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Transcript
sanofi pasteur
240 - BCG Vaccine (Freeze Dried)
Package Insert - English
PACKAGE INSERT
BCG VACCINE (FREEZE-DRIED)
Active Immunizing Agent
For Vaccination of Tuberculin Negative Persons Against Tuberculosis
Multidose Vial
R13-1105
Sanofi Pasteur Limited
Toronto, Ontario, Canada
Confidential/Proprietary Information
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sanofi pasteur
240 - BCG Vaccine (Freeze Dried)
Package Insert - English
BCG VACCINE (FREEZE-DRIED)
Active Immunizing Agent
For Vaccination of Tuberculin Negative Persons Against Tuberculosis
DESCRIPTION
BCG Vaccine (Freeze-Dried) is a culture preparation of Bacillus Calmette-Guérin, Connaught
substrain, an attenuated strain of Mycobacterium bovis suspended in monosodium glutamate.
BCG cultures are propagated on Sauton growth medium, then harvested, mixed with
monosodium glutamate and lyophilized (freeze-dried). BCG cultures are viable upon
reconstitution. BCG vaccine is supplied in multi-dose vials with accompanying diluent, which
consists of sterile phosphate-buffered saline containing 0.025% polysorbate 80. The
concentration of the reconstituted vaccine is 8 x 105 to 32 x 105 colony forming units (CFU) per
adult dose of 0.1 mL (= 0.1 mg BCG), equivalent to 4 x 105 to 16 x 105 CFU per infant dose of
0.05 mL (= 0.05 mg BCG).
Lyophilized vaccine for reconstitution with diluent:
Bacillus Calmette-Guérin
1.5 mg
Excipient:
monosodium glutamate
1.5% w/v
Diluent:
sodium chloride
0.85%
disodium hydrogen phosphate
0.25%
sodium dihydrogen phosphate
0.06%
polysorbate 80
0.025%
water for injection
q.s. 1.5 mL
CLINICAL PHARMACOLOGY
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Mortality and
morbidity from TB have declined significantly in Canada since the Second World War.1 After
decades of continuous decline, however, the notification rate has essentially levelled off since
1987 to the current level.2 The incidence of TB varies from one geographic region to another.
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sanofi pasteur
240 - BCG Vaccine (Freeze Dried)
Package Insert - English
Groups at highest risk include Aboriginal populations and immigrants from areas with a high
prevalence of the disease. Other persons at high risk include those infected with both HIV and
tubercle bacilli, close contacts of persons with untreated TB, the elderly and the homeless.1
BCG (Bacille Calmette-Guérin) is a live, attenuated vaccine derived from Mycobacterium bovis.
BCG has been used as a vaccine against TB since 1921. Its use in North America is confined to
selected groups of people who still have high rates of tuberculosis.2
Two meta-analyses have calculated summary estimates of BCG efficacy. Both studies concluded
that there were very high rates of protection against meningeal and miliary tuberculosis, as high
as 86% in one clinical trial. It was concluded from the clinical trials and case-control studies that
BCG offered an overall protective effect of 51% and 50% against pulmonary tuberculosis.2,3,4 The
protective effect is long lasting and has been demonstrated nearly 20 years after vaccination.2
The protective effect was greater among infants and children than among adults. An enhanced
protective effect was also noted in studies in which BCG was given to newborns or infants. The
protective effect of vaccination increases with increased distance from the equator.1
Clinical Trials with BCG Vaccine (Freeze-Dried)
Two retrospective case-control studies assessed the protective effect of BCG Vaccine (FreezeDried) in Aboriginal Canadian Indians. In one study, comparing the BCG vaccination status of
160 persons treated for tuberculosis between 1975 and 1979 with 232 controls, the protective
effect of BCG vaccination was 57% (95% confidence interval (CI) 23 - 75%).5
In the other study, the BCG vaccination history of 71 children, aged 15 years and under, newly
diagnosed with TB (37 bacteriologically confirmed) between 1979 and 1983 was compared with
213 controls. A record of BCG vaccination was found in 49% of the tuberculosis cases compared
to 77% of the controls. The protective effect for those who received BCG Vaccine (Freeze-Dried)
at birth was 60%.6
In a clinical trial in Chile in 1984, 148 neonates received 0.05 mg in 0.05 mL of BCG Vaccine
(Freeze-Dried) and 105 neonates received the same dose of the WHO-reference BCG vaccine.
