Prescription Drugs

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. 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.3 A booster response for IgG has been demonstrated in children 12 months of age or older who previously received two or three doses of ActHIB vaccine. Bactericidal activity against H influenzae type b was demonstrated in serum after immunization and correlated with the anti-PRP antibody response induced by ActHIB vaccine.4 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.5 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.6 In clinical studies, ActHIB vaccine induced, on average, anti-PRP levels ≥ 1.0 mcg/mL in 90% of infants after the primary series (2, 4, and 6 months) and in more than 98% of infants following a booster dose given at 15 to 19 months of age.4 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 Tennessee7 (TABLE 1) and in Minnesota, Missouri, and Texas (8) (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 whole cell DTP vaccines at separate sites. Neither Poliovirus Vaccine Live Oral nor whole cell DTP vaccines are licensed or distributed in the US. TABLE 1: Anti-PRP Antibody Responses Following a Two or Three Dose Series of a Haemophilus b Vaccine at 2, 4, and 6 Months of Age - Tennessee7 VACCINE Na GEOMETRIC MEAN CONCENTRATION (GMC) (mcg/mL) Post Third Immunization % ≥ 1.0 mcg/mL PreImmunization at 2 months Post Second Immunization at 6 months Post Third Immunization at 7 months PRP-Tb (ActHIB vaccine) 65 0.10 0.30 3.64 83% PRP-OMPc (PedvaxHIB®) 64 0.11 0.84 N/A 50%d HbOCe (HibTITER®) 61 0.07 0.13 3.08 75% a N = Number of Children b Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) c Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) d Seroconversion after the recommended 2-dose primary immunization series is shown e Haemophilus b Conjugate Vaccine (Diphtheria CRMW7 Protein Conjugate) N/A Not applicable in this comparison trial although third dose data have been published7 TABLE 2: Anti-PRP Antibody Responses Following a Two or Three Dose Series of a Haemophilus b Vaccine at 2, 4, and 6 Months of Age - Minnesota, Missouri, and Texas8 VACCINE Na GEOMETRIC MEAN CONCENTRATION (GMC) (mcg/mL) Post Thirdb Immunization % ≥ 1.0 mcg/mL Pre Immunization at 2 months Post Second Immunization At 6 months Post Thirdb Immunization At 7 months PRP-Tc (ActHIB vaccine) 142 0.25 1.25 6.37 97% PRP-OMPd (PedvaxHIB) 149 0.18 4.00 N/A 85%e HbOCf (HibTITER) 167 0.17 0.45 6.31 90% a N = Number of Children b Sera were obtained after the third dose from 86 and 110 infants, in PRP-T and HbOC vaccine groups, respectively c Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) d Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) e Seroconversion after the recommended 2-dose primary immunization series is shown f Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) N/A Not applicable in this comparison trial although third dose data have been published8 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. In a clinical study enrolling Alaskan Native Americans, following the administration of a three dose series of ActHIB at 6 weeks, 4 months, and 6 months of age, 75% of subjects achieved an anti-PRP antibody titer of ≥ 1.0 mcg/mL at 7 months of age (1 month after the last vaccination).9 In four separate studies, 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 (TABLE 3). GMC 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.10 TABLE 3: Anti-PRP Antibody Responses in 12- to 24-month-old Children Immunized with a Single Dose of ActHIB10 AGE GROUP Na GEOMETRIC MEAN CONCENTRATION (GMC) (mcg/mL) % SUBJECTS WITH ≥ 1.0 mcg/mL Pre Immunization Post Immunizationb Pre Immunization Post Immunizationb 12 to 15 months 256 0.06 5.12 1.6 90.2 17 to 24 months 81 0.10 4.40 3.7 81.5 a N = Number of Children b Post immunization responses measured at approximately 1 month after vaccination 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. Following two doses of ActHIB vaccine given at two-month intervals, 89% of these children (mean age 11 months) had anti-PRP antibody titers of ≥ 1.0 mcg/mL. This is comparable to anti-PRP antibody levels demonstrated in normal children of similar age following two doses of ActHIB vaccine.11 TriHIBit Vaccine (ActHIB vaccine combined with Tripedia vaccine by reconstitution) Randomized comparative clinical trials demonstrated that the anti-PRP response achieved in 15- to 20-month-old children 1 month after one dose of TriHIBit vaccine (ActHIB vaccine reconstituted with Tripedia vaccine) was similar to that achieved when the ActHIB and Tripedia vaccines were given concomitantly at different sites with