Rx only

DESCRIPTION

ActHIB®, Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), produced by Sanofi Pasteur SA, is a sterile, lyophilized powder which is reconstituted at the time of use with either saline diluent (0.4% Sodium Chloride) or Sanofi Pasteur Inc. Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (whole-cell pertussis vaccine DTP) or Tripedia®, Sanofi Pasteur Inc. Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) (when reconstituted known as TriHIBit®) for intramuscular use only. The vaccine consists of the Haemophilus b capsular polysaccharide (polyribosyl-ribitol-phosphate, PRP), a high molecular weight polymer prepared from the Haemophilus influenzae type b (HiB) strain 1482 grown in a semi-synthetic medium, covalently bound to tetanus toxoid. (1) The lyophilized ActHIB vaccine powder and saline diluent contain no preservative. The tetanus toxoid is prepared by extraction, ammonium sulfate purification, and formalin inactivation of the toxin from cultures of Clostridium tetani (Harvard strain) grown in a modified Mueller and Miller medium. (2) Further manufacturing process steps reduce residual formaldehyde to levels below 0.5 micrograms (mcg) per dose by calculation. The toxoid is filter sterilized prior to the conjugation process. Potency of ActHIB vaccine is specified on each lot by limits on the content of PRP polysaccharide and protein in each dose and the proportion of polysaccharide and protein in the vaccine which is characterized as high molecular weight conjugate.

When ActHIB vaccine is reconstituted with saline diluent, each single dose of 0.5 mL is formulated to contain 10 mcg of purified capsular polysaccharide conjugated to 24 mcg of inactivated tetanus toxoid, and 8.5% of sucrose.

When ActHIB vaccine is combined with Sanofi Pasteur Inc. DTP vaccine by reconstitution, each single dose (0.5 mL) is formulated to contain 10 mcg of purified capsular polysaccharide conjugated to 24 mcg of inactivated tetanus toxoid, 8.5% of sucrose, 6.7 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid and an estimate of 4 protective units of pertussis vaccine. Thimerosal (mercury derivative) 1:10,000 is added as a preservative to Sanofi Pasteur Inc. DTP vaccine. (Refer to product insert for Sanofi Pasteur Inc. whole-cell DTP.)

When ActHIB vaccine is combined with Tripedia vaccine (TriHIBit vaccine) by reconstitution for booster dose, each single dose (0.5 mL) is formulated to contain 10 mcg of purified capsular polysaccharide conjugated to 24 mcg of inactivated tetanus toxoid, 8.5% of sucrose, 6.7 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid and 46.8 mcg of pertussis antigens. The 0.6 mL vial of Tripedia vaccine is formulated without preservatives but contains a trace amount of thimerosal [(mercury derivative), (≤0.3 mcg mercury/dose)] from the manufacturing process. (Refer to product insert for Tripedia vaccine.)

The reconstituted vaccine, using saline diluent, appears clear and colorless. The reconstituted vaccine, using Sanofi Pasteur Inc. DTP vaccine, appears whitish in color. TriHIBit vaccine, the reconstituted vaccine, using Tripedia vaccine, is a homogenous white suspension.

CLINICAL PHARMACOLOGY

H influenzae type b was the leading cause of invasive bacterial disease among children in the United States prior to licensing of Haemophilus b conjugate vaccines. Based on its active surveillance areas, the Centers for Disease Control and Prevention (CDC) now estimate that H influenzae type b disease in children under the age of 5 years has been reduced by 95%. (3) Before effective vaccines were introduced, it was estimated that one in 200 children developed invasive H influenzae type b disease by the age of 5 years. In children less than 5 years of age, the mortality rate for invasive H influenzae type b disease ranged between 3% and 6%. (3) In more than 60% of these children, meningitis was the clinical syndrome and permanent sequelae ranging from mild hearing loss to mental retardation affecting 20% to 30% of all survivors. (3) Ninety-five percent of the cases of invasive H influenzae disease among children <5 years of age were caused by organisms with the type b polysaccharide capsule. Approximately two-thirds of all cases of invasive H influenzae type b disease affected infants and children <15 months of age, a group for which a vaccine was not available until late 1990. (4), (5)

