Hepatitis B Vaccine

Mechanism Of Action

RECOMBIVAX HB has been shown to elicit antibodies to hepatitis B virus as measured by ELISA.

Antibody concentrations ≥ 10mIU/mL against HBsAg are recognized as conferring protection against hepatitis B infection.2

Infection with hepatitis B virus can have serious consequences including acute massive hepatic necrosis and chronic active hepatitis. Chronically infected persons are at increased risk for cirrhosis and hepatocellular carcinoma.

Clinical Studies

Efficacy in Neonates with Peripartum Exposure to Hepatitis B

The protective efficacy of three 5 mcg doses of RECOMBIVAX HB has been demonstrated in neonates born of mothers positive for both HBsAg and HBeAg (a core-associated antigenic complex which correlates with high infectivity). In a clinical study of infants who received one dose of HBIG at birth followed by the recommended three-dose regimen of RECOMBIVAX HB, chronic infection had not occurred in 96% of 130 infants after nine months of follow-up.4 The estimated efficacy in prevention of chronic hepatitis B infection was 95% as compared to the infection rate in untreated historical controls.5 Significantly fewer neonates became chronically infected when given one dose of HBIG at birth followed by the recommended three-dose regimen of RECOMBIVAX HB when compared to historical controls who received only a single dose of HBIG.6 As demonstrated in the above study, HBIG, when administered simultaneously with RECOMBIVAX HB at separate body sites, did not interfere with the induction of protective antibodies against hepatitis B virus elicited by the vaccine.6

Immunogenicity Of A Three-Dose Regimen In Healthy Infants, Children, And Adolescents

Three 5 mcg doses of RECOMBIVAX HB induced a protective level of antibody in 100% of 92 infants, 99% of 129 children, and in 99% of 112 adolescents [see DOSAGE AND ADMINISTRATION].

Immunogenicity Of A Two-Dose Regimen In Healthy Adolescents 11 through 15 Years Of Age

For adolescents (11 through 15 years of age), the immunogenicity of a two-dose regimen (10 mcg at 0 and 4-6 months) was compared with that of the standard three-dose regimen (5 mcg at 0, 1, and 6 months) in an open, randomized, multicenter study. The proportion of adolescents receiving the two-dose regimen who developed a protective level of antibody one month after the last dose (99% of 255 subjects) appears similar to that among adolescents who received the three-dose regimen (98% of 121 subjects). After adolescents (11 through 15 years of age) received the first 10-mcg dose of the two-dose regimen, the proportion who developed a protective level of antibody was approximately 72%.

Immunogenicity In Healthy Adults

Clinical studies have shown that RECOMBIVAX HB when injected into the deltoid muscle induced protective levels of antibody in 96% of 1213 healthy adults who received the recommended three-dose regimen. Antibody responses varied with age; a protective level of antibody was induced in 98% of 787 young adults 20-29 years of age, 94% of 249 adults 30-39 years of age and in 89% of 177 adults ≥ 40 years of age.

Efficacy And Immunogenicity In Specific Populations

In one published study, the seroprotection rates in individuals with chronic hepatitis C virus (HCV) infection given the standard regimen of RECOMBIVAX HB was approximately 70%.7 In a second published study of intravenous drug users given an accelerated schedule of RECOMBIVAX HB, infection with HCV did not affect the response to RECOMBIVAX HB.8

Predialysis and dialysis adult patients respond less well to hepatitis B vaccines than do healthy individuals; however, vaccination of adult patients early in the course of their renal disease produces higher seroconversion rates than vaccination after dialysis has been initiated.9 In addition, the responses to these vaccines may be lower if the vaccine is administered as a buttock injection. When 40 mcg of Hepatitis B Vaccine (Recombinant), was administered in the deltoid muscle, 89% of 28 participants developed anti-HBs with 86% achieving levels ≥ 10 mIU/mL. However, when the same dosage of this vaccine was administered inappropriately either in the buttock or a combination of buttock and deltoid, 62% of 47 participants developed anti-HBs with 55% achieving levels of ≥ 10 mIU/mL.

REFERENCES

4. Stevens, C.E.; Taylor, P.E.; Tong, M.J., et al.: Prevention of Perinatal Hepatitis B Virus Infection with Hepatitis B Immune Globulin and Hepatitis B Vaccine, in Zuckerman, A.J. (ed.), “Viral Hepatitis and Liver Diseases”, Alan R. Liss, 982-983, 1988.

5. Stevens, C.E.; Taylor, P.E.; Tong, M.J., et al.: Yeast-Recombinant Hepatitis B Vaccine, Efficacy with Hepatitis B Immune Globulin in Prevention of Perinatal Hepatitis B Virus Transmission, JAMA 257(19): 2612-2616, 1987.

6. Beasley, R.P.; Hwang, L.; Stevens, C.E.; Lin, C.; Hsieh, F.; Wang, K.; Sun, T.; Szmuness, W.: Efficacy of Hepatitis B Immune Globulin for Prevention of Perinatal Transmission of the Hepatitis B Virus Carrier State: Final Report of a Randomized Double-Blind, Placebo-Controlled Trial, Hepatology 3: 135-141, 1983.

7. Wiedmann, M.; Liebert, U.G.; Oesen, U.; Porst, H.; Wiese, M.; Schroeder, S.; Halm, U.; Mossner, J.; Berr, F.: Decreased Immunogenicity of Recombinant Hepatitis B Vaccine in Chronic Hepatitis C, Hepatology, 31: 230-234, 2000.

8. Minniti, F.; Baldo, V.; Trivello, R.; Bricolo, R.; Di Furia, L.; Renzulli, G.; Chiaramonte, M.: Response to HBV vaccine in Relation to anti-HCV and anti-HBc Positivity: a Study in Intravenous Drug Addicts, Vaccine, 17: 3083-3085, 1999.

9. Recommendations of the Advisory Committee on Immunization Practices (ACIP): Hepatitis B Virus Infection: A Comprehensive Strategy to Eliminate Transmission in the United States, 1996 update, MMWR (draft January 13, 1996).

Contraindications

Hypersensitivity to yeast

Cautions

Not protective against hepatitis A, C, or E

Gluteal muscle not recommended

Heptavax B (plasma-derived) no longer used in the US

Pregnancy Category: C

Lactation: not known if excreted in breast milk

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

In healthy infants and children (up to 10 years of age), the most frequently reported systemic adverse reactions ( > 1% injections), in decreasing order of frequency, were irritability, fever, diarrhea, fatigue/weakness, diminished appetite, and rhinitis. In healthy adults, injection site reactions and systemic adverse reactions were reported following 17% and 15% of the injections, respectively.

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.

In three clinical studies, 434 doses of RECOMBIVAX HB, 5 mcg, were administered to 147 healthy infants and children (up to 10 years of age) who were monitored for 5 days after each dose. Injection site reactions and systemic adverse reactions were reported following 0.2% and 10.4% of the injections, respectively. The most frequently reported systemic adverse reactions ( > 1% injections), in decreasing order of frequency, were irritability, fever ( ≥ 101°F oral equivalent), diarrhea, fatigue/weakness, diminished appetite, and rhinitis.

