HAVRIX (Hepatitis A Vaccine) is a sterile suspension of inactivated virus for intramuscular administration. The virus (strain HM175) is propagated in MRC-5 human diploid cells. After removal of the cell culture medium, the cells are lysed to form a suspension. This suspension is purified through ultrafiltration and gel permeation chromatography procedures. Treatment of this lysate with formalin ensures viral inactivation. Viral antigen activity is referenced to a standard using an enzyme linked immunosorbent assay (ELISA), and is therefore expressed in terms of ELISA Units (EL.U.).

Each 1-mL adult dose of vaccine consists of 1440 EL.U. of viral antigen, adsorbed on 0.5 mg of aluminum as aluminum hydroxide.

Each 0.5-mL pediatric dose of vaccine consists of 720 EL.U. of viral antigen, adsorbed onto 0.25 mg of aluminum as aluminum hydroxide.

HAVRIX contains the following excipients: Amino acid supplement (0.3% w/v) in a phosphate-buffered saline solution and polysorbate 20 (0.05 mg/mL). From the manufacturing process, HAVRIX also contains residual MRC-5 cellular proteins (not more than 5 mcg/mL), formalin (not more than 0.1 mg/mL), and neomycin sulfate (not more than 40 ng/mL), an aminoglycoside antibiotic included in the cell growth media.

HAVRIX is formulated without preservatives.

The tip cap and the rubber plunger of the needleless prefilled syringes contain dry natural latex rubber. The vial stopper is latex-free.

Last updated on RxList: 10/20/2008

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

Preparation for Administration

Shake vial or syringe well before withdrawal and use. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit. With thorough agitation, HAVRIX is a homogeneous, turbid, white suspension. Discard if it appears otherwise.

Recommended Dose and Schedule

HAVRIX should be administered by intramuscular injection. Do not administer intravenously, intradermally, or subcutaneously. In adults, the injection should be given in the deltoid region. HAVRIX should not be administered in the gluteal region; such injections may result in suboptimal response.

Children and Adolescents: Primary immunization for children and adolescents (12 months through 18 years of age) consists of a single 0.5-mL dose and a 0.5-mL booster dose administered anytime between 6 and 12 months later in order to ensure the highest antibody titers.

Adults: 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 order to ensure the highest antibody titers.

Dosage Forms And Strengths

HAVRIX is a suspension available in single-dose vials and prefilled syringes for intramuscular injection.

Each 0.5-mL pediatric dose of vaccine consists of 720 EL.U. of viral antigen.

Each 1-mL adult dose of vaccine consists of 1440 EL.U. of viral antigen.

Storage And Handling

HAVRIX is available in single-dose vials and prefilled TIP-LOK® syringes.

720 EL.U./0.5 mL in Single-Dose Vials and Prefilled Syringes (Preservative Free Formulation)

NDC 58160-825-11 Package of 10 Single-Dose Vials
NDC 58160-825-46 Package of 5 Prefilled Disposable TIP-LOK Syringes (packaged without needles)

1440 EL.U./mL in Single-Dose Vials and Prefilled Syringes (Preservative Free Formulation)

NDC 58160-826-11 Package of 10 Single-Dose Vials
NDC 58160-826-46 Package of 5 Prefilled Disposable TIP-LOK Syringes (packaged without needles)

Store refrigerated between 2° and 8° C (36° and 46° F). Do not freeze. Discard if the vaccine has been frozen. Do not dilute to administer.

Manufactured by: GlaxoSmithKline Biologicals, Rixensart, Belgium. Distributed by: GlaxoSmithKline, Research Triangle Park, NC 27709. FDA revision date: n/a

Last updated on RxList: 10/20/2008

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. As with any vaccine, there is the possibility that broad use of HAVRIX could reveal adverse reactions not observed in clinical trials.

The safety of HAVRIX has been evaluated in clinical trials involving approximately 32,500 individuals receiving doses ranging from 360 EL.U. to 1440 EL.U.