Incidence rates of invasive H influenzae type b disease have been shown to be increased in certain high-risk groups, such as native Americans (both American Indians and Eskimos), blacks, individuals of lower socioeconomic status, and patients with asplenia, sickle cell disease, Hodgkin's disease, and antibody deficiency syndromes. (5),(6) Studies also have suggested that the risk of acquiring primary invasive H influenzae type b disease for children under 5 years of age appears to be greater for those who attend day-care facilities. (7), (8), (9),(10)

The potential for person to person transmission of the organism among susceptible individuals has been recognized. Studies of secondary spread of disease in household contacts of index patients have shown a substantially increased risk among exposed household contacts under 4 years of age. (11) Adults can be colonized with H influenzae type b from children infected with the organism. (12)

The response to ActHIB vaccine is typical of a T-dependent immune response to antigen. The prominent isotype of anti-capsular PRP antibody induced by ActHIB vaccine is IgG. (13) A substantial booster response has been demonstrated in children 12 months of age or older who previously received two or three doses. Bactericidal activity against H influenzae type b is demonstrated in serum after immunization and statistically correlates with the anti-PRP antibody response induced by ActHIB vaccine. (14)

Antibody to H influenzae capsular polysaccharide (anti-PRP) titers of >1.0 mcg/mL following vaccination with unconjugated PRP vaccine correlated with long-term protection against invasive H influenzae type b disease in children older than 24 months of age. (15) Although the relevance of this threshold to clinical protection after immunization with conjugate vaccines is not known, particularly in light of the induced, immunologic memory, this level continues to be considered as indicative of long-term protection. (4) The immunogenicity and safety of ActHIB vaccine has been demonstrated in the United States and worldwide. ActHIB vaccine induced, on average anti-PRP levels ≥1.0 mcg/mL in 90% of infants after the primary series and in more than 98% of infants after a booster dose.(14)

Two clinical trials supported by the National Institutes of Health (NIH) have compared the anti-PRP antibody responses to three Haemophilus b conjugate vaccines in racially mixed populations of children. These studies were done in Tennessee (16) (TABLE 1) and in Minnesota, Missouri and Texas (17) (TABLE 2) in infants immunized with ActHIB vaccine and other Haemophilus b conjugate vaccines at 2, 4 and 6 months of age. All Haemophilus b conjugate vaccines were administered concomitantly with Poliovirus Vaccine Live Oral and DTP vaccines at separate sites.

Native American populations have had high rates of H influenzae type b disease and have been observed to have low immune responses to Haemophilus b conjugate vaccines. Following three doses of ActHIB vaccine at six weeks, four and six months of age, 75% of Native Americans in Alaska showed an anti-PRP antibody titer of ≥1.0 mcg/mL. (18)

Children 12 to 24 months of age who had not previously received Haemophilus b conjugate vaccination were immunized with a single dose of ActHIB vaccine. GMT anti-PRP antibody responses were 5.12 mcg/mL (90% responding with ≥1.0 mcg/mL) for children 12 to 15 months of age and 4.4 mcg/mL (82% responding with ≥1.0 mcg/mL) for children 17 to 24 months of age. (18)

These trials demonstrated that ActHIB vaccine consistently conferred an anti-PRP antibody response previously shown to correlate with protection, when administered either as a regimen of three doses at least four to eight weeks apart in infants 2 to 6 months of age or as a single dose in children 12 months of age and older. (18)

ActHIB vaccine has been found to be immunogenic in children with sickle cell anemia, a condition which may cause increased susceptibility to Haemophilus b disease. Two doses of ActHIB vaccine given at two-month intervals induced anti-PRP antibody titers of ≥1.0 mcg/mL in 89% of these children with a mean age of 11 months. This is comparable to anti-PRP antibody levels demonstrated in normal children of similar age following two doses of ActHIB vaccine.(19)

INDICATIONS AND USAGE

ActHIB vaccine or ActHIB vaccine combined with Sanofi Pasteur Inc. DTP vaccine by reconstitution is indicated for the active immunization of infants and children 2 through 18 months of age for the prevention of invasive disease caused by H influenzae type b and/or diphtheria, tetanus and pertussis.

TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution, is indicated for the active immunization of children 15 to 18 months of age for prevention of invasive disease caused by H influenzae type b and diphtheria, tetanus and pertussis.

Antibody levels associated with protection may not be achieved earlier than two weeks following the last recommended dose.

Only Sanofi Pasteur Inc. whole-cell DTP, Tripedia vaccine or 0.4% Sodium Chloride diluent may be used for reconstitution of lyophilized ActHIB vaccine. TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution, should not be administered to infants younger than 15 months of age.

As with any vaccine, vaccination with ActHIB vaccine reconstituted with Sanofi Pasteur Inc. DTP or ActHIB vaccine reconstituted with Tripedia vaccine (TriHIBit vaccine) or 0.4% Sodium Chloride diluent may not protect 100% of individuals.

A single injection containing diphtheria, tetanus, pertussis and Haemophilus b conjugate antigens may be more acceptable to parents and may increase compliance with vaccination programs. Therefore, in these situations it may be the judgment of the physician that it is of benefit to administer a single injection of whole-cell DTP or DTaP and Haemophilus b conjugate vaccines.

CONTRAINDICATIONS

ActHIB VACCINE IS CONTRAINDICATED IN CHILDREN WITH A HISTORY OF HYPERSENSITIVITY TO ANY COMPONENT OF THE VACCINE AND TO ANY COMPONENT OF DTP OR TRIPEDIA VACCINE WHEN COMBINED BY RECONSTITUTION WITH THESE VACCINES. ANY CONTRAINDICATION FOR DTP IS A CONTRAINDICATION FOR ActHIB VACCINE RECONSTITUTED WITH DTP. ANY CONTRAINDICATION FOR TRIPEDIA VACCINE IS A CONTRAINDICATION FOR TriHIBit VACCINE, ActHIB VACCINE RECONSTITUTED WITH TRIPEDIA VACCINE. (Refer to product inserts for Sanofi Pasteur Inc. whole-cell DTP and Tripedia vaccine.)

WARNINGS

If ActHIB vaccine or ActHIB vaccine reconstituted with Sanofi Pasteur Inc. DTP or ActHIB vaccine reconstituted with Tripedia vaccine (TriHIBit vaccine) is administered to immunosuppressed persons or persons receiving immunosuppressive therapy, the expected antibody responses may not be obtained. This includes patients with asymptomatic or symptomatic HIV-infection, (21) severe combined immunodeficiency, hypogammaglobulinemia, or agammaglobulinemia; altered immune states due to diseases such as leukemia, lymphoma, or generalized malignancy; or an immune system compromised by treatment with corticosteroids, alkylating drugs, antimetabolites or radiation. (22) (Refer to product inserts for Sanofi Pasteur Inc. whole-cell DTP and Tripedia vaccine.)

TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution, should not be administered to infants younger than 15 months of age.

PRECAUTIONS

ADVERSE REACTIONS

More than 7,000 infants and young children (≤2 years of age) have received at least one dose of ActHIB vaccine during US clinical trials. Of these, 1,064 subjects 12 to 24 months of age who received ActHIB vaccine alone reported no serious or life threatening adverse reactions.

Adverse reactions commonly associated with a first ActHIB vaccine immunization of children 12 to 15 months of age who were previously unimmunized with any Haemophilus b conjugate vaccine, include local pain, redness and swelling at the injection site. Systemic reactions include fever, irritability and lethargy. (14),(18)

In a multicenter trial, ActHIB vaccine was administered to US infants at 2, 4, and 6 months of age concomitantly, at separate sites, with Sanofi Pasteur Inc. DTP. The adverse events observed are summarized in TABLE 5.

