Geometric Mean Titre (GMT) (µg/mL)

Table II – Act-Hib
Anti-PRP Antibody Responses in 2-Month-Old Infants NIH Trial in Minnesota and Texas

Geometric Mean Titre (GMT) (µg/mL)

(a) N = Number of children

(b) Haemophilus b Conjugate vaccine (Tetanus Protein-Conjugate)

(c) Haemophilus b Conjugate vaccine (Diphtheria Toxoid-Conjugate)

(d) Haemophilus b Conjugate vaccine (Meningococcal Protein Conjugate)

(e) Haemophilus b Conjugate vaccine (Diphtheria CRM 197 Protein Conjugate)

(f) P=0.0001 for PRP-T vs HbOC

(g) P=0.0001 for PRP-OMP vs PRP-T, and for PRP-OMP vs HbOC

Table III – Act-Hib
Summary of Anti-PRP Responses with Various Diluents

(a) whole-cell DPT.

(b) whole cell DPT-Polio.

(top)

Older children or adults with chronic conditions associated with increased risk of invasive Hib disease such as persons with splenic dysfunction (e.g., sickle cell disease, asplenia), antibody deficiency, HIV infection or certain malignancies may be immunized with a single dose of the vaccine.

Aventis Pasteur Limited's Quadracel may be used for the reconstitutuion of lyophilized Act-HIB in place of the saline diluent. This provides an efficient means of administering routine immunization against diphtheria, tetanus, pertussis, poliomyelitis and H. influenzae type b in a single injection at a single visit.

Aventis Pasteur Limited's Tripacel may be used for the reconstitutuion of lyophilized Act-HIB in place of the saline diluent. This provides an efficient means of administering routine immunization against diphtheria, tetanus, pertussis, and H. influenzae type b in a single injection at a single visit.

Act-HIB may be administered simultaneously with whole-cell DT, whole-cell DPT Polio, IPV, Quadracel or Tripacel at separate sites with separate syringes and OPV.

Act-HIB may also be given simultaneously with MMR at separate sites with separate syringes. This is based on data for MMR and Act-HIB alone. Because simultaneous administration of common childhood vaccines is not known to affect the efficacy or safety of any of the routine recommended childhood vaccines, if return of a vaccine recipient for further immunization is doubtful, simultaneous administration of all vaccines appropriate for age and previous vaccination status (including MMR, other H. influenzae type b conjugate vaccines, hepatitis b vaccine) at separate sites with separate syringes is indicated.

Data on whether vaccination prevents acquisition and carriage of Hib are still limited. Thus, rifampin or other appropriate chemoprophylaxis should be used, in accordance with the usual recommendations, for families and people in daycare centres in which a case of invasive Hib disease has occurred and in which there are one or more contacts less than 48 months of age who have not been fully vaccinated against Hib.

Currently, Haemophilus b conjugate vaccines are not recommended for infants younger than 2 months of age.

Contraindications: General: Immunization with Act-HIB should be deferred in the presence of any acute illness, including febrile illness to avoid superimposing adverse effects from the vaccine on the underlying illness or mistakenly attributing to the vaccine a manifestation of the underlying illness. A minor afebrile illness such as mild upper respiratory infection is not usually reason to defer immunization.

Absolute Contraindications: Allergy to any component of Haemophilus b Conjugate Vaccine including tetanus protein, or an allergic or anaphylactic reaction to a previous dose of Act-HIB are contraindications to vaccination. When Act-HIB is reconstituted with Connaught's Tripacel or Quadracel the contraindications for Tripacel or Quadracel must also be considered.

Elective immunization of individuals over six months of age should be deferred during an outbreak of poliomyelitis because of the risk of provocation paralysis.

Warnings: I.M. injections should be given with care in patients suffering from coagulation disorders because of the risk of hemorrhage.