separate needles and syringes (TABLE 4).10 All children had received three doses of a Haemophilus b conjugate vaccine (HibTITER or ActHIB vaccine) and three doses of a whole-cell DTP vaccine prior to entry into this clinical trial. TABLE 4: Anti-PRP Responses in 15- to 20-month-old Children Following Immunization with TriHIBit Vaccine Compared to ActHIB Vaccine and Tripedia Vaccine Given Concomitantly at Separate Sites10 IMMUNOGENICITY Pre-Dose Post-Dose (1 month post-vaccination) TriHIBit vaccine Separate Injectionsa TriHIBit vaccine Separate Injectionsa Nb 88 94 93 98 Anti-PRP (mcg/mL) 0.89 1.15 90.30 80.90 % > 1 mcg/mL 45.50 53.20 100.00 100.00 a ActHIB and Tripedia administered concomitantly at separate sites b N= Number of Children For data on the antibody responses to diphtheria, tetanus and pertussis (PT and FHA) antigens in this study, refer to the Tripedia vaccine product insert. REFERENCES 3 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. 4 Data on file, Sanofi Pasteur SA. 5 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. 6 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. 7 Decker MD, et al. Comparative trial in infants of four conjugate Haemophilus influenza type b vaccines. J Pediatr 120:184-189, 1992. 8 Granoff DM, et al. Differences in the immunogenicityof three Haemophilus influenzae type b conjugate vaccines in infants. J Pediatr 121:187-194, 1992. 9 Bulkow LR, et al. Comparative immunogenicity of four Haemophilus influenzae type b conjugate vaccines in Alaska Native infants. Pediatr Infect Dis J 12:484-92, 1993. 10 Data on file, Sanofi Pasteur Inc. 11 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.

Find Lowest Prices on ActHIB® Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) Intramuscular Administration Only DESCRIPTION ActHIB ®, Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), produced by Sanofi Pasteur SA, is a sterile, lyophilized powder which is reconstituted with either saline diluent (0.4% Sodium Chloride) or Tripedia®, Sanofi Pasteur Inc. Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) (when reconstituted known as TriHIBit®) for intramuscular administration 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 The culture medium contains milk derived raw materials (casein derivatives). 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 is reconstituted with saline diluent (0.4% Sodium Chloride), each 0.5 mL dose 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 is reconstituted with Tripedia vaccine to formulate TriHIBit vaccine, each 0.5 mL dose contains10 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. Tripedia vaccine (vial presentation 0.6 mL) 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.) 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.

INDICATIONS ActHIB vaccine is indicated for the active immunization of infants and children 2 months through 5 years of age for the prevention of invasive disease caused by H influenzae type b. TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution, is indicated for the active immunization of children 15 through 18 months of age for prevention of invasive disease caused by H influenzae type b and diphtheria, tetanus and pertussis. Vaccination with ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or Tripedia vaccine (TriHIBit vaccine) may not protect 100% of individuals. DOSAGE AND ADMINISTRATION For intramuscular injection only The ActHIB vaccine, reconstituted with saline diluent (0.4% Sodium Chloride), appears clear and colorless. TriHIBit vaccine, the reconstituted vaccine using Tripedia vaccine, is a homogenous white suspension. 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 ActHIB is to be reconstituted only with the accompanying saline diluent (0.4% Sodium Chloride) or Tripedia vaccine to formulate TriHIBit vaccine. TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution, should not be administered to infants younger than 15 months of age. To prepare ActHIB vaccine, withdraw 0.6 mL of saline diluent (0.4% Sodium Chloride) and inject into the vial of lyophilized ActHIB vaccine. Agitate the vial to ensure complete reconstitution. The vaccine will appear clear and colorless. Withdraw a 0.5 mL dose of the reconstituted vaccine and inject intramuscularly. After reconstitution with saline diluent (0.4% Sodium Chloride), ActHIB vaccine should be administered promptly or stored refrigerated between 2° to 8°C (35° to 46°F) and administered within 24 hours. If the vaccine is not administered promptly, agitate the vial again before injection. Refer to Figures 1, 2, 3, 4, and 5. To prepare TriHIBit vaccine, thoroughly