By 6 months of age, PPD positivity (>10 mm induration to 5 TU of PPD) was demonstrated in 40
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sanofi pasteur
240 - BCG Vaccine (Freeze Dried)
Package Insert - English
out of 97 (41.2%) of BCG Vaccine (Freeze-Dried) recipients and 38 out of 69 (55.0%) of WHOreference BCG vaccine recipients.7
In a clinical trial in Colombia in 1984, 445 PPD negative school children aged 5 - 14 years
received 0.1 mg in 0.1 mL of BCG Vaccine (Freeze-Dried) and 138 received the same dose of
the WHO-reference BCG vaccine. PPD positivity (>10 mm induration to 5 TU of PPD) was
demonstrated among 305 out of 407 (74.9%) of BCG Vaccine (Freeze-Dried) recipients and 100
out of 130 (76.9%) of WHO-reference BCG vaccine recipients.7
In a clinical trial of safety and immunogenicity of BCG Vaccine (Freeze-Dried) administered to
PPD negative, healthy adult health-care workers aged 18 - 45 years in St. Louis, Missouri in
1994, PPD conversion (>5 mm induration to 5 or 10 TU of PPD) was demonstrated in 91% of 31
subjects.7
INDICATIONS
BCG Vaccine (Freeze-Dried) is indicated for the prevention of tuberculosis in persons not
previously infected with M. tuberculosis who are at high risk of exposure.
In accordance with the Canadian Tuberculosis Standards, BCG Vaccine may be considered for
the following groups:2
•
Newborn First Nations infants, particularly those living on reserve.
•
Individuals who are repeatedly exposed to persistently untreated or inadequately treated
tuberculosis, particularly children from families in which there is a strong history of
tuberculosis.
•
Communities or groups of persons in which high rates of new infection are demonstrated
(annual infection rate >1%), for which other control measures have proved ineffective.
•
Health-care workers who may be at particular risk of exposure to unrecognized infectious
forms of tuberculosis or who handle tubercle bacilli in laboratory cultures.
•
Newborn infants born to infectious mothers. Alternatively, BCG may be given 3 months after
INH prophylaxis once the mother has ceased to be infectious, if the infant remains tuberculin
negative.
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240 - BCG Vaccine (Freeze Dried)
•
Package Insert - English
Travellers visiting countries with a high prevalence of TB. A tuberculin skin test is
recommended before departure except for those with known previous positive skin tests.2
BCG Vaccine should be given only to persons who have not been infected with M. tuberculosis
or who have a negative tuberculin skin test (Mantoux 5 TU). Infants <6 weeks of age do not need
to be tuberculin tested before receiving BCG Vaccine since reactivity does not develop before
this age.1
BCG vaccination has NO value in the treatment of tuberculous disease.
In accordance with the recommendations of the National Advisory Committee on Immunization
(NACI), BCG vaccination is recommended for the following persons:1
a) Infants and children belonging to groups with high rates of new infections, i.e., in excess of
1% per year, when other control measures have proved ineffective.
b) Infants and children with negative tuberculin skin tests who are at high risk of intimate and
prolonged exposure to persistently untreated or ineffectively treated patients (e.g., because of
multidrug resistance) with infectious pulmonary TB, unless they can be removed from the
source of exposure or given long-term preventive therapy.
c) Individuals repeatedly exposed to persons with untreated or inadequately treated active TB in
conditions under which normal preventive measures are not possible or have been
unsuccessful, e.g., when multidrug-resistant TB is involved.
d) BCG vaccination may be considered for health-care workers (including medical laboratory
workers) at considerable risk of exposure to tubercle bacilli, especially drug-resistant bacilli,
when protective measures against infection are known to be ineffective or not feasible.