If Act-Hib is used in persons with malignancies, receiving immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, or who are otherwise immunocompromised (including HIV infected individuals, transplant recipients, and persons suffering from autoimmune disorders), the expected immune response may not be obtained.

Corticosteroid therapy can result in immunosuppression although the exact dose and duration of therapy required to suppress the immune system is not well defined. Persons treated with high doses of systemic steroids, e.g., ≥ 2 mg/kg/ day of prednisone orally for more than 2 weeks, should be considered to have a compromised immune system.

As with any vaccine, immunization with Act-HIB may not protect 100% of susceptible individuals.

Capsular polysaccharide antigen can be detected in the urine of vaccinees for up to 2 weeks following immunization with conjugate vaccines. This phenomenon should not be confused with invasive Hib infections.

Precautions: General: The possibility of allergic reactions in individuals sensitive to components of the vaccine should be evaluated. Epinephrine Hydrochloride Solution (1:1 000) must be immediately available to combat unexpected anaphylactic or allergic reactions. When Act-HIB is reconstituted with Aventis Pasteur's Tripacel or Quadracel the possibility of allergic reactions to the components of these vaccines must also be evaluated. Health care providers should be familiar with current recommendations for the initial management of anaphylaxis in non-hospital settings, including proper airway management.

Before administration 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 hypersensitivity to the vaccine or similar vaccine, determination of previous immunization history, and the presence of any contraindications to immunization, current health status, and a current knowledge of the literature concerning the use of the vaccine under consideration.

Special care should be taken to ensure that the injection does not enter a blood vessel.

Caution: A separate sterile syringe and needle should be used for each individual patient to prevent transmission of infectious agents.

There have been case reports of transmission of HIV and hepatitis by failure to scrupulously observe sterile technique. Needles should not be recapped and should be disposed of properly.

Before administration of Act-HIB, health-care personnel should inform the parent or guardian of the patient to be immunized of the benefits and risks of immunization, inquire about the recent health status of the patient and comply with any local requirements with respect to information to be provided to the patient before immunization.

Act-HIB may be of benefit in preventing the occurrence of secondary cases. However, epidemiological studies have not been done and rifampin prophylaxis is still recommended. Because the vaccine will not protect against non-typeable strains of H. influenzae which cause recurrent upper respiratory disease, otitis media and sinusitis, the vaccine is not recommended for these conditions.

Although some immune response to the tetanus protein component may occur, immunization with this vaccine does not substitute for routine tetanus immunization. Individuals who have received multiple doses of products containing tetanus toxoid show no differences in reaction rates when immunized with this vaccine.

Pregnancy: Animal reproduction studies have not been conducted with Act-HIB. It is also not known whether Act-HIB can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Act-HIB is not recommended for use in pregnant women.

No evaluation of Act-Hib has been made with respect to its potential for carcinogenesis or mutagenesis.

Human Immunodeficiency Virus (HIV) Infected person: HIV - infected individuals, both asymptomatic and symptomatic, should be immunized with DPT(Diphtheria, Pertussis and Tetanus) and Act-HIB vaccine according to standard schedules.

Adverse Effects: Local reactions including pain, redness, swelling and induration are seen in 5 to 30% of vaccinees. It is generally early, transient, and of moderate intensity. There have been rare cases of edematous reactions of the lower extremities reported. These consist of oedema with cyanosis or transient purpura which appears within soon after immunization and resolves rapidly and spontaneously. There has been no accompanying cardiorespiratory signs or symptoms. These reactions have been reported mainly when Act-HIB is administered concurrently with another vaccine.

Systemic reactions: Systemic reactions including fever, irritability, drowsiness, prolonged or abnormal crying, anorexia and vomiting have occurred after immunization with Act-HIB in conjunction with whole-cell DPT. The rates of reactions observed were generally comparable to those usually reported following whole-cell DPT with the exception that there were slightly more febrile reactions reported among PRP-T recipients within 6 to 24 hours of vaccination. Table IV shows systemic reactions reported in a controlled clinical trial.

