml) against diphtheria and tetanus were achieved in 97.6–100% of children one month after the last dose of primary vaccination (2nd or 3rd dose depending on the schedule used) against diphtheria and tetanus in 100% of children.

After completion of primary vaccination, 88–96.2% of infants were seroconverted (seroconversion: at least a 4-fold increase in antibody titers against pertussis toxoid (PT) and antifilamentous haemagglutinin (FHA) compared to pre-vaccination antibody levels (before the 1st dose)). The vaccine response (if the pre-vaccination antibody concentration is <8 OE/ml (enzyme-linked immunosorbent assay units (ELISA)/ml), the post-vaccination antibody concentration must be ≥ 8 OE/ml, otherwise the post-vaccination antibody concentration must be ≥ the pre-vaccination level) of these antibodies was 98.4–100%.

After primary vaccination, at least 99% of children vaccinated with 3 doses and at least 90.8% of children vaccinated with 2 doses of Hexaxim® vaccine had seroprotective antibody titers against poliovirus types 1, 2 and 3 (≥ 8 in the reciprocal of the dilution in the seroneutralization reaction).

71.5% (after two primary doses) and 98% of infants (after three primary doses) achieved anti-polyribosylribitol phosphate (PRP) antibody titers ≥ 0.15 μg/mL.

At least 95.7% of infants vaccinated with 3 doses of Hexaxim® vaccine (without hepatitis B vaccination immediately after birth) achieved anti-hepatitis B antibody (anti-HBs) titers ≥10 mIU/ml one month after the last dose and 97.2% of infants achieved this after the second dose (using the 2-dose vaccination schedule and without hepatitis B vaccination at birth). At least 99% of infants vaccinated with hepatitis B vaccine at birth achieved anti-HBs antibody levels ≥10 mIU/ml.

After booster vaccination with Hexaxim® vaccine at the age of 11-12 months (after a 2-dose primary vaccination course at the age of 3-5 months) and after booster vaccination in the second year of life (after a 3-dose primary vaccination course at the age of 6 weeks to 6 months), 97.2-100% and 100% of children had protective antibody concentrations (> 0.1 IU/ml) against diphtheria and tetanus, respectively. All children achieved seroprotective antibody titers against all three types of polioviruses (≥8 (1/dilution)). The seroconversion rate for anti-PT antibodies and anti-FHA antibodies was 86-96.2% and 94.3-99.4%, respectively. The vaccine response for anti-PT antibodies and anti-FHA antibodies was 100%. From 93.5% to 98.9% of all children achieved antibody titers to the PRF antigen ≥ 1.0 μg/ml. 99.7–100% of children with hepatitis B vaccination at birth and 96.4–99.4% without hepatitis B vaccination at birth achieved antibody concentrations to HBs ≥ 10 mIU/ml.

Immune response to Hib and pertussis antigens after 2 doses at 2 and 4 months of age

The immune response to Hib (PRF) and pertussis (PT and FHA) antigens was evaluated after 2 doses in a subgroup of patients receiving Hexaxim® (N = 148) at 2, 4 and 6 months of age. The immune response to PRF, PT and FHA antigens 1 month after 2 doses administered at 2 and 4 months of age was similar to that observed 1 month after the 2-dose primary vaccination course administered at 3 and 5 months of age: PRF antibody titers ≥ 0.15 μg/ml were observed in 73.0% of subjects, PT vaccine response in 97.9% of subjects, FHA vaccine response in 98.6% of subjects.

Persistence of the immune response

Studies of the long-term persistence of vaccine-induced antibodies following different primary vaccination schedules in infants and young children (primary vaccination at 6, 10, and 14 weeks of age and booster vaccination at 15–18 months of age with or without hepatitis B vaccination at birth (in South Africa) and primary vaccination at 2, 4, and 6 months of age and booster vaccination at 12–24 months of age with hepatitis B vaccination at birth (Colombia)) have shown maintenance of immune protection levels above the established protective antibody levels for the vaccine antigens.

Seroprotection levels (generally accepted surrogates for antibodies to RT and FHA or correlates of protection (other components)) at the age of 4.5 years after vaccination with Hexaxim® vaccine:

antibodies to the diphtheria pathogen: 97–100% (≥ 0.01 IU/ml) and in 57.2–75.3% (≥ 0.1 IU/ml); antibodies to the tetanus pathogen: 100% (≥ 0.01 IU/ml) and 80.0–89.5% (≥ 0.1 IU/ml); antibodies to pertussis toxin RT: 22.2–42.5% (≥ 8 OE/ml correspond to 4 LLOQ (lower threshold level of quantification (2 OE/ml) in the enzyme-linked immunosorbent assay); antibodies to filamentous hemagglutinin FHA: 85.6–93.8% (≥ 8 OE/ml); antibodies to HBs antigen: 73.3–96.1% (≥ 10 mIU/ml).