The frequency of solicited adverse events tended to decrease with successive doses of HAVRIX.

Of solicited adverse events in clinical trials, the most frequently reported by volunteers was injection-site soreness (56% of adults and 21% of children); however, 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 events 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 ( > 37.5°C), injection site induration, injection site redness, injection site swelling, 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.

Outbreak Setting and a Field Efficacy Trial: Safety data were obtained from 2 additional sources in which large populations were vaccinated. In an outbreak setting in which 4,930 individuals were immunized with a single dose of either 720 EL.U. or 1440 EL.U. of HAVRIX, no serious adverse events due to vaccination were reported. Overall, less than 10% of vaccinees reported solicited general adverse events following the vaccine. The most common solicited local adverse reaction was pain at the injection site, reported in 22.3% of subjects at 24 hours and decreasing to 2.4% by 72 hours.

In a field efficacy trial, 19,037 children received the 360 EL.U. dose of HAVRIX. The most commonly reported adverse events following administration of HAVRIX were injection-site pain (9.5%) and tenderness (8.1%), which were reported following first doses of HAVRIX. Other adverse events were infrequent and comparable to the control vaccine ENGERIX-B® [Hepatitis B Vaccine (Recombinant)]. Additionally, no serious adverse events due to the vaccine were reported. The large trial further allowed for analysis of rare adverse events, including hospitalization and death. No significant differences were found between the cohorts.

HAVRIX 720 EL.U./0.5 mL at 11 Months of Age and Older: In a multicenter study, parents/guardians recorded local and general symptoms on diary cards for 4 days (Days 0 to 3) after vaccination [see Clinical Studies]. In the 3 groups of children who received HAVRIX alone, safety data were available for 723 children who received 1,396 documented doses of HAVRIX. Additional safety data were available for 181 children who received HAVRIX coadministered with INFANRIX® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) (DTaP) and Haemophilus influenzae type b (Hib) conjugate vaccine (tetanus toxoid conjugate) (PRP-T) (Sanofi Pasteur SA).

The frequencies of solicited local and general events following receipt of HAVRIX were monitored during the 4-day observation period. The following ranges of solicited adverse event rates were observed among 3 groups of children that received their first dose of HAVRIX alone at between 11 and 25 months of age: Injection site pain in 15-21% of subjects, redness in 16-21% of subjects, swelling in 8% of subjects, irritability in 24-36% of subjects, loss of appetite in 16-19% of subjects, drowsiness in 15-17% of subjects and fever > 39.5° C in ≤ 2% of subjects. Following the booster dose of HAVRIX, among local reactions: Pain was reported in 16-21% of subjects, redness in 17-22%, swelling in 8-10% of subjects. Following the booster dose of HAVRIX, among general events, irritability was reported in 19-29% of subjects, loss of appetite in 14-18% of subjects, drowsiness in 13-16% of subjects and fever > 39.5° C in ≤ 1% of subjects.

Drowsiness and loss of appetite occurred at statistically significantly higher rates in subjects 15 to 18 months of age who received Hib conjugate vaccine (PRP-T) (Sanofi Pasteur SA) and INFANRIX concomitantly with HAVRIX as compared to subjects 15 to 18 months of age who received Hib conjugate vaccine (PRP-T) and INFANRIX (drowsiness 34% and 22% and loss of appetite 29% and 19%, respectively). With the exception of fever ( > 39.5° C), the solicited general symptoms occurred at statistically significantly higher rates in subjects 15 to 18 months of age who received Hib conjugate vaccine (PRP-T) and INFANRIX concomitantly with HAVRIX as compared to subjects 15 to 18 months of age who received HAVRIX alone (irritability 46% and 30%, drowsiness 34% and 17%, and loss of appetite 29% and 17%, respectively).

A febrile seizure was reported in an 18-month-old subject 2 days after receiving the first dose of HAVRIX. Other serious adverse events reported during the course of this study included a single case each of hepatitis 5 months post dose 1, insulin-dependent diabetes 4 months post dose 1, and Kawasaki's disease 3½ months post dose 1. The association of these events with vaccination is unknown.

