Consumer medicine information

Hexaxim

Diphtheria toxoid; Haemophilus B conjugate vaccine; Tetanus toxoid; Hepatitis B vaccine; Pertussis vaccine; Poliomyelitis vaccine (inactivated)

BRAND INFORMATION

Brand name

Hexaxim

Active ingredient

Diphtheria toxoid; Haemophilus B conjugate vaccine; Tetanus toxoid; Hepatitis B vaccine; Pertussis vaccine; Poliomyelitis vaccine (inactivated)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Hexaxim.

What is in this leaflet

Read all of this leaflet carefully before your child is vaccinated.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This vaccine has been prescribed for your child. Do not pass it on to others.
  • If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

  • What Hexaxim is and what it is used for
  • Before your child is given Hexaxim
  • How Hexaxim is given
  • Possible side effects
  • Storing Hexaxim
  • Further information

What Hexaxim is and what it is used for

Hexaxim (DTPa-hepB-IPV-Hib) is a vaccine used to protect against infectious diseases.

Hexaxim helps to protect against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and serious diseases caused by Haemophilus influenzae type b. Hexaxim can be given to children from six weeks of age.

The vaccine works by causing the body to produce its own protection (antibodies) against the bacteria and viruses that cause these different infections:

  • Diphtheria is an infectious disease that usually first affects the throat. In the throat, the infection causes pain and swelling which can lead to suffocation. The bacteria that cause the disease also make a toxin (poison) that can damage the heart, kidneys and nerves.
  • Tetanus (often called lock jaw) is usually caused by the tetanus bacteria entering a deep wound. The bacteria make a toxin (poison) that causes spasms of the muscles, leading to inability to breathe and the possibility of suffocation.
  • Pertussis (often called whooping cough) is a highly infectious illness that affects the airways. It causes severe coughing that may lead to problems with breathing. The coughing often has a "whooping" sound. The cough may last for one to two months or longer. Whooping cough can also cause ear infections, chest infections (bronchitis) which may last a long time, lung infections (pneumonia), fits, brain damage and even death.
  • Hepatitis B is caused by the hepatitis B virus. It causes the liver to become swollen (inflamed). In some people, the virus can stay in the body for a long time, and can eventually lead to serious liver problems, including liver cancer.
  • Poliomyelitis (often just called polio) is caused by viruses that affect the nerves. It can lead to paralysis or muscle weakness most commonly of the legs. Paralysis of the muscles that control breathing and swallowing can be fatal.
  • Haemophilus influenzae type b infections (often just called Hib) are serious bacterial infections and can cause meningitis (inflammation of the outer covering of the brain), which can lead to brain damage, deafness, epilepsy, or partial blindness. Infection can also cause inflammation and swelling of the throat, leading to difficulties in swallowing and breathing, and infection can affect other parts of the body such as the blood, lungs, skin, bones, and joints.

Important information about the protection provided

Hexaxim will only help to prevent these diseases if they are caused by the bacteria or viruses targeted by the vaccine. Your child could get diseases with similar symptoms if they are caused by other bacteria or viruses.

The vaccine does not contain any live bacteria or viruses and it cannot cause any of the infectious diseases against which it protects.

This vaccine does not protect against infections caused by other types of Haemophilus influenzae nor against meningitis due to other micro-organisms.

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

Because symptoms of hepatitis B take a long time to develop, 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.

Remember that no vaccine can provide complete, lifelong protection in all people who are vaccinated.

Before your child is given Hexaxim

When your child must not be given Hexaxim

Do not give Hexaxim if your child:

  • has had respiratory disorder or swelling of the face (anaphylactic reaction) after administration of Hexaxim.
  • has had an allergic reaction
    - to any of the ingredients listed in FURTHER INFORMATION
    - after previous administration of Hexaxim or any other diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B or Hib containing vaccines.
  • suffered from a severe reaction affecting the brain (encephalopathy) within 7 days of a prior dose of a pertussis vaccine (acellular or whole cell pertussis).
  • has an uncontrolled condition or severe illness affecting the brain and nervous system (uncontrolled neurologic disorder) or uncontrolled epilepsy.