In a study that compared the three-dose regimen (5 mcg) with the two-dose regimen (10 mcg) of RECOMBIVAX HB in adolescents, the overall frequency of adverse reactions was generally similar.

In a group of studies, 3258 doses of RECOMBIVAX HB, 10 mcg, were administered to 1252 healthy adults who were monitored for 5 days after each dose. Injection site reactions and systemic adverse reactions were reported following 17% and 15% of the injections, respectively. The following adverse reactions were reported:

Incidence Equal To or Greater Than 1% of Injections

Injection site reactions consisting principally of soreness, and including pain, tenderness, pruritus, erythema, ecchymosis, swelling, warmth, nodule formation.

The most frequent systemic complaints include fatigue/weakness; headache; fever ( ≥ 100°F); malaise.

Nausea; diarrhea

Pharyngitis; upper respiratory infection

Incidence Less Than 1% of Injections

Sweating; achiness; sensation of warmth; lightheadedness; chills; flushing

Vomiting; abdominal pains/cramps; dyspepsia; diminished appetite

Rhinitis; influenza; cough

Vertigo/dizziness; paresthesia 5

Pruritus; rash (non-specified); angioedema; urticaria

Arthralgia including monoarticular; myalgia; back pain; neck pain; shoulder pain; neck stiffness

Lymphadenopathy

Insomnia/disturbed sleep

Earache

Dysuria

Hypotension

Post-Marketing Experience

The following additional adverse reactions have been reported with use of the marketed vaccine. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to a vaccine exposure.

Hypersensitivity reactions including anaphylactic/anaphylactoid reactions, bronchospasm, and urticaria have been reported within the first few hours after vaccination. An apparent hypersensitivity syndrome (serum-sickness-like) of delayed onset has been reported days to weeks after vaccination, including: arthralgia/arthritis (usually transient), fever, and dermatologic reactions such as urticaria, erythema multiforme, ecchymoses and erythema nodosum [see WARNINGS AND PRECAUTIONS]. Autoimmune diseases including systemic lupus erythematosus (SLE), lupus-like syndrome, vasculitis, and polyarteritis nodosa have also been reported.

Elevation of liver enzymes; constipation

Guillain-Barr� syndrome; multiple sclerosis; exacerbation of multiple sclerosis; myelitis including transverse myelitis; seizure; febrile seizure; peripheral neuropathy including Bell's Palsy; radiculopathy; herpes zoster; migraine; muscle weakness; hypesthesia; encephalitis

Stevens-Johnson syndrome; alopecia; petechiae; eczema

Arthritis

Pain in extremity

Increased erythrocyte sedimentation rate; thrombocytopenia

Irritability; agitation; somnolence

Optic neuritis; tinnitus; conjunctivitis; visual disturbances; uveitis

Syncope; tachycardia

The following adverse reaction has been reported with another Hepatitis B Vaccine (Recombinant) but not with RECOMBIVAX HB: keratitis.

Read the entire FDA prescribing information for Recombivax (Hepatitis B Vaccine (Recombinant))

Inactivated (recombinant) vaccine.132 133 213 281 Hepatitis B vaccine contains hepatitis B surface antigen (HBsAg) and is used to stimulate active immunity to hepatitis B virus (HBV) infection.132 133 213 281 Commercially available in the US as monovalent vaccines (HepB; Engerix-B, Recombivax HB).132 133 Also commercially available in a fixed-combination vaccine with Haemophilus influenzae type b (Hib) vaccine (Hib-HepB; Comvax),251 in a fixed-combination vaccine with hepatitis A virus vaccine (HepA-HepB; Twinrix),262 and in a fixed-combination vaccine that contains diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix).104

Prevention of Hepatitis B Virus (HBV) Infection

Prevention of HBV infection in neonates, children, adolescents, and adults.105 112 132 133 213 241 280 281 282

Acute HBV infection may be self-limited resulting in production of antibody to HBsAg (anti-HBs) and immunity against reinfection; however, it may progress to chronic HBV infection (especially in infants or young children, immunocompromised individuals, patients with diabetes) or fatal, fulminant hepatitis.105 213 281 282 Case fatality rate is 0.5–1.5% among those with acute HBV infection;213 281 290 highest fatality rates are in adults >60 years of age.213 281 Chronic HBV infection develops in ≥90% of infants infected perinatally, 25–50% of children infected at 1–5 years of age, and <5% of those infected at ≥5 years of age.105 213 281 282 290 291 Chronic infection is associated with persistent HBV replication in the liver and may result in liver cirrhosis, liver cancer, liver failure, and death.105 213 281 282 290 HBV is transmitted by percutaneous or mucosal exposure to hepatitis B surface antigen-positive (HBsAg-positive) blood, serum, plasma, semen, or saliva105 130 213 269 281 282 and can be transmitted perinatally from mother to infant at birth, usually as the result of blood exposures during labor and delivery.105 213 282

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and American Academy of Family Physicians (AAFP) recommend that all neonates and infants and all previously unvaccinated children and adolescents through 18 years of age be vaccinated against HBV infection, unless contraindicated.105 112 213 241 (See Contraindications under Cautions.)

ACIP, AAFP, American College of Obstetricians and Gynecologists (ACOG), and American College of Physicians (ACP) recommend that all unvaccinated adults at risk for HBV infection be vaccinated against HBV.280 281 (See Preexposure Vaccination Against Hepatitis B Virus [HBV] Infection in High-risk Groups under Uses.) ACIP also states that any unvaccinated adult requesting protection from HBV can receive the vaccine, unless contraindicated.280 281 (See Contraindications under Cautions.)

For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity.131 For hepatitis B vaccine (HepB vaccine), ACIP states initiate or complete the age-appropriate HepB vaccine series if vaccination history is uncertain or <3 doses were previously given.131 (See Dosage and Administration.) If child’s records indicate ≥3 doses of HepB vaccine, ACIP states that additional doses not necessary if ≥1 dose was given at ≥24 weeks of age; if most recent dose was at <24 weeks, give an additional dose at ≥24 weeks.131 Regardless of vaccination status, test for HBsAg if individual was born in Asia, Pacific Islands, Africa, or other regions where HBV is highly endemic.131 AAP recommends serologic testing for HBsAg in all internationally adopted children and states that the HepB vaccine series should be given if such testing is not available and vaccination history is uncertain.105

Combined active immunization with HepB vaccine and passive immunization with hepatitis B immune globulin (HBIG) is used to prevent perinatal HBV infection in neonates born to women known or suspected to be HBsAg-positive.105 112 132 133 213 (See Prevention of Perinatal Hepatitis B Virus [HBV] Infection under Uses.)

