HEXAXIM

Abbreviated Prescribing Information

See local prescribing information for full details prior to prescribing

TRADE NAME OF THE MEDICINAL PRODUCT AND PRESENTATION

HEXAXIM (DTaP-IPV-HB-Hib) suspension for injection of diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) is available in a 0.5 mL pre-filled syringe.

THERAPEUTIC INDICATIONS

HEXAXIM (DTaP-IPV-HB-Hib) is indicated for primary and booster vaccination of infants and toddlers from six weeks to 24 months of age against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib).

POSOLOGY AND METHOD OF ADMINISTRATION

Posology

Primary vaccination

The primary vaccination consists of 3 doses of 0.5 mL to be administered at intervals of at least four weeks and as per schedules 6, 10, 14 weeks; 2, 4, 6 months and 2, 3, 4 months. All vaccination schedules including the WHO Expanded Program on Immunisation (EPI) at 6, 10, 14 weeks of age can be used whether or not a dose of hepatitis B vaccine has been given at birth.

Where a dose of hepatitis B vaccine is given at birth; Hexaxim can be used for supplementary doses of hepatitis B vaccine from the age of six weeks. If a second dose of hepatitis B vaccine is required before this age, monovalent hepatitis B vaccine should be used.

The use of this vaccine should be in accordance with official recommendations.

Booster vaccination:

After a 3-dose primary vaccination with Hexaxim (6,10,14 weeks; 2,4,6 months and 2,3,4 months), a booster dose of HepB and Hib must be administered during the second year of life and at least 6 months after the last priming dose.

Booster doses should be given in accordance with the official recommendations. As a minimum, a dose of Hib vaccine must be administered.

After a 3-dose WHO EPI schedule with Hexaxim (6, 10, 14 weeks) and in the absence of hepatitis B vaccination at birth, a hepatitis B vaccine booster must be given. At the very least, a booster dose of polio vaccine should be given. Hexaxim can be considered for the booster.

When a hepatitis B vaccine is given at birth, after a 3-dose primary vaccination, Hexaxim or a pentavalent DTaP-IPV/Hib vaccine can be administered for the booster.

Hexaxim may be used as a booster in individuals who have previously been vaccinated with another hexavalent vaccine or a pentavalent DTaP-IPV/Hib vaccine associated with a monovalent hepatitis B vaccine.

Other paediatric population:

The safety and efficacy of Hexaxim in children over 24 months of age have not been established.

Method of administration

Immunisation must be carried out by intramuscular (IM) injection. The recommended injection sites are the antero-lateral area of the upper thigh (preferred site) or the deltoid muscle in older children (possibly from 15 months of age).

CONTRA-INDICATIONS

History of an anaphylactic reaction after a previous administration of Hexaxim.

Hypersensitivity to the active substances, to any of the excipients of vaccine, to trace residuals (glutaraldehyde, formaldehyde, neomycin, streptomycin and polymyxin B), to any pertussis vaccine, or after previous administration of Hexaxim or a vaccine containing the same components or constituents.

Vaccination with Hexaxim is contraindicated if the individual has experienced an encephalopathy of unknown aetiology, occurring within 7 days following prior vaccination with a pertussis containing vaccine (whole cell or acellular pertussis vaccines).

In these circumstances pertussis vaccination should be discontinued and the vaccination course should be continued with diphtheria, tetanus, hepatitis B, poliomyelitis and Hib vaccines.

Pertussis vaccine should not be administered to individuals with uncontrolled neurologic disorder or uncontrolled epilepsy until treatment for the condition has been established, the condition has stabilised and the benefit clearly outweighs the risk.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

Hexaxim will not prevent disease caused by pathogens other than Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis, hepatitis B virus, poliovirus or Haemophilus influenzae type b. However, it can be expected that hepatitis D will be prevented by immunisation as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection.

Hexaxim will not protect against hepatitis infection caused by other agents such as hepatitis A, hepatitis C and hepatitis E or by other liver pathogens.

Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B infection to be present at the time of vaccination. The vaccine may not prevent

hepatitis B infection in such cases.

Hexaxim does not protect against infectious diseases caused by other types of Haemophilus influenzae or against meningitis of other origins.

Prior to immunisation

Immunisation should be postponed in individuals suffering from moderate to severe acute febrile illness or infection. The presence of a minor infection and/or low-grade fever should not result in the deferral of vaccination.

Vaccination should be preceded by a review of the person’s medical history (in particular previous vaccinations and possible adverse reactions). The administration of Hexaxim must be carefully considered in individuals who have a history of serious or severe reactions within 48 hours following administration of a vaccine containing similar components.

