Hepatitis B Immune Globulin (Monograph)

Brand names: HepaGam B, HyperHEP B, Nabi-HB
Drug class: Antitoxins and Immune Globulins
ATC class: J06BB04
VA class: IM100

Medically reviewed by Drugs.com on Sep 23, 2024. Written by ASHP.

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

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^{† [off-label]} 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^{† [off-label]} 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

Drug Interactions

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

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 days^{112 116 132} 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.

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

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