Before your child is given Hexaxim

Tell your doctor if your child:

  • has a moderate or high temperature or an acute illness (e.g. fever, sore throat, cough, cold or flu). Vaccination with Hexaxim may need to be delayed until your child is better.
  • has had any of the following events after receiving a pertussis vaccine, as the decision to give further doses of pertussis containing vaccine will need to be carefully considered:
    - fever of 40°C or above within 48 hours not due to another identifiable cause.
    - collapse or shock-like state with hypotonic-hyporesponsive episode (drop in energy) within 48 hours of vaccination.
    - persistent, inconsolable crying lasting 3 hours or more, occurring within 48 hours of vaccination.
    - fits (convulsions) with or without fever, occurring within 3 days of vaccination.
  • previously had Guillain-Barre syndrome (temporary inflammation of nerves causing pain, paralysis and sensitivity disorders) or brachial neuritis (severe pain and decreased mobility of arm and shoulder) after being given a vaccine containing tetanus toxoid (an inactivated form of tetanus toxin). In this case, the decision to give any further vaccine containing tetanus toxoid should be evaluated by your doctor.
  • is having a treatment that suppresses her/his immune system (the body's natural defences) or has any disease that causes the weakness of the immune system. In these cases the immune response to the vaccine may be decreased. It is normally recommended to wait until the end of the treatment or disease before vaccinating. However children with long standing problems with their immune system such as HIV infection (AIDS) may still be given Hexaxim but the protection may not be as good as in children whose immune system is healthy.
  • is born prematurely. Lower responses to the vaccine may be observed in relation with immaturity of the immune system. However, according to national recommendations, vaccination should not be delayed. In addition, longer gaps than normal between breaths may occur for 2 -3 days after vaccination.
  • suffers from an acute or chronic illness including chronic renal insufficiency or failure (inability of the kidneys to work properly).
  • suffers from any undiagnosed illness of the brain or epilepsy which is not controlled. Your doctor will assess the potential benefit offered by vaccination.
  • has any problems with the blood that cause easy bruising or bleeding for a long time after minor cuts. Your doctor will advise you whether your child should have Hexaxim.

Taking other medicines

Please tell your doctor if your child is taking or has recently taken any other medicines, including medicines obtained without prescription.

Having other vaccines

Your doctor will advise you if Hexaxim is to be given with another vaccine.

How Hexaxim is given

Hexaxim is administered to your child by your doctor or nurse.

Hexaxim is injected into the muscle in the upper part of your child's leg or upper arm.

First course of vaccination (primary vaccination)
Your child will receive two injections given at an interval of at least eight weeks apart, or three injections given at an interval of at least four weeks apart. This vaccine should be used according to the local vaccination programme.

Additional injections (booster)
After the first course of injections, your child may require a booster dose, in accordance with local recommendations. Your doctor will advise you if your child requires a booster dose.

If you forget one dose of Hexaxim

If your child misses a scheduled injection, it is important that you discuss with your doctor or nurse who will decide when to give the missed dose.

It is important to follow the instructions from the doctor or nurse so that your child completes the course of injections. If not, your child may not be fully protected against the diseases.

If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse.

Possible side effects

Like all medicines, Hexaxim can cause side effects, although not everybody gets them.

Serious allergic reactions

Serious allergic reactions are a very rare possibility (may affect up to 1 in 10,000 people) after receiving any vaccine.

Signs and symptoms of serious allergic reactions usually develop quickly after the injection is given and while the child is still in the clinic or doctor’s surgery

If any of these symptoms occur after leaving the place where your child has received Hexaxim, you must consult a doctor IMMEDIATELY:

  • difficulty in breathing
  • blueness of the tongue or lips
  • a rash
  • swelling of the face or throat
  • low blood pressure causing dizziness or collapse.

Other side effects:
If your child experiences any of the following side effects, please tell your doctor, nurse or pharmacist.

Very common (may affect more than 1 in 10 people):

  • pain, redness or swelling at the injection site
  • loss of appetite
  • crying
  • sleepiness
  • vomiting
  • irritability
  • fever (temperature 38°C or higher)

Common (may affect up to 1 in 10 people):

  • abnormal crying (prolonged crying)
  • diarrhoea
  • injection site hardness

Uncommon (may affect up to 1 in 100 people):

  • allergic reaction
  • lump at the injection site
  • high fever (temperature 39.6°C or higher)

Rare (may affect up to 1 in 1000 people):

  • rash
  • large reactions at the injection site (larger than 5 cm), including extensive limb swelling from the injection site beyond one or both joints. These reactions start within 24-72 hours after vaccination, may be associated with redness, warmth, tenderness or pain at the injection site, and get better within 3-5 days without the need for treatment.

