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

Registered South African indications:

• Active immunisation against diphtheria, tetanus, pertussis and poliomyelitis as a booster dose following primary immunisation
• Passive protection against pertussis in early infancy following maternal immunisation during pregnancy

Contraindications

South African manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• History of life-threatening reaction to Tdap-IPV or to
  - Formaldehyde
  - Glutaraldehyde
  - Neomycin
  - Streptomycin
  - Polymyxin B
  - Bovine serum albumin
  - Hank's medium
  - Phenylalanine
  - Vaccine containing the same components
• Acute or febrile illness
• History of encephalopathy (e.g. coma, decreased level of consciousness or prolonged seizures) within 7 days of a previous dose of pertussis-containing vaccine, not attributable to another identifiable cause

International manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to
  - Neomycin
  - Polymyxin B
  - Formaldehyde
  - Glutaraldehyde
  - Streptomycin
  - Bovine serum albumin
• History of encephalopathy of unknown origin within 7 days following previous vaccination with pertussis-containing vaccine
• Acute severe febrile illness

Cautions

South African manufacturer recommendations

• Pregnancy (first trimester)
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Guillain Barré syndrome or brachial neuritis occurring within 6 weeks following receipt of prior vaccine containing tetanus toxoid (See additional prescribing points)
• Progressive or unstable neurological disorder
• Uncontrolled epilepsy
• Progressive encephalopathy
• Immunosuppression
• Bleeding disorders
  - Haemophilia
  - Thrombocytopenia
• Phenylketonuria (PKU)
• History of serious or severe reaction within 48 hours of a previous injection with a vaccine containing similar components
• Coadministration with anticoagulants 

International manufacturer recommendations

• Pregnancy (first trimester)
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Guillain Barré syndrome occurring within 6 weeks following receipt of prior vaccine containing tetanus toxoid
• Progressive or unstable neurological disorder
• Uncontrolled epilepsy
• Progressive encephalopathy
• Coagulation disorders
• Immunosuppression
• Pre-existing antitoxins
• History of serious or severe reaction within 48 hours of a previous injection with a vaccine containing similar components
• Coadministration with anticoagulants

Forms avail. in SA and covered in this monograph: inj, vac

Active immunisation against diphtheria, tetanus, pertussis and poliomyelitis as a booster dose following primary immunisation
- Chronic immunodeficiency
- Unknown or incomplete diphtheria or tetanus vaccination status against diphtheria or tetanus
- Repeat vaccination to boost immunity at 5-10 year intervals
Tetanus prone injuries with or without concomitant administration of tetanus immunoglobulin according to official recommendations

• IM: 0.5ml, as a single dose

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Tdap-IPV should not be used for primary immunisation

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Persons who have had pertussis, tetanus or diphtheria, should still be immunised since these clinical infections do not always confer immunity. Although well-documented pertussis disease is likely to confer immunity, the duration of protection is unknown. Tdap-IPV is not to be used for the treatment of disease caused by B. pertussis, C. diphtheriae or C. tetani or poliomyelitis infections

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Chronic immunodeficiency: HIV-infected persons, both asymptomatic and symptomatic, should be immunised against diphtheria, tetanus, pertussis and poliomyelitis according to standard schedules

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In those with an unknown or incomplete diphtheria or tetanus vaccination status against diphtheria or tetanus, one dose of Tdap-IPV can be administered as part of a vaccination series to protect against pertussis and poliomyelitis and in most cases also against tetanus and diphtheria. One additional dose of a diphtheria- and tetanus- (dT) containing vaccine can be administered one month later followed by a third dose of a diphtheria- or dT-containing vaccine 6 months after the first dose to optimise protection against disease. The number and schedule of doses should be determined according to local recommendations

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Administer the vaccine intramuscularly. The preferred site is into the deltoid muscle. The vaccine should not be injected into the gluteal area

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Do not administer Tdap-IPV intravenously. The subcutaneous route should not be used (see additional prescribing points for exceptions). Fractional doses (doses <0,5ml) should not be given. The effect of fractional doses on the frequency of serious adverse events and on efficacy has not been determined