Active immunization with HepB vaccine with or without passive immunization with HBIG is used for HBV postexposure prophylaxis (PEP) in certain individuals exposed to HBV or HBsAg-positive materials (e.g., health-care personnel, sexual assault victims, sexual or intimate contacts of individuals with acute or chronic HBV infection).101 130 269 281 290 (See Postexposure Prophylaxis of Hepatitis B Virus [HBV] Infection under Uses.)

With the exception of hepatitis D virus (HDV) infection,105 133 monovalent HepB vaccine will not prevent hepatitis caused by other viruses known to infect the liver, including hepatitis A virus (HAV), hepatitis C virus (HCV), or hepatitis E virus (HEV).105 132 133 HDV occurs only as a coinfection or superinfection in patients with HBV infection; individuals immune to HBV also should be immune to HDV.105 133

When a dose of HepB vaccine and a dose of Haemophilus influenzae type b (Hib) vaccine are both indicated in an infant 6 weeks to 15 months of age born to an HBsAg-negative woman, the commercially available fixed-combination vaccine containing Hib conjugate (meningococcal protein conjugate) vaccine and HepB vaccine (Hib-HepB; Comvax) can be used.213 251 ACIP states this fixed-combination vaccine also may be used to complete the HepB vaccine series in infants 6 weeks to 15 months of age born to HBsAg-positive women†.213 Comvax should not be used for the initial (birth) dose of HepB vaccine that is indicated in neonates.105 213

When there are no contraindications to any of the individual components, the commercially available fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix) can be used in infants and children 6 weeks through 6 years of age born to HBsAg-negative women.104 ACIP states this fixed-combination vaccine also may be used to complete the HepB vaccine series in infants ≥6 weeks of age born to HBsAg-positive women†.213 Pediarix should not be used for the initial (birth) dose of HepB vaccine that is indicated in neonates.104 105 Pediarix contains diphtheria, tetanus, and pertussis antigens identical to those contained in Infanrix DTaP vaccine and contains HBV antigen identical to that contained in Engerix-B HepB vaccine.104

When vaccination against both HBV and HAV is indicated in adults ≥18 years of age, the commercially available fixed-combination vaccine containing hepatitis A virus vaccine inactivated and HepB vaccine (HepA-HepB; Twinrix) can be used.213 262 281

Preexposure Vaccination Against Hepatitis B Virus (HBV) Infection in High-risk Groups

Preexposure vaccination in previously unvaccinated children, adolescents, or adults at risk of exposure to HBsAg-positive materials (e.g., blood, plasma, serum).130 132 133 233

ACIP recommends preexposure vaccination for all unvaccinated adults in settings in which a high proportion of individuals are likely to be at risk for HBV infection.130 132 133 233 This includes health-care personnel, selected patients and patient contacts, populations with high risk of infection, individuals at risk because of their sexual practices, military personnel identified as being at increased risk, and other individuals at risk of exposure (e.g., injection drug abusers).130 132 133 233

In settings in which a high proportion of individuals are likely to be at risk for HBV, ACIP recommends universal vaccination for all adults who have not completed the HepB vaccine series and suggests standing orders to administer the vaccine as part of routine services to all susceptible individuals who visit these settings.281 This includes facilities that test and treat sexually transmitted diseases (STDs) and HIV, facilities that provide drug abuse treatment and prevention, health-care facilities targeting services for injection drug abusers or men who have sex with men, and correctional facilities.281 In addition, because not all adults with HBV risk factors visit these settings, ACIP recommends that primary care and specialty medical settings (e.g., physician offices, community health centers, family planning clinics, liver disease clinics, travel clinics) implement standing orders to identify susceptible adults and provide HepB vaccine whenever indicated or requested as part of regular preventive care.281

Health-care personnel at risk of exposure to blood, blood-contaminated body fluids, other body fluids, and/or needles that might be contaminated with HBsAg are at risk of HBV infection and should be vaccinated against HBV.180 181 182 183 185 206 233 269 282 ACIP and Hospital Infection Control Practices Advisory Committee (HICPAC) recommend HBV vaccination for all such health-care personnel (e.g., physicians, nurses, emergency medical personnel, dental professionals and students, medical and nursing students, phlebotomists, medical and laboratory technicians, hospital volunteers, administrative and support staff in health-care institutions).233 Ideally, the HepB vaccine series should be completed during medical, dental, nursing, laboratory technology, and other allied health professional training so that immunity is provided before exposure in high-risk environments.233 (For information on HBV postexposure prophylaxis in unvaccinated health-care personnel, see Postexposure Prophylaxis of Hepatitis B Virus [HBV] Infection under Uses.)

Individuals with hemophilia or other congenital bleeding disorders who are seronegative for HBV should be vaccinated against HBV.100 101 132 133 288 If immunization against HBV was not initiated at birth, initiate HepB vaccine series at the time hemophilia or other congenital bleeding disorders are diagnosed.288 Improved donor screening, more effective viral-inactivation procedures, and/or purification or filtration procedures have reduced, but not completely eliminated, the risk of transmission of blood-borne viruses (HBV, HCV, HIV) from plasma-derived clotting factors.288 The National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) recommends postvaccination testing in individuals with hemophilia100 288 and states that nonresponders (i.e., those who do not respond to the primary HepB vaccine series) should receive ≥1 additional doses of the vaccine.100 (See Pre- and Postvaccination Serologic Testing under Cautions.)

Patients and staff of hemodialysis, organ transplant, or oncology wards are at high risk of exposure to HBsAg-positive materials and should be vaccinated against HBV.101 220 Although seroconversion rates and anti-HBs titers induced by vaccination are lower in hemodialysis patients than in healthy individuals, vaccination provides protection against HBV infection in responders and reduces the need for frequent serologic screening.101 203 204 220 ACIP recommends identifying potential candidates as early as possible in the course of their renal disease; there is some evidence that higher seroconversion rates and anti-HBs titers are achieved in uremic patients if they are vaccinated before requiring dialysis.101 199 220

Residents and staff of institutions for the developmentally disabled, including those in small (group) residential settings, are at high risk of exposure to HBsAg-positive materials and should be vaccinated.101 Residents discharged from residential institutions into community settings should be screened for HBsAg so that appropriate measures can be taken to prevent transmission in the community; such measures include both environmental controls and appropriate vaccination.101

Classroom contacts (teachers or classmates) of aggressive, deinstitutionalized developmentally disabled individuals are at high risk of exposure to HBsAg-positive materials.101 186 HBV vaccination of classroom contacts of HBsAg carriers is strongly encouraged when the carrier is aggressive or has special medical problems that increase the risk of exposure to their blood or serous secretions.101 186 In addition, staff of nonresidential day-care programs (e.g., schools, sheltered workshops for the developmentally disabled) attended by known HBsAg carriers have a risk of infection comparable to that among health-care personnel and should be vaccinated.101 200 205 Also consider vaccination of other enrollees in such day-care programs.101 205