In a US multicenter study, children 15 months of age (range 14 to 16 months) received either HAVRIX coadministered with a US-licensed pneumococcal 7-valent conjugate vaccine (Wyeth Pharmaceuticals Inc.) followed by a second dose of HAVRIX 6 to 9 months later; HAVRIX administered alone followed by a second dose of HAVRIX 6 to 9 months later; or pneumococcal 7-valent conjugate vaccine administered alone followed by a first dose of HAVRIX one month later and a second dose of HAVRIX 6 to 9 months after the first[see Clinical Studies]. Parents/guardians recorded local and general symptoms on diary cards for 4 days (Days 0 to 3) after vaccination.

Solicited local adverse events were reported as follows among children who received the first dose HAVRIX coadministered with pneumococcal 7-valent conjugate vaccine: Pain was reported in 36% of subjects, redness in 41% of subjects, and swelling in 29% of subjects. The reported rates of these local adverse events were similar to those reported in children who received the first dose of pneumococcal 7-valent conjugate vaccine alone (44%, 46%, and 27%, respectively). Among children who received the first dose of HAVRIX alone, pain was reported in 28% of subjects, redness in 22% of subjects, and swelling in 7% of subjects.

Solicited general adverse events were reported as follows among children who received the first dose HAVRIX coadministered with pneumococcal 7-valent conjugate vaccine: Irritability was reported in 35% of subjects, drowsiness in 26% of subjects, loss of appetite in 25% of subjects, and fever in 14% of subjects. The reported rates of these general adverse events were similar to those reported in children who received the first dose of pneumococcal 7-valent conjugate vaccine alone (41%, 32%, 25%, and 16%, respectively). Among children who received the first dose of HAVRIX alone, irritability was reported in 35% of subjects, drowsiness in 29% of subjects, loss of appetite in 26% of subjects, and fever in 9% of subjects.

Postmarketing Experience

In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for HAVRIX since market introduction of this vaccine are listed below. This list includes serious adverse events or events which have a suspected causal connection to components of HAVRIX or other vaccines or drugs. 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 the vaccine.

Blood and lymphatic system disorders: Thrombocytopenia.

Immune system disorders: Anaphylactic reaction, anaphylactoid reaction.

Nervous system disorders: Convulsion, dizziness, encephalopathy, Guillain-Barré syndrome, multiple sclerosis, myelitis, neuropathy, paresthesia, somnolence, syncope.

Respiratory, thoracic, and mediastinal disorders: Dyspnea.

Hepatobiliary disorders: Hepatitis, jaundice.

Skin and subcutaneous tissue disorders: Angioedema, erythema multiforme, hyperhidrosis.

Congenital, familial and genetic disorders: Congenital anomaly.

General disorders and administration site conditions: Local swelling.

Concomitant Administration With Vaccines and Immune Globulin (IG)

HAVRIX may be given concurrently with Haemophilus influenzae type b (Hib) conjugate vaccine (tetanus toxoid conjugate) (PRP-T) (Sanofi Pasteur SA) in children 15 to 18 months of age [see ADVERSE REACTIONS and Clinical Studies].

HAVRIX may be given concurrently with the fourth dose of pneumococcal 7-valent conjugate vaccine (Wyeth Pharmaceuticals Inc.) in children 15 months of age (range 14 to 16 months) [see ADVERSE REACTIONS and Clinical Studies].

The safety of HAVRIX given concomitantly with INFANRIX has been evaluated [see ADVERSE REACTIONS]. Insufficient data are available to assess the immune response of a fourth dose of DTaP vaccine when administered with HAVRIX.

HAVRIX may be administered concomitantly with IG.

When concomitant administration of other vaccines or IG is required, they should be given with different syringes and at different injection sites. Do not mix HAVRIX with any other vaccine or product in the same syringe or vial.