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

Active immunisation against diphtheria, tetanus, pertussis and poliomyelitis as a booster dose following primary immunisation
- Chronic immunodeficiency
- Unknown or incomplete diphtheria or tetanus vaccination status against diphtheria or tetanus
- Repeat vaccination to boost immunity at 5-10 year intervals
Tetanus prone injuries with or without concomitant administration of tetanus immunoglobulin according to official recommendations

Younger than 3 years

• Not established for use 

Older than 3 years

• IM: 0.5ml, as a single dose

Passive protection in early infancy against pertussis following maternal immunisation during pregnancy

• See adult dosage (adult active immunisation dosage applicable for pregnant women)

---

Tdap-IPV should not be used for primary immunisation

---

Persons who have had pertussis, tetanus or diphtheria, should still be immunised since these clinical infections do not always confer immunity. Although well-documented pertussis disease is likely to confer immunity, the duration of protection is unknown. Tdap-IPV is not to be used for the treatment of disease caused by B. pertussis, C. diphtheriae or C. tetani or poliomyelitis infections

---

Chronic immunodeficiency: HIV-infected persons, both asymptomatic and symptomatic, should be immunised against diphtheria, tetanus, pertussis and poliomyelitis according to standard schedules

---

In those with an unknown or incomplete diphtheria or tetanus vaccination status against diphtheria or tetanus, one dose of Tdap-IPV can be administered as part of a vaccination series to protect against pertussis and poliomyelitis and in most cases also against tetanus and diphtheria. One additional dose of a diphtheria- and tetanus- (dT) containing vaccine can be administered one month later followed by a third dose of a diphtheria- or dT-containing vaccine 6 months after the first dose to optimise protection against disease. The number and schedule of doses should be determined according to local recommendations

---

Administer the vaccine intramuscularly. The preferred site is into the deltoid muscle. The vaccine should not be injected into the gluteal area

---

Do not administer Tdap-IPV intravenously. The subcutaneous route should not be used (see additional prescribing points for exceptions). Fractional doses (doses <0,5ml) should not be given. The effect of fractional doses on the frequency of serious adverse events and on efficacy has not been determined

Pregnancy

South African manufacturer recommendations

• First trimester: Caution; no evidence of risk in studies
• Second and third trimester: Safe; no evidence of risk in studies
• Tdap-IPV may be administered to pregnant women during the second and third trimester to provide passive protection to infants against pertussis
• No teratogenic effect of vaccines containing diphtheria or tetanus toxoids, or inactivated poliovirus has been observed following use in pregnant women
• Safety data from 4 randomised controlled trials (310 pregnancy outcomes), 2 prospective observational studies (2670 pregnancy outcomes), 4 retrospective observational studies (81701 pregnancy outcomes), and from passive surveillance of women who received Tdap-IPV or diphtheria/ tetanus/ acellular pertussis (DTaP & Tdap) during the 2nd or 3rd trimester have shown no vaccine related adverse effect on pregnancy or on the health of the fetus/newborn child
• As with other inactivated vaccines, it is not expected that vaccination with Tdap-IPV during any trimester would harm the fetus. The benefits versus the risks of administering the vaccine during pregnancy should be evaluated
• Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development
  (See additional prescribing points)

International manufacturer recommendations

• First trimester: Caution; no evidence of risk in studies
• Second and third trimester: Safe; no evidence of risk in studies
• Tdap-IPV can be used during the second or third trimester of pregnancy in accordance with official recommendations
• Safety data from 4 randomized controlled trials (310 pregnancy outcomes), 1 prospective observational study (546 pregnancy outcomes), 5 retrospective observational studies (124810 pregnancy outcomes), and from passive surveillance of women who received Tdap-IPV or DTaP & Tdap during the second or third trimester have shown no vaccine related adverse effect on pregnancy or on the health of the fetus/newborn child
• As with other inactivated vaccines, it is not expected that vaccination with Tdap-IPV during any trimester would harm the foetus
• Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development

Breastfeeding

South African manufacturer recommendations

• Caution; no information available 
• It is not known whether the active substances included in Tdap-IPV are excreted in human milk
• The effect on breastfed infants of the administration of Tdap-IPV to their mothers has not been studied
• Tdap-IPV is inactivated; any risk to the mother or the infant is improbable
• The risks and benefits of vaccination should be assessed before making the decision to immunise a breastfeeding woman