Very rare (may affect up to 1 in 10,000 people):

  • episodes when your child goes into a shock-like state or is pale, floppy and unresponsive for a period of time (hypotonic reactions or hypotonic hyporesponsive episodes HHE).
  • serious allergic reaction (anaphylactic reaction)
  • fits (convulsions) with or without fever

Other side effects not listed above have been reported occasionally with other diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B or Hib containing vaccines and not directly with Hexaxim:

  • temporary inflammation of nerves causing pain, paralysis and sensitivity disorders (Guillain-Barré syndrome) and severe pain and decreased mobility of arm and shoulder (brachial neuritis) have been reported after administration of a tetanus containing vaccine.
  • inflammation of several nerves causing sensory disorders or weakness of limbs (polyradiculoneuritis), facial paralysis, visual disturbances, sudden dimming or loss of vision (optic neuritis), inflammatory disease of brain and spinal cord (central nervous system demyelination, multiple sclerosis) have been reported after administration of a hepatitis B antigen containing vaccine.
  • swelling or inflammation of the brain (encephalopathy/encephalitis).
  • in babies born very prematurely (at or before 28 weeks of gestation) longer gaps than normal between breaths may occur for 2 -3 days after vaccination.
  • swelling of one or both feet and lower limbs which may occur along with bluish discolouration of the skin, redness, small areas of bleeding under the skin and severe crying following vaccination with Haemophilus influenzae type b containing vaccines. If this reaction occurs, it is mainly after first injections and within the first few hours following vaccination. All symptoms should disappear completely within 24 hours without the need for treatment.

If your child gets any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

Storing Hexaxim

Hexaxim is usually stored in the doctor's surgery or clinic, or at the pharmacy. However, if you need to store Hexaxim

  • Keep out of reach and sight of children.
  • Keep Hexaxim in the original pack until it is time for it to be given.
  • Keep it in the refrigerator, store at 2C to 8C. Do not freeze Hexaxim.

Do not use Hexaxim after the expiry date which is stated on the carton after EXP.

Do not use Hexaxim if the packaging is torn or shows signs of tampering.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information

What Hexaxim contains

Each 0.5 ml dose of Hexaxim contains:

  • At least 20 IU of diphtheria toxoid
  • At least 40 IU of tetanus toxoid
  • 25 micrograms of pertussis toxoid and 25 micrograms of pertussis filamentous haemagglutinin
  • 10 micrograms of hepatitis B surface antigen
  • 40 D antigen Units of poliovirus Type 1, 8 D antigen Units of poliovirus Type 2, 32 D antigen Units of poliovirus Type 3
  • 12 micrograms of Haemophilus type B polysaccharide conjugated to 22 - 36 micrograms of tetanus protein

The other ingredients include dibasic sodium phosphate-, mono basic potassium phosphate-, trometamol, sucrose, essential amino acids (cystine, tyrosine, arginine hydrochloride, histidine, isoleucine, leucine, lysine hydrochloride, methionine, phenylalanine, threonine, tryptophan and valine) and water for injections.

The vaccine may contain traces of glutaral, formaldehyde, neomycin, streptomycin and polymyxin B.

The manufacture of this product includes exposure to bovine materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

What Hexaxim looks like and contents of the pack

Hexaxim is provided as a fully liquid suspension for injection in pre-filled syringe (0.5 mL).

Hexaxim is available in a pack containing 1 pre-filled syringe with 1 or 2 needles.

Hexaxim is available in a pack containing 10 pre-filled syringes with 10 or 20 needles.

Not all pack sizes may be marketed.

After shaking, the normal appearance of the vaccine is a whitish cloudy suspension.