Immunosuppressive Therapies

Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to HAVRIX.

Last updated on RxList: 10/20/2008

Included as part of the PRECAUTIONS section.

Latex

The tip cap and the rubber plunger of the needleless prefilled syringes contain dry natural latex rubber that may cause allergic reactions in latex sensitive individuals. The vial stopper is latex-free.

Altered Immunocompetence

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

Limitations of Vaccine Effectiveness

Hepatitis A has a relatively long incubation period (15 to 50 days). Hepatitis A vaccine may not prevent hepatitis A infection in individuals who have an unrecognized hepatitis A infection at the time of vaccination. Additionally, it may not prevent infection in individuals who do not achieve protective antibody titers (although the lowest titer needed to confer protection has not been determined).

Preventing and Managing Allergic Vaccine Reactions

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

HAVRIX has not been evaluated for its carcinogenic potential, mutagenic potential, or potential for impairment of fertility.

Use In Specific Populations

Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with HAVRIX. It is also not known whether HAVRIX can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HAVRIX should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether HAVRIX is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when HAVRIX is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of HAVRIX have been evaluated in 20,869 subjects 1 year to 18 years of age.

The safety and effectiveness of HAVRIX have not been established in subjects younger than 12 months of age.

Geriatric Use

Clinical studies of HAVRIX did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in overall safety between these subjects and younger adult subjects.

Hepatic Impairment

Subjects with chronic liver disease had a lower antibody response to HAVRIX than healthy subjects [see Clinical Studies].

Last updated on RxList: 10/20/2008

No information provided.

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].

Last updated on RxList: 10/20/2008

Mechanism of Action

The hepatitis A virus belongs to the picornavirus family. It is one of several hepatitis viruses that cause systemic disease with pathology in the liver.

The incubation period for hepatitis A averages 28 days (range: 15 to 50 days).¹ The course of hepatitis A infection is extremely variable, ranging from asymptomatic infection to icteric hepatitis and death.

The presence of antibodies to HAV confers protection against hepatitis A infection. However, the lowest titer needed to confer protection has not been determined.

Clinical Studies

Pediatric Effectiveness Studies

Protective efficacy with HAVRIX has been demonstrated in a double-blind, randomized controlled study in school children (age 1 to 16 years) in Thailand who were at high risk of HAV infection. A total of 40,119 children were randomized to be vaccinated with either HAVRIX 360 EL.U. or ENGERIX-B at 0, 1, and 12 months. 19,037 children received a primary course (doses at 0 and 1 months) of HAVRIX and 19,120 children received a primary course (doses at 0 and 1 months) of ENGERIX-B. 38,157 children entered surveillance at day 138 and were observed for an additional 8 months. Using the protocol-defined endpoint ( ≥ 2 days absence from school, ALT level > 45 U/mL, and a positive result in the HAVAB-M test), 32 cases of clinical hepatitis A occurred in the control group. In the HAVRIX group, 2 cases were identified. These 2 cases were mild in terms of both biochemical and clinical indices of hepatitis A disease. Thus the calculated efficacy rate for prevention of clinical hepatitis A was 94% (95% Confidence Interval [CI]: 74, 98).

In outbreak investigations occurring in the trial, 26 clinical cases of hepatitis A (of a total of 34 occurring in the trial) occurred. No cases occurred in vaccinees who received HAVRIX.

Using additional virological and serological analyses post hoc, the efficacy of HAVRIX was confirmed. Up to 3 additional cases of mild clinical illness may have occurred in vaccinees. Using available testing, these illnesses could neither be proven nor disproven to have been caused by HAV. By including these as cases, the calculated efficacy rate for prevention of clinical hepatitis A would be 84% (95% CI: 60, 94).

In a study designed to interrupt an epidemic of hepatitis A among Native Americans in Alaska, vaccination with a single dose of HAVRIX (1440 EL.U./mL in adults, 720 EL.U./0.5 mL in children and adolescents) appeared to be efficacious.

