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Hepatitis B Immune Globulin

Class: Serums
ATC Class: J06BB04
VA Class: IM100
Brands: HepaGam B, HyperHEP B, Nabi-HB

Introduction

Specific immune globulin (hyperimmune globulin).110 Hepatitis B immune globulin (HBIG) contains antibody to hepatitis B surface antigen (anti-HBs) prepared from plasma of donors with high titers of anti-HBs and is used to provide temporary passive immunity to hepatitis B virus (HBV).101 112 116 128 129 132

Uses for Hepatitis B Immune Globulin

Prevention of Perinatal Hepatitis B Virus (HBV) Infection

Prevention of perinatal HBV infection in neonates born to hepatitis B surface antigen-positive (HBsAg-positive) women.101 128 129 132

A combined regimen that includes active immunization with hepatitis B vaccine (HepB vaccine) and passive immunization with hepatitis B immune globulin (HBIG) is 85–95% effective in preventing acute and chronic HBV infection in infants born to women positive for both HBsAg and HBeAg.101 112 128

HBIG has been used alone for prevention of perinatal HBV infection in neonates born to HBsAg-positive women, but use of passive immunization alone is no longer recommended since a regimen that includes both HBIG and HepB vaccine is more effective.112 a

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.101 128 129 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 sexually transmitted diseases (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.101 128

To prevent perinatal HBV infection, ACIP and AAP recommend that all neonates born to HBsAg-positive women receive a dose of HBIG and a dose of HepB vaccine as soon as possible after birth (within 12 hours of birth), regardless of gestational age or birthweight.101 124 126 127 128 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.101 128 127

If maternal HBsAg status is unknown at birth, give infant the first dose of HepB vaccine (within 12 hours of birth).101 124 127 128 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).101 124 127 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.101 127 128

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 or intimate contacts of HBsAg-positive individuals).100 109 112 116 122 128 129 132

Depending on exposure circumstances, PEP regimen may include combined passive immunization with HBIG and active immunization with HepB vaccine to provide both short- and long-term protection.100 109 122 129

Multiple-dose regimen of HBIG alone (e.g., first dose at time of exposure and second dose 1 month later) is about 75% effective in preventing HBV infection following percutaneous exposure.10 22 100 112 122 However, since health-care personnel and others at risk of HBV exposure are candidates for preexposure vaccination with HepB vaccine and since combined passive and active immunization is more effective than HBIG alone following perinatal HBV exposure, combined active and passive immunization is preferred when PEP is indicated following an exposure to HBsAg-positive material.109 112 122 129

HBIG is most effective when administered as soon as possible after exposure (preferably within 24 hours) and may be ineffective if administered >7 days after a percutaneous exposure or >14 days after a sexual exposure.109 122 129

HBIG not indicated for treatment of acute or chronic HBV infection.101

PEP may be indicated in susceptible, unvaccinated health-care personnel following occupational exposure to blood and other body fluids that might contain HBV.122 If an occupational exposure to HBV occurs, review vaccination status and vaccine-response status (if known) of exposed individual and HBsAg status of source.122 (See Table 1.)

If exposed individual was not previously vaccinated against HBV, initiate HepB vaccine series as soon as possible (preferably within 24 hours).122 In addition, if source is found to be HBsAg-positive, give a dose of HBIG as soon as possible (preferably within 24 hours).122

If exposed individual was previously vaccinated against HBV and is a known responder (serum anti-HBs ≥10 mIU/mL), PEP is not necessary.122 If exposed individual was previously vaccinated but is a known nonresponder (serum anti-HBs <10 mIU/mL), PEP is not necessary if source is HBsAg-negative.122 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.122 A 2-dose regimen of HBIG (without HepB vaccine) is preferred in individuals who already previously failed to respond to a second vaccine series.122

If antibody status of exposed individual is unknown, test them for anti-HBs prior to initiation of PEP.122 If exposed individual is found to be a responder (serum anti-HBs ≥10 mIU/mL), PEP is not necessary.122 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.122 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.122

Table 1. Postexposure Prophylaxis of HBV following Occupational (Percutaneous or Mucosal) Exposure to Blood122

 

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 HepB vaccine series (within 24 hours)

Initiate HepB vaccine series

Initiate HepB vaccine series

Previously vaccinated

 

 

 

 Known responder (anti-HBs ≥10 mIU/mL)

No treatment

No treatment

No treatment

 Known nonresponder (anti-HBs <10 mIU/mL)

Single HBIG dose and initiate HepB 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 HepB vaccine

 