Antibodies to poliovirus were only analyzed in the aforementioned study in Colombia: the seroprotection rate (≥8 (1/dilution)) was 99.5% (antibodies to poliovirus type 1) and 100% (antibodies to poliovirus types 2 and 3). Antibodies to poliovirus were not analyzed in the study conducted in the Republic of South Africa (primary vaccination at 6, 10 and 14 weeks of age and booster vaccination at 15-18 months of age with or without hepatitis B vaccination at birth) due to the implementation of National Vaccination Days with OPV (oral polio vaccine).

The persistence of immune responses to the hepatitis B component of the Hexaxim® vaccine was evaluated in infants who received the vaccine according to two different schedules.

After a 2-dose primary vaccination course of infants aged 3 and 5 months without hepatitis B vaccination at birth who received a booster dose at 11–12 months of age, 53.8% of children were seroprotected (antibodies to HBsAg ≥ 10 mIU/mL) at age 6 years and 96.7% demonstrated an anamnestic response after a single dose of hepatitis B vaccine.

After a primary vaccination course consisting of a single dose of hepatitis B vaccine administered immediately after birth and a 3-dose course at 2, 4, and 6 months of age without a booster dose, 49.3% of children were seroprotected (antibodies to HBsAg ≥ 10 mIU/mL) at 9 years of age and 92.8% demonstrated an anamnestic response after a single dose of hepatitis B vaccine.

These data confirm the presence of a persistent immune memory that developed in infants who received the Hexaxim® vaccine.

Immune response to Hexaxim® in premature infants

The immune response to Hexaxim® vaccine antigens in preterm (105) infants (gestational age 28 to 36 weeks), including 90 infants whose mothers were vaccinated with the DTP vaccine during pregnancy and 15 infants whose mothers were not vaccinated during pregnancy, was evaluated after a 3-dose primary vaccination course at 2, 3, and 4 months of age and a booster dose at 13 months of age.

One month after primary vaccination, all patients were seroprotected against diphtheria (≥ 0.01 IU/ml), tetanus (≥ 0.01 IU/ml) and poliomyelitis types 1, 2 and 3 (≥ 8 (1/dilution)); 89.8% of patients were seroprotected against hepatitis B (≥ 10 IU/ml) and 79.4% were seroprotected against invasive Hib disease (≥ 0.15 μg/ml).

For pertussis, 98.7% and 100% of patients developed antibodies ≥ 8 IU/ml to PT and FHA antigens, respectively, one month after primary vaccination. 98.8% of patients developed antibodies ≥ 8 IU/ml to both PT and FHA antigens one month after booster dose. Pertussis antibody concentrations increased 13-fold after primary vaccination and 6-14-fold after booster dose.

Immune response to Hexaxim® in infants whose mothers were vaccinated with the KDP vaccine during pregnancy

Immune responses to Hexaxim® vaccine antigens in term (119) and preterm (90) infants whose mothers were vaccinated with the DTP vaccine during pregnancy (between 24 and 36 weeks of gestation) were evaluated after a 3-dose primary vaccination course at 2, 3 and 4 months of age and after receiving a booster dose at 13 (preterm infants) or 15 (preterm infants) months of age.

One month after primary vaccination, all patients were seroprotected against diphtheria (≥ 0.01 IU/ml), tetanus (≥ 0.01 IU/ml), and poliomyelitis types 1 and 3 (≥ 8 (1/dilution)); 97.3% of patients were seroprotected against poliovirus type 2 (≥ 8 (1/dilution)); 94.6% of patients were seroprotected against hepatitis B (≥ 10 IU/ml), and 88.0% against invasive Hib disease (≥ 0.15 μg/ml).

One month after receiving the booster dose, all patients were seroprotected against diphtheria (≥ 0.1 IU/ml), tetanus (≥ 0.1 IU/ml), and poliomyelitis types 1, 2, and 3 (≥ 8 (1/dilution)); 93.9% of patients were seroprotected against hepatitis B (≥ 10 IU/ml), and 94.0% were seroprotected against invasive Hib disease (≥ 1 μg/ml).

