Diphtheria/ Tetanus/ Acellular Pertussis/ Inactivated Poliomyelitis (DTaP-IPV)

Registered South African indications:

• Active immunisation against diphtheria, tetanus, pertussis and poliomyelitis
  - For primary vaccination in infants
  - For booster vaccination in children who have previously received a primary vaccination with this vaccine or a diphtheria-tetanus-whole cell or acellular pertussis-poliomyelitis vaccine

Registered South African contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Known systemic hypersensitivity to pertussis vaccines (acellular or whole cell pertussis), or a life- threatening reaction after previous administration of the vaccine or a vaccine containing the same substances
• Vaccination must be postponed in case of febrile or acute disease
• Evolving encephalopathy
• Encephalopathy within 7 days of administration of a previous dose of any vaccine containing pertussis antigens (whole cell or acellular pertussis vaccines)

South African recommendations

Caution in the following patient groups

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment

Hypersensitivity

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

Immunosuppressive treatment

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

Guillain-Barré syndrome or brachial neuritis

• If Guillain-Barré syndrome or brachial neuritis has occurred following the 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
• Vaccination is usually justified for infants whose primary immunisation schedules are incomplete (i.e. fewer than three doses have been received)

Risk of apnoea

• 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

Injection route

• Do not administer by the intravascular route – ensure that the needle does not enter a blood vessel

Thrombocytopenia or bleeding disorder

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

Pre-administration questions

• Prior to the administration of any dose, the parent or guardian of the recipient or the adult recipient him/herself must be asked about their personal history, family history and recent health status, including immunisation history, current health status and any adverse event after previous immunisations

Syncope

• Syncope can occur following, or even before, any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent falling and injury and to manage syncope

Pertussis-containing vaccine reaction

• If any of the following events are known to have occurred following a previous pertussis-containing vaccine injection, the decision to give further doses of pertussis-containing vaccine should be carefully considered:
• Fever greater than or equal to 40 °C within 48 hours of vaccination not due to another identifiable cause
• Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of vaccination
• Persistent, inconsolable crying lasting for three hours or longer and occurring within 48 hours of vaccination
• Febrile or non-febrile convulsions occurring within 3 days of vaccination

Precautions before biological injection

• Before the injection of any biological, 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 be readily available for immediate use in case of a rare anaphylactic reaction following administration of vaccine

Excipient(s) with known effect

• DTaP-IPV contains 12.5 micrograms of phenylalanine in each 0.5ml dose. Phenylalanine may be harmful for people who have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly
• DTaP-IPV contains 2mg of alcohol (ethanol) in each 0.5ml dose. The small amount of alcohol in this medicine will not have any noticeable effects
• DTaP-IPV contains less than 1 mmol sodium (23mg) per dose, that is to say essentially sodium free

Effects on the ability to drive and use machines

• Not applicable. DTaP-IPV is intended for paediatric use only

• Not intended for administration to adults

Forms avail. in SA and covered in this monograph: sng

South African registered indications and dosages

Active immunisation against diphtheria, tetanus, pertussis and poliomyelitis
- For primary vaccination in infants

6 weeks and older

• IM: 0.5ml, admin. as three successive doses at an interval of one or two months (see below for potential schedules)

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Potential schedules: 6, 10 and 14 weeks OR 2, 3, 4 months OR 2, 4, 6 months OR 3, 4, 5 months OR 3, 5, 12 months (OR according to national vaccination policies)

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- For booster vaccination in children who have previously received a primary vaccination with this vaccine or a diphtheria-tetanus-whole cell or acellular pertussis-poliomyelitis vaccine

Within the 2nd year of life

Booster vaccination

• IM: 0.5ml, admin. as a fourth dose in children who received DTaP-IPV (or a diphtheria-tetanus-whole cell or acellular pertussis-poliomyelitis vaccine, whether mixed or not with the freeze-dried conjugate Haemophilus influenzae type b vaccine) as a three-dose primary series

Late booster vaccination

Between 5-12 years old

• IM: 0.5ml, admin. in children previously immunised with an acellular vaccine (3 or 4 doses) or 3 doses of a whole cell vaccine followed by a booster dose of either acellular or whole cell vaccine

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Booster doses in 5 through 12 years old individuals should be given in accordance with the official national vaccination policies

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Method of administration
Before injection, shake to obtain a homogenous whitish-turbid suspension. This vaccine must be administered intramuscularly. The intradermal or intravenous routes must not be used. The recommended injection sites are the antero-lateral aspect of the upper thigh in infants and the deltoid muscle in older children. The vaccine must neither be mixed with other medical products, except Act-HIB vaccine, nor with other substances for parenteral use