In general, the rates of minor systemic reactions after ActHIB vaccine and DTP immunization were comparable to those usually reported after DTP vaccine alone. (30),(31),(32),(33)

When ActHIB vaccine reconstituted with Sanofi Pasteur Inc. whole-cell DTP was administered in infants at 2, 4, and 6 months of age, the systemic adverse experience profile (TABLE 6) was comparable to that observed when the two vaccines were given separately (TABLE 5). An increase in the rates of local reactions was observed within the 24-hour period after immunization. (18)

In a third US trial when ActHIB vaccine was combined with DTP by reconstitution, approximately 1,450 doses were administered to infants starting at 2 months of age. Adverse reactions observed at 6 and 24 hours respectively after the first immunization (n = 498) were tenderness 66.9% and 30.7%; erythema (>1") 8.6% and 2.2%; induration 38.2% and 21.7%; irritability 77.9% and 35.7%; drowsiness 63.7% and 34.1%; anorexia 26.1% and 12.9%; diarrhea 6.8% and 9.0%; and vomiting 3.4% and 3.8%. (18) One hypotonic/hyporesponsive episode (HHE) was seen in an infant following the second dose in this trial. This is consistent with the HHE incidence rate observed with DTP vaccination alone. (4)

Adverse reactions associated with ActHIB vaccine generally subsided after 24 hours and usually do not persist beyond 48 hours after immunization.

No data are available on the safety of a booster dose of ActHIB vaccine combined with Sanofi Pasteur Inc. DTP vaccine by reconstitution given in 15 to 20-month-old children.

In a US trial, safety of TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution, in 110 children aged 15 to 20 months was compared to ActHIB vaccine given with Tripedia vaccine at separate sites to 110 children. All children received three doses of Haemophilus b conjugate vaccine (ActHIB vaccine or HibTITER) and three doses of whole-cell DTP at approximately 2, 4, and 6 months of age.

TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution, was administered to approximately 850 children, aged 15 to 20 months. All children received three doses of a Haemophilus b conjugate vaccine (ActHIB vaccine or HibTITER®) and three doses of whole-cell DTP at approximately 2, 4, and 6 months of age. Local reactions were typically mild and usually resolved within the 24 to 48 hour period after immunization. The most common local reactions were pain and tenderness at the injection site. Systemic reactions occurring were usually mild and resolved within 72 hours of immunization. The reaction rates were similar to those observed in TABLE 7 when TriHIBit vaccine, ActHIB vaccine reconstituted with Tripedia vaccine was administered and when Tripedia vaccine was administered alone as a booster. (18)

In a randomized, double-blind US clinical trial, ActHIB vaccine was given concomitantly with DTP to more than 5,000 infants and Hepatitis B vaccine was given with DTP to a similar number. In this large study, deaths due to sudden infant death syndrome (SIDS) and other causes were observed but were not different in the two groups. In the first 48 hours following immunization, two definite and three possible seizures were observed after ActHIB vaccine and DTP in comparison with none after Hepatitis B vaccine and DTP. (18) This rate of seizures following ActHIB vaccine and DTP was not greater than previously reported in infants receiving DTP alone. (Refer to product insert for Sanofi Pasteur Inc. DTP.) Other adverse reactions reported with administration of other Haemophilus b conjugate vaccines include urticaria, seizures, hives, renal failure and Guillain-Barré syndrome (GBS). (18),(34) A cause and effect relationship among any of these events and the vaccination has not been established.

When ActHIB vaccine was given with DTP and inactivated poliovirus vaccine to more than 100,000 Finish infants, the rate and extent of serious adverse reactions were not different from those seen when other Haemophilus b conjugate vaccines were evaluated in Finland (ie, HibTITER, ProHIBiT®). (18)

However, the number of subjects studied with TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution, was inadequate to detect rare serious adverse events.