Spouses and nonsexual household and sexual contacts of HBsAg carriers are at high risk of exposure to HBsAg-positive materials.101 When carriers are identified through routine screening of donated blood, diagnostic testing in hospitals, prenatal screening, screening of refugees from certain areas, or other screening programs, they should be notified of their HBsAg status.101 Although some unvaccinated spouses and nonsexual household and sexual contacts of HBsAg carriers may develop immunity against HBV infection during continuous, long-term exposure, all such contacts should be tested and those who are susceptible should be vaccinated.101

Certain US population groups with high endemic rates of HBV (e.g., native Alaskans, Pacific Islanders, refugees from HBV-endemic areas) are at increased risk and should be vaccinated against HBV.101 105 213 222 Because transmission occurs principally during childhood in such populations, initiation of the HepB vaccine series at birth and completion of the series by 6–12 months of age is particularly important in these groups.105 213 222 Because of high rate of interfamily transmission among children in these populations, vaccination efforts should target all susceptible children and adolescents who have ≥1 parent born in a highly endemic area.105 281

Individuals at high risk of HBV because of their sexual practices (e.g., men who have sex with men, individuals with >1 sexual partner in the previous 6 months, sexual partners of HBsAg-positive individuals,101 130 132 133 281 female prostitutes132 133 ) and individuals seeking evaluation or treatment for STDs should be vaccinated against HBV.101 130 132 133 281 282 HepB vaccine is recommended for all susceptible adolescent and adult men who have sex with men (homosexual, bisexual), regardless of age or duration of such sexual practices.130 132 133 282

Travelers to areas with levels of endemic HBV that are intermediate (2–7%) or high (≥8%) are at risk of exposure to the disease.101 125 274 ACIP, CDC, and others recommend preexposure vaccination for previously unvaccinated travelers (neonates, infants, adolescents, adults) traveling to such areas.101 125 274 HBV prevalence is intermediate in South Central and Southwest Asia, Israel, Japan, Eastern and Southern Europe, Russia, and most areas surrounding the Amazon River basin, Honduras, and Guatemala; prevalence is high in Africa, Southeast Asia (including China, Korea, Indonesia, and Philippines), Middle East (except Israel), southern and western Pacific islands, interior Amazon Basin, and certain parts of the Caribbean (e.g., Haiti, Dominican Republic).125 274

Morticians and embalmers are at high risk of exposure to HBsAg-positive materials; the manufacturers recommend use of HepB vaccine in these individuals.132 133

Military personnel may be at increased risk of exposure to HBV; the manufacturers recommend use of HepB vaccine in these individuals.132 133

Prisoners may be at increased risk of exposure to HBV; the manufacturers recommend use of HepB vaccine in these individuals.132 133

Public-safety personnel (e.g., police, fire department personnel) may be at risk for occupational exposure to HBV (depending on tasks performed); those who have contact with blood or blood-contaminated body fluids should be vaccinated.281

Individuals with chronic HCV infection may be at increased risk for HBV exposure and should be vaccinated.132 133 Optimal HepB vaccine regimen for such individuals has not been identified; response to HepB vaccine may be reduced in individuals with chronic HCV infection.267 268

Individuals addicted to parenterally administered drugs are at high risk of exposure to HBsAg-positive materials and should be vaccinated against HBV as soon as their drug use is identified.133

Individuals in casual contact with HBsAg carriers in settings such as schools, offices, and business environments are at minimal risk of HBV exposure.101 ACIP does not recommend routine use of HepB vaccine in these individuals.101 At child-care centers (other than those for the developmentally disabled), HBV transmission between children or between children and staff has rarely been documented.101 ACIP states that vaccination of contacts of HBsAg carriers in child-care settings is not necessary unless there are special circumstances that might facilitate transmission (e.g., behavior problems such as biting or scratching, medical conditions such as severe skin disease).101

Prevention of Perinatal Hepatitis B Virus (HBV) Infection

Prevention of perinatal HBV infection in neonates born to HBsAg-positive women.105 112 132 133 213

A combined regimen that includes active immunization with HepB vaccine and passive immunization with HBIG is 85–95% effective in preventing acute and chronic HBV infection in infants born to women positive for both HBsAg and HBeAg.105 213

ACIP and AAP recommend routine serologic screening of all pregnant women during an early prenatal visit (e.g., first trimester) to determine their HBsAg status, even if they were tested previously or have already been vaccinated against HBV.105 112 213 Women who were not tested prenatally, those who engage in behaviors that put them at high risk for HBV (e.g., >1 sex partner in the previous 6 months, HBsAg-positive sex partner, evaluation or treatment for STDs, recent or current injection drug abuse) and those with clinical hepatitis should be tested for HBsAg status when admitted to the hospital for delivery.105 213

To prevent perinatal HBV infection, ACIP and AAP recommend that all neonates born to HBsAg-positive women receive a dose of HepB vaccine and a dose of HBIG as soon as possible after birth (within 12 hours of birth), regardless of gestational age or birthweight.105 112 213 For neonates <2 kg, do not count the birth vaccine dose toward completion of the HepB vaccine series; begin usual 3-dose vaccine series when infant is 1 month of age.105 213

If maternal HBsAg status is unknown at birth, give infant the first dose of HepB vaccine (within 12 hours of birth).105 112 213 Determine mother’s HBsAg status as quickly as possible and, if positive, give infant a dose of HBIG as soon as possible (no later than 7 days of age).105 112 For neonates weighing <2 kg, if the mother’s HBsAg status cannot be determined within 12 hours of birth, give a dose of HBIG as soon as possible (within 12 hours of birth) and do not count the birth vaccine dose toward completion of the HepB vaccine series; begin usual 3-dose vaccine series when infant is 1 month of age.105 213

Postexposure Prophylaxis of Hepatitis B Virus (HBV) Infection

HBV postexposure prophylaxis (PEP) in certain individuals exposed to HBV or HBsAg-positive materials (e.g., health-care personnel, sexual assault victims, sexual or intimate contacts of individuals with acute or chronic HBV infection).101 130 269 281 290

Depending on exposure circumstances, PEP regimen may include combined active immunization with HepB vaccine and passive immunization with HBIG to provide both short- and long-term protection.101 130 269 281 290

PEP may be indicated in susceptible, unvaccinated health-care personnel following occupational exposure to blood and other body fluids that might contain HBV.269 If an occupational exposure to HBV occurs, review vaccination status and vaccine-response status (if known) of exposed individual and HBsAg status of source.269 (See Table 1.)