Consultation with a regional TB and/or infectious disease expert is recommended before
BCG Vaccine is administered.
e) BCG vaccination may be considered for travellers planning extended stays in areas of high
tuberculosis prevalence, particularly where a program of serial skin testing and appropriate
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240 - BCG Vaccine (Freeze Dried)
Package Insert - English
chemotherapy may not be feasible or where primary isoniazid resistance of Mycobacterium
tuberculosis is high. Travellers are advised to consult a specialist in travel medicine or
infectious disease when considering a decision for or against BCG immunization.
CONTRAINDICATIONS
Allergy to any component of BCG Vaccine (Freeze-Dried) including monosodium glutamate and
polysorbate 80 or an anaphylactic or other allergic reaction to a previous dose of BCG vaccine
are contraindications to vaccination.
BCG Vaccine (Freeze-Dried) should not be administered to persons with immune deficiency
diseases, including HIV, congenital immunodeficiency such as chronic granulomatous disease or
interferon gamma receptor deficiency,8,9 altered immune status due to malignant disease, or
impaired immune function secondary to treatment with corticosteroids, chemotherapeutic agents,
or radiation.1,10 (See ADVERSE REACTIONS.)
Extensive skin disease or burns is also a contraindication to immunization with BCG Vaccine
(Freeze-Dried).1
BCG Vaccine (Freeze-Dried) is contraindicated for persons with a positive tuberculin skin test
although vaccination of tuberculin reactors has frequently occurred without incident.1
Immunization with BCG Vaccine (Freeze-Dried) should be deferred during the course of a
moderate or severe febrile illness or acute infection1 (see PRECAUTIONS) to avoid
superimposing potential adverse effects of the vaccine on the underlying illness. A minor afebrile
illness such as mild upper respiratory infection is not usually reason to defer immunization.
WARNINGS
As with any vaccine, immunization with BCG Vaccine (Freeze-Dried) may not protect 100% of
persons.
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240 - BCG Vaccine (Freeze Dried)
Package Insert - English
BCG immunization will not prevent the development of active TB in persons who are already
infected with M. tuberculosis.
BCG Vaccine (Freeze-Dried) is NOT a treatment for superficial cancer of the urinary
bladder.
PRECAUTIONS
The stopper of the vial for this product contains dry natural latex rubber. Natural latex rubber has
been associated with allergic reactions.
The possibility of allergic reactions in persons sensitive to components of the vaccine should be
evaluated. Epinephrine Hydrochloride Solution (1:1,000) should be available for immediate use in
case an anaphylactic or acute hypersensitivity reaction occurs.1 Health-care providers should be
familiar with current recommendations for the initial management of anaphylaxis in non-hospital
settings, including proper airway management.1
For instructions on recognition and treatment of anaphylactic reactions, see the current edition of
the Canadian Immunization Guide, or visit the Health Canada website.
Before administration take all appropriate precautions to prevent adverse reactions. This includes
a review of the patient's history concerning possible hypersensitivity to the vaccine or similar
vaccine, previous immunization history, the presence of any contraindications to immunization
and current health status.
BCG Vaccine (Freeze-Dried) should not be administered to persons receiving drugs with
antituberculous activity, since these agents may be active against the vaccine strain.1
Providers of BCG Vaccine should ascertain any family history suggestive of congenital
immunodeficiency and any risk factors for HIV infection before administering BCG Vaccine.
Infants who have potentially been exposed to HIV perinatally should not be given BCG Vaccine
until they have been confirmed not to be infected with HIV.
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sanofi pasteur
240 - BCG Vaccine (Freeze Dried)
Package Insert - English
Before administration of BCG Vaccine (Freeze-Dried) health-care providers should inform the
patient, parent or guardian of the benefits and risks of immunization, inquire about the recent
health status of the patient and comply with any local requirements regarding information to be
provided to the patient before immunization.
Administer BCG Vaccine (Freeze-Dried) intradermally; do not inject subcutaneously,
intramuscularly or intravenously.
Use a separate sterile needle and syringe, or a sterile disposable unit, for each individual patient
to prevent disease transmission.