DOSAGE AND ADMINISTRATION

Parenteral drug products should be inspected visually for particulate matter and/or discoloration prior to administration, whenever solution and container permit. If these conditions exist, the vaccine should not be administered

RECONSTITUTION

Using Sanofi Pasteur Inc. DTP, cleanse both the DTP and ActHIB vaccine vial rubber stoppers with a suitable germicide prior to reconstitution. Thoroughly agitate the vial of Sanofi Pasteur Inc. DTP then withdraw a 0.6 mL dose and inject into the vial of lyophilized ActHIB vaccine. After reconstitution and thorough agitation, the combined vaccines will appear whitish in color. Withdraw and administer 0.5 mL dose of the combined vaccines intramuscularly. Vaccine should be used within 24 hours after reconstitution. Refer to Figures 1, 2, 3, 4 and 5.

To prepare TriHIBit vaccine, cleanse both the Tripedia vaccine and ActHIB vaccine vial rubber stoppers with a suitable germicide prior to reconstitution. Thoroughly agitate the vial of Sanofi Pasteur Inc. Tripedia vaccine then withdraw a 0.6 mL dose and inject into the vial of lyophilized ActHIB vaccine. After reconstitution and thorough agitation, the combined vaccines will appear whitish in color. Withdraw and administer 0.5 mL dose of the combined vaccines intramuscularly. Vaccine should be used immediately (within 30 minutes) after reconstitution. Refer to Figures 1, 2, 3, 4 and 5.

Using saline diluent (0.4% Sodium Chloride) cleanse the vaccine vial rubber stopper with a suitable germicide and inject the entire volume of diluent contained in the vial or syringe into the vial of lyophilized vaccine. Thorough agitation is advised to ensure complete reconstitution. The entire volume of reconstituted vaccine is then drawn back into the syringe before injecting one 0.5 mL dose intramuscularly. The vaccine will appear clear and colorless. Vaccine should be used within 24 hours after reconstitution. Refer to Figures 1, 2, 3, 4 and 5.

INSTRUCTIONS FOR RECONSTITUTION OF ActHIB VACCINE WITH SANOFI PASTEUR INC. DTP OR RECONSTITUTION OF ActHIB VACCINE WITH TRIPEDIA VACCINE (TriHIBit VACCINE) OR SALINE DILUENT (0.4% SODIUM CHLORIDE):

Figure 1. Cleanse stopper and agitate the vial of DTP, Tripedia vaccine, or 0.4% Sodium Chloride used to reconstitute ActHIB vaccine.	Figure 2.Withdraw volume of DTP, Tripedia vaccine or 0.4% Sodium Chloride as indicated.	Figure 3. Cleanse the ActHIB vaccine stopper, insert syringe needle through the rubber stopper and inject volume as indicated.	Figure 4. Agitate vial thoroughly.	Figure 5. After reconstitution with either DTP, or reconstitution with Tripedia vaccine (TriHIBit vaccine) or with 0.4% Sodium Chloride withdraw 0.5 mL of reconstituted vaccine and administer intramuscularly.

Before injection, the skin over the site to be injected should be cleansed with a suitable germicide. After insertion of the needle, aspirate to ensure that the needle has not entered a blood vessel.

DO NOT INJECT INTRAVENOUSLY.

Each dose of ActHIB vaccine reconstituted with Sanofi Pasteur Inc. DTP or ActHIB vaccine reconstituted with Tripedia vaccine (TriHIBit vaccine) or saline diluent (0.4% Sodium Chloride) is administered intramuscularly in the outer aspect of the vastus lateralis (mid-thigh) or deltoid. The vaccine should not be injected into the gluteal area or areas where there may be a nerve trunk. During the course of primary immunizations, injections should not be made more than once at the same site.