Table IV – Act-HIB
Systemic Reactions (%) Within 24 Hours of Vaccination

(a) PRP-T Vaccine and DPT Vaccine administered at 2 different sites

(b) P›0.001

(top)

Act-HIB reconstituted with Quadracel: In clinical trials conducted in Canada, 215 infants received 3 doses of either Act-HIB reconstituted with Quadracel or the same vaccines administered simultaneously at separate sites at 2, 4 and 6 months of age. An additional 186 18-month old children received a single dose of either Act-HIB reconstituted with Quadracel or the same vaccines administered simultaneously at separate sites. The rates of local and systemic reactions for the combination of Act-HIB and Quadracel were consistently lower than for the combination of Act-Hib and DPT-Polio Adsorbed (PENTA 1). The incidence of local reactions at the Quadracel site was lower when the vaccines are given separately, but severe local reactions are uncommon (< 6% for any dose). Systemic reactions were comparable between the 2 groups. No hypotonic-hyporesponsive episodes following Quadracel and Act-HIB administration were reported during these trials. There were 3 reports of febrile seizures (6 days to 1 month following immunization with Quadracel and Act-HIB, all attributed to intercurrent febrile illness.

Act-HIB Reconstituted with Tripacel: In a clinical trial conducted in Canada, 17 to 19 month old children previously immunized with Tripacel (CP 10/5/5/3 DT) at 2, 4 and 6 months of age received either a single injection of Tripacel used to reconstitute Act-HIB (n=33), or separate injections of Tripacel and Act-HIB reconstituted with diluent at the same visit (n=33). All subjects received OPV at the same visit. There was no significant differences in rates of local or systemic reactions. No serious adverse events were observed during this study.

In a clinical trial conducted in Taiwan, 68 infants received a different formulation of Tripacel (CP 20/20/5/3 DT) used to reconstitute Act-HIB and a control group of 67 received the same vaccines administered at separate sites at 2, 4 and 6 months of age. A 4th dose of the same vaccines given at 18 months of age to 62 children who had received the combined vaccines and 66 who had received separate injections. No consistent differences in reaction rates were seen between the two methods of administration. Reaction rates were low in both vaccine groups; local reactions tended to be mild or moderate and systemic reactions tended to be mild. No serious adverse events were observed during this study.

Rare cases of allergic reactions including urticaria, pruritis, and facial and laryngeal edema have been reported. Physicians should be aware that recipients of Haemophilus b vaccine are not protected against Hib disease in the week after vaccination, prior to the onset of the protective effects of the vaccine.

Other adverse events reported with administration of other H. b conjugate vaccines include urticaria, seizures, rash, renal failure and Guillain-Barre syndrome (GBS). A cause and effect relationship among any of these events and the vaccination has not been established.

As with any vaccine, there is the possibility that broad use of the vaccine could reveal rare adverse reactions not observed in clinical trials. A temporal association of neurological disorders has been reported following the parenteral injection of other biological products and should always be carefully considered when an immunization is indicated. Physicians should be familiar with the adverse reactions associated with whatever vaccine is used to reconstitute Act-HIB and read carefully the direction leaflet which accompanies such vaccine.

Physicians, nurses and pharmacists should report any occurrences temporally related to the administration of the product in accordance with local requirements and to the Medical Director, Aventis Pasteur Limited, 1755 Steeles Avenue West, North York, Ontario, Canada, M2R 3T4.

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

This vaccine is indicated for routine immunization against invasive disease caused by H. influenzae type b in infants and children starting at 2 months of age (see Indications). Each dose is a single injection of 0.5 mL given i.m.

Reconstitution of Freeze-Dried Vaccine: Reconstitute the vaccine using only the diluent supplied or Connaught's Tripacel or Quadracel. The use of any other vaccine to reconstitute Act-HIB is not recommended.

Do not remove the rubber stopper from the vial.