For pertussis, 99.4% and 100% of patients developed antibodies ≥ 8 IU/ml to PT and FHA antigens, respectively, one month after primary vaccination. 99.4% of patients developed antibodies ≥ 8 IU/ml to both PT and FHA antigens one month after booster dose. Pertussis antibody concentrations increased 5–9-fold after primary vaccination and 8–19-fold after booster dose.

Immune response to Hexaxim® vaccine in infants at risk of HIV infection

Immune responses to Hexaxim® vaccine antigens in 51 infants at risk of HIV infection (9 infected and 42 uninfected) were evaluated after a 3-dose primary vaccination course at 6, 10, and 14 weeks of age and a booster dose at 15 to 18 months of age.

One month after primary vaccination, all infants were seroprotected against diphtheria (≥ 0.01 IU/ml), tetanus (≥ 0.01 IU/ml), poliovirus types 1, 2 and 3 (≥ 8 (1/dilution)), hepatitis B (≥ 10 IU/ml) and more than 97.6% against invasive Hib disease (≥ 0.15 μg/ml).

One month after the booster dose, all patients were seroprotected against diphtheria (0.1 IU/ml), tetanus (≥ 0.1 IU/ml), poliovirus types 1, 2 and 3 (≥ 8 (1/dilution)), hepatitis B (≥ 10 IU/ml) and more than 96.6% against invasive Hib disease (≥ 1 μg/ml).

For pertussis, 100% of subjects developed antibodies ≥ 8 IU/ml to pertussis toxoid (PT) and antifilamentary haemagglutinin (FHA) antigens one month after the primary vaccination. 100% of subjects developed antibodies ≥ 8 IU/ml to pertussis toxoid and antifilamentary haemagglutinin antigens one month after the booster dose. The seroconversion rate, defined as a minimum 4-fold increase from pre-vaccination (pre-dose 1) level, was 100% in the HIV-infected group for antibodies to pertussis toxoid and antifilamentary haemagglutinin, 96.6% for antibodies to pertussis toxoid and 89.7% for antibodies to filamentary haemagglutinin in the uninfected infants.

Effectiveness and efficiency of protection against whooping cough

The efficacy of vaccination with acellular pertussis (aK) antigens contained in Hexaxim® vaccine for the prevention of the most severe, typical (as defined by WHO) form of pertussis (≥ 21 days of paroxysmal cough) has been documented in a randomized, double-blind study in which infants received a 3-dose primary vaccination course with aKDP vaccine in a country with a high endemic incidence (Senegal). This study identified the need for a booster dose of the vaccine in young children, starting at 6 weeks of age.

A 10-year national observational study conducted in Sweden, in which pentavalent aKDP-IPV/Hib vaccine was administered at 3, 5 and 12 months, demonstrated the long-term ability of the acellular pertussis antigens (aK) contained in Hexaxim® to reduce pertussis incidence and control pertussis disease in children. The results of the long-term follow-up showed a sharp decrease in pertussis incidence after the second dose of vaccine, regardless of which vaccine was used.

Effectiveness of protection against invasive infections caused by Hib (Haemophilus influenzae type b)

The efficacy of vaccination against invasive Hib disease using combined aDTP and Hib vaccines (pentavalent and hexavalent, including vaccines containing the Hib antigen of the Hexaxim® vaccine) was demonstrated in Germany in a long-term (with a 5-year follow-up period) post-marketing surveillance study. Vaccination efficacy was 96.7% after the primary vaccination course and 98.5% after the booster dose (regardless of the primary vaccination).

Pharmacokinetics

Not studied.

Indication

The drug Hexaxim® (aKDP-IPV-GB-Hib vaccine) is indicated for primary and booster vaccination of infants and young children, starting from 6 weeks of age, for the prevention of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib).

The vaccine should be used in accordance with the official recommendations of regulatory documents on preventive vaccinations in force in Ukraine.

Contraindication

History of anaphylactic reaction to previous administration of Hexaxim® vaccine.

Hypersensitivity to the active substances, to any of the excipients listed in the "Composition" section, to residues that may be present in the product in trace amounts (glutaraldehyde, formaldehyde, neomycin, streptomycin and polymyxin B), to any pertussis vaccine or to previous administration of Hexaxim® vaccine or a vaccine containing the same active ingredients or components.