There have been case reports of transmission of HIV and hepatitis by failure to scrupulously
observe sterile technique. In particular, the same needle and/or syringe must never be used to
re-enter a multidose vial to withdraw vaccine even when it is to be used for inoculation of the
same patient. This may lead to contamination of the vial contents and infection of patients who
subsequently receive vaccine from the vial.11
BCG Vaccine (Freeze-Dried) contains viable attenuated mycobacteria; it should be handled as
an infectious agent at all times. See "DOSAGE AND ADMINISTRATION" for recommended
procedures for proper handling and disposal.
Pregnancy and Lactation
Vaccination of pregnant women is usually delayed until after delivery, although no harmful effects
on the fetus have been observed.2
Animal reproduction studies have not been conducted with BCG Vaccine (Freeze-Dried). It is
also not known whether BCG Vaccine (Freeze-Dried) can cause fetal harm when administered to
a pregnant woman or can affect reproduction capacity.
It is not known whether BCG Vaccine (Freeze-Dried) is excreted in human milk. Because live
vaccines may be excreted in human milk, caution should be exercised when BCG Vaccine
(Freeze-Dried) is administered to a nursing woman.
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sanofi pasteur
240 - BCG Vaccine (Freeze Dried)
Package Insert - English
Simultaneous Use With Other Vaccines
Most inactivated and live vaccines may be given simultaneously at separate sites with separate
syringes.1 Studies to examine the simultaneous administration of BCG Vaccine (Freeze-Dried)
with hepatitis B immune globulin have not been conducted. A study which examined
simultaneous administration of BCG Vaccine and hepatitis B vaccine at birth, showed that
simultaneous administration impaired neither the immunogenicity nor the safety of either
vaccine.12 One live vaccine may interfere with the effectiveness of another. BCG Vaccine should
not be given within 4 weeks after administration of any live vaccine, since these vaccines are
known to suppress the tuberculin response.1
ADVERSE REACTIONS
The usual response to BCG vaccination is a red indurated area measuring 5 - 15 mm; the center
is soft for 3 to 4 weeks and a crust is formed. When the crust falls off between the 6th and 10th
week, a flat scar measuring 3 - 7 mm, usually with sharp punched-out edges which may be
regular or irregular, remains.13
Two studies of BCG Vaccine (Freeze-Dried) were conducted in Chile and in Colombia in 1984.
In Chile, 148 neonates received 0.05 mg in 0.05 mL of BCG Vaccine (Freeze-Dried) and
105 neonates received the same dose of the WHO-reference BCG vaccine. In Colombia,
445 PPD negative school children aged 5 - 14 years received 0.1 mg in 0.1 mL of BCG Vaccine
(Freeze-Dried) and 138 received the same dose of the WHO-reference BCG vaccine.7 The
following table outlines the reactions observed:
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sanofi pasteur
240 - BCG Vaccine (Freeze Dried)
Package Insert - English
Table 1: CHILE AND COLOMBIA STUDIES7 REACTIONS OBSERVED IN CHILEAN
NEONATES AND COLOMBIAN SCHOOL CHILDREN
Reaction Observed
Vaccine
Chili
Post-vaccination
4
8 à 10
Weeks
Weeks
Colombie
Post-vaccination
4
8 à 10
Weeks
Weeks
Induration
≥10 mm
BCG Vaccine (Freeze-Dried)
WHO BCG vaccine
39.2%
14.2%
7.4%
15.2%
29.4%
13.5%
16.2%
14.0%
Ulceration
5 - 9 mm
BCG Vaccine (Freeze-Dried)
WHO BCG vaccine
12.4%
3.8%
56.1%
59.0%
18.5%
5.3%
34.7%
21.5%
Ulceration
10 - 14 mm
BCG Vaccine (Freeze-Dried)
WHO BCG vaccine
0%
0%
2%
2%
0%
0%
0%
0%
Regional Lymphadenopathy BCG Vaccine (Freeze-Dried)
≥10 mm;<20 mm
WHO BCG vaccine
34.6%
41.5%
21.0%
49.6%
9.5%
0.8%
0.2%
0%
Regional Lymphadenopathy BCG Vaccine (Freeze-Dried)
≥20 mm
WHO BCG vaccine
0%
0.9%
0%
6.7%
0%
0%
0%
0%
For these two studies, safety follow-up was not continued past 10 weeks. Systemic reactions
were not monitored.7
In a study of safety and immunogenicity of BCG Vaccine (Freeze-Dried) administered to
32 healthy PPD negative, HIV-negative adult health-care workers aged 18 - 45 years, in St.
