Hepatitis B Vaccine Recombinant (Monograph)

Brand names: Engerix-B, Recombivax HB
Drug class: Vaccines
ATC class: J0BB04
VA class: IM100

Hepatitis B Vaccine is also contained as an ingredient in the following combinations:
Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined
Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine
Hepatitis A Inactivated and Hepatitis B (Recombinant) Vaccine

Medically reviewed by Drugs.com on Sep 21, 2023. Written by ASHP.

Introduction

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

Uses for Hepatitis B Vaccine Recombinant

Prevention of Hepatitis B Virus (HBV) Infection

Prevention of HBV infection in neonates, children, adolescents, and adults.

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. Case fatality rate is 0.5–1.5% among those with acute HBV infection; highest fatality rates are in adults >60 years of age. 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. Chronic infection is associated with persistent HBV replication in the liver and may result in liver cirrhosis, liver cancer, liver failure, and death. HBV is transmitted by percutaneous or mucosal exposure to hepatitis B surface antigen-positive (HBsAg-positive) blood, serum, plasma, semen, or saliva and can be transmitted perinatally from mother to infant at birth, usually as the result of blood exposures during labor and delivery.

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. (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. (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. (See Contraindications under Cautions.)

For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity. 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. (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. Regardless of vaccination status, test for HBsAg if individual was born in Asia, Pacific Islands, Africa, or other regions where HBV is highly endemic. 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.

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. (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). (See Postexposure Prophylaxis of Hepatitis B Virus [HBV] Infection under Uses.)

With the exception of hepatitis D virus (HDV) infection, 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). HDV occurs only as a coinfection or superinfection in patients with HBV infection; individuals immune to HBV also should be immune to HDV.

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. 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^{† [off-label]}. Comvax should not be used for the initial (birth) dose of HepB vaccine that is indicated in neonates.

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. 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^{† [off-label]}. Pediarix should not be used for the initial (birth) dose of HepB vaccine that is indicated in neonates. 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.

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.

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).

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. 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).

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. 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. 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.

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. 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). 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. (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. If immunization against HBV was not initiated at birth, initiate HepB vaccine series at the time hemophilia or other congenital bleeding disorders are diagnosed. 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. The National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) recommends postvaccination testing in individuals with hemophilia 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. (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. 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. 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.

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. 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.

Classroom contacts (teachers or classmates) of aggressive, deinstitutionalized developmentally disabled individuals are at high risk of exposure to HBsAg-positive materials. 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. 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. Also consider vaccination of other enrollees in such day-care programs.

Spouses and nonsexual household and sexual contacts of HBsAg carriers are at high risk of exposure to HBsAg-positive materials. 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. 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.

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. 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. 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.

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, female prostitutes ) and individuals seeking evaluation or treatment for STDs should be vaccinated against HBV. 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.

Travelers to areas with levels of endemic HBV that are intermediate (2–7%) or high (≥8%) are at risk of exposure to the disease. ACIP, CDC, and others recommend preexposure vaccination for previously unvaccinated travelers (neonates, infants, adolescents, adults) traveling to such areas. 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).

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

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

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

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.

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

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.

Individuals in casual contact with HBsAg carriers in settings such as schools, offices, and business environments are at minimal risk of HBV exposure. ACIP does not recommend routine use of HepB vaccine in these individuals. At child-care centers (other than those for the developmentally disabled), HBV transmission between children or between children and staff has rarely been documented. 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).

Prevention of Perinatal Hepatitis B Virus (HBV) Infection

Prevention of perinatal HBV infection in neonates born to HBsAg-positive women.

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.

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. 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.

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. 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.

If maternal HBsAg status is unknown at birth, give infant the first dose of HepB vaccine (within 12 hours of birth). 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). 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.

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).

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.

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

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

If exposed individual was previously vaccinated against HBV and is a known responder (serum anti-HBs ≥10 mIU/mL), PEP is not necessary. 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. 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. A 2-dose regimen of HBIG (without HepB vaccine) is preferred in individuals who already previously failed to respond to a second vaccine series.