Immunization should be postponed in individuals with moderate to severe acute febrile illness or infection. The presence of mild infections and/or a slight increase in body temperature should not be a reason to postpone vaccination.

Vaccination with Hexaxim® vaccine is contraindicated in individuals who have developed encephalopathy of unknown etiology within 7 days after previous vaccination with a vaccine containing a pertussis component (whole cell or acellular). In such conditions, vaccination against pertussis should be discontinued and the vaccination course should be continued with a vaccine against diphtheria, tetanus, hepatitis B, poliomyelitis and Hib infection.

Pertussis vaccine should not be administered to individuals with uncontrolled neurological disorders or uncontrolled epilepsy until appropriate treatment for the condition has been initiated, the patient's condition has stabilized, and the benefits of such vaccination clearly outweigh the risks.

Interaction with other medicinal products and other types of interactions

Hexaxim® can be administered concomitantly with pneumococcal polysaccharide conjugate vaccine, measles, mumps, rubella (MMR) vaccines, rotavirus vaccines, meningococcal C conjugate vaccine, or meningococcal groups A, C, W-135, and Y conjugate vaccines, as no clinically significant effect on antibody response to each of the administered antigens has been observed. A clinically significant effect on antibody response may be observed when Hexaxim® and varicella vaccines are administered concomitantly, and these vaccines should not be administered concomitantly.

If simultaneous administration with another vaccine is considered, these vaccines should be administered at different sites on the body.

Hexaxim® must not be mixed with any other vaccines or other medicinal products intended for parenteral administration.

There have been no reports of clinically significant interactions with other medicinal products or biological products, except for immunosuppressive therapy (see section "Special warnings and precautions for use").

Influence on laboratory test results: see section "Special instructions for use".

Before vaccination, you must inform your doctor about any medications you are taking (including over-the-counter medications).

Application features

Tracking

To improve the traceability of biological medicinal products, the name and batch number of the administered medicinal product should be clearly recorded in the medical record when administering vaccinations.

Before administering the vaccine, the pre-filled syringe or vial should be shaken until a homogeneous, cloudy, whitish suspension is obtained. The dose (0.5 ml) is withdrawn from the vial using an injection syringe.

The suspension should be inspected visually prior to administration. If any foreign matter and/or changes in appearance are observed, this pre-filled syringe or vial should be discarded.

When using syringes without an attached needle, the needle should be firmly attached to the syringe by rotating it one quarter of a turn.

Remaining vaccine or unused materials should be disposed of in accordance with current requirements for the disposal of biological waste.

Hexaxim® does not provide protection against diseases caused by pathogens other than Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis, hepatitis B virus, poliovirus and Haemophilus influenzae type b. However, it can be expected that such vaccination will prevent the development of hepatitis D (caused by the delta agent), since hepatitis D does not occur in the absence of hepatitis B virus in the body.

Hexaxim® does not provide protection against liver infections caused by hepatitis A, hepatitis C and hepatitis E viruses, or other liver pathogens.

Due to the long incubation period of hepatitis B, it is possible that at the time of vaccination an unrecognized infection caused by the hepatitis B pathogen will be present in the body. In such cases, this vaccine cannot prevent the development of hepatitis B.

Hexaxim® does not provide protection against infectious diseases caused by other types of Haemophilus influenzae, or against meningitis of other etiologies.

Patients should be under medical supervision for 30 minutes after vaccine administration.

Immunization should be postponed in individuals with moderate to severe acute febrile illness or infection. The presence of mild infections and/or a slight increase in body temperature should not be a reason to postpone vaccination.

Before vaccination, the patient's medical history should be reviewed (especially regarding previous vaccinations and possible adverse reactions to them). The appropriateness of using Hexaxim® vaccine should be carefully considered in patients with a history of serious or severe reactions occurring within the first 48 hours after the administration of any vaccine with similar components.

Before administering any biological medicinal product by injection, the person responsible for administering the vaccine should take all necessary precautions to avoid allergic or any other reactions. As with any injectable vaccine, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine.

If any of the following events are known to have occurred in a patient after receiving any pertussis-containing vaccine, the decision to administer further doses of pertussis-containing vaccine should be carefully considered:

body temperature ≥ 40 °C within 48 hours after vaccination, unless there is another identifiable cause;

collapse or shock-like state (hypotonic-hyporesponsive syndrome) within 48 hours after vaccination;

prolonged inconsolable crying for ≥ 3 hours within 48 hours after vaccination;

Convulsions, with or without fever, occurring within 3 days of vaccination.

