Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection [preservative free]:
HepaGam B: (1 mL, 5 mL) [contains polysorbate 80]
Solution, Intramuscular:
HyperHEP B S/D: (0.5 mL, 1 mL, 5 mL)
Nabi-HB: (1 mL, 5 mL) [thimerosal free; contains polysorbate 80]
Pharmacology
Mechanism of Action
Hepatitis B immune globulin (HBIG) is a nonpyrogenic sterile solution containing immunoglobulin G (IgG) specific to hepatitis B surface antigen (HBsAg). HBIG differs from immune globulin in the amount of anti-HBs. Immune globulin is prepared from plasma that is not preselected for anti-HBs content. HBIG is prepared from plasma preselected for high titer anti-HBs. In the US, HBIG has an anti-HBs high titer >1:100,000 by IRA.
Pharmacokinetics/Pharmacodynamics
Absorption
IM: Slow
Distribution
Vd: 7 to 15 L
Time to Peak
Serum: IM: 2 to 10 days
Duration of Action
Postexposure prophylaxis: 3 to 6 months
Half-Life Elimination
17 to 25 days
Use: Labeled Indications
Postexposure prophylaxis following acute exposure to hepatitis B surface antigen (HBsAg) blood, plasma, or serum (eg, parenteral exposure, direct mucus membrane contact, oral ingestion); perinatal exposure of infants born to HBsAg-positive mothers; sexual exposure to HBsAg-positive persons; and household exposure to persons with acute HBV infection
In addition, the Advisory Committee on Immunization Practices (ACIP) also recommends administration to neonates born to mothers in which HBsAg test results are not available and other evidence suggests possible maternal HBV infection; postexposure prophylaxis to a health care provider (HCP) in which the source has an unknown HBsAg status; in a nonoccupational setting, postexposure prophylaxis to a person who has not been completely vaccinated (CDC/ACIP [Schillie 2018]).
Prevention of hepatitis B virus recurrence after liver transplantation in HBsAg-positive transplant patients (HepaGam B only)
Note: Hepatitis B immune globulin is not indicated for treatment of active hepatitis B infection and is ineffective in the treatment of chronic active hepatitis B infection.
Contraindications
HepaGam B: Anaphylactic or severe systemic reaction to human globulin preparations; IgA deficiency; postexposure prophylaxis in patients with severe thrombocytopenia or other coagulation disorders which would contraindicate IM injections (administer only if benefit outweighs the risk)
HyperHEP B S/D: No contraindications listed in manufacturer's labeling
Nabi-HB: Anaphylactic or severe systemic reaction to human globulin preparations
Dosage and Administration
Dosing: Adult
Postexposure prophylaxis: IM: 0.06 mL/kg as soon as possible after exposure (ie, within 24 hours of needlestick, ocular, or mucosal exposure or within 14 days of sexual exposure); repeat at 28 to 30 days after exposure in non-responders to hepatitis B vaccine or in patients who refuse vaccination
Postexposure management of health care personnel (HCP) (CDC/ACIP [Schillie 2018]):
If the HCP has prior documentation of ≥3 doses of a hepatitis B vaccine and a post-vaccination anti-HBs ≥10 milliunits/mL, then HBIG is not needed, regardless of the patients HBsAg status.
If the HCP is unvaccinated or incompletely vaccinated, and if the source patient is HBsAg positive or their status is unknown, one dose HBIG should be administered. If the source patient is HBsAg negative, then HBIG is not needed.
If the HCP is vaccinated with 3 doses of hepatitis B vaccine but post-vaccination anti-HBs status is unknown, test HCP for anti-HBs. If anti-HBs ≥10 milliunits/mL then HBIG is not needed. If anti-HBs <10 milliunits/mL, and if the source patient is HBsAg positive or their status is unknown, 1 dose of HBIG should be administered. If anti-HBs <10 milliunits/mL, and if the source patient is HBsAg negative, then HBIG is not needed.
If the HCP is vaccinated with 6 doses of hepatitis B vaccine but documented as a non-responder to the vaccine, and if the source patient is HBsAg negative, then HBIG is not needed. If the source patient is HBsAg positive or unknown, administer 2 doses of HBIG separated by 1 month.
Postexposure management in nonoccupational settings (CDC [Schillie 2018]): IM:
If the exposed person is in the process of completing the hepatitis B vaccination series and the exposure was to an HBsAg-positive source, administer one dose of HBIG and complete the vaccination series. If exposure was to an HBsAg-unknown source, HBIG treatment is not required but the hepatitis B vaccine series should be completed.
If the exposed person is unvaccinated and the exposure was to an HBsAg-positive source, administer one dose of HBIG and hepatitis B vaccine as soon as possible (preferably within 24 hours after exposure [<7 days for percutaneous exposure or <14 days for sexual exposure]); complete the vaccination series. If exposure was to an HBsAg-unknown source, HBIG treatment is not required but the hepatitis B vaccine series should be completed.
If the exposed person has prior documentation of ≥3 doses of a hepatitis B vaccine then HBIG treatment is not required.
Prevention of hepatitis B virus recurrence after liver transplantation (HepaGam B): IV: 20,000 units/dose according to the following schedule:
Anhepatic phase (Initial dose): One dose (20,000 units) given with the liver transplant
Week 1 postop: One dose (20,000 units) daily for 7 days (days 1 to 7)
Weeks 2 to 12 postop: One dose (20,000 units) every 2 weeks starting day 14
Month 4 onward: One dose (20,000 units) monthly starting on month 4
Dose adjustment: Adjust dose to reach anti-HBs levels of 500 units/L within the first week after transplantation. In patients with surgical bleeding, abdominal fluid drainage >500 mL or those undergoing plasmapheresis, administer 10,000 units/dose every 6 hours until target anti-HBs levels are reached.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: For exposure prophylaxis, HBIG may be administered at the same time (but at a different site) or up to 1 month preceding hepatitis B vaccination without impairing the active immune response.