Louis, Missouri, in 1994, local and systemic reactions were monitored for 49 days, with any
unresolved reactions being monitored up to 84 days.7 The following local and systemic reactions
were noted:
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240 - BCG Vaccine (Freeze Dried)
Package Insert - English
Table 2: LOCAL AND SYSTEMIC REACTIONS TO BCG VACCINE (FREEZE-DRIED), IN
HEALTHY US ADULTS 7
Days Post-BCG
0
1
3
14
28
49
31 (97)
25 (78)
Number (%) of each reaction
Any Reaction at
Injection Site
24 (75)
31 (97)
32 (100)
32 (100)
>1 Erythema
2 (6.3)
1 (3.1)
5 (15.6)
2 (6.3)
Induration
1 (3.1)
3 (9.4)
12 (37.5)
12 (37.5)
Pani/Soreness
6 (19)
6 (19)
4 (13)
Ulceration
0
1 (3)
3 (9)
Fever >99.0°F
1 (3)
0
0
0
0
0
* Regional Adenopathy
1 (3)
1 (3)
1 (3)
1 (3)
1 (3)
1 (3)
**Chills
0
1 (3)
0
**Anorexia
1 (3,1)
0
1 (3.1)
**Malaise
6 (19)
5 (16)
4 (13)
0
22 (69)
0
0
4 (12.5)
0
2 (6)
0
22 (69)
*
Regional Adenopathy was observed in a single subject throughout the monitoring period.
**
Except for fever and regional adenopathy, systemic reactions were not recorded after day 3 post-dose.
15 (47)
There were no episodes of nausea or vomiting. Ulceration had completely healed by 7 weeks in
18 of 32 subjects (56.3%), by 8 weeks in another 9 subjects (28.1%) and by 12 weeks in the
remaining 5 (15.5%).
In studies of BCG Vaccine (Freeze-Dried) ulceration of >5 mm at the site of intradermal
vaccination (the most common adverse reaction) occurred in approximately 50% (35 - 69%) of
patients.
Regional (e.g., axillary) lymphadenopathy follows BCG vaccination (various strains from various
manufacturers), with a frequency ranging from 1 - 10%.13,14,15,16,17 Suppurative lymphadenitis is
much less common than lymphadenopathy, occurring in 0.03 - 0.5% of BCG vaccine recipients.12
Multiple lymphadenitis, hepatomegaly, splenomegaly and other nonfatal disseminated lesions
have occurred at rates of 0.31 to 0.39 per 1 million vaccinations.18
One case of osteomyelitis associated with Sanofi Pasteur Limited=s BCG Vaccine (Freeze-Dried)
was reported in 1998.7 Osteitis has been observed mostly in Scandinavian countries, possibly
related to the strain used.2 The risk for developing osteitis after BCG vaccination varies by
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240 - BCG Vaccine (Freeze Dried)
Package Insert - English
country; in one review this risk ranged from 0.01 cases/million vaccinees in Japan to 43.4
cases/million vaccinees in Finland.10
Disseminated Mycobacterium bovis, var BCG, infection occurred in four Aboriginal Canadian
infants who had been immunized with BCG Vaccine (Freeze-Dried) in the neonatal period. All
cases were in infants with immunodeficiencies (including severe combined immunodeficiency,
HIV/AIDS, defect in interferon gamma) which had not been detected before immunization.19
Disseminated BCG infection, which may be fatal, occurs very rarely (about 1 in 1 million
vaccinations), and is seen almost exclusively in persons with impaired immune responses. 1,14,15
HIV-infected individuals
Several case reports of disseminated BCG in HIV-seropositive infants immunized during the first
year of life and in adults with AIDS have raised concern that HIV infection may predispose to
disease caused by BCG. In adults who have acquired AIDS, BCG adenitis has been reported up
to 30 years after immunization with BCG.20
Physicians, nurses and pharmacists should report any adverse occurrences temporally related to
the administration of the product in accordance with local requirements and to the Global
Pharmacovigilance Department, Sanofi Pasteur Limited, 1755 Steeles Avenue West, Toronto,
ON, M2R 3T4, Canada. 1-888-621-1146 (phone) or 416-667-2435 (fax).