If antibody status of exposed individual is unknown, test them for anti-HBs prior to initiation of PEP. If exposed individual is found to be a responder (serum anti-HBs ≥10 mIU/mL), PEP is not necessary. 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. 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.

ACIP and CDC recommend PEP with HepB vaccine for victims of sexual assault (adult, adolescent, child) who are susceptible to HBV. PEP after a sexual assault is not necessary in those who previously received the complete HepB vaccine series. 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.

ACIP and CDC recommend PEP with HepB vaccine for sexual or needle-sharing partners and nonsexual household contacts of individuals with chronic HBV infection. 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. A dose of HBIG may be indicated if the most recent sexual exposure to an HBsAg-positive individual occurred within the last 14 days. Consider postvaccination serologic testing in sexual contacts of individuals with chronic HBV infection. Although most are expected to respond to vaccination, initiate a second complete HepB vaccine series in nonresponders. 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.

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). Completion of the vaccine series confers long-term protection in case the individual with acute HBV infection becomes chronically infected. Consider prevaccination serologic testing of sexual partners, but only if it does not delay postexposure vaccination beyond 14 days.

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. 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. HBIG is not required if, at the time of exposure, the infant has already received ≥2 doses of HepB vaccine.

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). However, encourage all household contacts of patients with acute HBV infection to receive HepB vaccine. 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.

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. 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. 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. Responders and other personnel in mass casualty settings should be managed using PEP regimens recommended for occupational exposures to HBV. (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).

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

Related/similar drugs

hepatitis b adult vaccine, Engerix-B, Heplisav-B, Pediarix, Twinrix

Hepatitis B Vaccine Recombinant Dosage and Administration

Administration

IM Injection

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

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

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

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

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

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

Depending on patient age, administer IM into the deltoid muscle or anterolateral thigh. 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.

For neonates and young children (up to 12 months of age), IM injections should be made into the anterolateral thigh. 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. For adults, adolescents, and children ≥3 years of age, the deltoid muscle is preferred, although the anterolateral thigh is an alternative.

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

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.

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

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).

May be given simultaneously with other age-appropriate vaccines during the same health-care visit (using different syringes and different injection sites). (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. Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur. 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.

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. Follow dosage recommendations for the specific preparation used.

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.

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

The complete HepB vaccine series must be administered to ensure optimal protection. 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.

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). If only the third dose is delayed, administer as soon as possible. Infants should receive the final dose at ≥24 weeks of age.

Pediatric Patients

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

Neonates and Infants (Engerix-B)

IM

Primary immunization consists of 3 doses. Use pediatric/adolescent formulation containing 10 mcg/0.5 mL.

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

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. ACIP, AAP, and AAFP recommend that second and third 10-mcg doses be given at 1–2 and 6 months of age, respectively. Give third dose no earlier than 24 weeks of age. (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). ACIP, AAP, and AAFP recommend that second and third 10-mcg doses be given at 1–2 and 6–18 months of age, respectively. If not given before hospital discharge, give initial dose no later than 2 months of age. Give third dose no earlier than 24 weeks of age.

Preterm neonates weighing <2 kg born to HBsAg-positive women or women with unknown HBsAg status: Give a dose of HepB vaccine and a dose of HBIG as soon as possible after birth (within 12 hours of birth). (See Prevention of Perinatal Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Do not count this initial (birth) dose toward completion of the HepB vaccine series; initiate usual 3-dose vaccine series when infant is 1 month of age.

Preterm neonates weighing <2 kg born to HBsAg-negative women: Give initial dose of 10 mcg at 1 month of age. Initial dose may be given at time of hospital discharge (before 1 month of age) if infant is medically stable and showing consistent weight gain. Give second and third 10-mcg doses at 1–2 and 6–18 months, respectively, after initial dose.

Neonates and Infants (Recombivax HB)

IM

Primary immunization consists of 3 doses. Use pediatric/adolescent formulation containing 5 mcg/0.5 mL.

Manufacturer recommends 5-mcg doses at 0, 1, and 6 months.

