Vaccine Information: HAVRIX

HAVRIX- hepatitis a virus strain hm175 antigen (formaldehyde inactivated) injection, suspension
GlaxoSmithKline Biologicals SA

1 INDICATIONS AND USAGE

HAVRIX is indicated for active immunization against disease caused by hepatitis A virus (HAV). HAVRIX is approved for use in persons 12 months of age and older. Primary immunization should be administered at least 2 weeks prior to expected exposure to HAV.

2 DOSAGE AND ADMINISTRATION

2.1 Preparation for Administration

Shake well before use. With thorough agitation, HAVRIX is a homogeneous, turbid, white suspension. Do not administer if it appears otherwise. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered. Attach a sterile needle to the prefilled syringe and administer intramuscularly.

2.2 Administration

HAVRIX should be administered by intramuscular injection only. HAVRIX should not be administered in the gluteal region; such injections may result in suboptimal response.

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

2.3 Recommended Dose and Schedule

Children and Adolescents (aged 12 months through 18 years)

Primary immunization for children and adolescents consists of a single 0.5-mL dose and a 0.5-mL booster dose administered anytime between 6 and 12 months later. The preferred sites for intramuscular injections are the anterolateral aspect of the thigh in young children or the deltoid muscle of the upper arm in older children.

Adults (aged 19 years and older)

Primary immunization for adults consists of a single 1-mL dose and a 1-mL booster dose administered anytime between 6 and 12 months later. In adults, the injection should be given in the deltoid region.

3 DOSAGE FORMS AND STRENGTHS

Suspension for injection available in the following presentations:

•

0.5-mL single-dose prefilled TIP-LOK syringes.

•

1-mL single-dose prefilled TIP-LOK syringes. [See How Supplied/Storage and Handling (16).]

4 CONTRAINDICATIONS

Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis A-containing vaccine, or to any component of HAVRIX, including neomycin, is a contraindication to administration of HAVRIX [see Description (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Latex

The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions.

5.2 Syncope

Syncope (fainting) can occur in association with administration of injectable vaccines, including HAVRIX. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.

5.3 Preventing and Managing Allergic Vaccine Reactions

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine [see Contraindications (4)].

5.4 Altered Immunocompetence

Immunocompromised persons may have a diminished immune response to HAVRIX, including individuals receiving immunosuppressant therapy.

5.5 Limitations of Vaccine Effectiveness

Hepatitis A virus has a relatively long incubation period (15 to 50 days). HAVRIX may not prevent hepatitis A infection in individuals who have an unrecognized hepatitis A infection at the time of vaccination. Additionally, vaccination with HAVRIX may not protect all individuals.

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 with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

The safety of HAVRIX has been evaluated in 61 clinical trials involving approximately 37,000 individuals receiving doses of 360 EL.U. (n = 21,928 in 3- or 4-dose schedule), 720 EL.U. (n = 12,274 in 2- or 3-dose schedule), or 1440 EL.U. (n = 2,782 in 2- or 3-dose schedule).

Of solicited adverse reactions in clinical trials of adults, who received HAVRIX 1440 EL.U., and children (aged 2 years and older), who received either HAVRIX 360 EL.U. or 720 EL.U., the most frequently reported was injection-site soreness (56% of adults and 21% of children); less than 0.5% of soreness was reported as severe. Headache was reported by 14% of adults and less than 9% of children. Other solicited and unsolicited reactions occurring during clinical trials are listed below.

Incidence 1% to 10% of Injections

Metabolism and Nutrition Disorders: Anorexia.

Gastrointestinal Disorders: Nausea.

General Disorders and Administration Site Conditions: Fatigue; fever >99.5°F (37.5°C); induration, redness, and swelling of the injection site; malaise.

Incidence <1% of Injections

Infections and Infestations: Pharyngitis, upper respiratory tract infections.

Blood and Lymphatic System Disorders: Lymphadenopathy.

Psychiatric Disorders: Insomnia.

Nervous System Disorders: Dysgeusia, hypertonia.

Eye Disorders: Photophobia.

Ear and Labyrinth Disorders: Vertigo.

Gastrointestinal Disorders: Abdominal pain, diarrhea, vomiting.

Skin and Subcutaneous Tissue Disorders: Pruritus, rash, urticaria.

Musculoskeletal and Connective Tissue Disorders: Arthralgia, myalgia.

General Disorders and Administration Site Conditions: Injection site hematoma.

