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Hepatitis B Vaccine (Recombinant)

Pronunciation

(hep a TYE tis bee vak SEEN ree KOM be nant)

Index Terms

  • Hepatitis B Inactivated Virus Vaccine (recombinant DNA)
  • HepB

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, suspension [adult, preservative free]:

Engerix-B: Hepatitis B surface antigen 20 mcg/mL (1 mL) [contains aluminum, yeast protein, may contain natural rubber/natural latex in prefilled syringe]

Engerix-B: Hepatitis B surface antigen 20 mcg/mL (1 mL) [contains aluminum, yeast protein; vial]

Recombivax HB: Hepatitis B surface antigen 10 mcg/mL (1 mL) [contains aluminum, natural rubber/natural latex in packaging, yeast protein]

Injection, suspension [dialysis formulation, preservative free]:

Recombivax HB: Hepatitis B surface antigen 40 mcg/mL (1 mL) [contains aluminum, natural rubber/natural latex in packaging, yeast protein]

Injection, suspension [pediatric/adolescent, preservative free]:

Engerix-B: Hepatitis B surface antigen 10 mcg/0.5 mL (0.5 mL) [contains aluminum, yeast protein, may contain natural rubber/natural latex in prefilled syringe]

Recombivax HB: Hepatitis B surface antigen 5 mcg/0.5 mL (0.5 mL) [contains aluminum, natural rubber/natural latex in packaging, yeast protein]

Brand Names: U.S.

  • Engerix-B
  • Recombivax HB

Pharmacologic Category

  • Vaccine
  • Vaccine, Inactivated (Viral)

Pharmacology

Recombinant hepatitis B vaccine is a noninfectious subunit viral vaccine, which confers active immunity via formation of antihepatitis B antibodies. The vaccine is derived from hepatitis B surface antigen (HBsAg) produced through recombinant DNA techniques from yeast cells. The portion of the hepatitis B gene which codes for HBsAg is cloned into yeast, which is then cultured to produce hepatitis B vaccine.

Duration of Action

Following a 3-dose series in children, up to 50% of patients will have low or undetectable anti-HB antibody 5 to 15 years postvaccination. However, anamnestic increases in anti-HB have been shown up to 23 years later suggesting a lifelong immune memory response (CDC/ACIP [Mast 2005]; CDC/ACIP [Mast 2006]).

Use: Labeled Indications

Hepatitis B disease prevention: Active immunization against infection caused by all known subtypes of hepatitis B virus (HBV)

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for the following:

- All neonates before hospital discharge (CDC/ACIP [Mast 2005])

- All unvaccinated infants and children (CDC/ACIP [Mast 2005])

- All unvaccinated adults requesting protection from HBV infection (CDC/ACIP [Mast 2006])

- All unvaccinated adults at risk for HBV infection such as those with:

Behavioral risks: Sexually-active persons with >1 partner in a 6-month period; persons seeking evaluation or treatment for a sexually-transmitted disease; men who have sex with men; injection drug users (CDC/ACIP [Mast 2006])

Occupational risks: Healthcare personnel (HCP) and public safety workers with reasonably anticipated risk for exposure to blood or blood contaminated body fluids (CDC/ACIP [Mast 2006])

Medical risks: Persons with end-stage renal disease (including predialysis, hemodialysis, peritoneal dialysis, and home dialysis); persons with HIV infection; persons with chronic liver disease (CDC/ACIP [Mast 2006]). Adults (19 through 59 years of age) with diabetes mellitus type 1 or type 2 should be vaccinated as soon as possible following diagnosis. Adults ≥60 years with diabetes mellitus may also be vaccinated at the discretion of their treating clinician based on the likelihood of acquiring HBV infection (CDC/ACIP 60[50] 2011).

Other risks: Household contacts and sex partners of persons with chronic HBV infection; residents and staff of facilities for developmentally disabled persons; international travelers to regions with high or intermediate levels of endemic HBV infection (CDC/ACIP [Mast 2006])

In addition, the ACIP recommends vaccination for any persons who are wounded in bombings or similar mass casualty events who have penetrating injuries or non-intact skin exposure, or who have contact with mucous membranes (exception - superficial contact with intact skin), and who cannot confirm receipt of a hepatitis B vaccination (CDC [Chapman 2008]).

Contraindications

Severe allergic or hypersensitivity reaction to yeast, hepatitis B vaccine, or any component of the formulation.

Canadian labeling: Additional contraindications (not in US labeling): Known hypersensitivity to any component of the formulation; severe febrile illness.

Dosing: Adult

Primary immunization: IM: Note: Adult formulations of hepatitis B vaccine products differ by concentration (mcg/mL) but when dosed in terms of volume (mL), the dose of Engerix-B and Recombivax HB are the same (both 1 mL).