There may be some circumstances in which the potential benefits would outweigh the possible risks, such as a high incidence of pertussis in a population.

A history of febrile seizures, a family history of seizures, or sudden infant death syndrome are not contraindications to the use of Hexaxim® vaccine. Individuals with a history of febrile seizures should be closely monitored after vaccination, as such adverse reactions may occur within 2–3 days after vaccination.

If a patient has developed Guillain-Barré syndrome or brachial neuritis after receiving a previous tetanus toxoid-containing vaccine, the decision to continue with any tetanus toxoid-containing vaccine should be based on a careful assessment of the potential benefits and possible risks of vaccination, for example, taking into account whether or not the primary vaccination course has been completed. Vaccination is usually justified in the case of incomplete primary vaccination course (for example, if fewer than three doses of vaccine have been administered).

The immunogenicity of this vaccine may be reduced if the patient is receiving immunosuppressive therapy or is immunodeficient. It is recommended to wait until such therapy has ended or the disease has resolved before administering the vaccine. However, vaccination of individuals with chronic immunodeficiency, such as HIV infection, is recommended, even though the antibody response may be limited.

Special patient groups

Immunogenicity data are available in 105 preterm infants. These data support the use of Hexaxim® vaccine in preterm infants. As expected, lower immune responses to some antigens were observed in preterm infants when indirectly compared to term infants, although seroprotective levels were achieved (see section 5.1). Safety data in preterm infants (born ≤ 37 weeks of gestation) were not collected in clinical trials.

The potential risk of apnoea and the need for respiratory monitoring for 48–72 hours in very preterm infants (born ≤ 28 weeks of gestation), especially those with a history of respiratory immaturity, should be considered when administering the primary vaccination course. Since the benefit of vaccination in this group of infants is high, vaccination should not be cancelled or postponed.

Variants of the immune response to the vaccine depending on genetic polymorphism have not been studied.

In individuals with chronic renal failure, an inadequate response to hepatitis B immunization has been observed. For such patients, the advisability of administering additional doses of hepatitis B vaccine should be considered depending on the levels of antibodies to the hepatitis B virus surface antigen (anti-HBsAg).

Immunogenicity data in infants at risk of HIV infection (infected and uninfected) showed that Hexaxim® vaccine is immunogenic in a potentially immunocompromised population of infants at risk of HIV infection, regardless of their HIV status at birth (see section 5.1). No specific safety concerns were observed in this population.

Precautions for use

The drug should not be administered intravascularly, intradermally, or subcutaneously.

As with all injectable vaccines, this vaccine should be administered with caution to individuals with thrombocytopenia or bleeding disorders, as bleeding may occur in such patients following intramuscular injection.

Impact on laboratory test results

Because the Hib antigen, which is a capsular polysaccharide, is excreted in the urine, a positive urine test for Hib may occur for 1–2 weeks after vaccination. Other tests should be performed to confirm Hib infection during this period.

Hexaxim® contains phenylalanine, potassium and sodium

Hexaxim® contains 85 mcg of phenylalanine per 0.5 ml dose. Phenylalanine may be harmful to people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body is unable to properly excrete it.

Hexaxim® contains less than 1 mmol potassium (39 mg) and less than 1 mmol sodium (23 mg) per dose, i.e. the drug is practically free of potassium and sodium.

Use during pregnancy or breastfeeding

Pregnancy

Not applicable. This vaccine is not for use in women of reproductive age.

Breast-feeding

Not applicable. This vaccine is not for use in women of reproductive age.

Fertility

Not applicable. This vaccine is not for use in women of reproductive age.

Ability to influence reaction speed when driving vehicles or other mechanisms

Not applicable.

Method of administration and doses

Dosage

Primary vaccination

The primary vaccination course consists of 2 doses (administered at least 8 weeks apart) or 3 doses (administered at least 4 weeks apart) according to official recommendations.

All vaccination schedules can be used, including the WHO Expanded Program on Immunization (EPI) with vaccination at 6, 10, 14 weeks of age, regardless of whether the child was given a dose of hepatitis B vaccine immediately after birth or not.

If a child is given a dose of hepatitis B vaccine immediately after birth:

- Hexaxim® can be used to administer additional doses of hepatitis B vaccine starting at 6 weeks of age. If a second dose of hepatitis B vaccine is to be administered before this age, a monovalent hepatitis B vaccine should be used.