Name and Address of Australian Sponsor

sanofi-aventis australia pty ltd
Talavera Corporate Centre - Building D
12-24 Talavera Road
Macquarie Park NSW 2113
Australia
Tel: 1800 818 806

Name and Address of New Zealand Sponsor

sanofi-aventis new zealand limited
Level 8
56 Cawley St
Ellerslie
Auckland
New Zealand
Tel: 0800 283 684

AUST R number

AUST R 215536

Date of preparation

28 March 2019

hexa-ccdsv7-cmiv3-28mar19

Published by MIMS May 2019

BRAND INFORMATION

Brand name

Hexaxim

Active ingredient

Diphtheria toxoid; Haemophilus B conjugate vaccine; Tetanus toxoid; Hepatitis B vaccine; Pertussis vaccine; Poliomyelitis vaccine (inactivated)

Schedule

S4

 

1 Name of Medicine

Hexaxim.
DTPa-hepB-IPV-Hib - Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed).

6.7 Physicochemical Properties

Not applicable.

2 Qualitative and Quantitative Composition

Hexaxim is a preservative free liquid formulation for intramuscular administration which combines: diphtheria and tetanus toxoids, acellular pertussis (2-component), recombinant hepatitis B surface antigen, inactivated poliomyelitis virus and Haemophilus influenzae type b polysaccharide conjugated to tetanus protein.
Each 0.5 mL, adsorbed to aluminium hydroxide hydrate (0.6 mg, expressed as Al3+), contains. See Table 1.
The vaccine may contain traces of glutaral, formaldehyde, neomycin, streptomycin and polymyxin B.
Contains phenylalanine. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Hexaxim is a whitish, cloudy suspension for injection.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: vaccines, bacterial and viral combined, ATC code: J07CA09.

Mechanism of action.

Hexaxim induces the production of antibodies against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae type b.

Clinical trials.

The primary vaccination schedules that have been used are: 3, 5 months without hepatitis B vaccination at birth; 6, 10, 14 weeks with and without hepatitis B vaccination at birth; 2, 3, 4 months without hepatitis B vaccination at birth; 2, 4, 6 months with and without hepatitis B vaccination at birth.
Results obtained in the clinical studies for each of the components are summarised in Tables 3 and 4.
The long term capability of the acellular pertussis antigens contained in Hexaxim to reduce pertussis incidence and control pertussis disease has been demonstrated in a 15-year national pertussis surveillance on pertussis disease in Sweden with the pentavalent DTPa-IPV/Hib vaccine using a 3, 5, 12 months schedule (1). Several types of acellular pertussis vaccines were used during the 15 year follow-up. It is not possible to detect differences in vaccine effectiveness using surveillance data due to different vaccines and schedules used during the study period, variability in vaccine coverage and surveillance systems and cyclic variations in infection and disease.
The vaccine effectiveness against Hib invasive disease of DTPa and Hib combination vaccines (pentavalent and hexavalent including vaccines containing the Hib antigen from Hexaxim) has been demonstrated in Germany via an extensive (over five years follow-up period) post-marketing surveillance study. The vaccine effectiveness was 96.7% for the full primary series, and 98.5% for booster dose (irrespective of priming) (2) (3).

5.2 Pharmacokinetic Properties

No pharmacokinetic studies have been performed.

5.3 Preclinical Safety Data

Genotoxicity.

Hexaxim has not been evaluated for genotoxic potential.

Carcinogenicity.

Hexaxim has not been evaluated for carcinogenic potential.

4 Clinical Particulars

4.1 Therapeutic Indications

Hexaxim is indicated for vaccination of infants from six weeks of age against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae type b.
Use of this vaccine should be in accordance with the national recommendation as per the current immunisation handbook.

4.3 Contraindications

Hexaxim should not be administered to anyone with a history of severe allergic reaction to any component of the vaccine or to any pertussis vaccine, after previous administration of the vaccine or a vaccine containing the same components or constituents.
Vaccination with Hexaxim is contraindicated if the individual has experienced an encephalopathy of unknown aetiology within 7 days of administration of a previous dose of any vaccine containing pertussis antigens (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.
Progressive neurological disorder, uncontrolled epilepsy, progressive encephalopathy. Pertussis vaccine should not be administered to individuals with these common conditions until the treatment regimen has been established, the condition has stabilised and the benefit clearly outweighs the risk.
Generally vaccination must be postponed in cases of moderate or severe febrile and/or acute disease and low-grade fever does not constitute a contraindication.