agitate the vial of Sanofi Pasteur Inc. Tripedia vaccine then withdraw 0.6 mL and inject into the vial of lyophilized ActHIB vaccine. After reconstitution and thorough agitation, the combined vaccines will appear whitish in color. Withdraw a 0.5 Ml dose of the combined vaccines and inject intramuscularly. TriHIBit vaccine (ActHIB reconstituted with Tripedia vaccine) should be administered within 30 minutes of reconstitution. Refer to Figures 1, 2, 3, 4, and 5. Instructions for Reconstitution of ActHIB Vaccine with Saline Diluent (0.4% Sodium Chloride) or Tripedia Vaccine (TriHIBit Vaccine) Figure 1. Agitate vial prior to disinfecting the vial stopper to avoid possible contamination. Figure 2. Withdraw 0.6 mL of 0.4% Sodium Chloride or Tripedia vaccine as indicated. Figure 3. Cleanse the ActHIB vaccine stopper, insert the syringe needle into the vial, and inject the total volume of diluent. Figure 4. Agitate vial thoroughly. Figure 5. After reconstitution, cleanse vial stopper. Using a new needle and syringe, 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. Each dose of ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or Tripedia vaccine (TriHIBit vaccine) 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. A 0.5 mL dose of ActHIB is approved for intramuscular administration in infants and children, 2 months through 5 years of age as a 4-dose series. The series consists of a primary immunization course of 3 doses administered at 2, 4, and 6 months of age, followed by one booster dose, administered at 15-18 months of age. The booster dose at 15-18 months of age may be given as TriHibit vaccine (ActHIB reconstituted with Tripedia). For previously unvaccinated children, the number of doses of Haemophilus b Conjugate Vaccine needed depends on the age at which the immunization series is begun. A previously unvaccinated infant, 7 to 11 months of age, should receive as primary immunizations, two doses of Haemophilus b Conjugate Vaccine at 8-week intervals, followed by a booster dose at 15 to 18 months of age. A previously unvaccinated child 12 to 14 months of age should receive one dose of Haemophilus b Conjugate Vaccine followed by a booster dose at 15 to 18 months of age (doses to be separated by an interval of 8 weeks). A previously unvaccinated child 15 months through 5 years of age should receive one dose of ActHIB vaccine. Preterm infants should be vaccinated according to their chronological age from birth.19 Interruption of the recommended schedule with a delay between doses should not interfere with the final immunity achieved with ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or with Tripedia vaccine (TriHIBit vaccine). There is no need to start the series over again, regardless of the time elapsed between doses. HOW SUPPLIED ActHIB Vaccine Reconstituted with Saline Diluent (0.4% Sodium Chloride) Single-dose, lyophilized vaccine vial (NDC 49281-547-58) packaged with single-dose diluent vial (NDC 49281-546-05). Supplied as package of 5 vials each (NDC 49281-545-05). TriHIBit Vaccine, ActHIB Vaccine Reconstituted with Tripedia Vaccine Single-dose, lyophilized vaccine vial (NDC 49281-545-50) packaged with single-dose diluent vial of Tripedia vaccine (NDC 49281-298-01). Supplied as package of 5 vials each (NDC 49281-59705). Storage Store lyophilized vaccine packaged with saline diluent (0.4% Sodium Chloride) or Tripedia vaccine at 2° to 8°C (35° to 46°F). DO NOT FREEZE. REFERENCES 19 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. 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). Revised: Jan 2014

PATIENT INFORMATION No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

OVERDOSE No information provided. CONTRAINDICATIONS ActHIB vaccine is contraindicated in children with a history of hypersensitivity to any component of the vaccine and to any component of Tripedia vaccine when it is used to reconstitute ActHIB. Any contraindication for Tripedia vaccine is a contraindication for TriHIBit vaccine, ActHIB vaccine reconstituted with Tripedia vaccine. (Refer to product insert for Tripedia vaccine.) TriHIBit vaccine (ActHIB reconstituted with Tripedia) is contraindicated in children who have shown symptoms of encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous dose of a pertussis-containing vaccine that is not attributable to another identifiable cause. TriHIBit is contraindicated in children who have a progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy. Pertussis-containing vaccines should not be administered to individuals with these conditions until a treatment regimen has been established and the condition has stabilized.