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

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

Temperature of ≥ 40°C within 48 hours of vaccination not due to another identifiable cause;
Collapse or shock-like state (hypotonic-hypo responsive episode) within 48 hours of vaccination;
Persistent, inconsolable crying lasting ≥ 3 hours, occurring within 48 hours of vaccination;
Convulsions with or without fever, occurring within 3 days of vaccination. There may be some circumstances, such as high incidence of pertussis, when the potential benefits outweigh possible risks

A history of febrile convulsions, a family history of convulsions or Sudden Infant Death Syndrome (SIDS) do not constitute a contraindication for the use of Hexaxim.

Individuals with a history of febrile convulsions should be closely followed up as such adverse events may occur within 2 to 3 days post vaccination.

If Guillain-Barre syndrome or brachial neuritis has occurred following receipt of prior vaccine containing tetanus toxoid, the decision to give any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks, such as whether or not the primary vaccination has been completed. Vaccination is

usually justified for individuals whose primary vaccination is incomplete (i.e. fewer than three doses have been received).

The immunogenicity of the vaccine may be reduced by immunosuppressive treatment or immunodeficiency. It is recommended to postpone vaccination until the end of such treatment or disease. Nevertheless, vaccination of individuals with chronic immunodeficiency such as HIV infection is recommended even if the antibody response may be limited.

Special populations:

Immunogenicity data are available for 105 preterm infants. These data support the use of Hexaxim in preterm infants. As expected in preterm infants, lower immune response has been observed for some antigens, when indirectly compared to term infants, although seroprotective levels have been achieved (see section Pharmacodynamic properties). No safety data were collected in preterm infants (born ≤ 37 weeks of gestation) in clinical trials.

The potential risk of apnoea and the need for respiratory monitoring for 48 to 72 hours should be considered when administering the primary immunisation series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

Immune responses to the vaccine have not been studied in the context of genetic polymorphism.

In individuals with chronic renal failure, an impaired hepatitis B response is observed and administration of additional doses of hepatitis B vaccine should be considered according to the antibody level against hepatitis B virus surface antigen (anti-HBsAg).

Precautions for use

Do not administer by intravascular, intradermal or subcutaneous injection.

As with all injectable vaccines, the vaccine must be administered with caution to individuals with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration.

The potential risk of apnoea and the need for respiratory monitoring for 48 to 72 hours should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

Interference with laboratory testing

Since the Hib capsular polysaccharide antigen is excreted in the urine, a positive urine test can be observed within 1 to 2 weeks following vaccination. Other tests should be performed in order to confirm Hib infection during this period.

Hexaxim contains phenylalanine, potassium and sodium

Hexaxim contains 85 micrograms phenylalanine in each 0.5 ml dose.

Phenylalanine may be harmful for individuals with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Special Precaution For Use

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Keep the container in the outer carton in order to protect from light.

Stability data indicate that the vaccine components are stable at temperatures up to 25°C for 72 hours. At the end of this period, Hexaxim should be used or discarded. These data are intended to guide healthcare professionals in case of temporary temperature excursion only.

INTERACTIONS

Hexaxim can be administered simultaneously with a pneumococcal polysaccharide conjugate vaccine, measles, mumps, rubella (MMR) containing vaccines, rotavirus vaccines, a meningococcal C conjugate vaccine or a meningococcal group A, C, W-135 and Y conjugate vaccine, as no clinically relevant interference in the antibody response to each of the antigens have been shown.

There may be a clinically relevant interference in the antibody response of Hexaxim and a varicella vaccine and these vaccines should not be administered at the same time.

If co-administration with another vaccine is considered, immunisation should be carried out on separate injection sites.

Hexaxim must not be mixed with any other vaccines or other parenterally administered medicinal products.

PREGNANCY AND LACTATION

Not applicable. This vaccine is not intended for administration to women of child-bearing age.

UNDESIRABLE EFFECTS

In clinical studies in individuals who received Hexaxim, the most frequently reported reactions include injection-site pain, irritability, crying, and injection-site erythema. Slightly higher solicited reactogenicity was observed after the first dose compared to subsequent doses.

Adverse Reactions from clinical trials and post marketing surveillance : the very common and common adverse reaction : anorexia, crying, somnolence, abnormal crying, vomiting, diarrhoea,injection site pain, injection-site erythema, injection-site swelling, irritability, Pyrexia, injection site induration. For detailed uncommon and rare adverse reaction, please see in full Product information.