Full-term neonates born to HBsAg-positive women or women with unknown HBsAg status: Give initial dose of 5 mcg within 12 hours of birth. ACIP, AAP, and AAFP recommend that second and third 5-mcg doses be given at 1–2 and 6 months of age, respectively. Give third dose no earlier than 24 weeks of age. (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 5 mcg at birth (before hospital discharge). ACIP, AAP, and AAFP recommend that second and third 5-mcg doses be given at 1–2 and 6–18 months of age, respectively. If not given before hospital discharge, give initial dose no later than 2 months of age. Give third dose no earlier than 24 weeks of age.

Preterm neonates weighing <2 kg born to HBsAg-positive women or women with unknown HBsAg status: Give a dose of HepB vaccine and a dose of HBIG as soon as possible after birth (within 12 hours of birth). (See Prevention of Perinatal Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Do not count this initial (birth) dose toward completion of the HepB vaccine series; initiate usual 3-dose vaccine series when infant is 1 month of age.

Preterm neonates weighing <2 kg born to HBsAg-negative women: Give initial dose of 5 mcg at 1 month of age. Initial dose may be given at time of hospital discharge (before 1 month of age) if infant is medically stable and showing consistent weight gain. Give second and third 5-mcg doses at 1–2 and 6–18 months, respectively, after initial dose.

Children ≤10 Years of Age (Engerix-B)

IM

Primary immunization (including catch-up vaccination) consists of a series of 3 doses. Use pediatric/adolescent formulation containing 10 mcg/0.5 mL

Give initial dose of 10 mcg on a selected date. Give second and third 10-mcg doses at 1 and 6 months, respectively, after initial dose.

Alternatively, manufacturer states that children ≤10 years of age can receive a 4-dose regimen consisting of 10-mcg doses given on a selected date and at 1, 2, and 12 months after the initial dose, or children 5–10 years of age can receive a 3-dose regimen consisting of 10-mcg doses given on a selected date and at 12 and 24 months after the initial dose.

Children ≤10 Years of Age (Recombivax HB)

IM

Primary immunization (including catch-up vaccination) consists of 3 doses. Use pediatric/adolescent formulation containing 5 mcg/0.5 mL.

Give initial dose of 5 mcg. Give second and third 5-mcg doses at 1 and 6 months, respectively, after initial dose.

Adolescents 11–19 Years of Age (Engerix-B)

IM

Primary immunization (including catch-up vaccination) consists of a series of 3 doses using the pediatric/adolescent formulation or the adult formulation.

If pediatric/adolescent formulation containing 10 mcg/0.5 mL is used, give initial dose of 10 mcg on a selected date. Give second and third 10-mcg doses at 1 and 6 months, respectively, after initial dose. Alternatively, in those 11–16 years of age, manufacturer states that 10-mcg doses can be given on a selected date and at 12 and 24 months after the initial dose.

If adult formulation containing 20 mcg/mL is used, give initial dose of 20 mcg on a selected date. Give second and third 20-mcg doses at 1 and 6 months, respectively, after initial dose. Alternatively, manufacturer states that a 4-dose regimen consisting of 20-mcg doses given on a selected date and at 1, 2, and 12 months after the initial dose can be used.

Adolescents 11–19 Years of Age (Recombivax HB)

IM

Primary immunization (including catch-up vaccination) consists of 3 doses using the pediatric/adolescent formulation. Alternatively, manufacturer states that adolescents 11–15 years of age can receive a 2-dose regimen using the adult formulation.

If pediatric/adolescent formulation containing 5 mcg/0.5 mL is used, give initial dose of 5 mcg. Give second and third 5-mcg doses at 1 and 6 months, respectively, after initial dose.

If adult formulation containing 10 mcg/mL is used, give 10 mcg dose on a selected date and give second 10-mcg dose 4–6 months later.

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

Infants and Children 6 Weeks to 15 Months of Age (Hib-HepB; Comvax)

IM

May be used when primary immunization against Hib and HBV is indicated in infants 6 weeks to 15 months of age born to HBsAg-negative women. ACIP states this 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^{† [off-label]}.