Immunocompetent adults: 1 mL/dose (adult formulation) for 3 total doses administered at 0, 1, and 6 months. Note: Refer to CDC guideline (Mast 2006) for other options. Manufacturer labeling may include alternate immunization schedules.

Adults with immunocompromising conditions (ACIP [Kim 2016]):

Engerix-B 20 mcg/mL: Administer 2 mL per dose at 0, 1, 2, and 6 months

Recombivax HB 40 mcg/mL: Administer 1 mL per dose at 0, 1, and 6 months

Bombings or similar mass casualty events: IM: In persons without a reliable history of vaccination against HepB and who have no known contraindications to the vaccine, vaccination should begin within 24 hours (but no later than 7 days) following the event (CDC [Chapman 2008]).

Postexposure management of health care personnel (HCP) (CDC [Schillie 2013]): IM:

Documented vaccine responder: If the HCP has prior documentation of ≥3 doses of a hepatitis B vaccine and a postvaccination anti-HBs ≥10 milliunits/mL, then additional hepatitis B vaccine is not needed, regardless of the patients HBsAg status. HCP is considered seroprotected.

Unvaccinated or incompletely vaccinated: The primary vaccination series should be completed regardless of the source patients HBsAg status. If the source patient is HBsAg positive or their status is unknown, 1 dose of hepatitis B vaccine and 1 dose of hepatitis B immunoglobulin (HBIG) should be administered as soon as possible.

Vaccinated with 3 doses of hepatitis B vaccine but postvaccination anti-HBs status is unknown: Test HCP for anti-HBs. If anti-HBs ≥10 milliunits/mL additional hepatitis B vaccine is not needed. If anti-HBs <10 milliunits/mL, initiate revaccination by administering a single dose of the vaccine and retesting for anti-HBs in 1 to 2 months; if needed 2 additional doses may be given and then retest anti-HBs level. Alternately, administer 3 consecutive doses of the vaccine and then retest anti-HBs level. Minimum dosing intervals are 4 weeks between doses 1 and 2, and 8 weeks between doses 2 and 3; maximum total 6 doses of hepatitis B vaccine (including the original series). If the source patient is HBsAg positive or their status is unknown, 1 dose of HBIG should also be administered.

Vaccinated with 6 doses of hepatitis B vaccine but documented as a nonresponder to the vaccine: No postexposure vaccination is recommended. If the source patient is HBsAg positive or unknown, administer two doses of HBIG separated by 1 month.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Primary immunization: IM:

Infants: Note: Doses are presented using the pediatric/adolescent formulations. Pediatric/adolescent formulations of hepatitis B vaccine products differ by concentration (mcg/mL). However, when dosed in terms of volume (mL), the dose of Engerix-B and Recombivax HB are the same (both 0.5 mL). Combination vaccines should not be used for the "birth" dose but may be used to complete the course beginning after the infant is ≥6 weeks of age (CDC/ACIP [Mast 2005]). Please see combination vaccine monographs for dose and schedule details.

US labeling: 0.5 mL/dose (pediatric/adolescent formulation) for 3 total doses administered at 0, 1 and 6 months. Alternate dosing regimens are also available for children who begin vaccination ≥1 year of age.

Canadian labeling: 0.5 mL/dose (pediatric/adolescent formulation) for 3 total doses administered at 0, 1, and 6 months. For accelerated protection, a 4 dose series can be administered at 0, 1, and 2 months plus a booster at 12 months.

ACIP recommendations (CDC/ACIP [Mast 2005]): IM:

Infants (HBsAg-negative mothers):

First dose: 0.5 mL at birth or before discharge (may be delayed in certain cases)

Second dose: 0.5 mL at 1 to 2 months of age

Third dose: 0.5 mL at 6 to 18 months of age, but no sooner than 24 weeks of age

Note: Premature neonates <2 kg should have the initial dose deferred up to 30 days of chronological age or at hospital discharge.

Infants (HBsAg-positive mothers):

First dose: 0.5 mL within first 12 hours of life, even if premature and regardless of birth weight (hepatitis immune globulin should also be administered at the same time at a different site)

Second dose: 0.5 mL at 1 to 2 months of age

Third dose: 0.5 mL at 6 months of age but no sooner than 24 weeks of age

Note: Anti-HBs and HBsAg levels should be checked at 9 to 18 months of age (ie, next well-child visit after series completion). If HBsAg negative and anti-HBs levels <10 milliunits/mL, reimmunize with 3 doses and reassess 1 to 2 months after the third dose.

Note: In premature neonates <2 kg, the birth dose should not be counted as part of the 3-dose vaccine series.

