Active immunisation against tuberculosis.

BCG Vaccine AJVaccines is to be used according to official national recommendations.

Posology:

Adults, adolescents and children aged 12 months or more: 

A dose of 0.1 mL of the reconstituted vaccine is injected strictly by the intradermal route.

Infants under 12 months of age:

A dose of 0.05 mL of the reconstituted vaccine is injected strictly by the intradermal route.

National recommendations should be consulted regarding the need for tuberculin testing before administration of BCG Vaccine AJVaccines.

Method of Administration:

The injection site should be clean and dry. If antiseptics (such as alcohol) are applied to swab the skin, they should be allowed to evaporate completely before the injection is given.

BCG Vaccine AJVaccines must be administered by personnel trained in the intradermal technique.

The vaccine must be injected strictly intradermally into the arm, over the distal insertion of the deltoid muscle onto the humerus (approx. one third down the upper arm), as follows:

·         The skin is stretched between thumb and forefinger.

·         Almost parallel with the skin surface, the needle is slowly inserted (bevel upwards) approximately 2 mm into the superficial layers of the dermis.

·         The needle should be visible through the epidermis during insertion.

·         The injection is given slowly.

·         A raised, blanched bleb is a sign of correct injection.

·         Slight induration, erythema and tenderness at the injection site are followed by a local lesion.

·         Some weeks later this lesion evolves into a small ulcer.

·         After some months this ulcer heals leaving a small, flat scar.

·         The injection site is best left uncovered to facilitate healing. The ulcer should be encouraged to dry, and abrasion (by tight clothes, for example) should be avoided.

BCG Vaccine AJVaccines should be administered with a 1 mL syringe with 0.01 mL subgraduations fitted with a short needle with a short bevel (25G/0.50 mm or 26G/0.45 mm). Jet injectors or multiple puncture devices should not be used to administer the vaccine.

For instructions on reconstitution of the vaccine before administration, see section 6.6.

BCG Vaccine AJVaccines should not be administered to individuals known to be hypersensitive to the active substance or to any excipients listed in section 6.1.Vaccination should be postponed in persons with pyrexia or generalised infected skin conditions. Eczema is not a contraindication, but the site of vaccination should be lesion-free. BCG Vaccine AJVaccines should not be given to persons with the following: • Persons in treatment with systemic corticosteroids or other immunosuppressive treatment, including radiotherapy. This also includes infants exposed to immunosuppressive treatment in utero or via breastfeeding, for as long as a postnatal influence of the immune status of the infant remains possible (e.g. maternal treatment with TNF-α antagonists). • Persons with malignant conditions (e.g. lymphoma, leukaemia, Hodgkin’s disease or other tumours of the reticulo-endothelial system). • Primary or secondary immunodeficiency, including HIV infection and infants born to HIV-positive mothers, even if they show no symptoms of HIV infection. • Persons whose immune status is in question. The effect of BCG vaccination may be exaggerated in these persons, and a generalised BCG infection is possible. BCG Vaccine AJVaccines must not be given to patients receiving anti-tuberculosis drugs.

Although anaphylaxis is rare, facilities for its management should always be available during vaccination. Whenever possible, vaccinated persons should be observed for allergic reactions for up to 20 minutes after immunisation.
Tuberculin-positive persons do not require the vaccine. Administration of the vaccine to such persons may result in a severe local reaction.
Consult national recommendations for the definition of a positive tuberculin reaction.

Administering the vaccine too deep increases the risk of a discharging ulcer, abscess formation and regional lymphadenitis.

BCG Vaccine AJVaccines should under no circumstances be administered intravascularly.

The potential risk of apnoea and the need for respiratory monitoring for 48–72 h 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.

Cases of Immune reconstitution inflammatory syndrome (IRIS) have been reported after the onset of antiretroviral therapy in HIV-infected children or after initiating treatment for other severe immune deficiencies in children who had prior BCG vaccination. Adenitis, suppurative adenitis, purulent discharge, skin ulceration, skin abscesses, fever, have been reported in association with IRIS, appearing within weeks to months after initiation of immune therapy. Clinicians should be aware of this syndrome when treating patients with primary or secondary immunodeficiency who had prior BCG vaccination.

Section 4.8 lists undesirable effects caused by BCG infection and section 5.1 lists the susceptibility of the strain to anti-tuberculosis drugs.

BCG Vaccine AJVaccines contains less than 1 mmol of potassium (39 mg) and sodium (23 mg) per dose and is essentially free of potassium and sodium.

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.

Other vaccines administered at the same time as BCG Vaccine AJVaccines should not be injected into the same arm.

Intradermal BCG vaccination may be given simultaneously with inactivated or live vaccines, including combined measles, mumps and rubella vaccines.

If not administered simultaneously, an interval of not less than 4 weeks should be left between the administrations of any two live vaccines.  

Further vaccinations in the arm used for the BCG vaccination must not be given for 3 months due to risk of regional lymphadenitis.

Women of childbearing potential:

BCG Vaccine AJVaccines has not been associated with harmful effects on the childbearing potential of women.

Pregnancy:

Although no harmful effects to the foetus have been associated with BCG Vaccine AJV, vaccination is not recommended during pregnancy.

Breastfeeding:

There is insufficient/limited information on the excretion of M. bovis BCG, Danish strain 1331 in human or animal breast milk. A risk to the suckling child cannot be excluded. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with BCG Vaccine AJVaccines should be made taking into account the benefit of breast-feeding to the child and the benefit of BCG Vaccine AJVaccines therapy to the woman.