Immunogenicity in Children and Adolescents

Immune Response to HAVRIX 720 EL.U./0.5 mL at 11 Months of Age and Older: In a prospective, open-label, multicenter study, 1,085 children were enrolled into one of 5 groups:

1. Children 11 to 13 months of age who received HAVRIX on a 0- and 6-month schedule;
2. Children 15 to 18 months of age who received HAVRIX on a 0- and 6-month schedule;
3. Children 15 to 18 months of age who received HAVRIX coadministered with INFANRIX and Hib conjugate vaccine (PRP-T) (Sanofi Pasteur SA) at month 0 and HAVRIX at month 6;
4. Children 15 to 18 months of age who received INFANRIX coadministered with Hib conjugate vaccine (PRP-T) (Sanofi Pasteur SA) at month 0 and HAVRIX at months 1 and 7;
5. Children 23 to 25 months of age who received HAVRIX on a 0- and 6-month schedule.

Among subjects in all groups, 52% were male; 61% of subjects were White, 9% Black, 3% Asian, and 27% were of other racial groups. The anti-hepatitis A antibody vaccine responses and GMTs, calculated on responders for groups 1, 2, and 5 are presented in Table 1. Vaccine response rates were similar among the 3 age groups that received HAVRIX. One month after the second dose of HAVRIX, the GMT in each of the younger age groups (11 to 13 and 15 to 18 months of age) was shown to be similar to that achieved in the 23 to 25 months of age group.

Table 1. Anti-hepatitis A Immune Response Following 2 Doses of HAVRIX 720 EL.U./0.5 mL Administered 6 Months Apart in Children Given the First Dose of HAVRIX at 11 to 13 Months of Age, 15 to 18 Months of Age, or 23 to 25 Months of Age

Immune Response to HAVRIX 360 EL.U. at 2 Years of Age and Older: In 6 clinical studies of subjects 2 to 18 years of age (n = 762) who received 2 doses of HAVRIX (360 EL.U.) given 1 month apart, the GMT ranged from 197 to 660 mIU/mL. Ninety-nine percent of subjects seroconverted following 2 doses. When a booster (third) dose of HAVRIX 360 EL.U. was administered 6 months following the initial dose, all subjects were seropositive 1 month following the booster dose, with GMTs rising to a range of 3,388 to 4,643 mIU/mL. In 1 study in which children were followed for an additional 6 months, all subjects remained seropositive.

Immune Response to HAVRIX 720 EL.U./0.5 mL at 2 Years of Age and Older: In 4 clinical studies, children and adolescents (n = 314), ranging from 2 to 19 years of age, were immunized with 2 doses of HAVRIX 720 EL.U./0.5 mL given 6 months apart. One month after the first dose, seroconversion (anti-HAV ≥ 20 mIU/mL [lower limit of antibody measurement by assay]) ranged from 96.8% to 100%, with GMTs of 194 mIU/mL to 305 mIU/mL. In studies in which sera were obtained 2 weeks following the initial dose, seroconversion ranged from 91.6% to 96.1%. One month following a booster dose at month 6, all subjects were seropositive, with GMTs ranging from 2,495 mIU/mL to 3,644 mIU/mL.

In an additional study in which the booster dose was delayed until 1 year following the initial dose, 95.2% of the subjects were seropositive just prior to administration of the booster dose. One month later, all subjects were seropositive, with a GMT of 2,657 mIU/mL.

Also, HAVRIX has been found to be efficacious in a clinical study of children at high risk of HAV infection [see Clinical Studies].

Immunogenicity in Adults

Over 400 healthy adults 18-50 years of age in 3 clinical studies were given a single 1440 EL.U. dose of HAVRIX. All subjects were seronegative for hepatitis A antibodies at baseline. Specific humoral antibodies against HAV were elicited in more than 96% of subjects when measured 1 month after vaccination. By day 15, 80% to 98% of vaccinees had already seroconverted (anti-HAV ≥ 20 mIU/mL [lower limit of antibody measurement by assay]). GMTs of seroconverters ranged from 264 to 339 mIU/mL at day 15 and increased to a range of 335 to 637 mIU/mL by 1 month following vaccination.