Extensive limb swelling: Large injection-site reactions (>50 mm), including extensive limb swelling from the injection site beyond one or both joints, have been reported in children. These reactions start within 24-72 hours after vaccination, may be associated with erythema, warmth, tenderness or pain at the injection site and resolve spontaneously within 3-5 days. The risk appears to be dependent on the number of prior doses of acellular pertussis containing vaccine, with a greater risk following the 4th doses.

Potential adverse events (i.e. adverse events which have been reported with other vaccines containing one or more of the components or constituents of Hexaxim and not directly with Hexaxim) :Anaphylactic reaction; convulsion with or without fever ; brachial neuritis and Guillain-Barre Syndrome after administration of a tetanus toxoid containing

Vaccine; peripheral neuropathy (polyradiculoneuritis, facial paralysis), optic neuritis,

central nervous system demyelination (multiple sclerosis) have been reported after administration of a hepatitis B antigen containing vaccine; encephalopathy/encephalitis, apnoea in very premature infants (≤ 28 weeks of gestation), Oedematous reaction affecting one or both lower limbs may occur following vaccination with Haemophilus influenzae

type b containing vaccines. If this reaction occurs, it is mainly after primary injections and within the first few hours following vaccination. Associated symptoms may include

cyanosis, redness, transient purpura and severe crying. All events should resolve spontaneously without sequel within 24 hours.

OVERDOSE

No cases of overdose have been reported.

10. PHARMACODYNAMIC PROPERTIES

ATC Code: J07CA09.

Persistence of immune response

Studies on long-term persistence of vaccine induced antibodies following varying infant / toddler primary series and following Hepatitis B vaccine given at birth or not have shown maintenance of levels above the recognized protective levels or antibody thresholds for the vaccine antigens. In addition, immunity against the hepatitis B component of the vaccine has been shown to persist up to 9 years of age after a primary series consisting of one dose of Hepatitis B vaccine given at birth followed by a 3-dose infant series at 2, 4, and 6 months of age without a toddler booster where 49.3% of vaccinees had antibodies ≥ 10 mIU/ml with geometric mean concentrations at 13.3 (95% CI: 8.82 – 20.0) mIU/ml..

Immune responses to Hexaxim in preterm infants

Immune responses to Hexaxim antigens in preterm (105) infants (born after a gestation period of 28 to 36 weeks), including 90 infants born to women vaccinated with Tdap vaccine during pregnancy and 15 to women not vaccinated during pregnancy, were evaluated following 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 subjects were seroprotected against diphtheria (≥ 0.01 IU/mL), tetanus (≥ 0.01 IU/mL) and poliovirus types 1, 2 and 3 (≥ 8 (1/dilution)); 89.8% of subjects were seroprotected against hepatitis B (≥ 10 IU/mL) and 79.4% were seroprotected against Hib invasive diseases (≥ 0.15 μg/mL).

One month after the booster dose, all subjects were seroprotected against diphtheria (≥ 0.1 IU/mL), tetanus (≥ 0.1 IU/mL) and poliovirus types 1, 2 and 3 (≥ 8 (1/dilution)); 94.6% of subjects were seroprotected against hepatitis B (≥ 10 IU/mL) and 90.6% were seroprotected against Hib invasive diseases (≥ 1 μg/mL).

Regarding pertussis, one month after primary vaccination 98.7% and 100% of subjects developed antibodies ≥ 8 EU/mL against PT and FHA antigens respectively. One month after the booster dose 98.8% of subjects developed antibodies ≥ 8 EU/mL against both PT and FHA antigens. Pertussis antibody concentrations were increased by 13-fold after primary vaccination and by 6- to 14-fold after the booster dose.

Immune responses to Hexaxim in infants born to women vaccinated with Tdap during pregnancy

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

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

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

Regarding pertussis, one month after primary vaccination 99.4% and 100% of subjects developed antibodies ≥ 8 EU/mL against PT and FHA antigens respectively. One month after the booster dose 99.4% of subjects developed antibodies ≥ 8 EU/mL against both PT and FHA antigens. Pertussis antibody concentrations were increased by 5- to 9-fold after primary vaccination and by 8- to 19-fold after the booster dose.

Presentation: Box , 1 Prefilled syringe @ 0.5 mL with 2 separate needles

(DKI1459703243A1)

Date of revision: 10 Mei 2023 (based on BPOM approval 09 Mei 2023)

This information is intended for Health Care Professional only. See local product information for full details information