May be used in infants who previously received a dose of monovalent HepB vaccine at or shortly after birth. Manufacturer states that Comvax can be used in children otherwise scheduled to receive concurrent PedvaxHIB and Recombivax HB.

Primary immunization consists of a series of 3 doses (0.5 mL) given ideally at 2, 4, and 12–15 months of age.

Interval between first 2 doses should be at least 6 weeks and interval between second and third dose should be as close as possible to 8–11 months.

Infants and Children 6 Weeks through 6 Years of Age (DTaP-HepB-IPV; Pediarix)

IM

May be used when immunization against diphtheria, tetanus, pertussis, HBV, and poliovirus is indicated in infants and children 6 weeks through 6 years of age born to HBsAg-negative women. ACIP states this 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^{† [off-label]}.

May be used to complete the HepB vaccine series in children <7 years of age who have previously received 1 or 2 doses of monovalent HepB vaccine, Infanrix DTaP vaccine (but not other commercially available DTaP vaccines), and/or monovalent IPV if such children are scheduled to receive the other components of the fixed-combination vaccine.

Primary immunization consists of a series of 3 doses (0.5 mL) given at 6- to 8-week intervals (preferably 8 weeks). Initial dose usually given at 2 months of age, but may be given as early as 6 weeks of age.

To complete the DTaP and IPV primary vaccination series in children who received a 3-dose primary series of Pediarix, administer a dose of Infanrix (DTaP) at 15–18 months of age and a dose of monovalent IPV (IPOL) at 4–6 years of age.

Prevention of Perinatal Hepatitis B Virus (HBV) Infection

Neonates Born to HBsAg-positive Women

IM

Combined passive immunization with HBIG and active immunization with HepB vaccine is indicated.

Give a dose of monovalent HepB vaccine and a dose of HBIG (0.5 mL) within 12 hours of birth (using different syringes and different injection sites).

Complete the 3-dose HepB vaccine series using usually recommended doses and intervals. (See Prevention of Hepatitis B Virus [HBV] Infection (Monovalent Vaccines) or Prevention of Hepatitis B Virus [HBV] Infection (Combination Vaccines) under Dosage and Administration.) Final dose of the vaccine series should be given at ≥24 weeks of age.

For preterm neonates weighing <2 kg at birth, do not count initial (birth) dose of HepB vaccine as part of the 3-dose vaccine series. In addition to the birth dose, give 3 vaccine doses beginning at 1 month of age (total of 4 doses).

At 9–18 months of age after completion of the vaccine series, test infant for anti-HBs and HBsAg. If anti-HBs level is <10 mIU/mL and HBsAg is negative, repeat the vaccine series by giving 3 additional doses of HepB vaccine (initial dose on a selected date and second and third dose at 1–2 and 6 months, respectively, after initial dose) and retest for anti-HBs 1–2 months after the third dose. Alternatively, test for anti-HBs 1 month after each dose to determine whether subsequent doses are needed. HBsAg-negative infants with anti-HBs levels ≥10 mIU/mL are protected from HBV and do not need additional doses of HepB vaccine.

Neonates Born to Women with Unknown HBsAg Status

IM

Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.

Give a dose of monovalent HepB vaccine within 12 hours of birth. Determine HBsAg status of the mother as soon as possible.

If mother is found to be HBsAg-positive, give neonate a dose of HBIG (0.5 mL) as soon as possible (no later than 1 week of age).

If neonate was preterm and weighed <2 kg at birth, give neonate a dose of HBIG (0.5 mL) within 12 hours of birth if mother is found to be HBsAg-positive or if results are not available.

Complete the 3-dose HepB vaccine series using usually recommended doses and intervals. (See Prevention of Hepatitis B Virus [HBV] Infection (Monovalent Vaccines) or Prevention of Hepatitis B Virus [HBV] Infection (Combination Vaccines) under Dosage and Administration.)

If neonate was preterm and weighed <2 kg at birth, do not count initial (birth) dose of HepB vaccine as part of the 3-dose vaccine series. In addition to the birth dose, give 3 vaccines doses beginning at 1 month of age (total of 4 doses).