The GMTs obtained following a single dose of HAVRIX are at least several times higher than that expected following receipt of IG.

In a clinical study using 2.5 to 5 times the standard dose of IG (standard dose = 0.02 to 0.06 mL/kg), the GMT in recipients was 146 mIU/mL at 5 days post-administration, 77 mIU/mL at month 1, and 63 mIU/mL at month 2.

In 2 clinical trials in which a booster dose of 1440 EL.U. was given 6 months following the initial dose, 100% of vaccinees (n = 269) were seropositive 1 month after the booster dose, with GMTs ranging from 3,318 mIU/mL to 5,925 mIU/mL. The titers obtained from this additional dose approximate those observed several years after natural infection.

In a subset of vaccinees (n = 89), a single dose of HAVRIX 1440 EL.U. elicited specific anti-HAV neutralizing antibodies in more than 94% of vaccinees when measured 1 month after vaccination. These neutralizing antibodies persisted until month 6. One hundred percent of vaccinees had neutralizing antibodies when measured 1 month after a booster dose given at month 6.

Immunogenicity of HAVRIX was studied in subjects with chronic liver disease of various etiologies. 189 healthy adults and 220 adults with either chronic hepatitis B (n = 46), chronic hepatitis C (n = 104), or moderate chronic liver disease of other etiology (n = 70) were vaccinated with HAVRIX 1440 EL.U. on a 0- and 6-month schedule. The last group consisted of alcoholic cirrhosis (n = 17), autoimmune hepatitis (n = 10), chronic hepatitis/cryptogenic cirrhosis (n = 9), hemochromatosis (n = 2), primary biliary cirrhosis (n = 15), primary sclerosing cholangitis (n = 4), and unspecified (n = 13). At each time point, geometric mean antibody titers (GMTs) were lower for subjects with chronic liver disease than for healthy subjects. At month 7, the GMTs ranged from 478 mIU/mL (chronic hepatitis C) to 1,245 mIU/mL (healthy). One month after the first dose, seroconversion rates in adults with chronic liver disease were lower than in healthy adults. However, 1 month after the booster dose at month 6, seroconversion rates were similar in all groups; rates ranged from 94.7% to 98.1%. The relevance of these data to the duration of protection afforded by HAVRIX is unknown.

In subjects with chronic liver disease, local injection site reactions with HAVRIX were similar among all 4 groups, and no serious adverse events attributed to the vaccine were reported in subjects with chronic liver disease.

Duration of Immunity

The duration of immunity following a complete schedule of immunization with HAVRIX has not been established.

Immune Response to Concomitantly Administered Vaccines

Concomitant Administration With Hib Conjugate Vaccine (PRP-T): The concomitant administrationof Hib conjugate vaccine (PRP -T) (Sanofi Pasteur SA) and INFANRIX with HAVRIX was evaluated in children receiving their first dose of HAVRIX at 15 to 18 months of age followed by a second dose of HAVRIX 6 months later. Anti-hepatitis A vaccine response was defined as seroconversion (anti-HAV ≥ 15 mIU/mL [lower limit of antibody measurement by assay]) in subjects initially seronegative or at least maintenance of pre-vaccination antibody concentration in subjects initially seropositive. One month after the second dose of HAVRIX, the vaccine response (100%) in those receiving the first dose of HAVRIX coadministered with INFANRIX and Hib conjugate vaccine (PRP-T) (Sanofi Pasteur SA) was shown to be non-inferior to that achieved (100%) in 15- to 18-month-olds who received HAVRIX alone (lower limit of 95% CI on difference for coadministered vaccine group minus HAVRIX alone group > -5%).