When ActHIB vaccine is reconstituted with Sanofi Pasteur Inc. DTP, the combined vaccines are indicated for infants and children 2 through 18 months of age for intramuscular administration in accordance with the schedule indicated in TABLE 8. (14) When ActHIB vaccine is reconstituted with Tripedia vaccine (TriHIBit vaccine), the combined vaccines are indicated for children 15 to 18 months of age for intramuscular administration in accordance with the schedule in TABLE 8. (14)

TABLE 8(14) RECOMMENDED IMMUNIZATION SCHEDULE FOR ActHIB VACCINE AND DTP PR TRIPEDIA VACCINE FOR PREVIOUSLY UNVACCINATED CHILDREN

DOSE	AGE	IMMUNIZATION
First, Second and Third	At 2, 4 and 6 months	ActHIB Vaccine reconstituted with DTP or with saline diluent (0.4% Sodium Chloride)
Forth	At 15 to 18 months	ActHIB vaccine reconstituted with DTP or with Tripedia vaccine (TriHIBit vaccine) or with saline diluent (0.4% Sodium Chloride)
Fifth	At 4 to 6 years	DTP or Tripedia vaccine

HOW SUPPLIED

REFERENCES

1

Chu CY, et al. Further studies on the immunogenicity of Haemophilus influenzae type b and pneumococcal type 6A polysaccharide-protein conjugate. Infect Immun 40:245-246, 1983.

2

Mueller JH, et al. Production of diphtheria toxin of high potency (100 Lf) on a reproducible medium. J Immunol 40:21-32, 1941.

3

Adams WG, et al. Decline of Childhood Haemophilus influenzae Type b (Hib) Disease in the Hib Vaccine Era. JAMA 269:221-226, 1993.

4

Recommendations of the Immunization Practices Advisory Committee (ACIP). Haemophilus b conjugate vaccines for prevention of Haemophilus influenzae type b disease among infants and children two months of age and older. MMWR 40:No. RR-1, 1991.

5

Broome CV. Epidemiology of Haemophilus influenzae type b infections in the United States. Pediatr Infect Dis J 6:779-782, 1987.

6

ACIP. Polysaccharide vaccine for prevention of Haemophilus influenzae type b disease. MMWR 34:201-205, 1985.

7

Istre GR, et al. Risk factors for primary invasive Haemophilus influenzae disease: Increased risk from day care attendance and school-aged household members.J Pediatr 106:190-195, 1985.

8

Redmond SR, et al. Haemophilus influenzae type b disease. An epidemiologic study with special reference to day-care centers. JAMA 252:2581-2584, 1984.

9

Murphy TV, et al. County-wide surveillance of invasive Haemophilus infections: Risk of associated cases in Child Care Programs (CCPs). Twenty-third Interscience Conference on Antimicrobial Agents and Chemotherapy (Abstract #788) 229, 1983.

10

Fleming D, et al. Haemophilus influenzae b (Hib) disease - secondary spread in day care. Twenty-fourth Interscience Conference on Antimicrobial Agents and Chemotherapy (Abstract #967) 261, 1984.

11

CDC.Prevention of secondary cases of Haemophilus influenzae type b disease. MMWR 31:672-680, 1982.

12

Michaels RH, et al.Pharyngeal colonization with Haemophilus influenzae type b: A longitudinal study of families with a child with meningitis or epiglottitis due to H influenzae type b. J Infec Dis 136:222-227, 1977.

13

Holmes SJ, et al. Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to 19-month-old children. J Pediatr 118:364-371, 1991.

14

Data on file, Sanofi Pasteur SA.

15

Peltola H, et al. Prevention of Haemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine. N Engl J Med 310:1561-1566, 1984.

16

Decker MD, et al. Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines. J Pediatr 120:184-189, 1992.

17

Granoff DM, et al. Differences in the immunogenicityof three Haemophilus influenzae type b conjugate vaccines in infants. J Pediatr 121:187-194, 1992.

18

Data on file, Sanofi Pasteur Inc.