SIDE EFFECTS 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.4,10 Adverse reactions associated with ActHIB vaccine generally subsided after 24 hours and usually do not persist beyond 48 hours after immunization. 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. Table 5: Local and Systemic Reactions at 6, 24, and 48 Hours Following Immunization with ActHIB and Tripedia Vaccines Given Concomitantly at Separate Sites Compared to TriHIBita Vaccine in Children 15- to 20-months-old10 Adverse Event 6 Hrs. Post-dose 24 Hrs. Post-dose 48 Hrs. Post-dose Separate Injectionsb N = 110 TriHIBit vaccine N = 110 Separate Injectionsb N = 110 TriHIBit vaccine N = 110 Separate Injectionsb N = 110 TriHIBit vaccine N = 110 Local (%) Tenderness 17.3/20.0 19.1 8.2/8.2 10.0 1.8/0.9 1.8 Erythema > 1” 0.9/0.0 3.6 2.7/0.9 3.6 0.9/0.0 1.8 Indurationc 3.6/5.5 2.7 2.7/3.6 8.2 4.5/0.9 3.6 Swelling 3.6/3.6 3.6 2.7/1.8 5.5 0.9/0.0 4.5 Systemic (%) N = 103-110 N = 102-109 N = 105-110 N = 103-108 N = 104-110 N = 103-109 Fever > 102.2°F (39.0°C) 0 2.0 1.0 1.9 1.9 0 Irritability 27.3 22.9 20.9 17.6 12.7 10.1 Drowsiness 36.4 30.3 17.3 13.9 12.7 11.0 Anorexia 12.7 9.2 10.0 6.5 6.4 2.8 Vomiting 0.9 1.8 0.9 1.9 0.9 2.8 Persistent Cry 0 0 0 0 0 0 Unusual Cry 0 0 0 0 0 0.9 a TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution b Tripedia vaccine injection site/ActHIB vaccine injection site c Induration is defined as hardness with or without swelling 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 5 when TriHIBit vaccine, ActHIB vaccine reconstituted with Tripedia vaccine, was administered and when Tripedia vaccine was administered alone as a booster.10 The number of subjects studied with TriHIBit vaccine, ActHIB vaccine combined with Tripedia vaccine by reconstitution, was inadequate to detect rare serious adverse events. Reporting of Adverse Events Reporting by the parent or guardian of all adverse events occurring after vaccine administration should be encouraged. Adverse events following immunization with vaccine should be reported by the health-care provider to the US Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS). Reporting forms and information about reporting requirements or completion of the form can be obtained from VAERS through a tollfree number 1-800-822-7967.15,16,18 Health-care providers also should report these events to Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370 or call 1-800-822-2463. Post-Marketing Experience The following events have been spontaneously reported during the post-approval use of ActHIB. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Immune System Disorders: Anaphylaxis, other allergic/hypersensitivity reactions (including urticaria, angioedema) Nervous System Disorders: Convulsions General Disorders and Administration Site Conditions: Extensive limb swelling, peripheral edema, pruritus, and rash DRUG INTERACTIONS When Tripedia vaccine is used to reconstitute ActHIB vaccine (TriHIBit vaccine) and administered to immunosuppressed persons or persons receiving immunosuppressive therapy, the expected antibody response may not be obtained. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to vaccines. Short-term ( < 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. Although no specific studies with pertussis vaccine are available, if immunosuppressive therapy will be discontinued shortly, it is reasonable to defer vaccination until the patient has been off therapy for one month; otherwise, the patient should be vaccinated while still on therapy.14 If ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or ActHIB vaccine reconstituted with Tripedia vaccine (TriHIBit vaccine) has been administered to persons receiving immunosuppressive therapy, a recent injection of immunoglobulin or having an immunodeficiency disorder, an adequate immunologic response may not be obtained. In clinical trials, ActHIB vaccine was administered, at separate sites, concomitantly with one or more of the following vaccines: DTP, DTaP, Poliovirus Vaccine Live Oral (OPV), Measles, Mumps and Rubella vaccine (MMR), Hepatitis B vaccine and occasionally Inactivated Poliovirus Vaccine (IPV). No impairment of the antibody response to the individual antigens, diphtheria, tetanus and pertussis, was demonstrated when ActHIB vaccine was given at the same time, at separate sites, with IPV or MMR.10 In addition, more than 47,000 infants in Finland have received a third dose of ActHIB vaccine concomitantly with MMR vaccine with no increase in serious or unexpected adverse events.10 No significant impairment of antibody response to Measles, Mumps and Rubella was noted in 15- to 20-month-old children who received TriHIBit vaccine, ActHIB vaccine reconstituted with Tripedia vaccine, concomitantly with MMR. No data are available to the manufacturer concerning the effects on immune response of OPV, IPV or Hepatitis B vaccine when given concurrently with ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or Tripedia vaccine (TriHIBit vaccine).10 Use with caution in patients on anticoagulant therapy. REFERENCES 4 Data on file, Sanofi Pasteur SA. 10 Data on file, Sanofi Pasteur Inc. 14 ACIP. Diphtheria, Tetanus, and Pertussis: Recommendations for Vaccine Use and Other Preventive Measures. MMWR 40:No. RR-10, 1991. 15 Vaccine Adverse Event Reporting System United States. MMWR 39:730-733, 1990. 16 CDC. National Childhood Vaccine Injury Act: Requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 37:197-200, 1988. 18 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.