Postexposure Prophylaxis of Hepatitis B Virus (HBV)

Unvaccinated or Incompletely Vaccinated Infants <12 Months of Age Exposed to Acute HBV Infection

IM

Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.

If mother or other primary caregiver has acute HBV infection, give a dose of HBIG and initiate or complete primary immunization with HepB vaccine. HBIG is not necessary if infant already received ≥2 doses of HepB vaccine.

Unvaccinated or Incompletely Vaccinated Sexual Assault Victims

IM

Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.

Initiate or complete HepB vaccine series. (See Prevention of Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Give initial dose within 14 days of the assault (preferably within 24 hours). Give second and third doses at 1–2 and 4–6 months, respectively, after initial dose.

If perpetrator is HBsAg-positive, also give victim a dose of HBIG (0.06 mL/kg) within 14 days of the assault (preferably within 24 hours).

Adults

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

Adults ≥20 Years of Age (Engerix-B)

IM

Primary immunization consists of 3 doses. Use adult formulation containing 20 mcg/mL.

Give initial dose of 20 mcg. Give second and third 20-mcg doses at 1–2 and 4–6 months, respectively, after initial dose.

Alternatively, a 4-dose regimen can be used. Give initial 20-mcg dose and give additional 20-mcg doses at 1, 2, and 12 months after initial dose.

Adults ≥20 Years of Age (Recombivax HB)

IM

Primary immunization consists of 3 doses. Use adult formulation containing 10 mcg/mL.

Give initial dose of 10 mcg. Give second and third 10-mcg doses at 1–2 and 4–6 months, respectively, after initial dose.

Adults Undergoing Hemodialysis (Engerix-B)

IM

Primary immunization consists of 4 doses. Use adult formulation containing 20 mcg/mL. Each dose consists of 40 mcg and may be given using 1 or 2 injections.

Give initial dose of 40 mcg. Give additional 40-mcg doses at 1, 2, and 6 months after initial dose.

Adults Undergoing Hemodialysis (Recombivax HB)

IM

Primary immunization in predialysis and dialysis patients consists of 3 doses. Use dialysis formulation containing 40 mcg/mL.

Give initial dose of 40 mcg. Give second and third 40-mcg doses at 1 and 6 months, respectively, after initial dose.

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

Adults ≥18 Years of Age (HepA-HepB; Twinrix)

IM

Primary immunization consists of a series of 3 doses. Each 1-mL dose contains at least 720 units of HAV antigen and 20 mcg of hepatitis B surface antigen (HBsAg).

For primary immunization, give initial dose on a selected date and give second and third doses at 1 and 6 months, respectively, after initial dose.

Alternatively, if an accelerated dosing schedule is needed, give initial dose on a selected date and give second and third doses at 7 and 21–30 days, respectively, after initial dose; also give a booster dose at 12 months after initial dose.

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

Primary immunization with the usually recommended HepB vaccine series before an expected exposure to HBV or HBsAg-positive materials (e.g., blood, plasma, serum) ensures the highest level of protection. (See Prevention of Hepatitis B Virus [HBV] Infection (Monovalent Vaccines) or Prevention of Hepatitis B Virus [HBV] Infection (Combination Vaccines) under Dosage and Administration.)

Travelers

IM

Individuals traveling to areas with intermediate or high levels of endemic HBV (see Preexposure Vaccination Against Hepatitis B Virus [HBV] Infection in High-risk Groups under Uses): Give initial dose on a selected date and give second and third doses 1 and 6 months, respectively, after initial dose. To ensure completion of the 3-dose series and optimal protection against HBV, begin HepB vaccine series 6 months prior to travel. Because a partial series offers some protection, initiate the series even if it cannot be completed before travel.

Alternatively, for travelers who will depart before the usual 3-dose series can be completed, CDC suggests an optional accelerated schedule^{† [off-label]} (initial dose given on a selected date and second and third doses given 7 and 21 days, respectively, after initial dose). If the accelerated schedule is used, give a booster dose 1 year after start of the series to promote long-term immunity.