If exposed individual was not previously vaccinated against HBV, initiate HepB vaccine series as soon as possible (preferably within 24 hours).269 In addition, if source is found to be HBsAg-positive, give a dose of HBIG as soon as possible (preferably within 24 hours).269

If exposed individual was previously vaccinated against HBV and is a known responder (serum anti-HBs ≥10 mIU/mL), PEP is not necessary.269 If exposed individual was previously vaccinated against HBV but is a known nonresponder (serum anti-HBs <10 mIU/mL), PEP is not necessary if source is HBsAg-negative.269 However, if source is HBsAg-positive or known to be high-risk for HBV, give exposed individual a dose of HBIG and initiate a second HepB vaccine series as soon as possible after exposure.269 A 2-dose regimen of HBIG (without HepB vaccine) is preferred in individuals who already previously failed to respond to a second vaccine series.269

If antibody status of exposed individual is unknown, test them for anti-HBs prior to initiation of PEP.269 If exposed individual is found to be a responder (serum anti-HBs ≥10 mIU/mL), PEP is not necessary.269 If exposed individual is found to be a nonresponder (anti-HBs levels <10 mIU/mL) and source is HBsAg-positive, give a dose of HBIG and a booster dose of HepB vaccine.269 If exposed individual is found to be a nonresponder and source is unknown or not available for testing, give a booster dose of HepB vaccine and recheck antibody titer in 1–2 months.269

ACIP and CDC recommend PEP with HepB vaccine for victims of sexual assault (adult, adolescent, child) who are susceptible to HBV.130 281 PEP after a sexual assault is not necessary in those who previously received the complete HepB vaccine series.130 If victim is unvaccinated or incompletely vaccinated and perpetrator is HBsAg-positive, give a dose of HBIG within 14 days of the assault (preferably within 24 hours) and initiate or complete HepB vaccine series.130 281

ACIP and CDC recommend PEP with HepB vaccine for sexual or needle-sharing partners and nonsexual household contacts of individuals with chronic HBV infection.130 281 Because most HBsAg-positive individuals are identified during routine screening (e.g., blood donation, prenatal evaluation) or clinical evaluation and it may be difficult to identify the time of last contact, use of HBIG is not considered necessary for PEP in contacts of such individuals.281 A dose of HBIG may be indicated if the most recent sexual exposure to an HBsAg-positive individual occurred within the last 14 days.130 Consider postvaccination serologic testing in sexual contacts of individuals with chronic HBV infection.281 Although most are expected to respond to vaccination, initiate a second complete HepB vaccine series in nonresponders.281 If there is no response to the second vaccine series, provide counsel about abstinence and use of other methods to protect themselves from HBV via sexual transmission.281

ACIP and CDC recommend that previously unvaccinated sexual partners of individuals with acute HBV infection receive PEP with a dose of HBIG and the initial dose of the HepB vaccine series (within 14 days of the most recent sexual contact).130 281 Completion of the vaccine series confers long-term protection in case the individual with acute HBV infection becomes chronically infected.130 281 Consider prevaccination serologic testing of sexual partners, but only if it does not delay postexposure vaccination beyond 14 days.281

AAP recommends that unvaccinated infants <12 months of age in close contact with a mother or other primary caregiver who has acute HBV infection receive combined passive immunization with HBIG and active immunization with HepB vaccine.105 If the infant previously received a single dose of HepB vaccine, give the second vaccine dose if the interval is appropriate or, if it is too soon to give a vaccine dose, give a dose of HBIG.105 HBIG is not required if, at the time of exposure, the infant has already received ≥2 doses of HepB vaccine.105

Other nonsexual household contacts of individuals with acute HBV infection are not at increased risk for infection unless they have other risk factors or are exposed to the blood of the infected patient (e.g., by sharing a toothbrush or razor).105 130 However, encourage all household contacts of patients with acute HBV infection to receive HepB vaccine.105 130 If the patient with acute HBV infection becomes chronically infected (i.e., remains HBsAg-positive after 6 months), all household contacts should be vaccinated with HepB vaccine.130

CDC recommends that individuals wounded in bombings or other mass casualty settings who are unvaccinated or have an uncertain vaccination history receive postexposure vaccination with HepB vaccine (without HBIG), unless contraindicated.290 HepB vaccine generally is warranted in such individuals if they have wounds (penetrating injuries), nonintact skin, or mucous membranes that may have been exposed to blood or body fluids from other individuals.290 If the vaccine is in short supply, consider that children <17 years of age and health-care personnel are more likely to have previously received the vaccine than other individuals.290 Responders and other personnel in mass casualty settings should be managed using PEP regimens recommended for occupational exposures to HBV.290 (See Table 1.)

PEP not necessary in individuals who previously received primary immunization with HepB vaccine and have serologic evidence of adequate levels of anti-HBs (≥10 mIU/mL).269

PEP not necessary in individuals previously infected with HBV; such individuals are immune to reinfection.269 282

Contraindications

Monovalent HepB Vaccine (HepB; Engerix-B, Recombivax HB)

• Hypersensitivity to any ingredient in the vaccine (including yeast).132 133

• Previous hypersensitivity to any HepB vaccine.133

Fixed-combination Vaccine Containing Hib vaccine and HepB Vaccine (Hib-HepB; Comvax)

• Hypersensitivity to any vaccine component (including yeast).251

Fixed-combination Vaccine Containing DTaP, HepB, and IPV Vaccines (DTaP-Hib-HepB; Pediarix)

• Hypersensitivity to any ingredient in the vaccine (e.g., yeast, neomycin, polymyxin B).104

• Serious allergic reaction (e.g., anaphylaxis) temporally associated with a previous dose of the vaccine or any vaccine component.104

• Encephalopathy (e.g., coma, decreased consciousness, prolonged seizures) within 7 days of a previous dose of vaccine containing pertussis antigens that is not attributed to another identifiable cause.104

• Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.104

Fixed-combination Vaccine Containing HepA Vaccine and HepB Vaccine (HepA-HepB; Twinrix)

• Hypersensitivity to any ingredient in the formulation, including the HepA vaccine component (Havrix), the HepB vaccine component (Engerix-B), yeast, or neomycin.262

• Previous hypersensitivity reaction to Twinrix or monovalent HepA or HepB vaccines.262

Warnings/Precautions

Sensitivity Reactions

Life-threatening hypersensitivity reactions reported rarely.234 235

Anaphylaxis and symptoms of immediate hypersensitivity, including rash, pruritus, urticaria, edema, angioedema, dyspnea, chest discomfort, bronchospasm (including asthma-like symptoms), palpitation, or symptoms consistent with a hypotensive episode, reported within the first few hours after administration of HepB vaccine.132

Take all known precautions to prevent adverse reactions, including a review of the patient’s history with respect to possible hypersensitivity to the vaccine or similar vaccines.104 132 133 262

Epinephrine and other appropriate agents should be readily available in case anaphylaxis or an anaphylactoid reaction occurs.132 133 262 If hypersensitivity reaction occurs, immediately institute appropriate therapy as indicated.133

Do not administer additional vaccine doses to individuals with symptoms of hypersensitivity after a previous dose.132 234

An apparent serum-sickness reaction with delayed onset reported days to weeks after administration of HepB vaccine.132 133

Delayed reaction consists of arthralgia and/or arthritis (usually transient), fever, and dermatologic reactions such as urticaria, erythema multiforme (including Stevens-Johnson syndrome), ecchymoses, and erythema nodosum.132 133

Manufacturing process for HepB vaccine involves baker’s yeast (Saccharomyces cerevisiae).104 132 133 251 262 Final products (monovalent and fixed-combination vaccines) contain ≤5% yeast protein.104 132 133 262