OVERDOSE
The recommended dosage for age should not be exceeded, as this may result in more extensive
local reactions. Subcutaneous or intramuscular injection may result in an abscess at the injection
site.
DOSAGE AND ADMINISTRATION
The recommended dose for newborns and infants ≤12 months of age is 0.05 mL (0.05 mg).
Children over 12 months of age and adults should be given a 0.1 mL (0.1 mg) dose.
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sanofi pasteur
240 - BCG Vaccine (Freeze Dried)
Package Insert - English
Reconstitution of Freeze-Dried Vaccine and Withdrawal from Stoppered Vial
DO NOT REMOVE THE STOPPER FROM THE VIAL.
Apply a sterile piece of cotton moistened with a suitable antiseptic to the surface of the stopper
of the vial of vaccine. Withdraw the diluent into a syringe. Holding the plunger of the syringe
containing the diluent steady, pierce the centre of the stopper in the vial and inject the required
volume of sterile diluent into the freeze-dried vaccine. Do not try to force all of the diluent into the
vial at once as this will create pressure. It is necessary gradually to allow air to escape into the
syringe by intermittently aspirating air from the vial while injecting the diluent into the vial. Do not
remove the needle from the stopper until the required volume of diluent has been injected. Shake
the vial gently. Avoid foaming since this will prevent withdrawal of the proper dose. Withdraw
the required dose of the reconstituted vaccine into a syringe. Aseptic technique must be used for
withdrawal of each dose. (See PRECAUTIONS.)
Inspect for extraneous particulate matter and/or discolouration before use. If these conditions
exist, the product should not be administered.
Cleanse the outer surface of the upper arm with a suitable germicide and allow to dry. Using a
1.0 mL sterile syringe with a 26-gauge needle, inject 0.1 mL (0.05 mL for infants) of the
reconstituted vaccine intradermally into the most superficial layers of the skin at one site. The
bevelled side of the needle should face upwards.
The preferred site is over the area of the deltoid muscle of the arm.
Do not inject subcutaneously, intramuscularly or intravenously.
Needles should not be recapped and should be disposed of properly.
BCG Vaccine (Freeze-Dried) contains viable attenuated mycobacteria and should be handled as
an infectious agent at all times. After use, any unused vaccine and all equipment, packaging
and materials exposed to the product should be immediately placed in a container for
biohazardous materials and disposed of as biohazardous waste.
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240 - BCG Vaccine (Freeze Dried)
Package Insert - English
Give the patient a permanent personal immunization record. In addition, it is essential that the
physician or nurse record the immunization and PPD history (if applicable) in the permanent
medical record of each patient. This permanent office record should contain the name of the
vaccine, date given, dose, manufacturer and lot number.
Revaccination
Revaccination with BCG is not recommended and should be addressed in consultation with
regional TB or infectious disease experts.1
STORAGE
Store at 2° to 8°C (35° to 46°F). DO NOT FREEZE. Discard product if exposed to freezing.
Do not use after expiration date.
BCG Vaccine can be adversely affected by exposure to light. The product should be stored in the
dark except when doses are actually being withdrawn from the vial.21
The vaccine should be used immediately after reconstitution and any reconstituted
vaccine not used within 8 hours MUST be discarded. Any reconstituted product which
exhibits flocculation or clumping that cannot be dispersed with gentle shaking should not be
used. The reconstituted vaccine should be maintained at 2° to 8°C (35° to 46°F).