- Hexaxim® vaccine can be used in mixed immunization regimens with hexavalent/pentavalent/hexavalent combination vaccines according to official recommendations.

Booster vaccination (revaccination)

After a 2-dose primary vaccination course with Hexaxim® vaccine, one booster dose of the drug should be administered.

After a 3-dose primary vaccination course with Hexaxim® vaccine, one booster dose of the drug should be administered.

Booster doses should be administered no earlier than 6 months after the last dose of the primary vaccination course in compliance with the requirements of officially approved regulatory documents on preventive vaccinations in force in Ukraine. At least one dose of Hib vaccine should be administered.

In addition, if hepatitis B vaccination was not performed immediately after birth, a booster dose of hepatitis B vaccine should be administered. Hexaxim® vaccine can be used for this booster vaccination.

If hepatitis B vaccination was performed immediately after birth, Hexaxim® or pentavalent aKDP-IPV/Hib vaccine can be used as a booster vaccine after a 3-dose primary vaccination schedule.

Hexaxim® can be used as a booster vaccine for individuals who have previously been vaccinated with another hexavalent vaccine or a pentavalent aKDP-IPV/Hib vaccine in combination with a monovalent hepatitis B vaccine.

After vaccination at the age of 6, 10, 14 weeks, according to the WHO EPI recommendations, a booster dose should be administered:

- at least one booster dose of polio vaccine must be administered;

- if the hepatitis B vaccination was not performed immediately after birth, a booster dose of the hepatitis B vaccine must be administered;

- Hexaxim® vaccine can be used for booster vaccination.

When carrying out immunization in Ukraine, the current orders of the Ministry of Health of Ukraine regarding preventive vaccinations should be followed regarding the scheme of use, contraindications and interactions with other drugs.

Vaccinations are carried out by medical personnel in vaccination rooms of medical and preventive institutions.

Method of application

Vaccination should be given by intramuscular injection. The recommended injection sites are the anterolateral aspect of the upper thigh (preferred) in infants and young children from 6 weeks of age, or the deltoid muscle of the shoulder in older children from 15 months of age (the vaccine can be administered at this site from 15 months of age).

Children

The safety and efficacy of Hexaxim® in children under 6 weeks of age have not been established. There are no data on this.

There are also no data on the use of this drug in older children (see sections “Adverse reactions” and “Immunological and biological properties”).

Overdose

No cases of overdose have been reported.

Adverse reactions

a) Summary of the safety profile of the drug

During clinical trials, the most commonly observed reactions in individuals receiving Hexaxim® were injection site pain, irritability, crying, and injection site erythema.

The safety of Hexaxim® vaccine in children over 24 months of age has not been studied in clinical trials.

1. b) Tabulated list of adverse reactions

The following conventions were used to classify adverse reactions:

very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), frequency unknown (cannot be estimated from the available data).

Adverse reactions reported during clinical trials and post-marketing surveillance

* Adverse reactions reported from spontaneous reports.

† See section (c).

c) Description of selected adverse reactions

Extensive swelling of the limb. Extensive injection site reactions (> 50 mm) have been reported in children, including extensive swelling of the limb that may extend from the injection site to one or two adjacent joints. These reactions begin within 24–72 hours after vaccination, may be accompanied by symptoms such as erythema, local skin temperature, tenderness or pain at the injection site, and resolve spontaneously within 3–5 days. The risk of developing them depends on the number of previous doses of acellular pertussis vaccines, with a higher risk after the 4th dose.

d) Potential adverse reactions (i.e. adverse reactions that were not observed specifically after vaccination with the Hexaxim® vaccine, but were reported after the use of other vaccines containing one or more components included in the Hexaxim® vaccine).

Nervous system disorders

- Cases of brachial neuritis and Guillain-Barré syndrome have been reported following the use of tetanus toxoid-containing vaccines.

- Cases of peripheral neuropathy (polyradiculoneuritis, facial nerve palsy), optic neuritis, central nervous system demyelination, and central nervous system demyelinating diseases (multiple sclerosis) have been reported following the use of a vaccine containing hepatitis B antigen.

- Encephalopathy/encephalitis.

Respiratory, thoracic and mediastinal disorders

Apnea in very premature infants (born ≤ 28 weeks of gestation) (see section "Special warnings and precautions for use").

General disorders and administration site conditions

Following vaccination with vaccines containing Haemophilus influenzae type b antigen, oedematous reactions affecting one or both lower limbs may occur. This reaction is mainly observed after the first injection and lasts for the first