Diphtheria/ Tetanus/ Acellular Pertussis/ Hepatitis B/ Inactivated Poliomyelitis/ Haemophilus Influenzae Type B Conjugate Vaccine (DTaP-HB-IPV-Hib)

Registered South African indications:

• Primary and booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae type B

Contraindications

South African manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• 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
• Moderate or severe febrile and/ or acute disease
• Encephalopathy within 7 days of administration of a previous dose of any vaccine containing pertussis antigens (whole cell or acellular pertussis vaccines)
• Progressive neurologic disorder, uncontrolled epilepsy, and progressive encephalopathy
  (See additional prescribing points)

International manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to trace residuals in the vaccine
  - Glutaraldehyde
  - Formaldehyde
  - Neomycin
  - Streptomycin
  - Polymyxin B
  - Bovine serum albumin
• Encephalopathy of unknown aetiology occurring within 7 days following previous vaccination with pertussis containing vaccine
• Uncontrolled neurologic disorder or uncontrolled epilepsy
  (See additional prescribing points) 

Cautions

South African manufacturer recommendations

• Hypersensitivity to
  - Glutaraldehyde
  - Formaldehyde
  - Neomycin
  - Streptomycin
  - Polymyxin B
• Renal impairment
• Hepatic impairment
• Hepatitis infection caused by other agents such as hepatitis A, hepatitis C and hepatitis E or by other liver pathogens (See additional prescribing points)
• Unrecognised hepatitis B infection (See additional prescribing points)
• Other types of Haemophilus influenzae or meningitis of other origins (See additional prescribing points)
• Immunocompromised persons (See additional prescribing points)
  - Patients requiring immunosuppressive treatment
• Premature infants
  - ≤28 weeks of gestation
  - Previous history of respiratory immaturity
  - Malnourished
  - Small for gestational age
  - Multiples births
• Guillain Barré syndrome or brachial neuritis occurring following receipt of prior vaccine containing tetanus toxoid (See additional prescribing points)
• Thrombocytopenia
• Bleeding disorder
• Low-grade fever
• Events that are known to have occured in temporal relation to receipt of pertussis-containing vaccine
  - Temperature of ≥40°C within 48 hours, not due to another identifiable cause
  - Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48hrs of vaccination
  - Persistent, inconsolable crying lasting ≥3hrs, occurring within 48hrs of vaccination
  - Seizures with or without fever, occurring within 3 days of vaccination

International manufacturer recommendations

• Renal impairment
• Hepatic impairment
• Hepatitis infection caused by other agents such as hepatitis A, hepatitis C and hepatitis E or by other liver pathogens (See additional prescribing points)
• Unrecognised hepatitis B infection (See additional prescribing points)
• Other types of Haemophilus influenzae or other microorganisms that cause invasive disease such as meningitis or sepsis, including N. meningitidis (See additional prescribing points)
• Moderate to severe acute disease, with or without fever
• Events that are known to have occured in temporal relation to receipt of pertussis-containing vaccine
  - Temperature of ≥40.5°C within 48 hours, not due to another identifiable cause
  - Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48hrs of vaccination
  - Persistent, inconsolable crying lasting ≥3hrs, occurring within 48hrs of vaccination
  - Seizures with or without fever, occurring within 3 days of vaccination
• Guillain Barré syndrome or brachial neuritis occurring following receipt of prior vaccine containing tetanus toxoid (See additional prescribing points)
• Premature infants
  - ≤28 weeks of gestation
  - Previous history of respiratory immaturity
• Immunocompromised persons (See additional prescribing points)
  - Patients requiring immunosuppressive treatment
• Thrombocytopenia
• Bleeding disorder
• History of febrile seizures
• Family history of seizures 
• Sudden Infant Death Syndrome (SIDS) 
• Minor illness and /or low-grade fever
• Genetic polymorphism

Not indicated for use in adults

Paed. forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

The use of DTaP-HB-IPV-Hib should be in accordance with official recommendations

South African manufacturer recommendations

EPI Schedule 2016

Primary and booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae type B

Younger than 6 weeks

• Not established for use

Between 6 weeks - 5 years

• IM: 1st dose: 0.5ml, given from 6 weeks of age; 2nd and 3rd dose: 0.5ml, given at intervals of at least 4 weeks; Booster: 0.5ml, given ≥6 months after last dose of the 3-dose primary series

OR

• IM: 1st dose: 0.5ml, given from 6 weeks of age; 2nd dose: 0.5ml, given at an interval of at least 8 weeks; Booster: 0.5ml, given ≥6 months after last dose of the 2-dose primary series

Older than 5 years

• Not indicated for use

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Invasive infections caused by Haemophilus influenzae type B include meningitis, septicaemia, cellulitis, arthritis, epiglottitis, respiratory illness (pneumopathy),  and osteomyelitis. DTaP-HB-IPV-Hib does not protect against infectious diseases caused by other types of Haemophilus influenzae or against meningitis of other origins

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DO NOT administer via IV route

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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

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Where a dose of hepatitis B vaccine is given at birth, DTaP-HB-IPV-Hib can be used for supplementary doses of hepatitis B vaccine from the age of 6 weeks. If a second dose of hepatitis B vaccine is required before this age, monovalent hepatitis B vaccine should be used

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International manufacturer recommendations

Primary and booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib)

Younger than 6 weeks

• Not established for use

Between 6 weeks - 15 months

• IM: 1st dose: 0.5ml, given from 6 weeks of age; 2nd and 3rd dose: 0.5ml, given at intervals of at least 4 weeks; Booster: 0.5ml, given ≥6 months after last dose of the 3-dose primary series