1. If inadequate, give a booster dose of HepB 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 with or without HBIG for victims of sexual assault (adult, adolescent, child) who are susceptible to HBV.109 129 PEP after a sexual assault is not necessary in those who previously received the complete HepB vaccine series.109 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.109 129

ACIP and CDC recommend that previously unvaccinated sexual partners of individuals HbsAg-positive individuals 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).109 129 Completion of the vaccine series confers long-term protection in case the individual with acute HBV infection becomes chronically infected.109 129

AAP recommends that unvaccinated infants <12 months of age in close contact with a mother or other primary care-giver who has acute HBV infection receive combined passive immunization with HBIG and active immunization with HepB vaccine.101 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.101 HBIG is not required if, at the time of exposure, the infant has already received ≥2 doses of HepB vaccine.101

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).101 109 However, encourage all household contacts of patients with acute HBV infection to receive HepB vaccine.101 109 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.109

ACIP and CDC recommend PEP with HepB vaccine for sexual or needle-sharing partners and nonsexual household contacts of individuals with chronic HBV infection.109 129 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, HBIG is not considered necessary for PEP in contacts of such individuals.129 A dose of HBIG may be indicated if the most recent sexual exposure to an HBsAg-positive individual occurred within the last 14 days.109

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).144 Responders and other personnel in mass casualty settings should be managed using PEP regimens recommended for occupational exposures to HBV.144 (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).122

PEP not necessary in individuals previously infected with HBV; such individuals are immune to reinfection.122 134

Prevention of Hepatitis B Virus (HBV) Recurrence in Liver Transplant Recipients

Prevention of HBV recurrence in liver transplant recipients who are HBsAg-positive.132 135 136 137 138 139 140 141 142

HBIG has been used alone or in conjunction with an antiviral (e.g., lamivudine, adefovir) to suppress HBV replication and prevent recurrence of HBV infection in patients with chronic HBV infection undergoing liver transplantation.132 135 136 137 138 139 140 141 142 Optimum regimens for such prophylaxis (i.e., dosage, route, and duration of HBIG; specific antiviral for a combined regimen) not established.135 137 138 139 140 141 142

HepaGam B given by IV infusion is labeled by the FDA for prevention of HBV recurrence in liver transplant recipients based on interim results of a clinical study in HBsAg-positive, HBeAg-negative transplant recipients who had only low or undetectable levels of HBV replication at time of transplant.132

Although safety and efficacy not established, other HBIG preparations have been administered IM or IV for prevention of HBV recurrence in liver transplant recipients and have been used alone or in conjunction with an antiviral active against HBV.135 136 137 138 139 140 141 142

Hepatitis B Immune Globulin Dosage and Administration

Administration

IM Administration

HepaGam B, HyperHEP B, and Nabi-HB: Administer by IM injection for prevention of perinatal HBV infection and for postexposure prophylaxis of HBV infection.112 116 128 132 Do not administer IV for this indication.112 116

Inspect visually for particulate matter and discoloration.112 116 132

Administer undiluted.116 132 Do not mix with any other drug or solution.116 132

Depending on patient age, administer IM into the deltoid muscle or anterolateral thigh.110 112 116 128 129 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.110 128 129

For neonates and young children (up to 12 months of age), IM injections should be made into the anterolateral aspect of the thigh.110 128 For children 1–2 years of age, IM injections should preferably be administered into the anterolateral thigh; deltoid muscle is an alternative if muscle mass is adequate.110 128 For children and adolescents 3–18 years of age and adults, deltoid muscle is preferred, although anterolateral thigh is an alternative.110 128 129

Because of the risk of injection-associated injury to the sciatic nerve, use gluteal region only when necessary (e.g., when a large volume or multiple doses are indicated).110 112 116 If use of gluteal area is considered necessary, use only the upper, outer quadrant; avoid central region.112 116

Although some manufacturers recommend that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) should be performed to ensure that a blood vessel has not been entered,112 ACIP and AAP state this procedure is not required because large blood vessels are not present at recommended IM injection sites.101 110

May be given simultaneously with HepB vaccine (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).101 110 112 124 128 129 132

IV Infusion

HepaGam B: Administer by IV infusion for prevention of HBV recurrence in liver transplant recipients.132 Although safety and efficacy not established, other HBIG preparations have been administered by IV infusion for this use.135 136 137 140 141

Do not mix with any other drug or solution.132 Administer using a separate IV line using an IV administration set via infusion pump.132

Do not shake vial; avoid foaming.132

Rate of Administration

HepaGam B: Administer by IV infusion at a rate of 2 mL/minute.132 Decrease to ≤1 mL/minute if patient develops discomfort or infusion-related adverse effects or if there is concern about the rate of infusion.132