Manufacturers state monovalent and fixed-combination vaccines containing HepB vaccine should not be used in individuals with yeast allergy.132 133 251 262 A theoretical risk of allergic reaction in individuals allergic to yeast exists, but no evidence to date that such reactions have occurred when HepB vaccine used in such individuals.101 119 132 133 213 281

Fixed-combination vaccine containing diphtheria, tetanus, pertussis, HBV, and poliovirus antigens (DTaP-HepB-IPV; Pediarix) contains trace amounts of neomycin sulfate (≤0.05 ng) and polymyxin B (≤0.01 ng).104 Fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) contains trace amounts of neomycin sulfate (≤20 ng).262 Manufacturers state these vaccines contraindicated in individuals hypersensitive to these anti-infectives.104 262

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.105 131 ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh the risks.105 131

Some packaging components (e.g., needle cover, syringe plunger) of the single-dose prefilled syringes of Engerix-B or single-dose prefilled syringes of DTaP-HepB-IPV (Pediarix) contain dry natural latex;104 133 the stopper on the single-dose vial of Engerix-B does not contain latex.133 The stopper on vials of Comvax contains natural rubber latex.251

Some individuals may be hypersensitive to natural latex proteins found in a wide range of medical devices, including such packaging components, and the level of sensitivity may vary depending on the form of natural rubber present;275 276 277 rarely hypersensitivity reactions to natural latex proteins have been fatal.275 276 277

ACIP states that vaccines supplied in vials or syringes containing dry natural rubber or natural rubber latex may be administered to individuals with latex allergies other than anaphylactic allergies (e.g., history of contact allergy to latex gloves), but should not be used in those with a history of severe (anaphylactic) allergy to latex, unless the benefits of vaccination outweigh the risk of a potential allergic reaction.131

General Precautions

Whenever a fixed-combination vaccine is used, consider the adverse effects, precautions, and contraindications related to each antigen.104 251 262

May not protect all vaccine recipients against HBV infection,132 133 especially individuals who have not achieved protective titers of anti-HBs (≥10 mIU/mL measured 1–2 months after completion of HepB vaccine series).132 133

Consider possibility that unrecognized HBV infection may be present in some individuals at the time of vaccination (infection has an incubation period of 6 weeks to 6 months) and that the vaccine may not prevent infection in such individuals.130 132 133 282

Monovalent HepB vaccine (Engerix-B, Recombivax HB) provides protection only against HBV.132 133 Fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) provides protection only against HAV and HBV.262 Monovalent and fixed-combination vaccines containing HepB vaccine generally will also prevent HDV infection by preventing HBV infection since HDV occurs only as a coinfection or superinfection in patients infected with HBV.105 133 These vaccines do not provide protection against other hepatitis viruses (e.g., HCV, HEV).132 133 262

Duration of protection from HBV infection following primary immunization with HepB vaccine and need for additional (booster) doses of the vaccine have not been fully determined.101 120 132 133 213 252 254 278 279 282

Vaccine-induced levels of anti-HBs decline over time,125 213 282 but immunologic memory may persist for at least 10–20 years and may confer protection.105 125 213 252 253 282

Booster doses of vaccine may not be necessary in immunocompetent individuals, even if antibody titers decline after vaccination.253 254 282 Subsequent exposure to HBV results in an anamnestic anti-HBs response that prevents clinically significant HBV infection.213 282

Data are limited regarding the extent and duration of immunologic memory following HBV vaccination in immunocompromised individuals, including HIV-infected individuals, transplant recipients, hemodialysis patients, or those receiving chemotherapy or immunosuppressive therapy.213 252 278 279

Routine booster doses not recommended for immunocompetent children, adolescents, or adults.105 125 282

In hemodialysis patients and other immunocompromised individuals (e.g., HIV-infected individuals, hematopoietic stem-cell transplant recipients, individuals receiving chemotherapy or immunosuppressive therapy), assess anti-HBs levels annually (see Pre- and Postvaccination Serologic Testing under Cautions) to determine need for booster doses; give booster dose when anti-HBs level decreases to <10 mIU/mL.105 213 278 279 281

Recommendations regarding use of HepB vaccine in individuals with altered immunocompetence generally are the same as those for individuals who are not immunocompromised.220

May be used in immunocompromised individuals, including those who are HIV-infected or immunocompromised because of congenital immunodeficiency, leukemia, lymphoma, generalized malignancy, or therapy with alkylating agents, antimetabolites, radiation, or corticosteroids.213 220 278 279 Also may be used in solid organ or hematopoietic stem cell transplant recipients, patients with asplenia, renal failure, diabetes, alcoholism, or alcoholic cirrhosis.213 220 Consider possibility that the immune response to the vaccine may be reduced in these individuals.101 127 128 129 133 212 213 220 278 279

Recommendations regarding use in HIV-infected children, adolescents, or adults are the same as those for individuals who are not HIV-infected.240 278 279 Some HIV-infected individuals may not have a satisfactory response to HepB vaccine, and anti-HBs may persist for shorter periods of time in HIV-infected individuals.101 127 128 129 212 220 278 279 In HIV-infected adults, some experts recommend that HepB vaccine be administered before CD4+ T-cell count decreases to <350/mm3, but vaccination should not be deferred until T-cell count increases to >350/mm3.278 Because HIV-infected individuals (especially children with CD4+ T-cell counts <200/mm3 or adults with CD4+ T-cell counts <350/mm3) may not have an adequate response, postvaccination serologic testing should be performed.220 278 279 (See Pre- and Postvaccination Serologic Testing under Cautions.) Immunogenicity of higher or additional doses of HepB vaccine in HIV-infected individuals not fully evaluated; firm recommendations cannot be made regarding use of such doses in these individuals.101 147 148 153 160 220 278 279

Anti-HBs response generally is lower and persists for shorter periods in hemodialysis patients than in healthy adults.101 132 133 Only 50–86% of hemodialysis patients reportedly develop protective levels of anti-HBs after receiving a 3-dose series consisting of 40-mcg doses of HepB vaccine.132 133 Larger vaccine doses (e.g., 2–4 times the usual adult dose) or an increased number of doses (4 doses) are required to induce protective antibody levels in a large proportion of patients undergoing hemodialysis.101 136 137 138 139 140 141 142 143 144 145 146

Manufacturer of Recombivax HB states use caution and exercise appropriate care in individuals with severely compromised cardiopulmonary status or in others in whom a febrile or systemic reaction could pose a significant risk.132

A decision to administer or delay vaccination in an individual with a current or recent febrile illness depends on the severity of symptoms and etiology of the illness.131 132 133 217

Some manufacturers state the vaccine may be given to individuals with acute infection or febrile illness if withholding the vaccine poses greater risk to the patient.132

ACIP states that minor acute illness, such as mild diarrhea or mild upper respiratory tract infection (with or without fever), generally does not preclude vaccination, but defer vaccination in individuals with moderate or severe acute illness (with or without fever).131 217