OR

• IM: 1st dose: 0.5ml, given from 6 weeks of age; 2nd dose: 0.5ml, given at an interval of at least 4 weeks; Booster: 0.5ml, given ≥6 months after last dose of the 2-dose primary series

Older than 15 months

• Not established for use

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Where a dose of hepatitis B vaccine is given at birth, DTaP-HB-IPV-Hib can be used for supplementary doses of hepatitis B vaccine from the age of 6 weeks. If a second dose of hepatitis B vaccine is required before this age, monovalent hepatitis B vaccine should be used. DTaP-HB-IPV-Hib can be used for a mixed hexavalent/pentavalent/hexavalent combined vaccine immunisation schedule

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DTaP-HB-IPV-Hib should only be administered by intramuscular (IM) injection. The recommended injection sites are the anterolateral area of the thigh (preferred site for infants under one year of age) or the deltoid muscle of the upper arm

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DO NOT administer via IV route

Pregnancy

• Not indicated for use in adults
• This vaccine is not intended for administration to women of childbearing age

Breastfeeding

• Not indicated for use in adults
• This vaccine is not intended for administration to women of childbearing age

Fertility

• No information available

Renal Impairment

South African manufacturer recommendations

• Caution; dose adjustment recommended 
  In chronic renal impairment subjects, 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)

International manufacturer recommendations

• Caution; no information available 

Hepatic Impairment

• Caution; no information available 

Elderly

• Not indicated for use in geriatric patients 

Porphyria Information

• Not yet classified (NC) 

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Irritability
• Abnormal crying
• Restlessness
• Nervousness
• Somnolence
• Convulsions
• Hypotonic reactions
• Hypotonic-hyporesponsiveness episodes
• Fatigue
• Convulsions

Respiratory Disorders

• Upper respiratory tract infection
• Cough
• Bronchitis
• Apnoea

Gastrointestinal Disorders

• Vomiting
• Diarrhoea

Endocrine and Metabolic Disorders

• Loss of appetite

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Rash
• Dermatitis
• Urticaria
• Injection site pain
• Injection site redness
• Injection site swelling  
• Injection site induration
• Injection site nodule
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Fever
• Hypersensitivity reaction

Others

• Diffuse swelling of the injected limb, sometimes involving the adjacent joint

• Immunosuppressive agents

None routine

Contraindications

South African manufacturer recommendations

• Pertussis vaccine should not be administered to individuals with progressive neurologic disorder, uncontrolled epilepsy, and progressive encephalopathy until the treatment regimen has been established, the condition has stabilised and the benefit clearly outweighs the risk

International manufacturer recommendations

• Pertussis vaccination 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

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

Excipients

• The vaccine may contain traces of glutaraldehyde, formaldehyde, neomycin, streptomycin and polymyxin B 

Interference with laboratory and diagnostic tests

South African manufacturer recommendations

• Interference of DTaP-HB-IPV-Hib 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

International manufacturer recommendations

• Since the Hib capsular polysaccharide antigen is excreted in the urine, a false positive urine test can be observed using sensitive tests, for at least 30 days following vaccination. Other tests should be performed in order to confirm Hib infection during this period

Administration directions

• DO NOT administer the vaccine intravascularly or intradermally
• Before use, the vaccine should be shaken in order to obtain a homogeneous whitish cloudy suspension
• After use, any remaining vaccine and container must be disposed of safely, preferably by heat inactivation or incineration, according to locally agreed procedures

Co-vaccination

• Due to an increased risk of fever, pain at the injection site, appetite loss and irritability when co-administered with MenB vaccine and 7-valent pneumococcal conjugate vaccine, separate vaccinations can be considered when possible
• DTaP-HB-IPV-Hib must not be mixed with other vaccines or other parenterally administered drugs. Separate injection sites must be used in case of concomitant administration
• Coadministration of DTaP-HB-IPV-Hib with pneumococcal polysaccharide conjugated vaccines, measles-mumps-rubella vaccines, rotavirus vaccines, meningococcal C-TT conjugate vaccines or meningococcal A/C/W-135/Y–TT conjugate vaccines have shown no clinically relevant interference in the antibody response to each of the antigens

Special precautions

• Before the injection of any biological, the person responsible for administration must take 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 event following administration of the vaccine
• Epinephrine injection (1:1 000) and other appropriate agents used for the control of immediate allergic reactions must be available to treat unexpected reactions (e.g. anaphylaxis)

Guillain Barré syndrome

• 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)

Protection

• DTaP-HB-IPV-Hib primary and booster vaccination protects against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae type b (such as meningitis, septicaemia, cellulitis, arthritis, epiglottitis, respiratory illness (pneumopathy), osteomyelitis)
• DTaP-HB-IPV-Hib 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
• DTaP-HB-IPV-Hib 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 DTaP-HB-IPV-Hib may not protect 100% of susceptible individuals
• DTaP-HB-IPV-Hib 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

Immunocompromised persons

• 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 subjects with chronic immunodeficiency such as HIV infection is recommended even if the antibody response may be limited

This vaccine contains active substances derived from diphtheria, tetanus and pertussis toxoids; inactivated poliomyelitis virus; Hepatitis B surface antigen and Haemophilus influenzae type b (Hib) polysaccharide conjugated to tetanus protein. After administration, antibodies are produced against the bacteria and viruses included in the vaccine, thus incurring immunity.

COMBINATION PREPARATIONS

Diphtheria/ Tetanus/ Acellular Pertussis/ Hepatitis B/ Inactivated Poliomyelitis/ Haemophilus Influenzae Type B conjugate vaccine (DTaP-HB-IPV-Hib)

Injection 0.5ml

• Infanrix hexa (GSK) originator
• Hexaxim (Sanofi) originator