1. NAME OF MEDICINAL PRODUCT
Arapenta inj. (DTP-HepB-Hib fully liquid combination vaccine), suspension for Injection.
Diphtheria, tetanus, pertusis, hepatitis B recombinant and Haemophilus influenzae type b (Hib) combined vaccine.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Arapenta inj. (DTP-HepB-Hib fully liquid combined vaccine) is a ready-to-use, fully liquid combined vaccine containing diphtheria and tetanus toxoids, Bordetella pertussis inactivated cellular suspension, hepatitis B surface antigen (HBsAg), and Haemophilus influenzae type b conjugated oligosaccharide.
The diphtheria and tetanus toxoids are obtained from Corynebacterium diphtheriae and Clostridium
tetani cultures, respectively, by formaldehyde inactivation and purification.
The pertussis suspension component is obtained from B. pertussis cultures after inactivation and purification.
The hepatitis B surface antigen is produced in genetically engineered yeast cells (Hansenula polymorpha)
carrying the relevant gene of the HBsAg.
The antigen is purified and inactivated by several physicochemical steps.
The H. influenzae type b component is made of purified capsular oligosaccharides conjugated to CRM 197 (Cross Reacting Material), a non-toxic mutant of diphtheria toxin, prepared from C. diphtheriae cultures.
The vaccine contains aluminium phosphate as adjuvant, forming a whitish sediment.
One 0.5 mL dose of vaccine contains:
Purified diphtheria toxoid . . . . not less than 7.5 Lf (not less than 30 IU)
Purified tetanus toxoid . .. . . . not less than 3.25 Lf (not less than 60 IU)
Inactivated B. pertussis . . . ...... . not less than 15 OU (not less than 4 IU)
Hib oligosaccharide . . . . . 10 μg, conjugated to approx. 25 μg of CRM 197
Hepatitis B surface antigen, purified ....... . . . . . . . . . . . .. . . . . ...... . 10 μg
Aluminium phosphate (adjuvant) . .. . ............. .. . . . . . . . . . . . .0.3 mg Al3+ Arapenta inj. (DTP-HepB-Hib fully liquid combined vaccine) is free of preservatives. Thiomersal may be present in traces as a residue of the manufacturing process.
For list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Suspension for intramuscular injection.
After shaking, the product has a milky appearance.
4. CLINICAL PARTICULARS
4.1 THERAPEUTIC INDICATIONSActive primary and booster immunization of infants and toddlers for protection against diphtheria, tetanus, pertussis, hepatitis B, and invasive illness caused by H. influenzae type b. The vaccine is indicated for infants regardless of whether or not they have received hepatitis B vaccination at birth.
Based on available evidence and recommendations it is concluded, that ARAPENTA inj.(DTP-HepB-Hib fully liquid combination vaccine) can, like similar combination vaccines, be used in infants interchangeably for basic immunisation with other DTP-HepB-Hib vaccines, or components thereof, as well as for boosting children primed in infancy with another combination vaccine.
4.2 POSOLGY AND METHOD OF ADMINSTERATION
Applicable national vaccination recommendations and/or the WHO guidelines are to be followed.
Primary vaccination of infants (first year of life): 3 doses of 0.5 mL each, at least one month apart, starting as early as 6 weeks of age. The vaccine is indicated for infants regardless of whether or not they have received hepatitis B vaccination at birth.
Based on available evidence and recommendations it is concluded, that Arapenta inj. (DTP-HepB-Hib fully liquid combined vaccine) can, like similar combination vaccines, be used in infants interchangeably for basic immunisation with other DTP-HepB-Hib vaccines, or components thereof, as well as for boosting children primed in infancy with another combination vaccine.
Reinforcing vaccination of toddlers (13-24 months after birth): one booster dose of 0.5 mL.
4.2.2 METHOD OF ADMINISTRATION
The vaccine is to be administered by intramuscular injection in the anterolateral thigh or alternatively in
the deltoid region in children 13-24 months after birth. See section
4.4 for administration of the vaccine to children with bleeding disorders.
The vaccine can be administered simultaneously, as a separate injection, with other common childhood vaccines, according to locally recommended immunisation schedules.
Arapenta inj. (DTP-HepB-Hib fully liquid combined vaccine) should not be administered to children with known hypersensitivity to any vaccine component or to children having shown signs of hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, or Hib vaccines.
Children who have experienced an encephalopathy of unknown aetiology after a previous vaccination with vaccine containing pertussis should not be vaccinated with Arapenta inj. (DTP-HepB-Hib fully liquid combined vaccine). In these circumstances, the vaccination course should be continued with diphtheria, tetanus, hepatitis B, and Hib vaccines.
As with other vaccines, vaccination should be postponed in children suffering from acute febrile illness.
Minor illnesses, such as the common cold or other infections of the upper respiratory tract (body temperature < 38 °C) are not to be considered contraindications to vaccination.
Equally, it is not necessary to postpone vaccination in the case of treatment with topical corticosteroids or systemic use of corticosteroids at low dosage (< 0.5 mg/kg of prednisone or equivalent) or in case of skin diseases like dermatitis, eczema, or other localised skin disorders.