4.4 Special Warnings and Precautions for Use

Do not administer intravenously, intradermally or subcutaneously.

Prior to vaccination.

Anaphylaxis.

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following administration of the vaccine.

Hypersensitivity.

As each dose may contain undetectable traces of glutaraldehyde, formaldehyde, neomycin, streptomycin and polymyxin B, caution should be exercised when the vaccine is administered to individuals with hypersensitivity to these substances.

Bleeding disorder.

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.

Previous pertussis vaccination.

If any of the following events are known to have occurred in temporal relation to receipt of pertussis-containing vaccine, the decision to give further doses of pertussis-containing vaccine should be carefully considered:
temperature of ≥ 40°C within 48 hours not due to another identifiable cause;
collapse or shock-like state (hypotonic-hyporesponsive 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.

Family and individual history.

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.

Protection.

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.
As with any vaccine, vaccination with Hexaxim may not protect 100% of susceptible individuals.

Special patient groups.

Premature and low birth weight infants.

No data are available for premature infants and infants of low birth weight < 2.5 kg. Lower immune response may be observed in this population in relation with immaturity of the immune system. However, according to several national recommendations, vaccination should not be delayed.
The potential risk of apnoea and the need for respiratory monitoring for 48-72 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.

Immunocompromised individuals.

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.

Neurological disorder.

If Guillain-Barré 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 immunisation schedule has been completed. Vaccination is usually justified for infants whose primary immunisation schedules are incomplete (i.e. fewer than three doses have been received).
Some case reports of multiple sclerosis have been reported after administration of hepatitis B vaccine. To date a causal relationship has not been demonstrated with hepatitis B vaccine.

Chronic renal failure.

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).

Genetic polymorphism.

Immune responses to the vaccine have not been studied in the context of genetic polymorphism.
The immunogenicity of Hexaxim has not been studied in the Australian indigenous populations.

Use in the elderly.

Not applicable.

Paediatric use.

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

Effects on laboratory tests.

Interference of Hexaxim with laboratory and/or diagnostic tests has not been studied.
However, antigenuria (PRP antigen) has been detected in some instances following receipt of Haemophilus influenzae type b conjugate vaccine. Therefore, urine antigen detection may not have definite diagnostic value in suspected Haemophilus influenzae type b disease within two weeks of immunisation.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Hexaxim must not be mixed with other vaccines or other parenterally administered drugs.
Separate injection sites must be used in case of concomitant administration.
Data on concomitant administration of Hexaxim with 7-valent or 13-valent pneumococcal polysaccharide conjugate vaccines have shown no clinically relevant interference in the antibody response to each of the individual antigens.
Data on concomitant administration of Hexaxim with measles-mumps-rubella vaccine and with varicella vaccine have shown no clinically relevant interference in the antibody response to each of the antigens when given as a booster vaccination.
Data on concomitant administration of rotavirus vaccines have shown no clinically relevant interference in the antibody response to each of the antigens.
Data on concomitant administration of Hexaxim with a meningococcal serogroup C-tetanus toxoid conjugate vaccine or a meningococcal serogroups A, C, W-135, Y-tetanus toxoid conjugate vaccine have shown no clinically relevant interference in the antibody response to each of the antigens.
Except in the case of immunosuppressive therapy (see Section 4.4 Special Warnings and Precautions for Use), no significant clinical interaction with other treatments or biological products has been reported.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Animal studies have not been conducted to determine the effects of Hexaxim on fertility.
(Category B2)
Hexaxim is not indicated for use during pregnancy and has not been evaluated for potential harmful effects during pregnancy in animals or humans.
Hexaxim is not indicated for use in breastfeeding women and it is not known whether Hexaxim components are excreted in human milk.

4.8 Adverse Effects (Undesirable Effects)

The adverse events are ranked under headings of frequency per dose, using the following convention: very common ≥ 1/10 (≥ 10%); common ≥ 1/100 to < 1/10 (≥ 1% and < 10%); uncommon ≥ 1/1,000 to < 1/100 (≥ 0.1% and < 1%); rare ≥ 1/10,000 to < 1/1000 (≥ 0.01% and < 0.1%); very rare < 1/10,000 (< 0.01%); not known: cannot be estimated from available data.