Apply a sterile piece of cotton moistened with a suitable antiseptic to the surface of the rubber 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 rubber stopper in the vial and slowly inject the 0.5 mL of 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 to allow air to escape gradually 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 until a clear, colorless solution results. Avoid foaming since this will prevent withdrawal of the proper dose. Withdraw the entire contents of the reconstituted vaccine into the syringe and inject the total volume (about 0.5 mL). Aseptic technique must be used for withdrawal of each dose (see precautions).

When Aventis Pasteur Limited's Tripacel or Quadracel is used for the reconstitution of Act-HIB, shake the single dose ampul well to uniformly distribute the suspension before withdrawing entire contents (about 0.5 mL). Before withdrawing the contents from an ampul, tap the container first to ensure that alt the vaccine is in the lower portion. Once the ampul has been opened, any of its contents not used immediately should be discarded. Before withdrawing the contents from a rubber-stoppered vial, do not remove either the rubber stopper or the metal seal holding it in place. Inject all the Tripacel or Quadracel into the vial of Act-HIB vaccine. Swirl the vial until a cloudy, uniform suspension results. Avoid foaming since this will prevent withdrawal of the proper dose. Use a sterile needle and syringe to withdraw the entire contents for 1 dose.

Before injection, the skin over the site to be injected should be cleansed with a suitable germicide.

Administer the vaccine i.m. The preferred site is into the anterolateral aspect of the mid-thigh (vastus lateralis muscle) or into the deltoid muscle.

In children > 1 year of age, the deltoid is the preferred site since use of the anterolateral thigh results in frequent complaints of limping due to muscle pain.

After insertion of the needle, aspirate to ensure that the needle has not entered a blood vessel.

Do not inject i.v.

Each person who is immunized should be given a permanent personal immunization record. In addition, it is essential that the health care provider also maintain a permanent record of the immunization history of each individual. This office record should contain the name of the vaccine, date given, dose, manufacturer and lot number.

Supplied: Act-HIB: Haemophilus b Conjugate Vaccine (Tetanus Protein-Conjugate) (PRP-T) is a lyophilized vaccine of purified polyribose ribitol phosphate capsular polysaccharide (PRP) of H. influenzae type b, covalently bound to tetanus protein. Each single dose of 0.5 mL contains: purified capsular polysaccharide 10 µg covalently bound to 20 µg of tetanus protein.

Act-Hib reconstituted with Diluent: The diluent for reconstitution is a 0.4% saline solution. After reconstitution the vaccine appears clear and colorless and does not contain a preservative.

Act-HIB reconstituted with Aventis Pasteur's Quadracel: After reconstitution, the vaccine appears cloudy and uniform. From the Quadracel, the solution contains 0.6% ± 0.1% 2-phenoxyethanol as preservative and trace amounts of polymyxin B and neomycin may be present from the cell growth medium.

Act-HIB reconstituted with Aventis Pasteur's Tripacel: After reconstitution, the vaccine appears cloudy and uniform. From the Tripacel the solution contains 0.6% ± 0.1% 2-phenoxyethanol as preservative.

Packages containing 5 single dose vials of Act-HIB and 5x0.5 ml (single dose) ampuls of Aventis Pasteur's diluent, 0.4% Saline for reconstitutuion of Haemophilus b Conjugate Vaccine.

Packages containing 5 single dose vials of Act-Hib and 5x0.5 ml (single dose) ampuls of Aventis Pasteur's Quadracel to be used for reconstitution in place of the diluent and sold under the trade name Pentacel.

Packages containing 5 single dose vials of Act-HIB and 5x0.5 ml (single dose) vials of Aventis Pasteur's Tripacel to be used for reconstitution in place of the diluent and sold under the tradename Actacel.

Store between 2 and 8°C. Do not freeze. Product which has been exposed to freezing should not be used. The vaccine should be used immediately after reconstitution. Do not use after the expiration date.

Reviewed 2001