Dosage

Pediatric Patients

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.101 124 127 128

Give 0.5 mL of HBIG and a dose of monovalent HepB vaccine within 12 hours of birth (using different syringes and different injection sites).101 112 116 124 127 128 132

If first dose of HepB vaccine is delayed for ≥3 months, manufacturer of HyperHEP B recommends a second 0.5-mL dose of HBIG at 3 months of age.112 If HepB vaccine is contraindicated or not available, this manufacturer recommends second and third 0.5-mL doses of HBIG at 3 and 6 months of age, respectively.112

Neonates Born to Women with Unknown HBsAg Status
IM

Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.100 101 124 127 128

Give a dose of monovalent HepB vaccine within 12 hours of birth.101 124 127 128 Determine HBsAg status of the mother as soon as possible.101 124 127 128

If mother is found to be HBsAg-positive, give neonate 0.5 mL of HBIG as soon as possible (no later than 1 week of age).101 124 127 128

If neonate was preterm and weighed <2 kg at birth, give neonate 0.5 mL of HBIG within 12 hours of birth if mother is found to be HBsAg-positive or if results are not available.101 127 128

Postexposure Prophylaxis of Hepatitis B Virus (HBV) Infection
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.101 112

If mother or other primary care-giver has acute HBV infection, give 0.5 mL of HBIG and initiate or complete primary immunization with HepB vaccine.101 112 HBIG is not necessary if infant already received ≥2 doses of HepB vaccine.101

Unvaccinated or Incompletely Vaccinated Sexual Assault Victims
IM

Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.109 129

If perpetrator is HBsAg-positive, give 0.06 mL/kg of HBIG within 14 days of the assault (preferably within 24 hours).109 129 Initiate or complete primary immunization with HepB vaccine.109 129

Adults

Postexposure Prophylaxis of Hepatitis B Virus (HBV) Infection
Occupational Exposure in Susceptible Health-care Personnel
IM

When source is known to be HBsAg-positive and exposed individual is unvaccinated or a known nonresponder to HepB vaccine (anti-HBs <10 mIU/mL), combined active immunization with HepB vaccine and passive immunization with HBIG is indicated.122 129 (See Table 1 under Uses.)

Give 0.06 mL/kg of HBIG within 24 hours of the exposure and initiate or complete primary immunization with HepB vaccine.122 129

In those who previously failed to respond to a second HepB vaccine series, give 0.06 mL/kg of HBIG within 24 hours of the exposure and 0.06 mL/kg 1 month later.122

Unvaccinated or Incompletely Vaccinated Sexual Assault Victims
IM

Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.109 129

If perpetrator is HBsAg-positive, give 0.06 mL/kg of HBIG within 14 days of the assault (preferably within 24 hours).109 129 Initiate or complete primary immunization with HepB vaccine.109 129

Sexual or Intimate Exposure to Individuals with Acute HBV Infection
IM

Active immunization with HepB vaccine is indicated; passive immunization with HBIG also may be indicated.101 129

Give 0.06 mL/kg of HBIG within 14 days of the last sexual or intimate exposure and initiate or complete primary immunization with HepB vaccine.109 129

Prevention of HBV Recurrence in Liver Transplant Recipients (HepaGam B)
IV

Give initial dose of 20,000 international units concurrently with grafting of transplanted liver (anhepatic phase).132 Give 20,000 international units once daily on postoperative days 1–7, once every 2 weeks during postoperative weeks 2–12, and once monthly beginning at postoperative month 4.132

Track treatment response by monitoring serum HBsAg and anti-HBs antibody levels.132

Dosage is designed to provide serum anti-HBs levels >500 international units/L.132 Adjust dosage if anti-HBs levels do not increase to ≥500 international units/L within the first postoperative week.132 In such cases, increase dosage to 10,000 international units every 6 hours until target anti-HBs level is reached.132 Individuals with surgical bleeding or abdominal fluid drainage (>500 mL) and those undergoing plasmapheresis are particularly susceptible to extensive loss of circulating anti-HBs.132

Cautions for Hepatitis B Immune Globulin

Contraindications

  • HepaGam B: Individuals with history of anaphylactic or severe systemic reactions to parenteral human immune globulin.132

  • HyperHEP B: Manufacturer states no known contraindications.112

  • Nabi-HB: Individuals with history of anaphylactic or severe systemic reactions to human immune globulin.116

Warnings/Precautions

Warnings

Risk of Transmissible Agents in Plasma-derived Preparations

Because HBIG is prepared from pooled human plasma, it is a potential vehicle for transmission of human viruses, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).112 116 117 132