Clinical trials experience.

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

Immune system disorders.

Uncommon: hypersensitivity reaction.

Metabolism and nutrition disorders.

Very common: anorexia.

Nervous system disorders.

Very common: crying, somnolence.
Common: abnormal crying (prolonged crying).
Very rare: hypotonic reactions or hypotonic-hyporesponsive episodes (HHE).

Gastrointestinal disorders.

Very common: vomiting.
Common: diarrhoea.

Skin and subcutaneous tissue disorders.

Rare: rash.

General disorders and administration site conditions.

Very common: injection site pain, injection site erythema, injection site swelling, irritability, pyrexia (body temperature ≥ 38.0°C).
Common: injection site induration.
Uncommon: injection site nodule, pyrexia (body temperature ≥ 39.6°C).
Rare: 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 and 5th doses.

Adverse reactions from post-marketing surveillance.

Immune system disorders.

Very rare: anaphylactic reactions.

Nervous system disorders.

Very rare: convulsions with or without fever.

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).
Brachial neuritis and Guillain-Barré syndrome have been reported after administration of a tetanus toxoid containing vaccine.
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 resolve spontaneously without sequel within 24 hours.
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) (see Section 4.4 Special Warnings and Precautions for Use).
Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.2 Dose and Method of Administration

Hexaxim is for intramuscular injection according to the dosing schedule in Table 2.
For further information, refer to the current immunisation handbook.

Administration.

Before use, the vaccine should be shaken in order to obtain a homogeneous whitish cloudy suspension.
Hexaxim should be administered intramuscularly. The recommended injection sites are generally the antero-lateral aspect of the upper thigh in infants and toddlers and the deltoid muscle in older children.
Do not administer via intravascular route: ensure that the needle does not penetrate a blood vessel.
Do not administer by intradermal or subcutaneous injection.
Separate syringes, separate injection sites and preferably separate limbs must be used in case of concomitant administration with other vaccines.
Hexaxim is for single use only and must not be used in more than one individual. Discard any remaining unused contents.

4.7 Effects on Ability to Drive and Use Machines

Not applicable.

4.9 Overdose

Not documented.
For general advice on overdose management, contact the Poisons Information Centre, telephone number 13 11 26 (Australia) or the National Poisons Centre, 0800 POISON or 0800 764 766 (New Zealand).

7 Medicine Schedule (Poisons Standard)

S4.

References

1. The Public Health Agency of Sweden, Pertussis Surveillance in Sweden - Fifteen Year Report, 2013 http://www.folkhalsomyndigheten.se/pagefiles/17379/pertussis-surveillance%20in-sweden-fifteen-year-report%282%29.pdf.
2. Kalies H et al, Four and one-half year follow-up of the effectiveness of diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b and diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus/H. influenzae type b combination vaccines in Germany. Pediatr Infect Dis J 2004;23(10):944-950.
3. Schmitt HJ et al. Haemophilus influenzae type b disease: impact and effectiveness of diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b combination vaccines. Pediatr Infect Dis J 2001;20(8):767-774.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hexaxim contains the excipients; dibasic sodium phosphate, monobasic potassium phosphate, trometamol, sucrose, essential amino acids (cystine, tyrosine, arginine hydrochloride, histidine, isoleucine, leucine, lysine hydrochloride, methionine, phenylalanine, threonine, tryptophan and valine) and water for injections.
The manufacture of this product includes exposure to bovine materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

6.2 Incompatibilities

Hexaxim must not be mixed with other vaccines or other parenterally administered drugs.
Separate injection sites must be used in case of concomitant administration.

6.3 Shelf Life

36 months.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C-8°C). Do not freeze. Discard if vaccine has been frozen.
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.

6.5 Nature and Contents of Container

Hexaxim is supplied in:
0.5 mL single dose in pre-filled syringe without attached needle and one separate needle in a pack;
0.5 mL single dose in pre-filled syringe without attached needle and two separate needles in a pack.
Pack size of 1 or 10. Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

After use, any remaining vaccine and container must be disposed of safely according to locally agreed procedures.

Summary Table of Changes