WARNINGS The stopper of the diluent vial contains natural rubber latex which may cause allergic reactions. The lyophilized vaccine vial is not made with natural rubber latex. If ActHIB vaccine 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 infection12, 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.13 (Refer to product insert for Tripedia vaccine.) PRECAUTIONS General Care is to be taken by the health-care provider for the safe and effective use of this vaccine. Epinephrine injection (1:1000) must be immediately available should an anaphylactic or other allergic reactions occur due to any component of the vaccine. Prior to an injection of any vaccine, all known precautions should be taken to prevent adverse reactions. This includes a review of the patient's history with respect to possible sensitivity and any previous adverse reactions to the vaccine or similar vaccines, and to possible sensitivity to natural rubber latex, previous immunization history, current health status (see CONTRAINDICATIONS and WARNINGS sections), and a current knowledge of the literature concerning the use of the vaccine under consideration. (Refer to product insert for Tripedia vaccine.) The health-care provider should ask the parent or guardian about the recent health status of the infant or child to be immunized including the infant's or child's previous immunization history prior to administration of ActHIB vaccine or Tripedia vaccine. If Guillain-Barre syndrome has occurred within 6 weeks of receipt of a prior vaccine containing tetanus toxoid, the decision to give any tetanus toxoid-containing vaccine, including ActHIB or TriHIBit, should be based on careful consideration of the potential benefits and possible risks. Minor illnesses such as upper respiratory infection with or without low-grade fever are not contraindications for use of ActHIB vaccine.14 Immunization with ActHIB vaccine does not substitute for routine tetanus immunization. Information For Parents And Guardians Of Vaccine Recipients The health-care provider should inform the parent or guardian of the benefits and risks of the vaccine. Prior to administration of ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or Tripedia vaccine (TriHIBit vaccine), the parent or guardian should be asked about the recent health status of the infant or child to be immunized. The health-care provider should inform the parent or guardian of the importance of completing the immunization series. The physician should inform the parent or guardian about the significant adverse reactions that have been temporally associated with the administration of ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or ActHIB vaccine reconstituted with Tripedia vaccine (TriHIBit vaccine). The parent or guardian should be instructed to report any serious adverse reactions to their health-care provider. As part of the child's immunization record, the date, lot number, and manufacturer of the vaccine administered should be recorded.15,16,17 The US Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine, including but not limited to the reporting of events required by the National Childhood Vaccine Injury Act of 1986.15 The toll-free number for VAERS forms and information is 1-800-822-7967. The National Vaccine Injury Compensation Program, established by the National Childhood Vaccine Injury Act of 1986, requires physicians and other health-care providers who administer vaccines to maintain permanent vaccination records and to report occurrences of certain adverse events to the US Department of Health and Human Services. Reportable events include those listed in the Act for each vaccine and events specified in the package insert as contraindications to further doses of the vaccine.16,17 The health-care provider should provide the Vaccine Information Statements (VISs), which are required to be given with each immunization. Carcinogenesis, Mutagenesis, Impairment Of Fertility ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or Tripedia vaccine (TriHIBit vaccine) has not been evaluated for its carcinogenic, mutagenic potential or impairment of fertility. Pregnancy Category C Animal reproduction studies have not been conducted with ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or Tripedia vaccine (TriHIBit vaccine). It is also not known whether ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or Tripedia vaccine (TriHIBit vaccine) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) or Tripedia vaccine (TriHIBit vaccine) is not approved for use in pregnant women. Pediatric Use Safety and effectiveness of ActHIB vaccine reconstituted with saline diluent (0.4% Sodium Chloride) in infants below the age of 6 weeks have not been established. (See DOSAGE AND ADMINISTRATION section.) Safety and effectiveness of TriHIBit vaccine, ActHIB vaccine reconstituted with Tripedia vaccine, in infants below the age of 15 months have not been established. (See DOSAGE AND ADMINISTRATION section.) REFERENCES 10 Data on file, Sanofi Pasteur Inc. 12 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. 13 ACIP. General recommendations on immunization. MMWR 38:205-227, 1989. 14 ACIP. Diphtheria, Tetanus, and Pertussis: Recommendations for Vaccine Use and Other Preventive Measures. MMWR 40:No. RR-10, 1991. 15 Vaccine Adverse Event Reporting System United States. MMWR 39:730-733, 1990. 16 CDC. National Childhood Vaccine Injury Act: Requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 37:197-200, 1988. 17 National Childhood Vaccine Injury Act of 1986 (Amended 1987).