One month after vaccination with Hib conjugate vaccine (PRP-T) (Sanofi Pasteur SA), the seroprotection rates to this vaccine were shown to be non-inferior in subjects who received Hib conjugate vaccine (PRP-T) concomitantly with their first dose of HAVRIX (100% achieved ≥ 1 mcg/mL of anti-PRP antibody; 95% CI: 97, 100) as compared to those who did not receive HAVRIX (100% achieved ≥ 1 mcg/mL of anti-PRP antibody; 95% CI: 97, 100). Both groups received INFANRIX concomitantly with Hib conjugate vaccine (PRP-T) with and without HAVRIX.

Concomitant Administration With Pneumococcal 7-Valent Conjugate Vaccine: In a US multicenter study, children 15 months of age (range 14 to 16 months) received one of 3 regimens: (Group 1) HAVRIX coadministered with pneumococcal 7-valent conjugate vaccine (Wyeth Pharmaceuticals Inc.) followed by a second dose of HAVRIX 6 to 9 months later; (Group 2) HAVRIX administered alone followed by a second dose of HAVRIX 6 to 9 months later; or (Group 3) pneumococcal 7-valent conjugate vaccine administered alone followed by a first dose of HAVRIX one month later and a second dose of HAVRIX 6 to 9 months after the first.

One month after the second dose, the anti-hepatitis A GMT of HAVRIX coadministered with pneumococcal 7-valent conjugate vaccine was non-inferior to HAVRIX given alone (Group 1 GMT = 1,518 mIU/mL; Group 2 GMT = 1,666 mIU/mL). The difference in anti-hepatitis A seropositivity rates between groups (HAVRIX coadministered with pneumococcal 7-valent conjugate vaccine minus HAVRIX alone) was marginally lower than the pre-defined non-inferiority limit of -5% (lower limit of the two-sided 95% CI -5.78%). However, in all 3 groups, the seropositivity rate ranged between 98% and 100% one month after the second dose of HAVRIX (Group 1, 93/94; Group 2, 106/106; Group 3, 113/115).

One month after vaccination, non-inferiority was demonstrated with respect to GMTs for anti-pneumococcal antibodies to all 7 serotypes after the coadministration of pneumococcal 7-valent conjugate vaccine with HAVRIX compared to pneumococcal 7-valent conjugate vaccine alone. At least 98% of subjects who received pneumococcal 7-valent conjugate vaccine coadministered with HAVRIX and those who received pneumococcal 7-valent conjugate vaccine alone were seropositive for all 7 pneumococcal serotypes.

There are limited data on the coadministration of HAVRIX with other vaccines.

REFERENCES

1. Centers for Disease Control. Prevention of hepatitis A through active or passive immunization: Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 2006;55(RR-7):1-23.

2. Centers for Disease Control. Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2007;56(41):1080-1084.

Last updated on RxList: 10/20/2008

• Vaccine recipients and parents or guardians should be informed by their healthcare provider of the potential benefits and risks of immunization with HAVRIX.
• When educating vaccine recipients and parents or guardians regarding potential side effects, clinicians should emphasize that HAVRIX contains non-infectious killed viruses and cannot cause hepatitis A infection.
• Vaccine recipients and parents or guardians should be instructed to report any adverse events to their healthcare provider where the vaccine was administered.
• The vaccine recipients or guardian should be given the Vaccine Information Statements, which are required by the National Childhood Vaccine Injury Act of 1986 to be given prior to immunization. These materials are available free of charge at the CDC website (www.cdc.gov/nip).

Last updated on RxList: 10/20/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

HEPATITIS A VACCINE - INJECTION

(hep-uh-TIE-tuss A)

COMMON BRAND NAME(S): Havrix, Vaqta

USES: This medication is used to help prevent infection from the hepatitis A virus. Hepatitis A infection can be mild with no symptoms or a severe illness that can rarely cause liver failure and death. Preventing infection can prevent these problems.