HOW SUPPLIED
BCG Vaccine (Freeze-Dried) is supplied in a package containing a multidose 1.5 mg vial of
vaccine and accompanying 1.5 mL vial of diluent.
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REFERENCES
1. National Advisory Committee on Immunization: Canadian Immunization Guide, Sixth Edition.
Her Majesty the Queen in Right of Canada, represented by the Minister of Public Works and
Government Services Canada, 2002:4,14-16,32,71-76.
2. Canadian Lung Association: Canadian Tuberculosis Standards, 5th Edition. 2000:223-228.
3. Rodrigues LC, et al. Protective effect of BCG against tuberculous meningitis and miliary
tuberculosis: a meta-analysis. Int J Epidemiol 1993;22:1154-1158.
4. Colditz GA, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of
the published literature. JAMA 1994;271:698-702.
5. Houston S, et al. The effectiveness of Bacillus Calmette-Guérin (BCG) vaccination against
tuberculosis. Am J Epidemiol 1990;131:340-348.
6. Young TK, Hershfield E. A case-control study to evaluate the effectiveness of mass neonatal
BCG vaccine among Canadian Indians. Am J Public Health 1986;76:783-786.
7. Unpublished clinical data available from Sanofi Pasteur Limited.
8. Casanova JL, et al. Idiopathic disseminated Bacillus Calmette-Guérin infection: A French
national retrospective study. Pediatrics 1996;98(4):774-778.
9. Jouanguy E, et al. Interferon-y-receptor deficiency in an infant with fatal Bacille CalmetteGuérin infection. New Eng J Med 1996;335(26):1956-1961.
10. CDC. The role of BCG vaccine in the prevention and control of tuberculosis in the United
States. MMWR 1996;45(RR-4):1-18.
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240 - BCG Vaccine (Freeze Dried)
Package Insert - English
11. Plott RT, et al. Iatrogenic contamination of multidose vials in simulated use. Arch Dermatol
1990;126:1441-1444.
12. Coursaget P, et al. Simultaneous injection of hepatitis B vaccine with BCG and killed
poliovirus vaccine. Vaccine 1992;10(5):319-321.
13. Fitzgerald MJ and Duclos P. The reporting and management of adverse reactions to Bacillus
Calmette-Guérin (BCG) vaccination. Can Dis Wkly Rep 1991;17:98-100.
14. Connelly Smith K and Starke JR. Bacille Calmette-Guérin Vaccine. In: Plotkin SA and
Orenstein WA (eds.), Vaccines WB Saunders Company, Philadelphia. 1999:111-139.
15. Lotte A, et al. BCG complications: estimates of the risks among vaccinated subjects and
statistical analysis of their main characteristics. Adv Tuberc Res 1984;21:107-193.
16. Belcourt RJ-P. Experiments in dosage requirements of BCG intradermal for infants. In:
International Symposium on BCG Vaccine, Frankfurt (Main) 1970; Symposium Series in
Immunobiological Standardization. Basel, Karger 1971;17:85-88.
17. Guld J, et al. Suppurative lymphadenitis following intradermal BCG vaccination of the
newborn. Br Med J 1955;2:1048-1054.
18. Lotte, et al. Second IUATLD study on complications induced by intradermal BCG-vaccination.
Bull Int Union Tuberc. 1988;63(2):47-59.
19. Health Protection Branch - Laboratory Centre for Disease Control. Disseminated Bacille
Calmette-Guérin infection: Three recent Canadian cases. CCDR 1998;24-9:1-5.
20. Reynes J, et al. Bacille Calmette-Guérin adenitis 30 years after immunization in a patient with
AIDS [letter]. J Infect Dis 1989;160:727.
21. Landi S, et al. Effect of light on freeze-dried BCG vaccines. J Biol Stand 1977;5:321-326.
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240 - BCG Vaccine (Freeze Dried)
Package Insert - English
Vaccine Information Service: 1-888-621-1146 or 416-667-2779.
Visit us at www.sanofipasteur.ca
Product Information as of September 2002.
Manufactured by:
Sanofi Pasteur Limited
Toronto, Ontario, Canada
R13-1105 Canada
Confidential/Proprietary Information
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