Infants (mother's HBsAg status unknown):

First dose: 0.5 mL within 12 hours of birth even if premature and regardless of birth weight; if the mother's blood HBsAg test is positive, the infant should receive hepatitis immune globulin as soon as possible (no later than 12 hours of age if <2 kg or age 1 week if ≥2 kg).

Second dose: 0.5 mL at 1 to 2 months of age

Third dose: 0.5 mL at 6 months of age but no sooner than 24 weeks of age

Note: In premature neonates <2 kg, the birth dose should not be counted as part of the 3-dose vaccine series.

Children and Adolescents: 0.5 mL/dose (pediatric/adolescent formulation) administered at 0, 1, and 6 months (for 3 total doses). Alternate dosing regimens are also available for children who begin vaccination ≥1 year of age. Note: Refer to CDC guideline (Mast, 2005) for other options. Manufacturer labeling may include alternate immunization schedules, refer to CDC Catch-up Schedules for guidance (ACIP [Robinson 2016]).

Bombings or similar mass casualty events: Refer to adult dosing.

Dosing: Renal Impairment

Adults ≥20 years:

Predialysis patients: Recombivax HB 40 mcg/mL: Administer 1 mL per dose at 0, 1, and 6 months

Dialysis patients:

Engerix-B 20 mcg/mL: Administer 2 mL per dose at 0, 1, 2, and 6 months

Recombivax HB 40 mcg/mL: Administer 1 mL per dose at 0, 1, and 6 months

Note: Serologic testing is recommended 1 to 2 months after the final dose of the primary vaccine series and annually to determine the need for booster doses. Persons with anti-HBs concentrations of <10 milliunits/mL should be revaccinated with 3 doses of the vaccine (CDC/ACIP [Mast 2006]).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Administration

Pediatric/adolescent formulations of hepatitis B vaccine products differ by concentration (mcg/mL). However, when dosed in terms of volume (mL), the dose of Engerix-B and Recombivax HB are the same (both 0.5 mL). Adult formulations of hepatitis B vaccine products also differ by concentration (mcg/mL), but when dosed in terms of volume (mL), the dose of Engerix-B and Recombivax HB are the same (both 1 mL). It is possible to interchange the vaccines for completion of a series or for booster doses; the antibody produced in response to each type of vaccine is comparable, however, the quantity of the vaccine will vary.

IM injection (preferred); do not administer IV or intradermally; in adults, the deltoid muscle is the preferred site; the anterolateral thigh is the recommended site in infants and young children. Not for gluteal administration. Shake well prior to withdrawal and use. Obese patients may require an adjustment of needle length (CDC [Schillie 2013]). To prevent syncope related injuries, adolescents and adults should be vaccinated while seated or lying down (NCIRD/ACIP, 2011). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.

For patients at risk of hemorrhage following intramuscular injection, hepatitis B vaccine may be administered subcutaneously although lower titers and/or increased incidence of local reactions may result. The ACIP recommends that the vaccine should be administered intramuscularly if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, intramuscular vaccination can be scheduled shortly after such therapy is administered. A fine needle (23-gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (NCIRD/ACIP, 2011).

Vaccination at the time of HBsAg testing: For persons in whom vaccination is recommended, the first dose of hepatitis B vaccine can be given after blood is drawn to test for HBsAg.

Compatibility

Do not mix with other vaccines or injections. Separate needles and syringes should be used for each injection.

Storage

Refrigerate at 2°C to 8°C (36°F to 46°F); do not freeze. Discard if product has been frozen. The following stability information has also been reported for Engerix-B: May be stored at room temperature for up to 72 hours (Cohen, 2007).

Drug Interactions

Belimumab: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Patients should receive inactivated vaccines prior to initiation of belimumab therapy whenever possible, due to the risk for an impaired response to the vaccine during belimumab therapy. Consider therapy modification

Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting fingolimod. If vaccinated during fingolimod therapy, revaccinate 2 to 3 months after fingolimod discontinuation. Consider therapy modification

Immunosuppressants: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Exceptions: Cytarabine (Liposomal). Consider therapy modification

Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy

Adverse Reactions

All serious adverse reactions must be reported to the U.S. Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 or online at https://vaers.hhs.gov/esub/index.

Frequency not defined. The most common adverse effects reported with both products included injection site reactions (>10%).