19

Kaplan SL, et al. Immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in children with sickle hemoglobinopathy or malignancies, and after systemic Haemophilus influenzae type b infection. J Pediatr 120:367-370, 1992.

20

Clemens JD, et al. Impact of Haemophilus influenzae Type b Polysaccharide-Tetanus Protein Conjugate Vaccine on responses to concurrently administered Diphtheria-Tetanus-Pertussis Vaccine. JAMA 267:673-678, 1992.

21

Steinhoff MC, et al. Antibody responses to Haemophilus influenzae type b vaccines in men with human immunodeficiency virus infection. N Engl J Med 325 (26): 1837-1842, 1991.

22

ACIP. General recommendations on immunization. MMWR 38:205-227, 1989.

23

ACIP. Diphtheria, Tetanus, and Pertussis: Recommendations for Vaccine Use and Other Preventive Measures. MMWR 40:No. RR-10, 1991.

24

FDA Workshop on Haemophilus b Polysaccharide Vaccine – A Preliminary Report. MMWR 36:529-531, 1987.

25

IOM. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Haemophilus Influenzae Type b Vaccines. In: Stratton KR, Howe CJ, Johnston Jr. RB, eds. 1993. National Academy Press. Washington DC, pp. 236-273, 1993.

26

Rothstein EP, et al. Comparison of antigenuria after immunization with three Haemophilus influenzae type b conjugate vaccines. Pediatr Infect Dis J 10:311-314, 1991.

27

Vaccine Adverse Event Reporting System United States. MMWR 39:730-733,1990.

28

CDC. National Childhood Vaccine Injury Act: Requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 37:197-200, 1988.

29

National Childhood Vaccine Injury Act of 1986 (Amended 1987).

30

Cody CL, et al. Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children. Pediatr 68:650-660, 1981.

31

Barkin RM, et al. Diphtheria-tetanus-pertussis vaccine: reactogenicity of commercial products. Pediatr 63:256-260, 1979.

32

Baraff LJ, et al. DTP-associated reactions: an analysis by injection site, manufacturer, prior reactions and dose. Pediatr 73:31-39, 1984.

33

Long SS, et al. Longitudinal study of adverse reactions following diphtheria tetanus-pertussis vaccine in infancy. Pediatr 85:294-302, 1990.

34

D'Cruz OF, et al. Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré Syndrome) after immunization with Haemophilus influenzae type b conjugate vaccine. J Pediatr 115:743-746, 1989.

35

American Academy of Pediatrics. Immunization in Special Clinical Circumstances. In: Peter G, ed.1994 Red Book: Report of the Committee on Infectious Diseases. 23rd ed. Elk Grove Village, IL 51-52, 1994.

Product Information
as of May 2009

Manufactured by:
Sanofi Pasteur SA
Lyon France
US Govt License #1724

Distributed by:
Sanofi Pasteur Inc.
Swiftwater PA 18370 USA
1-800-VACCINE (1-800-822-2463)

5750

Hib

095 3112269

PRINCIPAL DISPLAY PANEL - Carton Label

NDC 49281-545-05

Haemophilus b
Conjugate Vaccine
(Tetanus Toxoid Conjugate)

ActHIB®

Hib

5 VIALS
1 Dose
each

Rx only

sanofi pasteur

PRINCIPAL DISPLAY PANEL - 0.5 mL Vial Label

NDC 49281-545-05

Haemophilus b
Conjugate Vaccine
(Tetanus Toxoid
Conjugate)

ActHIB®

Hib
1 Dose
(0.5 mL)

IM only

Rx only

Mfd by: Sanofi Pasteur SA

5639

(L)

(E)

PRINCIPAL DISPLAY PANEL - 0.6 mL Vial Label

NDC 49281-546-05

Diluent for
Haemophilus b
Conjugate
Vaccine
(Tetanus Toxoid Conjugate)
(0.4% Sodium Chloride)

0.6 mL

Rx only

Mfd by: Sanofi Pasteur Inc.
Swiftwater PA 18370 USA

5491