Hepatitis B Vaccine

Class: Vaccines
ATC Class: J0BB04
VA Class: IM100
Brands: Comvax, Engerix-B, Pediarix, Recombivax HB, Twinrix

Introduction

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

Uses for Hepatitis B Vaccine

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 saliva^{105 130 213 269 281 282} 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 hemophilia^{100 288} 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 prostitutes^{132 133} ) 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

Table 1. Postexposure Prophylaxis of HBV following Occupational (Percutaneous or Mucosal) Exposure to Blood269

	Treatment when Source Is:
Vaccination and Antibody Status of Exposed Individual	HBsAg-positive	HBsAg-negative	Source Unknown or Not Available for Testing
Unvaccinated	Single HBIG dose (within 24 hours) and initiate hepatitis B vaccine series (within 24 hours)	Initiate hepatitis B vaccine series	Initiate hepatitis B vaccine series
Previously vaccinated
Known responder (anti-HBs 10 mIU/mL or greater)	No treatment	No treatment	No treatment
Known nonresponder (anti-HBs less than 10 mIU/mL)	Single HBIG dose and initiate hepatitis B revaccination series or 2 HBIG doses (first dose as soon as possible; second dose 1 month later)	No treatment	If known high-risk source, treat as if source were HBsAg-positive
Antibody response unknown	Test exposed individual for anti-HBs	No treatment	Test exposed individual for anti-HBs
	1. If inadequate, single dose of HBIG and a booster dose of hepatitis B vaccine		1. If inadequate, give a booster dose of hepatitis B vaccine and recheck titer in 1–2 months
	2. If adequate, no treatment		2. If adequate, no treatment

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}

Hepatitis B Vaccine Dosage and Administration

Administration

IM Injection

Administer monovalent HepB vaccine (Engerix-B, Recombivax HB) by IM injection.^{132 133} May be administered by sub-Q injection when necessary in individuals at risk of hemorrhage following IM injection.^{132 133} (See Individuals with Bleeding Disorders under Cautions.) Do not administer IV or intradermally;^{101 132 133 251 262} there is evidence that intradermal administration may be associated with reduced immunogenicity.^{101 207 209}

Administer fixed-combination vaccine containing Hib vaccine and HepB vaccine (Hib-HepB; Comvax) by IM injection.²⁵¹ Do not administer sub-Q or IV.²⁵¹

Administer fixed-combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HepB-IPV; Pediarix) by IM injection.¹⁰⁴ Do not administer sub-Q or IV.¹⁰⁴

Administer fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) by IM injection.²⁶² Do not administer sub-Q or IV.²⁶²

Shake vaccine well immediately prior to administration to provide a uniform, turbid, white suspension.^{104 133} Discard vaccine if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.^{104 133}

Do not dilute.¹³³ Do not mix with any other vaccine or solution.¹⁰⁴

Depending on patient age, administer IM into the deltoid muscle or anterolateral thigh.^{101 104 105 131 132 133 213} To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass, the thickness of adipose tissue and muscle at the injection site, and the injection technique.¹³¹

For neonates and young children (up to 12 months of age), IM injections should be made into the anterolateral thigh.^{101 104 105 132 133 213 282} For children 1–2 years of age, IM injections should preferably be administered into the anterolateral thigh; the deltoid muscle is an alternative if muscle mass is adequate.¹³¹ For adults, adolescents, and children ≥3 years of age, the deltoid muscle is preferred, although the anterolateral thigh is an alternative.^{101 104 105 131 132 133 282}

Generally do not administer vaccines into buttock muscle in children because of potential for injection-associated injury to sciatic nerve.¹³¹

Although some experts state that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) can be performed to ensure that a blood vessel has not been entered, ACIP and AAP state this procedure is not required because large blood vessels are not present at recommended IM injection sites.^{105 131}

Since syncope may occur following vaccination, observe vaccinee for approximately 15 minutes after the vaccine dose is administered.¹³¹ If syncope occurs, observe the patient until symptoms resolve.¹³¹ Syncope after vaccination occurs most frequently in adolescents and young adults.¹³¹

Monovalent HepB may be given simultaneously with HBIG (using different syringes and different injection sites) when passive immunization is considered necessary in addition to active immunization with the vaccine (e.g., in neonates born to HBsAg-positive women, PEP regimen in certain individuals exposed to HBV or HBsAg-positive materials).^{105 112 131 213 281}

May be given simultaneously with other age-appropriate vaccines during the same health-care visit (using different syringes and different injection sites).^{131 133 213} (See Interactions.)

When multiple vaccines are administered during a single health-care visit, each vaccine should be given with a different syringe and at different injection sites.^{131 213} Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.^{131 213} If multiple vaccines must be given into a single limb, the deltoid may be used in older children and adults, but the anterolateral thigh is preferred in infants and younger children.^{131 213}

Dosage

Dose and dosing schedule vary depending on the individual's age and specific vaccine administered, HBsAg status of the mother (for neonates), and presence of underlying disease.^{104 105 125 132 133 213 217} Follow dosage recommendations for the specific preparation used.^{101 105}

Currently available monovalent HepB vaccines (Engerix-B, Recombivax HB) generally are considered interchangeable; HepB vaccine series started with one monovalent vaccine may be completed using a different vaccine given in dosage recommended for the specific formulation.^{105 213}

Use only monovalent HepB vaccine (Engerix-B, Recombivax HB) for the initial (birth) dose in neonates or infants <6 weeks of age.^{105 112} Complete the vaccine series using monovalent or age-appropriate fixed-combination vaccines.^{105 112}

The complete HepB vaccine series must be administered to ensure optimal protection.^{105 213} Interruptions resulting in an interval between doses longer than recommended should not interfere with the final immunity achieved; it is not necessary to give additional doses or start the vaccine series over.^{104 105 213}

If the vaccine series is interrupted after the initial dose, give second dose as soon as possible (minimum interval between first and second dose is 4 weeks) and give third dose at least 8 weeks after the second dose (minimum interval between first and third dose is 16 weeks).^{112 213 269 281 282} If only the third dose is delayed, administer as soon as possible.^{213 269} Infants should receive the final dose at ≥24 weeks of age.^{112 213 282}

Pediatric Patients

Prevention of Hepatitis B Virus (HBV) Infection (Monovalent Vaccines)

Neonates and Infants (Engerix-B)

IM

Primary immunization consists of 3 doses.^{112 133 213} Use pediatric/adolescent formulation containing 10 mcg/0.5 mL.¹³³

Manufacturer recommends 10-mcg doses at 0, 1, and 6 months.¹³³ Alternatively, manufacturer recommends a 4-dose regimen consisting of 10-mcg doses at 0, 1, 2, and 12 months.¹³³

Full-term neonates born to HBsAg-positive women or women with unknown HBsAg status: Give initial dose of 10 mcg within 12 hours of birth.^{105 112 213} ACIP, AAP, and AAFP recommend that second and third 10-mcg doses be given at 1–2 and 6 months of age, respectively.^{105 112 213} Give third dose no earlier than 24 weeks of age.^{112 213} (See Prevention of Perinatal Hepatitis B Virus [HBV] Infection under Dosage and Administration.)

Full-term neonates born to HBsAg-negative women: Give initial dose of 10 mcg at birth (before hospital discharge).^{105 112 213} ACIP, AAP, and AAFP recommend that second and third 10-mcg doses be given at 1–2 and 6–18 months of age, respectively.^{112 213} If not given before hospital discharge, give initial d