Hepatitis A vaccine is made from whole, killed hepatitis A virus. It does not contain live virus, so you cannot get hepatitis from the vaccine. This vaccine causes the body to make defensive substances (antibodies) against hepatitis A virus that can protect you from infection with it. Hepatitis A vaccine does not protect you from other virus infections (e.g., HIV virus which causes AIDS, hepatitis B/C/E, HPV virus which causes genital warts and other problems).

The vaccine is recommended for persons aged 12 months and older, especially those at an increased risk of getting the infection. Those at an increased risk include household and intimate contacts of persons with hepatitis A infection, institutional or daycare workers, lab workers, persons with multiple sex partners, men who have sex with men, sex workers, injecting and non-injecting drug abusers, and persons traveling to high-risk areas.

HOW TO USE: This vaccine is usually given by injection into a shoulder muscle by a health care professional. Hepatitis A vaccine is a slightly milky, white suspension. Before giving this medication, inspect it visually for particles or discoloration. If either is present, do not use the liquid. Shake the vial or prefilled syringe well, and then measure the appropriate dose. Do not dilute. Use the full recommended dose of the vaccine. Discard any remaining vaccine left in the vial/syringe.

A series of 2 injections is usually given over a 6- to 18-month period. Your doctor will give you a vaccination schedule, which must be followed closely for best effectiveness. If you have an infection with fever at the time a vaccination is scheduled, your doctor may choose to delay the injection until you are better.

Dosage is based on your age. Different brands of hepatitis A vaccine are available and may be given differently. Make sure that you receive the same brand for each injection.

If you are receiving the first hepatitis A vaccine injection at a time when your doctor feels you may have been exposed to hepatitis A, you will also receive an injection of immune globulin (IG). IG contains antibodies against the hepatitis A virus. It will immediately help protect you against infection. These antibodies only last a few months. For long-term protection, it is important to follow your vaccination schedule exactly.

SIDE EFFECTS: Pain/redness/swelling at the injection site, fever, and headache may occur. Less common side effects may include bruising/itching at the injection site, pain/stiffness in the arm/shoulder/neck, sore throat, tiredness, weakness, muscle/joint aches, cold symptoms, nausea, vomiting, loss of appetite, abdominal cramps, diarrhea, irritability, agitation, and trouble sleeping. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects. Report all side effects to your doctor before you receive the next injection.

Tell your doctor immediately if any of these unlikely but serious side effects occur: irregular menstrual cycle.

Tell your doctor immediately if any of these rare but very serious side effects occur: inability to make muscles of the legs/arms work (paralysis), seizures, easy bruising/bleeding, signs of serious brain problems (e.g., unusual behavior, confusion, severe drowsiness, severe tiredness, stiff neck, eye sensitivity to light).

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before getting hepatitis A vaccine, tell your doctor or pharmacist if you are allergic to it; or to neomycin or formalin; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding problems (e.g., hemophilia, low platelets, anticoagulant treatment), current illness with fever.

If you have decreased immune function from other medications (see also Drug Interactions) or other illness (e.g., HIV, leukemia, lymphoma, other cancer), your body may not make enough antibodies to protect you from hepatitis A infection. Antibody levels should be checked after the vaccine series.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of medications that can decrease immune function: corticosteroids (e.g., prednisone), cancer chemotherapy, organ transplant drugs (e.g., cyclosporine, azathioprine).

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting the hepatitis A vaccine.

Other vaccines may be given at the same time as hepatitis A vaccine, but should be given with separate syringes and at different injection sites.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Hepatitis A spreads very easily, often through contaminated food or water, infected food handlers, sexual contact with an infected individual, eating raw shellfish from contaminated water, poor sanitary conditions, and rarely by blood transfusions or sharing needles with actively infected persons.

MISSED DOSE: It is important to receive each vaccination as scheduled. Be sure to ask when each dose should be received and make a note on a calendar to help you remember.

STORAGE: Store refrigerated between 36-46 degrees F (2-8 degrees C) away from light. Do not freeze. Discard any product that has been frozen. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.