Vaccine Information: ActHIB

ACTHIB- haemophilus influenzae type b strain 1482 capsular polysaccharide tetanus toxoid conjugate antigen
Sanofi Pasteur Inc.

1 INDICATIONS AND USAGE

ActHIB^® is a vaccine indicated for the prevention of invasive disease caused by Haemophilus influenzae (H. influenzae) type b. ActHIB is approved for use in children 2 months through 5 years of age.

2 DOSAGE AND ADMINISTRATION

For intramuscular use only

2.1 Immunization Series

ActHIB vaccine is administered as a four-dose series (0.5 mL per dose) as:

• A primary three-dose series of a single dose at 2, 4, and 6 months of age.
• A single booster dose at 15 through 18 months of age.

2.2 Reconstitution

ActHIB vaccine is a solution for injection supplied as single-dose vials of lyophilized vaccine (vial 1 of 2) to be reconstituted only with the accompanying saline diluent (0.4% Sodium Chloride) (vial 2 of 2). To reconstitute ActHIB vaccine, withdraw 0.6 mL of saline diluent and inject into the vial of lyophilized ActHIB vaccine. Agitate the vial to ensure complete reconstitution. The reconstituted ActHIB vaccine will appear clear and colorless. Withdraw a 0.5-mL dose of the reconstituted vaccine and inject intramuscularly. After reconstitution, if ActHIB vaccine is not administered promptly store at 2° to 8°C (35° to 46°F) and administer within 24 hours. Stored vaccine should be re-agitated prior to injection. Refer to Figures 1, 2, 3, and 4.

Instructions for Reconstitution of ActHIB Vaccine with Saline Diluent (0.4% Sodium Chloride)
Figure 1. Disinfect the diluent vial stopper, inject the needle and withdraw 0.6 mL of 0.4% Sodium Chloride diluent as indicated.	Figure 2. Cleanse the ActHIB vaccine stopper, insert the syringe needle into the vial, and inject the total volume of diluent.	Figure 3. Agitate vial thoroughly.	Figure 4. After reconstitution, withdraw 0.5 mL of reconstituted vaccine and administer intramuscularly.

2.3 Administration

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

ActHIB vaccine is administered as a single dose (0.5 mL) by intramuscular injection into the anterolateral aspect of the thigh or deltoid. Discard unused portion.

Do not administer this product intravenously, intradermally, or subcutaneously.

ActHIB vaccine should not be mixed in the same syringe with other parenteral products.

3 DOSAGE FORMS AND STRENGTHS

ActHIB vaccine is a solution for injection supplied as a single-dose vial of lyophilized powder to be reconstituted with the supplied 0.4% Sodium Chloride diluent. A single dose, after reconstitution is 0.5 mL.

4 CONTRAINDICATIONS

4.1 Hypersensitivity

Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any H. influenzae type b or tetanus toxoid-containing vaccine or any component of the vaccine is a contraindication to administration of ActHIB vaccine [see DESCRIPTION (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Management of Acute Allergic Reactions

Epinephrine and other appropriate agents must be available should an acute anaphylactic reaction occur.

5.2 Guillain-Barré Syndrome

If Guillain-Barré 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 vaccine, should be based on careful consideration of the potential benefits and possible risks.

5.3 Altered Immunocompetence

In immunosuppressed persons, including those receiving immunosuppressive therapy, the expected antibody responses may not be obtained.

5.4 Limitations of Vaccine Effectiveness

Vaccination with ActHIB vaccine may not protect 100% of individuals.

5.5 Tetanus Immunization

Immunization with ActHIB vaccine does not substitute for routine tetanus immunization.

5.6 Interference with Laboratory Tests

Urine antigen detection may not have a diagnostic value in suspected disease due to H. influenzae type b within 1 to 2 weeks after receipt of a H. influenzae type b-containing vaccine, including ActHIB [see DRUG INTERACTIONS (7.3)].

5.7 Syncope

Syncope (fainting) has been reported following vaccination with ActHIB. Procedures should be in place to avoid injury from fainting.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

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.(1) (2)

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

In a US trial, the safety of ActHIB vaccine was evaluated in 110 children 15 to 20 months of age. All children received three doses of Haemophilus influenzae type b conjugate vaccine (ActHIB vaccine or a previously licensed Haemophilus b conjugate vaccine) at approximately 2, 4, and 6 months of age. The incidence of selected solicited injection site and systemic adverse reactions which occurred within 48 hours following the dose of ActHIB vaccine is shown in Table 1.