Alternatively, a 4-dose regimen can be used. Give initial dose on a selected date and give other 3 doses at 1, 2, and 12 months after initial dose. This regimen induces immunity more rapidly than the usual 3-dose regimen and may be useful when there are time constraints; first 3 doses should be administered before travel (i.e., at 0, 1, and 2 months).

Postexposure Prophylaxis of Hepatitis B Virus (HBV)

Occupational Exposure in Susceptible Health-care Personnel

IM

Depending on exposure circumstances, combined active immunization with HepB vaccine and passive immunization with HBIG may be indicated. (See Table 1 under Uses.)

Initiate HepB vaccine series in unvaccinated individuals. (See Prevention of Hepatitis B Virus [HBV] Infection under Dosage and Administration.) If vaccine series was initiated prior to exposure, give remaining doses as originally scheduled.

Give initial dose as soon as possible following exposure (preferably within 24 hours). Give second and third doses at 1 and 6 months, respectively, after initial dose.

Unvaccinated or Incompletely Vaccinated Sexual Assault Victims

IM

Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.

Initiate or complete HepB vaccine series. (See Prevention of Hepatitis B Virus [HBV] Infection under Dosage and Administration.) Give initial dose at time of initial medical examination within 14 days of the assault (preferably within 24 hours). Give second and third doses at 1–2 and 4–6 months, respectively, after initial dose.

If perpetrator is HBsAg-positive, also give victim a dose of HBIG (0.06 mL/kg) within 14 days of the assault (preferably within 24 hours).

Unvaccinated or Incompletely Vaccinated Contacts of Individuals with Acute HBV Infection

IM

Initiate HepB vaccine series in unvaccinated individuals. (See Prevention of Hepatitis B Virus [HBV] Infection under Dosage and Administration.) If vaccine series was initiated prior to exposure, give remaining doses as originally scheduled.

Unvaccinated or Incompletely Vaccinated Individuals Wounded in Mass Casualty Settings

IM

Give a dose of HepB vaccine as soon as possible (preferably within 24 hours) and not later than 7 days after the event. Complete primary vaccine series at the time of discharge or during follow-up health-care visits.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

For dosage recommendations for patients undergoing hemodialysis, see Adults Undergoing Hemodialysis under Dosage and Administration.

Geriatric Patients

No specific dosage recommendations. HepB vaccine may be less immunogenic in geriatric individuals than in younger adults.

Cautions for Hepatitis B Vaccine Recombinant

Contraindications

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

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

• Previous hypersensitivity to any HepB vaccine.

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

• Hypersensitivity to any vaccine component (including yeast).

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).

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

• 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.

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

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.

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

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Life-threatening hypersensitivity reactions reported rarely.

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.

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.

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

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

Serum-sickness Reactions

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

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.

Yeast Allergy

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

Manufacturers state monovalent and fixed-combination vaccines containing HepB vaccine should not be used in individuals with yeast allergy. 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.

Allergy to Neomycin or Other Anti-infectives

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). Fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) contains trace amounts of neomycin sulfate (≤20 ng). Manufacturers state these vaccines contraindicated in individuals hypersensitive to these anti-infectives.

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis. 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.

Latex Sensitivity

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; the stopper on the single-dose vial of Engerix-B does not contain latex. The stopper on vials of Comvax contains natural rubber latex.

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; rarely hypersensitivity reactions to natural latex proteins have been fatal.

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.

General Precautions

Use of Combination Vaccines

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

Limitations of Vaccine Effectiveness

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

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.

Monovalent HepB vaccine (Engerix-B, Recombivax HB) provides protection only against HBV. Fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) provides protection only against HAV and HBV. 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. These vaccines do not provide protection against other hepatitis viruses (e.g., HCV, HEV).

Duration of Immunity

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.

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

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

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.

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

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.

Individuals with Altered Immunocompetence

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

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. Also may be used in solid organ or hematopoietic stem cell transplant recipients, patients with asplenia, renal failure, diabetes, alcoholism, or alcoholic cirrhosis. Consider possibility that the immune response to the vaccine may be reduced in these individuals.

Recommendations regarding use in HIV-infected children, adolescents, or adults are the same as those for individuals who are not HIV-infected. 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. 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. 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. (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.