 

Fertility:

No clinical or non-clinical data are available on the possible effects of BCG Vaccine AJVaccines on male and female fertility.

BCG Vaccine AJVaccines has no or negligible influence on the ability to drive and use machines.

A local reaction is expected after vaccination with BCG Vaccine AJVaccines. An induration appears at the site of the injection which is followed by a local lesion that may ulcerate some weeks later. This lesion normally heals spontaneously, almost always leaving a superficial scar 2–10 mm in diameter. Rarely, the ulceration may persist for a few months at the site of vaccination. An adhesive dressing is not recommended.
Transient enlargement of the regional lymph nodes (< 1 cm) is normal.
Enlargement of axillary lymph nodes may occasionally be seen in the months following immunisation. Suppurative lymphadenitis may occur rarely. This is a benign condition which heals spontaneously, although often only slowly.

Undesirable effects of the vaccine include the following:

	Uncommon (≥1/1000 to <1/100)	Rare (≥1/10000 to <1/1000)
Blood and lymphatic system disorders	·     Enlargement of lymph nodes > 1 cm	-
Nervous system disorders	·     Headache	-
Musculoskeletal and connective tissue disorders	-	·   Osteitis
Infections and infestations	·  Suppurative lymphadenitis	·   Osteomyelitis ·     Injection site abscess
General disorders and administration site conditions	·     Fever ·     Injection site ulceration ·     Injection site discharge	-
Immune system disorders	-	·     Anaphylactic reaction ·   Allergic reaction

 

Apnoea in very premature infants (born ≤ 28 weeks of gestation) (see section 4.4).

During post-marketing safety surveillance syncope among patients receiving injections have been reported. Also seizures and convulsions have been reported.

An exaggerated response to the BCG Vaccine AJVaccines may result in a discharging ulcer. This may be because the vaccine was administered incorrectly or because of overdosage.

Localised or disseminated infection with M. bovis BCG can occur in rare cases upon BCG vaccination. Expert advice should be sought regarding the appropriate medical treatment of such infections. The sensitivity of the BCG strain towards different anti-tuberculosis agents varies.
Section 5.1 includes a table with minimum inhibitory concentrations (MIC) for selected anti-tuberculosis drugs towards the BCG Danish strain 1331 [as determined by Bactec 460].

To report any side effect(s):

·         Saudi Arabia:

-        The National Pharmacovigilance Centre (NPC):

Fax: +966-11-205-7662

SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa

 

·         Other GCC States:

-          Please contact the relevant competent authority

Overdosage increases the risk of undesirable BCG complications.
For the treatment of disseminated infections with BCG, refer to Section 4.8.

Pharmacotherapeutic group (ATC code): J 07 AN 01.

Vaccination with BCG Vaccine AJVaccines confers a variable degree of protection against infection with M. tuberculosis. Protective immunity is normally achieved within 4–6 weeks after vaccination. The duration of immunity after BCG vaccination is not known. BCG Vaccine AJVaccines is effective against miliary and TB meningitis, and has been shown effective against M. leprae.

The MIC values (as determined by the Bactec 460 method) for selected anti-tuberculosis agents against the BCG Danish strain 1331 are as follows:

Anti-tuberculosis agent	Minimum inhibitory concentration (MIC)
Isoniazid	0.4 mg/L
Streptomycin	2.0 mg/L
Rifampicin	2.0 mg/L
Ethambutol	2.5 mg/L

BCG Danish strain 1331 is resistant towards pyrazinamide.

Not relevant for vaccines.

Relevant preclinical data are not available.

Powder:

Sodium glutamate

 

Solvent:

Magnesium sulphate heptahydrate

Dipotassium phosphate

Citric acid, monohydrate

L-asparagine monohydrate

Ferric ammonium citrate

Glycerol 85%

Water for injection

BCG Vaccine AJVaccines must not be mixed with other medicinal products.

12–24 months. From a microbiological point of view the product should be used immediately after reconstitution. In-use stability in terms of viability has been demonstrated for 4 hours after reconstitution.

Store in a refrigerator (2ºC –8ºC).
Do not freeze.
Store in original package to protect from light.
For storage conditions after reconstitution of the vaccine, see section 6.3.

Powder in amber Type I glass vial with bromobutyl stopper and aluminium cap; 1 mL of solvent in Type I glass vial with a chlorobutyl stopper and an aluminium cap.

Packages of 1, 5, 10 vials and a 1 vial presentation including 1 unidose injection kit (one polypropylene syringe and two injection needles [long: for adding solvent; short: for intradermal injection]).

One vial of reconstituted vaccine contains 1 mL, corresponding to 10 doses for adults and children aged 12 months or more (0.1 mL), or 20 doses for infants under 12 months of age (0.05 mL).

Not all pack sizes may be marketed.

Reconstitution:

Only the solvent provided with the BCG Vaccine AJVaccines may be used for reconstitution.

The rubber stopper must not be wiped with antiseptic or detergent. If alcohol is used to swab the rubber stopper of the vial, it must be allowed to evaporate before the stopper is penetrated with the syringe needle.

The vaccine should be visually inspected before and after reconstitution for any foreign particles before administration.

Using a syringe fitted with a long needle, transfer to the vial the volume of solvent given on the label. Carefully invert the vial a few times to resuspend the lyophilised BCG completely. DO NOT SHAKE. Gently swirl the vial of resuspended vaccine before drawing up each subsequent dose. When drawn up into the syringe the vaccine suspension should appear homogeneous, slightly opaque, and colourless.

Any unused vaccine or waste material should be disposed of in accordance with local requirements.