4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE
As with any injectable vaccine, appropriate medical supervision and treatment should always be readily available in case of immediate allergic reactions, such as anaphylactic shock or anaphylactic reaction, following administration of the vaccine.
Before administering the vaccine, precautions should be taken to avoid undesirable reactions.
These precautions include: review of the individual’s medical history, particularly regarding hypersensitivity reactions to previous administration of any type of vaccine, as well as the individual’s history of recent health disorders and any previous vaccinations.
The administration of any subsequent dose of a vaccine containing the whole-cell pertussis component should be carefully considered if, in connection with the administration of DTP vaccine, one or more of the following effects have been observed:
– 40.0°C temperature within 48 hours following vac cination (not due to other identifiable causes);
– collapse or shock (hypotonic hyporesponsive episodes) within 48 hours following vaccination;
– persistent crying lasting more than 3 hours during the 48 hours following vaccination;
– convulsions, with or without fever, within 3 days fol lowing vaccination.
There may be circumstances, such as high incidence of pertussis, when potential benefits outweigh possible risks.
HIV seropositivity does not represent a contraindication to vaccination. Patients with an immunodeficiency disorder or receiving immunosuppressive therapy may have a reduced immunological response.
The vaccine must not be injected into a blood vessel.
ARAPENTA inj. (DTP-HepB-Hib fully liquid combined (DTP- HepB-Hib fully liquid combination vaccine) vaccine) should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects.A fine needle should be used for the vaccination and firm pressure applied to the site (without rubbing) for at least two minutes following administration.
4.5 INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION
Arapenta inj. (DTP-HepB-Hib fully liquid combined vaccine) can be administered simultaneously with other vaccines (injectable or oral) at separate sites or in any temporal relationship with other paediatric
vaccines, if this fits conveniently in the immunisation schedule.
Arapenta inj. (DTP-HepB-Hib fully liquid combined vaccine) must not be mixed with other vaccines in the same syringe.
The immunological response may be reduced in patients undergoing immunosuppressive or corticosteroid treatment (see section 4.4).
4.6 PREGNANCY AND LACTATION
Not applicable. Arapenta inj. (DTP-HepB-Hib fully liquid combined vaccine) is a paediatric vaccine.
4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
4.8 UNDESIRABLE EFFECTS
Approximately 1500 doses of Arapenta inj. (DTPHepB- Hib fully liquid combined vaccine) have been
administered in clinical trials as a primary vaccination in 512 healthy infants from six weeks of age.
In these clinical studies, signs and symptoms were actively monitored in all subjects for five to seven days following the administration of the vaccine.
Solicited and unsolicited reported reactions are listed below.
Frequencies, based on number of doses, are reported as:
Very common (>1/10), Common (>1/100, ≤1/10), Uncommon (>1/1000, ≤1/100), Rare (>1/10 000, ≤ 1/1000), Very rare (≤1/10 000, incl. isolated reports).
Common: diarrhoea, vomiting
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS:
Very common: injection site reactions (erythema, induration, pain) Common: fever
Rare: influenza-like illness
METABOLISM AND NUTRITION DISORDERS:
Common: feeding disorders
NERVOUS SYSTEM DISORDERS:
Very common: crying
Uncommon: persistent crying
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS:
SKIN AND SUBCUTANEOUS TISSUE DISORDERS:
The systemic adverse reactions usually appeared within 48 hours after vaccination and in most cases disappeared spontaneously.
All local and systemic reactions resolved without sequelae.
Allergic reactions, including anaphylactic reactions and urticaria, have been reported very rarely following vaccination with DTP, hepatitis B and Hib containing vaccines.
5. PHARMACOLOGICAL PROPERTIES
5.1 PHARMACODYNAMIC PROPERTIES
Results from clinical studies show that more than 97% of children are protected against diph-theria, tetanus, pertussis, and invasive illnesses caused by H. influenzae type b after a three-dose primary vaccination course with Arapenta inj. (DTP-HepB-Hib fully liquid combined vaccine). More than 91% of children are protected against hepatitis B when the vaccine is administered using the most immunologically demanding vaccination schedule (6-10-14 weeks, without hepatitis B vaccination at birth).
It is known that hepatitis B seroprotection rates are influenced by the vaccination sche- dule used – increasing age at first vaccination and longer intervals between the second and third vaccinations generally result in higher final anti-HBs antibody titres.
5.2 PHARMACOKINETIC PROPERTIES
6. PHARMACEUTICAL PARTICULARS
6.1 LIST OF EXCIPIENTS
Sodium Chloride, water for injection ad 0.5 mL.
The vaccine must not be mixed with other medicinal products.
6.3 SHELF LIFE
The expiry date is indicated on the labels and packaging.
6.4 SPECIAL PRECAUTIONS FOR STORAGE
Store at a temperature between +2 °C and +8 °C. Do not freeze. Discard if vaccine has been frozen.
6.5 NATURE AND CONTENTS OF CONTAINERS
Neutral glass vial, type I, containing 0.5 mL of vaccine (1 dose) with a rubber stopper (chlorobutyl).
6.6 SPECIAL PRECAUTIONS FOR DISPOSAL
OF A USED MEDICINAL PRODUCT OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCT AND OTHER HANDLING OF THE PRODUCT
Important: shake well before use.
7. MARKETING AUTHORISATION HOLDER