Pregnancy

South African recommendations

• Caution; not recommended
• As DTaP-IPV is not intended for administration to adults, data on the use of this vaccine in pregnant women are not available. Therefore, DTaP-IPV is not recommended for pregnant women

Breastfeeding

South African recommendations

• Caution
• As DTaP-IPV is not intended for adults, it is not known whether this vaccine is excreted in human milk. Caution must be exercised when DTaP-IPV is administered to a nursing mother

Fertility

South African recommendations

• No information available

South African recommendations

• Caution; no information available

South African recommendations

• Caution; no information available

South African recommendations

• Not indicated for use in geriatric patients

Metabolism and Nutrition Disorders

Very common

• Anorexia (feeding disturbances)

Psychiatric Disorders

Very common

• Nervousness (irritability)
• Abnormal crying

Common

• Insomnia (sleep disturbances)

Uncommon

• Prolonged inconsolable crying

Nervous System Disorders

Very common

• Somnolence (drowsiness)
• Headache

Gastrointestinal Disorders

Very common

• Vomiting

Common

• Diarrhoea

Musculoskeletal and Connective Tissue Disorders

Very common

• Myalgia (muscle pain)

General Disorders and Administration Site Conditions

Very common

• Redness at the injection site
• Pain at the injection site
• Injection site swelling
• Pyrexia (fever) ≥ 38 °C
• Malaise (feeling of discomfort or uneasiness)

Common

• Induration at the injection site

Uncommon

• Redness and swelling ≥ 5 cm at the injection site
• Pyrexia (fever) ≥ 39 °C

Rare

• Pyrexia > 40 °C (high fever)

Post-marketing surveillance

Blood and Lymphatic System Disorders

Not known

• Lymphadenopathy

Immune System Disorders

Not known

• Anaphylactic reactions such as facial oedema, Quincke’s oedema

Nervous System Disorders

Not known

• Convulsions with or without fever
• Syncope

Skin and Subcutaneous Tissue Disorders

Not known

• Allergy-like symptoms, such as various types of rash, erythema and urticaria

General Disorders and Administration Site Conditions

Not known

• Large injection site reactions (> 50 mm), including extensive limb swelling from the injection site beyond one or both joints

Potential adverse events (i.e. adverse events which have been reported with other vaccines containing one or more of the antigenic constituents of DTaP-IPV and not directly with DTaP-IPV)

Nervous System Disorders

Not known

• Brachial neuritis 
• Guillain-Barré syndrome 

Other Adverse Events

Not known

• Hypotonic-hyporesponsive episodes (HHE), reported with other pertussis-containing vaccines
• Oedematous reaction affecting one or both lower limbs, associated with cyanosis, redness, transient purpura and severe crying, resolving within 24 hours (following vaccination with Haemophilus influenzae type b-containing vaccines) 

• Immunosuppressive therapy

• Observe for hypersensitivity and syncope

Specific cases may require

• Respiratory monitoring

Diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis vaccine.

Immune response after primary vaccination

Immunogenicity studies in infants given three doses of DTaP-IPV starting at 2 months of age have shown that all (100 %) developed a seroprotective antibody level (≥ 0.01 IU/mL) to both diphtheria and tetanus antigens. For pertussis, approximately 90 % of infants achieved a four-fold rise in PT and FHA antibody titres one to two months after completion of the primary vaccination. In the absence of a serological correlate of protection, a four-fold increase in post-immunisation titres is considered as a seroconversion. At least 99.5% of children had post-immunisation titres above the threshold of 5 (reciprocal of dilution in seroneutralisation) against poliovirus types 1, 2 and 3, and were considered protected against poliomyelitis.

Immune response after booster injection

Immunogenicity studies in toddlers in the second year of life who have received a 3-dose primary vaccination series with DTaP-IPV have shown high antibody responses to all the components following a fourth dose (booster). Studies in children 12 to 24 months of age who were given a 3-dose primary immunisation course with whole cell pertussis vaccines, DTP-IPV or DTP-IPV-ACT- HIB, have shown that a booster dose with DTaP-IPV is safe and immunogenic for all components of the vaccine. Studies in children 5 to 12 years of age who were given 4 doses of whole-cell pertussis vaccines, DTP-IPV (or DTP-IPV-Act-HIB) have shown that a booster dose with DTaP-IPV is immunogenic for all components and is well tolerated.