Perinatal exposure, prophylaxis (CDC 2005): Infants born to HBsAg-positive mothers: IM: 0.5 mL as a repeat of birth dose if the hepatitis B vaccination series is delayed for as long as 3 months (hepatitis B vaccine should also be administered at the same time/different site)
Postexposure, prophylaxis:
Infants <12 months: IM: 0.5 mL as soon as possible after exposure (eg, mother or primary caregiver with acute HBV infection); initiate hepatitis B vaccine series
Children ≥12 months and Adolescents: IM: 0.06 mL/kg as soon as possible after exposure (ie, within 24 hours of needlestick, ocular, or mucosal exposure or within 14 days of sexual exposure); repeat at 28 to 30 days after exposure
Reconstitution
HepaGamB: May dilute with NS prior to IV administration if preferred; do not dilute with D5W.
Administration
HBIG may be administered at the same time (but at a different site) or up to 1 month preceding hepatitis B vaccination without impairing the active immune response
IM: Post-exposure prophylaxis: IM injection only in anterolateral aspect of upper thigh and deltoid muscle of upper arm; to prevent injury from injection, care should be taken when giving to patients with thrombocytopenia or bleeding disorders
IV:
HepaGam B: Liver transplant: Administer at 2 mL/minute. Decrease infusion to ≤1 mL/minute for patient discomfort or infusion-related adverse events. Actual volume of infusion is dependent upon potency labeled on each individual vial.
Nabi-HB: Although not FDA-approved for this purpose, Nabi-HB has been administered intravenously in hepatitis B-positive liver transplant patients (Dickson 2006)
Storage
Refrigerate at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake vial; avoid foaming. Extended storage information at room temperature may be available; contact product manufacturer to obtain current recommendations.
HepaGamB; Nabi-HB: Use within 6 hours of entering vial.
Drug Interactions
Vaccines (Live): Immune Globulins may diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Influenza Virus Vaccine (Live/Attenuated); Poliovirus Vaccine (Live/Bivalent/Oral); Poliovirus Vaccine (Live/Trivalent/Oral); Rotavirus Vaccine; Yellow Fever Vaccine; Zoster Vaccine (Live/Attenuated). Consider therapy modification
Test Interactions
Glucose testing: HepaGam B™ contains maltose. Falsely-elevated blood glucose levels may occur when glucose monitoring devices and test strips utilizing the glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) based methods are used.
Serological testing: Antibodies transferred following administration of immune globulins may provide misleading positive test results (eg, Coombs’ test)
Adverse Reactions
Reported with postexposure prophylaxis. Adverse events reported in liver transplant patients included tremor and hypotension, were associated with a single infusion during the first week of treatment, and did not recur with additional infusions.
>10%:
Central nervous system: Headache (14%)
Dermatologic: Erythema (12%)
1% to 10%:
Cardiovascular: Hypotension (2%)
Central nervous system: Malaise (6%)
Dermatologic: Ecchymoses (2%)
Gastrointestinal: Nausea (2% to 4%), vomiting (2%)
Hematologic & oncologic: Change in WBC count (2%)
Hepatic: Increased serum alkaline phosphatase (4%), increased liver enzymes (2%)
Local: Pain at injection site (4%)
Neuromuscular & skeletal: Myalgia (10%), joint stiffness (2%)
Renal: Increased serum creatinine (2%)
<1%, postmarketing, and/or case reports: Abdominal pain, anaphylactic reaction (rare), angioedema, back pain, chills, diaphoresis, dizziness, dyspnea, fever, flu-like symptoms, hypersensitivity, increased serum lipase, increased serum transaminases, sinus tachycardia, tenderness at injection site, urticaria
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylaxis/hypersensitivity reactions: Hypersensitivity and anaphylactic reactions can occur; immediate treatment (including epinephrine 1 mg/mL) should be available. Use with caution in patients with isolated immunoglobulin A deficiency or a history of systemic hypersensitivity to human immunoglobulins.
- Infusion reactions: When administered IV, do not exceed recommended infusion rates; may increase risk of adverse events. Patients should be monitored for adverse events during and after the infusion.
- Thrombotic events: Thrombotic events have been reported with administration of intravenous immune globulin; use with caution in patients of advanced age, with a history of atherosclerosis or cardiovascular and/or thrombotic risk factors, patients with impaired cardiac output, coagulation disorders, prolonged immobilization, or patients with known/suspected hyperviscosity. Consider a baseline assessment of blood viscosity in patients at risk for hyperviscosity.
Disease-related concerns:
- Bleeding disorders: Use with caution in patients with thrombocytopenia or coagulation disorders; IM injections may be contraindicated.
Dosage form specific issues:
- Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.
- Maltose: Some products may contain maltose, which may result in falsely-elevated blood glucose readings.
- Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.
Monitoring Parameters
Liver transplant: Serum HBsAg; LFTs; infusion-related adverse events
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal reproduction studies have not been conducted. Use of HBIG is not contraindicated in pregnant females and may be used for postexposure prophylaxis when indicated (CDC 2001). In addition, use of HBIG has been evaluated to reduce maternal to fetal transmission of hepatis B virus during pregnancy (ACOG 2007)
Patient Education
What is this drug used for?
- It is used to prevent hepatitis B infection.
Frequently reported side effects of this drug
- Headache
- Muscle pain
- Loss of strength and energy
- Injection site pain
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