Anti-HBs response generally is lower and persists for shorter periods in hemodialysis patients than in healthy adults. 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. 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.

Concomitant Illness

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.

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.

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.

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).

Individuals with Bleeding Disorders

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.

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. 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. If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.

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

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). However, sub-Q administration of HepB vaccines has been associated with reduced antibody response. 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.

Exacerbation of Multiple Sclerosis

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

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

Pre- and Postvaccination Serologic Testing

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.

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

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.

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%).

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.

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

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). Postvaccination serologic testing also recommended in chronic hemodialysis patients, HIV-infected individuals, other immunocompromised individuals, individuals with hemophilia, and sexual or needle-sharing partners of HBsAg-positive individuals.

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. 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. Serologic testing not necessary in infants born to HBsAg-negative women.

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.

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.

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). 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. 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.

Improper Storage and Handling

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

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

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained. 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.

Specific Populations

Pregnancy

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

HepA-HepB (Twinrix): Category C. Pregnancy registry at 888-452-9622. Clinicians or vaccinees should report any vaccine exposures that occur during pregnancy.

Because HepB vaccine is an inactivated vaccine, ACIP states that the theoretical risk to the fetus is expected to be low. Pregnancy is not considered a contraindication to HepB vaccine 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.

Lactation

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

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

Pediatric Use

Monovalent HepB (Engerix-B, Recombivax HB): Highly immunogenic in infants and children. In neonates, passively acquired maternal anti-HBs does not appear to interfere with the active immune response to the vaccine. 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.

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

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

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

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

Geriatric Use

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. Other reported clinical experience indicates that immunologic response decreases with age. No overall differences in safety reported between geriatric individuals and younger adults.

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.

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

Common Adverse Effects

Monovalent HepB (Engerix-B, Recombivax HB): Injection site reactions (soreness, pain, induration, tenderness, pruritus, erythema, ecchymosis, swelling, warmth, burning, nodule formation), fatigue, weakness, headache, fever (i.e., ≥37.5°C), vertigo/dizziness, malaise.

Hib-HepB (Comvax): Injection site reactions (pain/soreness, erythema, swelling/induration), irritability, somnolence, crying, fever. 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.

DTaP-HepB-IPV (Pediarix): Injection site reactions (pain, erythema, swelling), loss of appetite, drowsiness, fever, fussiness. 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.

HepA-HepB (Twinrix): Injection site reactions (soreness, erythema, swelling). 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.

Drug Interactions

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.

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. 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.

Specific Drugs

Stability

Storage

Parenteral

Injectable Suspension for IM Use

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

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

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

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

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

Actions

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

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

• HepB vaccine stimulates active immunity to HBV infection. 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.

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

• Immunologic response decreases with age and anti-HBs titers attained in adults >40 years of age are lower than those attained in younger adults. 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.

• Immunologic response to HepB vaccine is lower in hemodialysis patients and immunocompromised patients than in immunocompetent individuals. Larger vaccine doses or an increased number of doses are required to induce protective antibody levels in a large proportion of patients undergoing hemodialysis.

• HBV is a DNA virus. 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).

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

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

• 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. HBsAg appears in serum about 30 days (range 6–60 days) after exposure and indicates ongoing HBV infection. HBsAg persists during acute infection and usually disappears as acute infection resolves; presence of HBsAg in serum for ≥6 months generally indicates chronic infection. 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. Antibody to hepatitis B core antigen (anti-HBc) appears during acute infection and persists in those with chronic infection. HBeAg usually disappears and antibody to hepatitis B e antigen (anti-HBe) becomes detectable in serum.

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

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

Advice to Patients

• Prior to administration of each vaccine dose, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative as required by the National Childhood Vaccine Injury Act (VISs are available at [Web]).

• Advise patient and/or patient’s parent or guardian of the risks and benefits of vaccination with HepB vaccine.

• Importance of receiving the complete primary immunization series to ensure the highest level of protection against HBV.

• Importance of informing clinicians if any severe or unusual adverse reactions occur. Clinicians or individuals can report any adverse reactions that occur following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or [Web].

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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