Improved donor screening, viral-inactivation procedures (e.g., solvent/detergent treatment), and/or filtration procedures have reduced, but not completely eliminated, risk of pathogen transmission with plasma-derived preparations.100 104 112 116 132

Solvent/detergent inactivation processes apparently can inactivate lipid-enveloped viruses (e.g., HBV, hepatitis C virus [HCV], HIV type 1 and type 2 [HIV-1 and HIV-2]), but are less effective against viruses that do not have a lipid envelope (e.g., hepatitis A virus [HAV], parvovirus B-19).116 132 Certain filtering procedures are effective in reducing levels of some enveloped and non-enveloped viruses.132

Because no purification method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge which may not be inactivated by the manufacturing process or the chemical (solvent/detergent) treatment procedures currently used, administer HBIG only when a benefit is expected.112 116 132

Any infection believed to have been transmitted by HBIG should be reported to the manufacturer.112 116 132

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.110 112 116 132 Administer IM in these patients only if expected benefits outweigh potential risks.112 116 132

ACIP states that IM injections can be used in individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient’s bleeding risk determines that the injection can be administered with reasonable safety.110 In these cases, use a fine needle (23 gauge) to administer the dose and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.110 If patient is receiving antihemophilia therapy, administer the IM dose shortly after a scheduled dose of such therapy.110

Advise individual and/or their family about the risk of hematoma from IM injections.110

Blood Glucose Testing

HBIG preparations that contain maltose (HepaGam B) may cause falsely elevated results in blood glucose determinations that use glucose dehydrogenase pyrroloquinequinone (GDH-PQQ).132 133 (See Specific Drugs and Laboratory Tests under Interactions.)

Sensitivity Reactions

Hypersensitivity Reactions

Although not reported to date with HBIG, anaphylaxis has been reported rarely following administration of human immune globulins.112 116 132

Use caution in individuals with history of systemic allergic reactions to immune globulins.112

Epinephrine should be readily available in case anaphylaxis occurs.112 132 If hypotension or a hypersensitivity reaction (e.g., anaphylaxis) occurs, immediately discontinue HBIG and institute appropriate therapy as indicated.132

Selective IgA Deficiency

Use caution in individuals with specific IgA deficiency; these individuals may have antibodies to IgA or may develop such antibodies following administration of HBIG preparations containing IgA.116 132 Anaphylaxis could occur.116 132

HepaGam B contains <40 mcg/mL and Nabi-HB contains <100 mcg/mL of IgA.116 132 Weigh potential benefits against potential for hypersensitivity reaction.116 132

General Precautions

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.110 130

Recommendations regarding use in HIV-infected individuals or use in neonates born to HIV-infected women are the same as those for individuals who are not infected with HIV.110 126 127 130

Infusion Reactions

HyperHEP B administered by IV infusion may be associated with certain adverse effects related to the rate of infusion.132 Do not exceed recommended infusion rate (2 mL/minute).132 Monitor closely during and immediately following infusion.132

Serologic Testing

All infants born to HBsAg-positive women should undergo serologic testing at 9–18 months of age (usually at 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.101 128 Do not test before 9 months of age to avoid detecting anti-HBs passively acquired from the HBIG dose administered at birth and to maximize the likelihood of detecting late HBV infections.101 This follow-up serologic testing not necessary in infants born to HBsAg-negative women.101 128

Prior to initiation of HBV postexposure prophylaxis, serologic testing usually is indicated to determine immune status of individuals exposed to HBV or HBsAg-positive materials (e.g., health-care personnel, sexual or intimate contacts of individuals with acute HBV infection).122 In those who have had sexual or intimate exposure to individuals with acute HBV infection, such testing should be done only if it will not delay administration of HBIG beyond 14 days.109

If a combined regimen of HBIG and HepB vaccine is used for postexposure prophylaxis following exposure to HBV or HBsAg-positive materials, postvaccination testing for anti-HBs should not be performed until 3–4 months after the HBIG dose.122 (See Specific Drugs and Laboratory Tests under Interactions.)

Specific Populations

Pregnancy

Category C.112 116 132

Because of potential risks to the neonate from exposure to HBV infection, pregnancy is not considered a contraindication to use of HBIG when indicated.122

ACIP states there are no known risks associated with use of immune globulins for passive immunization in pregnant women.110

Lactation

Not known whether HBIG is distributed into milk; use caution.116 132

Pediatric Use

HepaGam B: Labeled by the FDA for use in neonates and children.132

HyperHEP B and Nabi-HB: Although safety and efficacy not established in infants and children,112 116 safety and efficacy of similar HBIG preparations have been demonstrated in infants and children.116

HBIG is used in conjunction with HepB vaccine for postexposure prophylaxis in neonates born to HBsAg-positive mothers and for postexposure prophylaxis in unvaccinated children <12 months of age whose mother or primary care-giver has acute HBV infection.101 112 132 (See Uses.)