Because bleeding may occur following IM administration in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or in those receiving anticoagulant therapy, use caution in such individuals.100 131 132 133 262

ACIP states that vaccines may be given IM to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient’s bleeding risk determines that the preparation can be administered with reasonable safety.100 131 In these cases, use a fine needle (23 gauge) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.100 131 213 If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.100 131 213

Advise individual and/or their family about the risk of hematoma from IM injections.100 131

The manufacturers of Engerix-B and Recombivax HB state the vaccines can be administered sub-Q in individuals at risk of hemorrhage following IM injection (e.g., hemophiliacs).132 133 However, sub-Q administration of HepB vaccines has been associated with reduced antibody response.133 Also consider that an increased incidence of local reactions (e.g., sub-Q nodules) has occurred following sub-Q administration of vaccines containing an aluminum adjuvant.132 133

Exacerbation of multiple sclerosis reported following administration of HepB vaccine or other vaccines; causal relationship not established.133 282

Weigh benefit of HepB vaccine against risk of exacerbation of multiple sclerosis.133

Need for prevaccination serologic testing to determine whether an individual was previously infected with HBV generally based on whether such testing is less costly than unnecessarily vaccinating an individual who is already immune.130 213 281 282

For routine testing, use a single test (anti-hepatitis core antigen; anti-HBc) or a panel of tests (HBsAg and anti-HBs).130 213 281 Anti-HBc identifies individuals with previous HBV infection, including those with chronic HBV infection.130 213 281 Anti-HBc-negative individuals are susceptible and should be vaccinated against HBV.213 281 Anti-HBc-positive individuals should be tested for HBsAg.213 281

Prevaccination testing for serologic markers of HBV infection not usually necessary for groups with low prevalence of HBV serologic markers, including infants, children, or adolescents undergoing routine vaccination or health-care personnel undergoing vaccination during their training years.105 130 233 269 282

Prevaccination serologic testing recommended for all foreign-born individuals (e.g., immigrants, refugees, asylum seekers, internationally adopted children) born in Africa, Asia, the Pacific Islands, or other regions with high HBV endemicity (i.e., prevalence of HBsAg ≥8%).281 282

Prevaccination serologic screening recommended for individuals in risk groups with high rates of HBV infection, including HIV-infected individuals, injection-drug abusers, incarcerated individuals, men who have sex with men, individuals born in countries with intermediate HBV endemicity (i.e., prevalence of HBsAg 2–7%), and household, sexual, and needle-sharing contacts of HBsAg-positive individuals.105 130 213 281 282

Postvaccination serologic testing to confirm HBV immunity not necessary in most individuals because of high rate of immunologic response among children, adolescents, and adults.105 130 282

Postvaccination serologic testing to confirm an anti-HBs response recommended in health-care personnel who have blood or patient contact and are at ongoing risk for percutaneous or mucosal exposure to blood or body fluids (e.g., physicians or physician assistants, nurses or nurse practitioners, dentists or dental hygienists, phlebotomists, emergency medical technicians, first responders, laboratory technologists or technicians, acupuncturists, and students of these professions).105 233 269 281 282 Postvaccination serologic testing also recommended in chronic hemodialysis patients,105 HIV-infected individuals,105 220 278 279 282 other immunocompromised individuals,105 282 individuals with hemophilia,100 and sexual or needle-sharing partners of HBsAg-positive individuals.130 282

All infants born to HBsAg-positive women should undergo serologic testing at 9–18 months of age (usually at the next well-child visit) to document whether the combined regimen of active immunization with HepB vaccine and passive immunization with HBIG prevented perinatal HBV infection.105 213 Do not test before 9 months of age to avoid detecting anti-HBs passively acquired from the HBIG dose administered to neonates at birth and to maximize the likelihood of detecting late HBV infections.105 Serologic testing not necessary in infants born to HBsAg-negative women.105 213

If postvaccination serologic testing is indicated in adults, adolescents, and children (not neonates), including HIV-infected individuals, such testing usually is done 1–2 months after completion of the HepB vaccine series.105 130 219 233 253 255 269 278 279 281

In individuals who received a combined regimen of active immunization with HepB vaccine and passive immunization with HBIG, consider that anti-HBs acquired passively from HBIG may be present in serum for several months and may interfere with postvaccination serologic tests that measure anti-HBs.269

A repeat HepB vaccine series should be given to individuals who have an inadequate response to the initial vaccine series (i.e., anti-HBs <10 mIU/mL).105 213 269 278 279 In HIV-infected adults, some clinicians might delay revaccination until patient has had a sustained increase in CD4+ T-cell count in response to antiretroviral therapy.278 Individuals who do not respond to the second HepB vaccine series (i.e., total of 6 doses) are unlikely to respond to additional vaccine doses.105 213

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.286

Do not administer HepB vaccine that has been mishandled or has not been stored at the recommended temperature.286 (See Storage under Stability.)

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.286 If there are concerns about mishandling, the manufacturer or state or local health departments should be contacted for guidance on whether the vaccine is usable.131 286

Specific Populations

Monovalent HepB (Engerix-B, Recombivax HB): Category C.132 133

HepA-HepB (Twinrix): Category C.262 Pregnancy registry at 888-452-9622.262 Clinicians or vaccinees should report any vaccine exposures that occur during pregnancy.262

Because HepB vaccine is an inactivated vaccine, ACIP states that the theoretical risk to the fetus is expected to be low.213 Pregnancy is not considered a contraindication to HepB vaccine101 105 125 213 280 290 because of the potential risks from exposure to HBV infection in a pregnant woman and the potential for development of chronic infection in the neonate.101 105 125 213 280

Not known whether antigens contained in HepB vaccine are distributed into milk.132 133 Manufacturers recommend caution.132 133 262

Although specific data not available, ACIP, CDC, and AAP state that breast-feeding is not a contraindication to HepB vaccine.105 125 131

Monovalent HepB (Engerix-B, Recombivax HB): Highly immunogenic in infants and children.132 133 In neonates, passively acquired maternal anti-HBs does not appear to interfere with the active immune response to the vaccine.132 133 There is some evidence that the seroconversion rate is lower in low-birthweight infants when the initial dose of HepB vaccine is administered shortly after birth than when it is administered when the infant is older or weighs >2 kg.105 131 221

Recombivax HB Dialysis Formulation: Safety and efficacy in children not established.132

Hib-HepB (Comvax): Safety and efficacy not established in infants <6 weeks of age or in infants or children >15 months of age.251

DTaP-HepB-IPV (Pediarix): Safety and efficacy not established in infants <6 weeks of age or in children ≥7 years of age.104

HepA-HepB (Twinrix): Safety and efficacy not established in children <18 years of age.262

Monovalent HepB (Engerix-B, Recombivax HB): Clinical studies did not include sufficient numbers of individuals ≥65 years of age to determine whether geriatric individuals respond differently than younger adults.132 133 Other reported clinical experience indicates that immunologic response decreases with age.132 133 281 282 No overall differences in safety reported between geriatric individuals and younger adults.132 133