International manufacturer recommendations

• Caution; no information available
• The effect of administration of Tdap-IPV during breastfeeding has not been assessed. Nevertheless, as Tdap-IPV contains toxoids or inactivated antigens, no risk to the breastfed infant should be expected
• The benefits versus the risk of administering Tdap-IPV to breastfeeding women should carefully be evaluated by the healthcare providers

Fertility

• Tdap-IPV has not been evaluated in fertility studies

Renal Impairment

• Caution; no information available

Hepatic Impairment

• Caution; no information available

Elderly

South African manufacturer recommendations

• No dose adjustment recommended 
  Tdap-IPV has been used in clinical studies in elderly persons aged 59 to 91 years of age

International manufacturer recommendations

• No dose adjustment recommended 
  Tdap-IPV may be administered concomitantly with a dose of inactivated influenza vaccine, based on the results of a clinical trial conducted in persons 60 years of age and older

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Irritability
• Sleep disorder
• Apathy
• Somnolence
• Headache
• Paraesthesia
• Dizziness
• Fatigue

Respiratory Disorders

• Dry throat
• Asthma

Gastrointestinal Disorders

• Diarrhoea
• Abdominal pain
• Nausea and vomiting 

Endocrine and Metabolic Disorders

• Anorexia
• Decreased appetite

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Oral herpes
• Pruritus
• Injection site reactions
• Extensive swelling of vaccinated limb

Immune, Blood and Lymphatic System Disorders

• Lymphadenopathy
• Fever

• Vaccines
• Immunoglobulins
• Immunosupressants

None routine

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

Administration directions

• DO NOT administer as IV or intradermal injection
• Administer the vaccine IM. The preferred site is into the deltoid muscle
• The vaccine should not be injected into the gluteal area
• Administration by deep subcutaneous injection may be considered in those at risk of haematoma formation, although there is a risk of increased local reactions. A persistent nodule at the site of injection may occur with all adsorbed vaccines, particularly if administered into the superficial layers of the subcutaneous tissue
• Fractional doses (doses <0,5ml) should not be given. The effect of fractional doses on the frequency of serious adverse events and on efficacy has not been determined

Vaccination during pregnancy

• Limited clinical data have shown there is interference with the immune response to other antigens (i.e. diphtheria, tetanus, polio, pneumococcal, meningococcal) in infants born to women vaccinated with Tdap-IPV during pregnancy. However, in most of the cases, the antibody concentrations remain above the thresholds established as protective. The clinical relevance of this observation is unknown
• Pertussis antibody responses in pregnant women are generally similar to those in non pregnant women. Vaccination during the second or third trimester of pregnancy is optimal for antibody transfer to the developing fetus
• Maternal antibody directed against pertussis antigens persists for 2 to 4 months after birth and may be associated with blunting of the infant immune response to active immunisation against pertussis
• The effectiveness of maternal immunisation against pertussis in the first 3 months of life has been estimated to be >90%

Guillain Barré syndrome

• A review by the Institute of Medicine (IOM) found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain Barré syndrome
• If Guillain Barré syndrome or brachial neuritis has occurred within 6 weeks of receipt of prior vaccine containing tetanus toxoid, the decision to give any vaccine containing tetanus toxoid, including Tdap-IPV, 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

Special precautions

• As a precautionary measure adrenaline (epinephrine) injection (1:1 000) must be immediately available in case of unexpected anaphylactic or serious allergic reactions
• Syncope (fainting) has been reported following vaccination with Tdap-IPV. Procedures should be in place to prevent falling injury and manage syncopal reactions

This vaccine contains active substances derived from diphtheria, tetanus and pertussis toxoids, as well as inactivated poliomyelitis virus. After administration, antibodies are produced against the bacteria and viruses included in the vaccine, thus incurring immunity.

COMBINATION PREPARATIONS

Tetanus/ Diphtheria (reduced)/ Acellular Pertussis/ Inactivated Poliomyelitis (Tdap-IPV)

Injection 0.5ml

• Adacel Quadra (Sanofi) originator
• Boostrix Tetra (GSK) originator