Geriatric Use

Nabi-HB: Clinical studies did not include sufficient numbers of adults ≥65 years of age to determine whether geriatric adults respond differently than younger individuals.116 Other reported clinical experience has not identified differences in responses between geriatric and younger individuals.116

Common Adverse Effects

IM injection: Injection site reactions (pain, tenderness, swelling, erythema),112 116 122 headache,116 132 myalgia,116 malaise,116 GI effects (nausea, vomiting),116 132 flu or cold symptoms,132 lightheadedness/fainting.132

IV infusion: Tremor and hypotension reported with HepaGam B given by IV infusion.132 Chills, fever, headache, vomiting, allergic reactions, nausea, arthralgia, moderate low back pain have been reported with other IV immune globulins.132

Interactions for Hepatitis B Immune Globulin

Inactivated Vaccines and Toxoids

Immune globulins, including HBIG, are not expected to have a clinically important effect on the immune response to inactivated vaccines or toxoids; inactivated vaccines, recombinant vaccines, polysaccharide vaccines, or toxoids may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after HBIG.101 110 Neonates born to HBsAg-positive women who receive combined passive immunization with HBIG and active immunization with HepB vaccine at birth can receive other age-appropriate vaccines according to the usually recommend childhood immunization schedule.110

Live Vaccines

Antibodies present in immune globulins, including HBIG, may interfere with the immune response to certain live virus vaccines (e.g., measles virus vaccine live, mumps virus vaccine live, rotavirus vaccine live oral, rubella virus vaccine live, varicella virus vaccine live); these vaccines should not be administered simultaneously with or for specified intervals before or after HBIG.101 110 128 131 132 (See Specific Drugs and Laboratory Tests under Interactions.) There is no evidence that immune globulin preparations interfere with the immune response to yellow fever virus vaccine live, typhoid vaccine live oral, influenza virus vaccine live intranasal, or poliovirus vaccine live oral (OPV; no longer commercially available in the US).101 110

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Hepatitis B (HepB) vaccine

Passively acquired antibody to hepatitis B surface antigen (anti-HBs), which is present in HBIG, does not appear to interfere with the active immune response to HepB vaccine112

When combined active immunization with HepB vaccine and passive immunization with HBIG is indicated, the first dose of vaccine should be administered simultaneously with HBIG (using different syringes and injection sites)122 128 129 132

HepaGam B: May be given concurrently with (at a different site) or up to 1 month preceding HepB vaccine without impairing the active immune response to the vaccine132

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, radiation)

Recommendations for use of immune globulins in patients receiving immunosuppressive agents are the same as those for patients not receiving such agents130

Influenza vaccine

Intranasal live influenza vaccine: No evidence that immune globulin preparations interfere with the immune response to the vaccine110

Parenteral inactivated influenza vaccine: Interference with the immune response to this inactivated vaccine is not expected110

Intranasal live influenza vaccine or parenteral inactivated influenza vaccine may be given simultaneously with or at any interval before or after HBIG110

Measles, mumps, and rubella vaccine (MMR)

HBIG may interfere with the immune response to measles virus vaccine live and rubella virus vaccine live; the effect of HBIG on the immune response to mumps virus vaccine live is unknown101 110 128 132

MMR (or its individual components) should not be administered simultaneously with or within 3 months before or after HBIG101 110 128 132

If a dose of MMR (or its individual components) is given simultaneously with or within 14 days before or after a dose of HBIG, the MMR dose (or its individual components) should be repeated >3 months after the HBIG dose unless serologic testing is feasible and indicates a response to the vaccine was attained101 110 132

Rotavirus vaccine

Safety and efficacy data not available regarding use of rotavirus vaccine in infants who have received an immune globulin within 42 days131

If possible, defer dose of rotavirus vaccine until 42 days (6 weeks) after the immune globulin; use a shorter interval if the 42-day deferral would result in the first dose of rotavirus vaccine being scheduled at ≥13 weeks of age110

Tests for anti-HBs

Anti-HBs present in serum for 2–6 months following a dose of HBIG and may result in positive tests for anti-HBs that reflect passively-acquired antibody rather than an immune response to HepB vaccine122 128 129

In neonates who receive postexposure prophylaxis with both HBIG and HepB vaccine (i.e., those born to HBsAg-positive mothers), do not perform postvaccination testing for anti-HBs to confirm an immunologic response to the vaccine until ≥9 months of age to avoid detecting passively-acquired antibody from HBIG128

