Hepatitis B Immune Globulin

Hepatitis B immune globulin is not a vaccine. Therefore it will not provide long-term protection from hepatitis B. For long-term protection you must receive a hepatitis B vaccine such as Engerix-B, Recombivax HB, or Twinrix.

You should not receive this medication if you are allergic to human globulins, or if you have an immunoglobulin A deficiency. Hepatitis B immune globulin should not be injected into your muscle if you have a bleeding or blood clotting disorder such as hemophilia.

Hepatitis B immune globulin is made from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

To be sure this medication is helping your condition, your blood will need to be tested often. This will help your doctor determine how long to treat you with hepatitis B immune globulin. Your liver function will also need to be tested. Do not miss any scheduled visits to your doctor.

Do not receive a "live" vaccine while you are being treated with hepatitis B immune globulin, and for at least 3 months after your treatment ends. The live vaccine may not work as well during this time, and may not fully protect you from disease.

You should not receive this medication if you are allergic to human globulins, or if you have an immunoglobulin A deficiency. Hepatitis B immune globulin should not be injected into your muscle if you have a bleeding or blood clotting disorder such as hemophilia.

Hepatitis B immune globulin is made from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether hepatitis B immune globulin passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Overall Adverse Reaction Profile

The most common expected adverse drug reactions for intravenous immune globulins like HepaGam B (hepatitis b immune globulin (human)) are chills, fever, headaches, vomiting, allergic reactions, nausea, arthralgia and moderate low back pain.7-8 In a clinical trial in liver transplant patients, 2 adverse drug reactions of tremor and hypotension were reported in 2 of 14 patients who received intravenous infusions of HepaGam B.8 In studies with healthy volunteers, only 1 adverse drug reaction of nausea was reported in the 70 adult subjects who received an intramuscular administration of HepaGam B (hepatitis b immune globulin (human)) .8

Although no anaphylactic reactions have been reported following HepaGam B (hepatitis b immune globulin (human)) administration, anaphylactic reactions have been reported following the administration of other immune globulin products on rare occasions [see WARNINGS AND PRECAUTIONS].

Adverse Reactions in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In an ongoing clinical trial, only 2 adverse drug reactions occurred following the 313 (<1%) HepaGam B (hepatitis b immune globulin (human)) infusions in 14 liver transplant patients. A listing of all adverse events (including those assessed as unrelated to study drug) occurring in >10% of patients are summarized in Table 4 below. These adverse events were reported in an interim analysis from a one-year Phase 3 clinical trial examining HepaGam B (hepatitis b immune globulin (human)) for the prevention of hepatitis B recurrence following liver transplantation. This study utilized the recommended dosing regimen outlined in Table 1 [See DOSAGE AND ADMINISTRATION]. The 2 attributed adverse drug reactions of tremor and hypotension were reported in 2 patients. All reactions were associated with a single HepaGam B (hepatitis b immune globulin (human)) infusion during the first week post-transplant. All reactions resolved on the same day and did not recur with subsequent HepaGam B (hepatitis b immune globulin (human)) infusions.

Table 4 - Adverse Events (AEs) Occurring in >10% of Liver Transplant Patients

Seventy healthy male and female volunteers received a single dose of HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) intramuscularly in clinical trials.8 Seventeen (17) subjects reported 30 adverse events following administration of HepaGam B (hepatitis b immune globulin (human)) . The most frequently reported adverse events included 4 subjects (6%) who experienced headache. 7 subjects (10%) who had cold symptoms or flu and 2 subjects (3%) who experienced lightheadeness/ fainted. The majority of events were reported as mild and were not related to study drug. One adverse event, an episode of nausea, was considered to be drug related. There were no serious adverse events reported. A similar number of subjects in the comparator groups reported adverse events.

Postmarketing Experience

As of April 2007, there have been no postmarketing adverse events reported for HepaGam B (hepatitis b immune globulin (human)) administered i.m.

Read the entire FDA prescribing information for HepaGam B (Hepatitis B Immune Globulin (Human))

Hepatitis B immune globulin is injected into a muscle or into a vein through an infusion pump. A healthcare professional will give you this injection.

For prevention after exposure to contaminated blood: Hepatitis B immune globulin is usually given as soon as possible after exposure to an infected person, preferably within 7 days. A booster medication is then given 24 hours later. Your doctor may also recommend that you receive a hepatitis B vaccine when you start treatment with hepatitis B immune globulin.

For liver transplant: Hepatitis B immune globulin is given as part of the transplant procedure, and then for several weeks or months afterward. The medication is usually given to transplant patients every day for 7 days, then every 2 weeks for the next 11 weeks, followed by monthly injections from then on.

For prevention after sexual contact with an infected person: Hepatitis B immune globulin is given as a single dose within 14 days after the last contact. You should also receive a hepatitis B vaccine if you will continue to have contact with the infected person.

For prevention in people sharing the home of an infected person: This medicine should be given to infants younger than 12 months old, caregivers who may come into contact with the infected person's blood, and people who share razors, toothbrushes, or other personal items with the infected person. Household members may also need to receive hepatitis B vaccine.

For babies born to mothers infected with hepatitis B: This medicine is usually given within 12 hours after birth, or when the baby is medically stable.

In addition to hepatitis B immune globulin, the baby should also receive hepatitis B vaccine, which is given in a series of 3 shots.