Cardiovascular: Flushing, hypotension

Central nervous system: Body pain, chills, dizziness, drowsiness, fatigue, headache, insomnia, irritability, malaise, paresthesia, tingling sensation, vertigo

Dermatologic: Diaphoresis, pruritus, skin rash, urticaria

Gastrointestinal: Abdominal pain, anorexia, decreased appetite, diarrhea, dyspepsia, nausea, stomach cramps, vomiting

Genitourinary: Dysuria

Hematologic & oncologic: Lymphadenopathy

Hypersensitivity: Angioedema

Infection: Influenza

Local: Bruising at injection site, erythema at injection site, induration at injection site, injection site nodule, itching at injection site, local soreness/soreness at injection site, pain at injection site, swelling at injection site, tenderness at injection site, warm sensation at injection site

Neuromuscular & skeletal: Arthralgia, back pain, myalgia, neck pain, neck stiffness, shoulder pain, weakness

Otic: Otalgia

Respiratory: Cough, pharyngitis, rhinitis, upper respiratory tract infection

Miscellaneous: Fever (≥37.5°C/100°F)

Postmarketing and/or case reports (Limited to important or life-threatening): Acute exacerbations of multiple sclerosis, apnea, Bell's palsy, encephalitis, febrile seizures, Guillain-Barre syndrome, herpes zoster, hypersensitivity reaction, hypoesthesia, increased erythrocyte sedimentation rate, increased liver enzymes, keratitis, lupus-like syndrome, migraine, multiple sclerosis, myelitis, neuropathy, optic neuritis, paralysis, paresis, periarteritis nodosa, peripheral neuropathy, purpura, radiculopathy, seizure, serum-sickness like reaction (may be delayed days to weeks), Stevens-Johnson syndrome, syncope, systemic lupus erythematosus, tachycardia, thrombocytopenia, transverse myelitis, uveitis, vasculitis, visual disturbances

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (NCIRD/ACIP, 2011).

• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (NCIRD/ACIP, 2011).

Disease-related concerns:

• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Consider deferring administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (NCIRD/ACIP, 2011). Canadian labeling contraindicates use of the vaccine in patients with severe febrile illness.

• Bleeding disorders: Use with caution in patients with bleeding disorders (including thrombocytopenia) and patients on anticoagulant therapy; bleeding/hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (NCIRD/ACIP, 2011).

• Multiple sclerosis: Postmarketing reports of multiple sclerosis (MS) exacerbations have been reported; however, clinical studies indicate no association between vaccination and MS.

Special populations:

• Altered immunocompetence: Use with caution in severely immunocompromised patients (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination. In general, household and close contacts of persons with altered immunocompetence may receive all age appropriate vaccines (IDSA [Rubin 2014]; NCIRD/ACIP, 2011); inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible (IDSA [Rubin 2014]).

• Elderly: Patients >60 years of age may have lower response rates.

• Pediatric: In general, preterm infants should be vaccinated at the same chronological age as full-term infants (NCIRD/ACIP, 2011). However, infants born to HBsAg-negative mothers and weighing <2 kg at birth should have the initial dose deferred up to 30 days of chronological age or until hospital discharge. If the mothers HBsAg status at delivery is unknown or positive, hepatitis B vaccine and hepatitis B immune globulin should be administered within 12 hours of life and the first dose of the vaccine should not be counted as part of the vaccine series. Apnea has been reported following IM vaccine administration in premature infants; consider clinical status implications.

Concurrent drug therapy issues:

• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The use of combination vaccines is generally preferred over separate injections, taking into consideration provider assessment, patient preference, and adverse events. When using combination vaccines, the minimum age for administration is the oldest minimum age for any individual component; the minimum interval between dosing is the greatest minimum interval between any individual components. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible (NCIRD/ACIP, 2011).

Dosage form specific issues:

• Latex: Packaging may contain natural latex rubber.

Other warnings/precautions:

• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (NCIRD/ACIP, 2011). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula, 2009).

• Appropriate use: Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the ACIP Adult Recommended Immunization Schedule (ACIP [Kim 2016]). Specific recommendations for vaccination in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions are available in the IDSA guidelines (Rubin, 2014).

• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and is improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (NCIRD/ACIP, 2011). Due to the long incubation period for hepatitis, unrecognized hepatitis B infection may be present prior to vaccination; immunization may not prevent infection in these patients.

Monitoring Parameters

Monitor for syncope for 15 minutes following administration (NCIRD/ACIP, 2011). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion. In preterm infants, consider respiratory monitoring for 48 to 72 hours after administration.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. The ACIP recommends HBsAg testing for all pregnant women. Based on limited data, there is no apparent risk to the fetus when the hepatitis B vaccine is administered during pregnancy. Pregnancy itself is not a contraindication to vaccination; vaccination should be considered if otherwise indicated (CDC/ACIP [Mast 2006]).

Patient Education

• Discuss specific use of vaccine and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site pain, loss of strength and energy, or headache. Have patient report immediately to prescriber burning or numbness feeling, severe dizziness, passing out, abnormal movements, or vision changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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