If a combined regimen of HBIG and HepB vaccine is used for postexposure prophylaxis following exposure to HBV or HBsAg-positive materials, do not perform postvaccination testing for anti-HBs until 3–4 months after the HBIG dose122

Tests for glucose

Maltose contained in HepaGam B may interfere with blood glucose monitoring systems based on glucose dehydrogenase pyrroloquinequinone (GDH-PQQ) and cause falsely elevated blood glucose results; this may result in inappropriate insulin administration and life-threatening hypoglycemia or may mask true hypoglycemia132 133

Use only glucose-specific test methods not affected by maltose (e.g., glucose dehydrogenase nicotine adenine dinucleotide [GDH-NAD], glucose oxidase, glucose hexokinase) in patients receiving HepaGam B132 133

Carefully review product information for the blood glucose testing meter and test strips to determine if the testing system is appropriate;132 133 if any uncertainty exists, contact manufacturer of the glucose testing system to determine whether the system will provide accurate blood glucose determinations in patients receiving HepaGam B132 133

Tests, immunohematology

Passively transferred antibodies from HBIG may result in misleading positive serologic tests (e.g., direct antiglobulin [Coombs’] test)132

Typhoid vaccine

Typhoid vaccine live oral (Vivotif): No evidence that immune globulin preparations interfere with the immune response to the vaccine101 110 143

Typhoid Vi polysaccharide vaccine (Typhim Vi): Interference with the immune response to this inactivated vaccine is not expected101 110

Typhoid vaccine live oral (Vivotif): May be given simultaneously with or at any time before or after HBIG101 110 143

Typhoid Vi polysaccharide vaccine (Typhim Vi): May be given simultaneously with HBIG (using different syringes and injection sites) or at any time before or after HBIG101 110

Varicella vaccine

HBIG may interfere with the immune response to varicella virus vaccine live101 110 128

Varicella vaccine should not be administered simultaneously with or within 3 months before or after HBIG101 110 128

If a dose of varicella vaccine is given simultaneously with or within 14 days before or after a dose of HBIG, the vaccine dose should be repeated >3 months after the HBIG dose unless serologic testing is feasible and indicates a response to the vaccine was attained101 110

Yellow fever vaccine

No evidence that immune globulin preparations interfere with the immune response to yellow fever virus vaccine live101 110 143

Yellow fever vaccine may be given simultaneously with HBIG (using different syringes and injection sites) or at any time before or after HBIG101 110 143

Hepatitis B Immune Globulin Pharmacokinetics

Absorption

Bioavailability

Absorbed slowly following IM administration.a

Following an IM dose of HBIG, serum concentrations of anti-HBs usually peak within 3–7 days112 116 132 and persist for about 2–6 months.112 128 129 In a study using HepaGam B, mean peak concentrations occurred 4–5 days after an IM dose of 0.06 mL/kg.132

Distribution

Extent

Although specific information not available, it is likely that HBIG crosses the placenta since other immunoglobulins cross the placenta.a

Information on distribution of HBIG into milk not available;132 HBIG may be distributed into milk since immunoglobulins (e.g., IgA, IgM, IgG) are present in colostrum.a

Elimination

Half-life

HepaGam B: 22–25 days following IM administration.132

HyperHEP B: 17.5–25 days.112

Nabi-HB: 23 days.116

Stability

Storage

Parenteral

Injection, for IM Use

HyperHEP B and Nabi-HB: 2–8°C; do not freeze.112 116 Use single-dose vials within 6 hours after vial has been entered; discard any unused portion.116

HyperHEP B and Nabi-HB do not contain thimerosal or any other preservatives.112 116

Injection, for IV or IM Use

HepaGam B: 2–8°C; do not freeze.132 Use single-dose vial within 6 hours after vial has been entered; discard any unused portion.132

HepaGam B does not contain thimerosal or any other preservatives.132

Actions

  • HBIG is a sterile solution prepared from plasma of healthy individuals with high titers of antibody to hepatitis B surface antigen (anti-HBs) and without serologic evidence of HBsAg.112 116 128 129

  • HepaGam B contains 5% protein,132 HyperHEP B contains 15–18% protein,112 and Nabi-HB contains 4–6% protein.116

  • Anti-HBs present in HBIG combines with HBsAg and neutralizes circulating HBV so that its infective or pathogenic properties are inhibited.112 116 128 129

  • HBIG is used to provide temporary passive immunity to HBV infection in the prophylactic treatment of individuals exposed to HBV or HBsAg-positive materials (e.g., blood, plasma, serum).109 112 116 128 129

  • A single HBIG dose provides passive immunity against HBV for about 3–6 months.109 128 129