• The first hepatitis B vaccine is usually given when the child is 7 days old. The booster shots are then given 1 month and 6 months after the first hepatitis B vaccine.

• If the baby does not receive the first hepatitis B vaccine before the age of 3 months, a second dose of hepatitis B immune globulin must be given.

• Your child's individual booster schedule may be different from these guidelines. Follow your doctor's instructions or the schedule recommended by the health department of the state you live in.

• If the baby does not receive hepatitis B vaccine at all, a second and third dose of hepatitis B immune globulin must be given 3 and 6 months after the first dose. Follow your doctor's instructions.

While using hepatitis B immune globulin, you may need frequent blood tests.

This medication can cause unusual results with certain lab tests for glucose (sugar) in the blood. Tell any doctor who treats you that you are using hepatitis B immune globulin.

Call your doctor for instructions if you miss an appointment for your hepatitis B immune globulin injection.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• fever, mouth sores, red or swollen gums;

• a light-headed feeling, like you might pass out;

• liver problems--upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• symptoms of fluid buildup around your lungs--chest pain, pain when you breathe, rapid heart rate, feeling light-headed or short of breath (especially when lying down); or

• symptoms of a blood clot or stroke--sudden numbness or weakness (especially on one side of the body); chest pain, trouble breathing, rapid heart rate, coughing up blood; or pain, swelling, warmth, or redness in your arms or legs.

Common side effects may include:

• nausea, vomiting, diarrhea, upset stomach;

• back pain, tired feeling;

• tremors, memory problems, agitation, vision problems;

• cold symptoms such as stuffy nose, sneezing, sore throat;

• mild rash; or

• pain, redness, bruising, or tenderness where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Exposure to Hepatitis B Virus:

Prevention of recurrence following liver transplantation:
HBIG 20,000 intl units IV once with the grafting of the transplanted liver (the anhepatic phase)
Week 1 postoperative: 20,000 intl units IV daily from day 1 to 7
Week 2 to 12 postoperative: 20,000 intl units IV every two weeks from day 14
Month 4 onwards: 20,000 intl units IV monthly

If patients fail to reach anti-HBs levels of 500 intl units/L within the first week post-liver transplantation, dosage adjustments may be required.

Dosage regimen should be increased to 10,000 intl units IV every 6 hours until the target anti-HBs are reached in patients who are especially susceptible to extensive loss of circulated anti-HBs, such as those who have surgical bleeding or abdominal fluid drainage (greater than 500 mL) or patients who undergo plasmapheresis.

Percutaneous or permucosal blood exposure:
Source is HBsAg-positive and exposed person has been vaccinated:
If exposed person's anti-HBs level is less than 10 sample ratio units (10 million intl units) by RIA or negative by EIA:
Hepatitis B immune globulin (HBIG) 0.06 mL/kg IM once plus
hepatitis B vaccine booster dose or second dose of hepatitis B immune globulin 1 month later.

Source is HBsAg-positive and exposed person is unvaccinated:
HBIG 0.06 mL/kg IM once plus start hepatitis B vaccine series.

Source is high risk for HBsAg-positive and exposed person has been vaccinated:
Previously vaccinated exposed person:
If vaccine nonresponder and source is HBsAg-positive, give HBIG 0.06 mL/kg IM once plus hepatitis B vaccine booster dose or second dose of hepatitis B immune globulin 1 month later.
If exposed person does not respond to at least 4 doses of vaccine, give 2 doses of HBIG.

Source is high risk for HBsAg-positive and exposed person is unvaccinated:
Start hepatitis B vaccine series within 7 days of exposure
plus HBIG 0.06 mL/kg IM once if source tests positive for HBsAg.

Source unknown or low risk for HBsAg-positive and exposed person is vaccinated:
No treatment required.

Source unknown or low risk for HBsAg-positive and exposed person is unvaccinated:
Start hepatitis B vaccine series within 7 days of exposure.

Sexual exposure to HBsAg-positive source:
HBIG 0.06 mL/kg IM once
plus start hepatitis B vaccine series within 14 days of last contact or if contact will continue.

Usual Pediatric Dose for Exposure to Hepatitis B Virus:

Infants born to HBsAg-positive mothers:
HBIG 0.5 mL IM at birth (preferably within 12 hours) plus start hepatitis B vaccine series.
Test infant for HBsAg and anti-HBs at 12 to 15 months.

Household exposure:
Less than 12 months: HBIG 0.5 mL plus hepatitis B vaccine if the mother or primary caregiver has an acute HBV infection.

Other exposures:
See adult recommendations

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

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

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

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

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

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

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

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

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

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

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

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.)

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

• 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

Applies to hepatitis b immune globulin: solution

Along with its needed effects, hepatitis b immune globulin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking hepatitis b immune globulin:

• Blurred vision
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• sweating
• unusual tiredness or weakness

• Chills
• cough
• difficult or labored breathing
• difficulty with swallowing
• dizziness
• fast heartbeat
• fever
• hives
• itching
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• shortness of breath
• skin rash
• tightness in the chest
• wheezing

Some side effects of hepatitis b immune globulin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Back pain
• general feeling of discomfort
• headache
• muscle aches or pain
• nausea
• pain at the injection site

• Abdominal or stomach cramping
• burning, heat, and redness at the injection site
• diarrhea
• feeling as if you are going to vomit
• joint pain

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• cold sweats
• feeling cold
• flu-like symptoms
• upper abdominal or stomach pain