Investigations: Creatine phosphokinase increased.

Coadministration Studies of HAVRIX in Children Aged 11 to 25 Months

In 4 studies, 3,152 children aged 11 to 25 months received at least 1 dose of HAVRIX 720 EL.U. administered alone or concomitantly with other routine childhood vaccinations [see Clinical Studies (14.2, 14.5)]. The studies included HAV 210 (N = 1,084), HAV 232 (N = 394), HAV 220 (N = 433), and HAV 231 (N = 1,241).

In the largest of these studies (HAV 231) conducted in the U.S., 1,241 children aged 15 months were randomized to receive: Group 1) HAVRIX alone; Group 2) HAVRIX concomitantly with measles, mumps, and rubella (MMR) vaccine (manufactured by Merck and Co.) and varicella vaccine (manufactured by Merck and Co.); or Group 3) MMR and varicella vaccines. Subjects in Group 3 who received MMR and varicella vaccines received the first dose of HAVRIX 42 days later. A second dose of HAVRIX was administered to all subjects 6 to 9 months after the first dose of HAVRIX. Solicited local adverse reactions and general events were recorded by parents/guardians on diary cards for 4 days (Days 0 to 3) after vaccination. Unsolicited adverse events were recorded on the diary card for 31 days after vaccination. Telephone follow-up was conducted 6 months after the last vaccination to inquire about serious adverse events, new onset chronic illnesses, and medically significant events. A total of 1,035 children completed the 6-month follow-up. Among subjects in all groups combined, 53% were male; 69% of subjects were White, 16% were Hispanic, 9% were Black, and 6% were other racial/ethnic groups.

Percentages of subjects with solicited local adverse reactions and general adverse reactions following HAVRIX administered alone (Group 1) or concomitantly with MMR and varicella vaccines (Group 2) are presented in Table 1. The solicited adverse reactions from the 3 additional coadministration studies conducted with HAVRIX were comparable to those from Study HAV 231.

Table 1. Solicited Local Adverse Reactions and General Adverse Reactions Occurring within 4 Days of Vaccination^a in Children Aged 15 to 24 Months with HAVRIX Administered Alone or Concomitantly with MMR and Varicella Vaccines (TVC)

Total vaccinated cohort (TVC) = all subjects who received at least 1 dose of vaccine.
n = Number of subjects who received at least 1 dose of vaccine and for whom diary card information was available.
Grade 3: Drowsiness defined as prevented normal daily activities; irritability/fussiness defined as crying that could not be comforted/prevented normal daily activities; loss of appetite defined as no eating at all.
a Within 4 days of vaccination defined as day of vaccination and the next 3 days.
b MMR = Measles, mumps, and rubella vaccine; V = Varicella vaccine.
	Group 1 HAVRIX Dose 1 %	Group 2 HAVRIX+ MMR+Vb Dose 1 %	Group 1 HAVRIX Dose 2 %	Group 2 HAVRIX Dose 2 %
Local (at injection site for HAVRIX)
n	298	411	272	373
Pain, any	24	24	24	30
Redness, any	20	20	23	24
Swelling, any	9	10	10	10
General
n	300	417	271	375
Irritability, any	33	44	31	27
Irritability, Grade 3	0	2	2	0
Drowsiness, any	22	35	21	21
Drowsiness, Grade 3	1	2	1	0
Loss of appetite, any	18	26	20	21
Loss of appetite, Grade 3	1	1	0	0
Fever ≥100.6°F (38.1°C)	3	5	3	3
Fever ≥101.5°F (38.6°C)	2	3	2	2
Fever ≥102.4°F (39.1°C)	1	1	0	1

Serious Adverse Events in Children Aged 11 to 25 Months: Among these 4 studies, 0.9% (29/3,152) of subjects reported a serious adverse event within the 31-day period following vaccination with HAVRIX. Among subjects administered HAVRIX alone 1.0% (13/1,332) reported a serious adverse event. Among subjects who received HAVRIX concomitantly with other childhood vaccines, 0.9% (8/909) reported a serious adverse event. In these 4 studies, there were 4 reports of seizure within 31 days post-vaccination: these occurred 2, 9, and 27 days following the first dose of HAVRIX administered alone and 12 days following the second dose of HAVRIX. In 1 subject who received INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) and Hib conjugate vaccine followed by HAVRIX 6 weeks later, bronchial hyperreactivity and respiratory distress were reported on the day of administration of HAVRIX alone.