  • Once HBV infection becomes clinically apparent and/or serologic testing indicates presence of HBsAg, the virus may not be neutralized by HBIG, although HBIG may modify or ameliorate the infection.a

  • Without HBV prophylaxis administered at birth, about 70–90% of neonates born to women who are HBsAg-positive and HBeAg-positive at the time of delivery become infected with HBV and 85–95% of untreated infected neonates become chronic carriers of HBsAg.134 a

  • HBIG given by IV infusion to HBsAg-positive individuals undergoing liver transplantation may protect the new liver from HBV reinfection.132 Reinfection in such individuals may occur immediately at the time of liver reperfusion because of circulating HBV or may occur at a later time because of HBV retained in extrahepatic sites.132

  • The mechanism by which HBIG protects the transplanted liver against HBV reinfection has not been fully determined.132 HBIG may protect naive hepatocytes against infection by blocking a HBV receptor.132 Alternatively, HBIG may neutralize circulating HBV through immune precipitation and immune complex formation or may trigger an antibody-dependent cell-mediated cytotoxicity response resulting in target cell lysis.132 There is evidence that HBIG binds to hepatocytes and interacts with HBsAg within cells.132

Advice to Patients

  • Advise patient and/or patient’s parent or guardian of the risks and benefits of HBIG.112 116 132

  • Advise patient and/or patient’s parent or guardian that HBIG is prepared from pooled human plasma.112 116 117 132 Although improved donor screening and viral-inactivating and purification procedures used in manufacture of plasma-derived preparations have reduced the risk of pathogen transmission, HBIG is a potential vehicle for transmission of human viruses, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of CJD or vCJD.112 116 117 132 Importance of reporting any infection believed to have been transmitted by HBIG.112 116 132

  • Advise patients with IgA deficiency that HepaGam B and Nabi-HB contain trace amounts of IgA and potentially could result in life-threatening allergic reactions if used in patients who have developed IgA antibodies.116 132

  • Advise patients receiving HepaGam B that this preparation contains maltose and may cause falsely-elevated glucose readings when blood glucose monitoring systems based on GDH-PQQ are used; this could result in inappropriate administration of insulin and life-threatening hypoglycemia or may mask true hypoglycemia.132 133 Importance of using glucose-specific test methods not affected by maltose (e.g., GDH-NAD, glucose oxidase, glucose hexokinase).132 133

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses. 112 116 132

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.112 116 132

  • Importance of informing patients of other important precautionary information.112 116 132 (See Cautions.)

Preparations

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

Hepatitis B Immune Globulin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IM use

HyperHEP B S/D (solvent/detergent treated)

Talecris

Nabi-HB (solvent/detergent treated)

Nabi

Hepatitis B Immune Globulin Intravenous

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV or IM use

HepaGam B (solvent/detergent treated)

Cangene

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

10. Seeff LB, Wright EC, Zimmerman HJ et al. Type B hepatitis after needle-stick exposure: prevention with hepatitis immune globulin. Final report of the Veterans Administration Cooperative Study. Ann Intern Med. 1978; 88:285-93. [PubMed 343678]

22. Grady GF, Lee VA, Prince AM et al. Hepatitis B immune globulin for accidental exposures among medical personnel: final report of a multicenter controlled trial. J Infect Dis. 1978; 138:625-38. [IDIS 118739] [PubMed 361899]

100. Centers for Disease Control Immunization Practices Advisory Committee (ACIP). Protection against viral hepatitis: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1990; 39(RR-2):1-26.

101. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

104. Anon. Safety of therapeutic immune globulin preparations with respect to transmission of human T-lymphotropic virus type III/lymphadenopathy-associated virus infection. MMWR Morb Mortal Wkly Rep. 1986; 35:231-3. [PubMed 3007971]

105. Piszkiewicz D, Mankarious S, Holst S et al. HIV antibodies in commercial immune globulins. Lancet. 1986; 1:1327. [PubMed 2872451]

106. Nelson RP Jr, Ledford DK, DeVoe PW et al. Hepatitis hyperimmune globulin and exposure to human immunodeficiency virus. Ann Intern Med. 1986; 105:465. [PubMed 3461738]

108. Schlech WF, Lee SH, Cook J et al. Passive transfer of HIV antibody by hepatitis B immune globulin. JAMA. 1989; 261:411-3. [IDIS 249427] [PubMed 2909781]

109. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006; 55(RR-11):1-94.

110. Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-15):1-47.

112. Talecris. HyperHEP B S/D (hepatitis B immune globulin [human] solvent/detergent treated) prescribing information. 2007 Jun.