HepA-HepB (Twinrix): Clinical studies did not include sufficient numbers of individuals ≥65 years of age to determine whether geriatric individuals respond differently than younger adults.262

Hib-HepB (Comvax) and DTaP-HepB-IPV (Pediarix): Not indicated for use in adults, including geriatric adults.104 251

Common Adverse Effects

Monovalent HepB (Engerix-B, Recombivax HB): Injection site reactions101 132 133 234 (soreness,115 119 121 126 132 133 pain,117 132 133 234 induration,133 tenderness,132 pruritus,117 132 133 erythema,119 132 133 ecchymosis,132 133 swelling,117 132 133 warmth,132 burning,117 nodule formation),132 fatigue,115 121 126 132 133 weakness,132 headache,115 121 126 132 133 fever (i.e., ≥37.5°C),115 116 119 121 132 133 234 vertigo/dizziness,132 133 malaise.126 132 133

Hib-HepB (Comvax): Injection site reactions (pain/soreness, erythema, swelling/induration), irritability, somnolence, crying, fever.251 Adverse effects reported with Comvax in infants 6 weeks to 15 months of age are similar in type and frequency to those reported in infants who receive monovalent Hib vaccine and monovalent HepB vaccine simultaneously at separate sites.251

DTaP-HepB-IPV (Pediarix): Injection site reactions (pain, erythema, swelling), loss of appetite, drowsiness, fever, fussiness.104 Higher incidence of redness, swelling, and fever reported with Pediarix compared with incidence reported when all the individual components of the vaccine are administered concomitantly at different sites.104

HepA-HepB (Twinrix): Injection site reactions (soreness, erythema, swelling).262 Adverse effects reported with Twinrix in adults are similar to those reported when monovalent HepA vaccine and monovalent HepB vaccine are administered concurrently at different sites.262

Other Vaccines

Although specific studies may not be available evaluating concurrent administration with each antigen, simultaneous administration with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines, during the same health-care visit is not expected to affect immunologic responses or adverse reactions to any of the preparations.105 125 131 133 215 216

Immunization with HepB vaccine can be integrated with immunization against diphtheria, tetanus, pertussis, Hib, hepatitis A, human papillomavirus (HPV), influenza, measles, mumps, rubella, meningococcal disease, pneumococcal disease, poliomyelitis, rotavirus, and varicella.105 125 131 133 215 216 However, unless combination vaccines appropriate for the age and vaccination status of the recipient are used, each parenteral vaccine should be administered using a different syringe and different injection site.105 131

Specific Drugs

Storage

Parenteral

Monovalent HepB (Engerix-B, Recombivax HB): 2–8°C; storage above or below this temperature may reduce potency.132 133 286 Do not freeze; if freezing occurs, discard vaccine.132 133

Hib-HepB (Comvax): 2–8°C.251 Do not freeze.251

DTaP-HepB-IPV (Pediarix): 2–8°C.104 Do not freeze; if freezing occurs, discard vaccine.104

HepA-HepB (Twinrix): 2–8°C.262 Do not freeze;262 if freezing occurs, discard vaccine.262

Engerix-B, Recombivax HB, Comvax, Twinrix, and Pediarix do not contain thimerosal or any other preservatives.132 133 Discard any unused vaccine remaining in single-dose vial after dose is removed.132 133

• Commercially available as monovalent vaccine (Engerix-B, Recombivax HB)132 133 and in several fixed-combination preparations, including a vaccine containing HepB vaccine and Hib vaccine (Hib-HepB; Comvax),251 a vaccine containing both HBV and HAV antigens (HepA-HepB; Twinrix),262 and a vaccine containing antigens for diphtheria, tetanus, pertussis, hepatitis B, and poliovirus (DTaP-HepB-IPV; Pediarix).104

• Engerix-B and Recombivax HB both contain HBsAg prepared using yeast cells (Saccharomyces cerevisiae) and recombinant DNA technology.132 133

• HepB vaccine stimulates active immunity to HBV infection.282 HBsAg in the vaccine promotes production of antibody to HBsAg (anti-HBs); anti-HBs neutralizes HBV so that its infective or pathogenic properties are inhibited.282

• HepB vaccine is highly immunogenic in immunocompetent neonates, children, adolescents, and adults.132 133 282

• Immunologic response decreases with age and anti-HBs titers attained in adults >40 years of age are lower than those attained in younger adults.132 133 281 282 Over 90% of adults <40 years of age develop protective levels of anti-HBs following the recommended 3-dose vaccine series, but only 75% of those ≥60 years of age develop protective levels after the 3-dose series.281

• Immunologic response to HepB vaccine is lower in hemodialysis patients and immunocompromised patients than in immunocompetent individuals.101 133 136 137 138 139 140 141 142 143 144 145 146 281 Larger vaccine doses or an increased number of doses are required to induce protective antibody levels in a large proportion of patients undergoing hemodialysis.101 133 136 137 138 139 140 141 142 143 144 145 146 281

• HBV is a DNA virus.281 282 The major antigenic determinant of the viral surface is HBsAg; the viral core consists of DNA, DNA polymerase, hepatitis B core antigen (HBcAg), and hepatitis B e antigen (HBeAg).281 282

• Presence of HBsAg in serum indicates acute or chronic HBV infection or chronic carrier state.282 HBsAg also may be found in other body fluids and tissues.282 All HBsAg-positive individuals are infectious; those also positive for HBeAg have high HBV titers and are highly infectious.105 213 281 282

• Incubation period from exposure to HBV to onset of symptoms of HBV infection is 6 weeks to 6 months (average: 90–150 days).130 282

• Serologic markers of HBV infection (i.e., HBsAg, HBeAg, anti-HBc, anti-HBe, anti-HBs) are used to define clinical status of those exposed to HBV infection or virus.105 213 281 282 HBsAg appears in serum about 30 days (range 6–60 days) after exposure and indicates ongoing HBV infection.213 281 282 HBsAg persists during acute infection and usually disappears as acute infection resolves; presence of HBsAg in serum for ≥6 months generally indicates chronic infection.105 213 281 282 HBcAg appears in tissues (e.g., liver) and HBeAg appears in serum at about the same time as HBsAg and prior to onset of clinical symptoms.213 281 282 Antibody to hepatitis B core antigen (anti-HBc) appears during acute infection and persists in those with chronic infection.105 213 281 282 HBeAg usually disappears and antibody to hepatitis B e antigen (anti-HBe) becomes detectable in serum.213 282

• Antibody to HBsAg (anti-HBs) develops during convalescence after acute HBV infection (usually within 3–4 months).105 213 281 282 Presence of anti-HBs indicates recovery from and immunity to further HBV infection.105 213 281 282

• Protection against HBV infection is virtually complete in immunocompetent individuals who develop adequate levels of anti-HBs after immunization with HepB vaccine.101 213 281 282 ACIP defines a protective level of anti-HBs as ≥10 mIU/mL measured 1–2 months after completion of the HepB vaccine series.101 213 281