Table 1: Local and Systemic Reactions at 6, 24, and 48 Hours Following Immunization with ActHIB Vaccine in Children 15 to 20 months old (2)

Adverse Event	6 Hrs. Post-dose	24 Hrs. Post-dose	48 Hrs. Post-dose
* Induration is defined as hardness with or without swelling.
Local (%)	N=110	N=110	N=110
Tenderness	20.0	8.2	0.9
Erythema (>1″)	0.0	0.9	0.0
Induration *	5.5	3.6	0.9
Swelling	3.6	1.8	0.0
Systemic (%)	N=103-110	N=105-110	N=104-110
Fever (>102.2°F) (>39.0°C)	0	1.0	1.9
Irritability	27.3	20.9	12.7
Drowsiness	36.4	17.3	12.7
Anorexia	12.7	10.0	6.4
Vomiting	0.9	0.9	0.9
Persistent cry	0	0	0
Unusual cry	0	0	0

In a US clinical trial (P3T06), 1,454 children were enrolled and received one dose of ActHIB vaccine at 2 months of age and subsequent doses administered at 4 and 6 months of age (concomitantly with DAPTACEL® [a US-licensed diphtheria, tetanus and pertussis vaccine], IPOL® [a US-licensed inactivated poliovirus vaccine] and PCV7 [Pneumococcal conjugate vaccine, 7-valent]) vaccines at 2, 4, and 6 months of age and hepatitis B vaccine at 2 and 6 months of age). At 15-16 months of age, 418 children received a 4^th dose of ActHIB and DAPTACEL vaccines. The most frequent systemic reactions following any dose (>50% of participants) were decreased activity/lethargy, fussiness/irritability, and inconsolable crying.

Table 2: Number (Percentage) of Children with Selected Solicited Systemic Adverse Reactions by Severity Occurring within 0-3 days After Vaccination in Study P3T06

Systemic Reactions	DAPTACEL + IPOL + ActHIB Vaccines			DAPTACEL + ActHIB Vaccines
	Dose 1N=1,390-1,406%	Dose 2N=1,346-1,360%	Dose 3N=1,301-1,312%	Dose 4N=379-381%
Note. — Ages of study participants ranged from 1.3 to 19.5 months.
* Fever is based upon actual temperatures recorded with no adjustments to the measurement route. † Following Doses 1-3 combined, the proportion of temperature measurements that were taken by axillary, rectal or other routes, or not recorded were 44.8%, 54.0%, 1.0%, and 0.1%, respectively. Following Dose 4, the proportion of temperature measurements that were taken by axillary, rectal or other routes, or not recorded were 61.1%, 36.6%, 1.7%, and 0.5%, respectively. ‡ Moderate: interferes with or limits usual daily activity; Severe: disabling, not interested in usual daily activity.
Fever *†
≥38.0°C	9.3	16.1	15.8	8.7
>38.5°C	1.6	4.3	5.1	3.2
>39.5°C	0.1	0.4	0.3	0.8
Decreased Activity/Lethargy ‡
Any	51.1	37.4	33.2	24.1
Moderate or Severe	24.3	15.8	12.7	9.2
Severe	1.2	1.4	0.6	0.3
Inconsolable Crying
Any	58.5	51.4	47.9	36.2
≥1 hour	16.4	16.0	12.2	10.5
>3 hours	2.2	3.4	1.4	1.8
Fussiness/Irritability
Any	75.8	70.7	67.1	53.8
≥1 hour	33.3	30.5	26.2	19.4
>3 hours	5.6	5.5	4.3	4.5

In Study P3T06, within 30 days following any of Doses 1-3 of DAPTACEL + IPOL + ActHIB vaccines, 50 of 1,455 (3.4%) participants experienced a serious adverse event (SAE). One SAE of seizure with apnea occurring on the day of vaccination with the first dose of the three vaccines was determined by the investigators as possibly related. Within 30 days following Dose 4, four of 418 (1.0%) participants who received DAPTACEL + ActHIB vaccines experienced a serious adverse event. None was assessed by the investigators as related to the study of vaccines.