114. Centers for Disease Control and Prevention. Sensitivity of the test for antibody to hepatitis B surface antigen—United States. MMWR Morb Mortal Wkly Rep. 1993; 42:707-10.

115. Committee on Infectious Diseases. Update on timing of hepatitis B vaccination for premature infants and for children with lapsed immunization. Pediatrics. 1994; 94:403-4. [IDIS 335380] [PubMed 8065872]

116. Nabi. Nabi-HB (hepatitis B immune globulin [human] solvent/detergent treated and filtered) prescribing information. Boca Raton, FL; 2003 Jun.

117. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for industry. Revised preventive measures to reduce the possible risk of transmission of Creutzfeldt-Jacob disease (CJD) and variant Creutzfeldt-Jacob disease (vCJD) by blood and blood products. January 2002. From FDA website.

122. Centers for Disease Control and Prevention. Updated US Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2001; 50(RR-11):1-51.

124. Centers for Disease Control and Prevention. Recommended immunization schedules for persons 0 through 18 years–United States, 2009. MMWR Morb Mortal Wkly Rep. 2009; 57:Q1-4.

125. Centers for Disease Control and Prevention. Immunization of health-care workers: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 1997; 46( RR 18):3-5,22-4.

126. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009; 58:1-207; quiz CE1-4.

127. Guidelines for prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children. Recommendations of the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the HIV Medicine Association of the Infectious Diseases Society of America (HIVMA/IDSA). June 20, 2008. From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website.

128. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part I: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005; 54 (RR-16):1-33.

129. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part II: immunization in adults. MMWR Recomm Rep. 2006; 55 (RR-16):1-33.

130. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence. MMWR Recomm Rep. 1993; 42(RR-4):1-18.

131. Merck & Co. RotaTeq (Rotavirus Vaccine, Live, Oral, Pentavalent) prescribing information. Whitehouse Station, NJ; 2008 Jul.

132. Apotex. HepaGam B (hepatitis B immune globulin intravenous [human]) prescribing information. Weston, FL; 2007 Apr.

133. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Important safety information on interference with blood glucose measurement following use of parenteral maltose/parenteral galactose/oral xylose-containing products. From FDA website. Accessed 2008 Feb 18.

134. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 10th ed. Washington DC: Public Health Foundation; 2007.

135. Coffin CS, Terrault NA. Management of hepatitis B in liver transplant recipients. J Viral Hepatitis. 2007; 14(Suppl1):37-44.

136. Yilmaz N, Shiffman ML, Stravitz RT et al. Prophylaxis against recurrence of hepatitis B virus after liver transplantation: a retrospective analysis spanning 20 years. Liver Int. 2008; 28:72-8. [PubMed 17983429]

137. Gish RG, McCashland T. Hepatitis B in liver transplant recipients. Liver Transplant. 2006; 12:S54-64.

138. Anderson RD, Chinnakotla S, Guo L et al. Intramuscular hepatitis B immunoglobulin (HBIG) and nucleosides for prevention of recurrent hepatitis B following liver transplantation: comparison with other HBIG regimens. Clin Transplant. 2007; 21:510-7. [PubMed 17645711]

139. Gane EJ, Angus PW, Strasser S et al. Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation. Gastroenterology. 2007; 132:931-7. [PubMed 17383422]

140. Nath DS, Kalis A, Nelson S et al. Hepatitis B prophylaxis post-liver transplant without maintenance hepatitis B immunoglobulin therapy. Clin Transplant. 2006; 20:206-10. [PubMed 16640528]

141. Eisenbach C, Sauer P, Mehrabi A et al. Prevention of hepatitis B virus recurrence after liver transplantation. Clin Transplant. 2006; 20 (Suppl):111-6. [PubMed 17100710]

142. Zheng S, Chen Y, Liang T et al. Prevention of hepatitis B recurrence after liver transplantation using lamivudine or lamivudine combined with hepatitis B immunoglobulin prophylaxis. Liver Transplant. 2006; 12:253-8.

143. Centers for Disease Control and Prevention. Health information for international travel, 2008. Atlanta, GA: US Department of Health and Human Services; 2008. Updates available from CDC website.

144. Centers for Disease Control and Prevention. Recommendations for postexposure interventions to prevent infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus, and tetanus in persons wounded during bombings and similar mass-casualty events—United States, 2008. MMWR Recomm Rep. 2008 Aug; 57(RR-6):1-28.

145. Centers for Disease Control and Prevention. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008; 57(RR-8):1-20.

a. AHFS Drug Information 2008. McEvoy GK, ed. Hepatitis B immune globulin. Bethesda, MD: American Society of Health-System Pharmacists; 2008:3341-6.

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