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

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.

Connaught'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.

Connaught's DPT Polio Adsorbed may be used for the reconstitution 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.

Connaught'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.

Act-HIB may be administered simultaneously with DPT, DT, 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.

At the present time, haemophilus b conjugate vaccines are not recommended for infants younger than 2 months of age. Contraindications: I.M. injections should be given with care in patients suffering from coagulation disorders because of the risk of hemorrhage.

If Haemophilus b Conjugate Vaccine 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), 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 Haemophilus b Conjugate Vaccine 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.

General: Immunization with Act-HIB should be deferred in the presence of any acute illness, including febrile illness. A minor afebrile illness such as mild upper respiratory infection is not usually reason to deffer immunization. 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 DPT Adsorbed, DPT Polio Adsorbed or Quadracel the contraindications for DPT Adsorbed, DPT Polio Adsorbed or Quadracel must also be considered.

Elective immunization of individuals over six months of age should be deferred during an outbreak of poliomyelitis.

Warnings: I.M. injections should be given with care in patients suffering from coagulation disorders because of the risk of hemorrhage. If Haemophilus b Conjugate Vaccine 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), 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, vaccination 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: Care is to be taken by the health-care provider for the safe and effective use of Haemophilus b Conjugate vaccine.

The possibility of allergic reactions in individuals sensitive to components of the vaccine should be evaluated. Epinephrine Hydrochloride Solution (1:1000) must be immediately available to combat unexpected anaphylactic or allergic reactions. When Act-HIB is reconstituted with Connaught's DPT Adsorbed or DPT Polio Adsorbed, 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. Before 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 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.

A separate sterile syringe and needle should be used for each individual patient to prevent transmission of hepatitis or other 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 of the benefits and risks of immunization, and also inquire about the recent health status of the patient to be injected.

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.

Children with Symptomatic HIV Infection: Available data suggest that routine childhood immunizations are not hazardous to HIV-infected children. Furthermore, there is no evidence that immunization with routine vaccines leads to deterioration of the clinical condition of HIV-infected persons. Immunization with DPT (Diphtheria, Pertussis and Tetanus), IPV (Inactivated Poliomyelitis Vaccine) and Act-HIB is recommended, although immunization may be less effective than it would be for immune-competent children.

Adverse Effects:  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, Connaught Laboratories Limited, 1755 Steeles Avenue West, North York, Ontario, Canada, M2R 3T4.

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 Haemophilus b Conjugate Vaccine 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 DPT. The rates of reactions observed were generally comparable to those usually reported following 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 a clinical trial conducted in Canada, 442 infants received at least one dose of Act-HIB reconstituted with Connaught's DPT Adsorbed or the same vaccines administered simultaneously at separate sites.

Local adverse reactions to Act-HIB when administered alone were infrequent and mild. No increase was seen with successive doses. Mixed Act-HIB and DPT vaccines did not cause local redness or swelling more often than did DPT vaccine alone but tenderness increased from 18.1% with DPT alone to 26.2% with the combination (p < 0.001). No increase in systemic adverse effects was seen following the mixed vaccines. However, events were rated as moderate/severe slightly more often after mixed vaccines (12.4%) than after separate vaccinations (8.8%, p < 0.05). In the Canadian study, one hypotensive-hyporesponsive episode occurred after the administration of Act-HIB reconstituted with DPT Adsorbed. This child recovered fully with no sequelae. No other serious adverse reactions were reported.

Act-HIB reconstituted with DPT Polio Adsorbed: In a clinical trial in Canada, 427 infants received 3 doses of Act-Hib reconstituted with DPT Polio Adsorbed or the same vaccine administered simultaneously at separate sites. Local adverse reactions to Act-HIB alone were infrequent and mild. A slight increase was seen with successive doses. Although local redness, swelling and tenderness were significantly more common after vaccines containing DPT Polio Adsorbed compared with Act-HIB alone, reaction rates were lower after the combined vaccines than after DPT Polio Adsorbed alone.

No significant differences in systemic adverse events was seen following Act-HIB and DPT Polio Adsorbed administered at separate sites or combined.

Three severe adverse events temporally associated with vaccination resulted in hospitalization. These included 1 infant who developed supraventricular tachycardia 48 hours after dose 1 (combined), 1 infant who woke 3 hours after dose 1 (separate) with cough, respiratory distress and cyanosis whose diagnosis was suspected aspiration or gastroesophageal reflux, and 1 infant with an episode of screaming and apnea 4 hours after dose 1 (separate). All 3 infants recovered completely. No causal relationship between the adverse events and vaccination was demonstrated.

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.

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.

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.

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 DPT Adsorbed or DPT Polio Adsorbed 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. 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). When Connaught's DPT Adsorbed or DPT Polio Adsorbed 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. Inject all the DPT Adsorbed, DPT Polio Adsorbed 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 is a lyophilized vaccine of purified polyribose ribitol phosphate capsular polysaccharide (PRP) of H. influenzae type b, covalently bound to tetanus protein. The diluent for reconstitution is a 0.4% saline solution. The vaccine and diluent do not contain a preservative. When reconstituted with diluent, PRP-T is a clear, colorless solution. 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 0.5% saline solution. After reconstitution the vaccine appears clear and colorless and does not contain a preservative.

Act-HIB reconstituted with Connaught's DPT Adsorbed: After reconstitution, the vaccine appears cloudy and uniform and the solution contains thimerosal 0.01% used in DPT Adsorbed as a preservative.

Act-HIB reconstituted with Connaught's DPT Polio Adsorbed: After reconstitution, the vaccine appears cloudy and uniform. From the DPT Polio Adsorbed, the solution contains 2-phenoxyethanol 0.5% as a preservative and trace amounts of polymyxin B and neomycin may be present from the cell growth medium.

Act-HIB reconstituted with Connaught'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.

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

Store between 2 and 8°C. Do not freeze. The vaccine should be used immediately after reconstitution.

Reviewed 1998