Version July 2025
VBI vaccines is initiating a voluntary recall of PreHevbrio (hepatitis B vaccine [recombinant]) due to the termination of company operations. For health care providers needing to complete a hepatitis B vaccination series when the original vaccine administered is no longer available, please refer to the Centers for Disease Control and Prevention hepatitis B vaccination guidelines at https://www.cdc.gov/hepatitis-b/hcp/vaccine-administration/.
Further information may also be found at https://www.prehevbrio.com.
Note: According to Advisory Committee on Immunization Practices (ACIP), doses administered ≤4 days before minimum interval or age are considered valid; however, local or state mandates may supersede this timeframe (Ref).
Primary immunization: IM: 1 mL per dose given as a 3-dose series administered at 0, 1, and 6 months.
Revaccination: For certain persons who received a complete HBV vaccine series (eg, persons with HIV, persons who are immunocompromised, health care personnel, sex partners of persons who test positive for hepatitis B surface antigen [HBsAg]), anti-HBs testing is recommended 1 to 2 months after the final dose. If anti-HBs levels <10 milliunits/mL, revaccinate with either a second, complete vaccination series or with a single hepatitis B vaccine dose, followed by anti-HBs testing 1 to 2 months later. If only a single dose was given for revaccination and anti-HBs levels remain <10 milliunits/mL, complete the vaccine series; perform anti-HBs testing 1 to 2 months later (Ref).
Interchangeability: The ACIP recommends completing the vaccine series with the same product whenever possible. If continuing with same product will cause vaccination to be deferred, or if product used previously is unknown or unavailable, vaccination should be completed with the product available. A 2-dose HepB vaccine series is only appropriate when both doses in the series consist of HepB-CpG (Heplisav-B). If 1 dose of HepB-CpG and another dose from a different manufacturer were previously given, then a third vaccine dose should be given. For any 3-dose series, minimum intervals are as follows: 4 weeks between dose 1 and 2; 8 weeks between dose 2 and 3; 16 weeks between dose 1 and 3 (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Note: Serologic testing is recommended for patients receiving hemodialysis 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 receive a booster dose (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Local: Pain at injection site (27% to 59%), tenderness at injection site (30% to 60%)
Nervous system: Fatigue (12% to 30%), headache (7% to 34%)
Neuromuscular & skeletal: Myalgia (12% to 30%)
1% to 10%:
Gastrointestinal: Diarrhea (1% to 10%), nausea and vomiting (≤8%)
Local: Erythema at injection site (≤2%), itching at injection site (2% to 7%), swelling at injection site (≤3%)
<1%: Miscellaneous: Fever
Severe hypersensitivity (eg, anaphylaxis) to any hepatitis B vaccine or any component of the formulation.
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 (ACIP [Kroger 2023]).
• Shoulder injury related to vaccine administration: Vaccine administration that is too high on the upper arm may cause shoulder injury (eg, shoulder bursitis or tendinopathy) resulting in shoulder pain and reduced range of motion following injection. Use proper injection technique for vaccines administered in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013).
• 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 (ACIP [Kroger 2023]).
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. Postpone 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) (ACIP [Kroger 2023]).
• Bleeding disorders: Use with caution in patients with bleeding disorders (including thrombocytopenia); 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 (ACIP [Kroger 2023]).
Concurrent drug therapy issues:
• Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2023]).
• Vaccines: In order to maximize vaccination rates, the Advisory Committee on Immunization Practices (ACIP) recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or nonlive) for which a person is eligible at a single visit, unless contraindications exist. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible; however, vaccination should not be deferred because a specific brand name is unavailable (ACIP [Kroger 2023]).
Special populations:
• Altered immunocompetence: Postpone vaccination during periods of severe immunosuppression (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]) if appropriate; may have a reduced response to vaccination. In general, household and close contacts of persons with altered immunocompetence may receive all age-appropriate vaccines. Nonlive vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; nonlive vaccines administered during chemotherapy should be readministered after immune competence is regained (ACIP [Kroger 2023]; IDSA [Rubin 2014]).
• Older adults: Patients ≥65 years of age may have lower response rates.
Other warnings/precautions:
• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Kroger 2023]). 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).
• 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 (ACIP [Kroger 2023]). 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Suspension, Intramuscular [preservative free]:
PreHevbrio: 10 mcg/mL (1 mL [DSC]) [contains albumin bovine, formaldehyde solution]
No
Suspension (PreHevbrio Intramuscular)
10 mcg/mL (per mL): $77.70
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IM: Shake well prior to use to obtain a slightly opaque-white suspension free of particulate matter. Discard if any other discoloration or particulates are present. Administer by IM injection into the deltoid muscle. Use proper injection technique in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Ref). Not for gluteal administration. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (Ref). May be administered at the same time as hepatitis B immune globulin but at a different anatomical site. To prevent syncope-related injuries, adolescents and adults should be vaccinated while seated or lying down (Ref). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, vaccine information statement edition date and date it was provided, and the administering person's name, title, and address be recorded.
For patients at risk of hemorrhage following IM injection, the Advisory Committee on Immunization Practices recommends that the vaccine should be administered IM 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, IM 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 (Ref).
In the United States, the appropriate CDC-approved Vaccine Information Statement (VIS) should be provided to the patient/caregiver before administering each dose of this vaccine. If purchased under CDC contract, the VIS must be provided and the VIS edition date and date it was provided to the patient/caregiver should be recorded. VIS is available at https://www.cdc.gov/vaccines/hcp/current-vis/hepatitis-b.html.
Hepatitis B virus infection prevention : Prevention of infection caused by all known subtypes of hepatitis B virus in adults.
The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for the following adults (CDC/ACIP [Schillie 2018a]; CDC/ACIP [Weng 2022]): Note: ACIP recommends routine hepatitis B immunization in additional populations using different hepatitis B vaccine products.
- All unvaccinated adults 19 to 59 years of age; adults ≥60 years of age without known risk factors may also receive vaccination.
- All unvaccinated adults ≥60 years of age at risk for HBV infection such as those with:
Sexual exposure risk: Sex partners of persons who test positive for HBsAg; sexually active persons not in a long-term, mutually monogamous relationship; persons seeking evaluation or treatment for a sexually transmitted infection; men who have sex with men.
Exposure to blood: Persons with current or recent injection drug use; household contacts of persons who test positive for HBsAg; residents and staff of facilities for persons with developmental disabilities; health care personnel and public safety workers with reasonably anticipated risk for exposure to blood or blood contaminated body fluids.
Medical risks: Persons with HIV or hepatitis C virus infection; persons with chronic liver disease (eg, cirrhosis, steatotic liver disease, alcoholic liver disease, autoimmune hepatitis, ALT or AST level >2 times the ULN); persons with diabetes mellitus (per clinical discretion).
Other risks: International travelers to regions with high or intermediate levels of endemic HBV infection; incarcerated persons.
Hepatitis B vaccine (trivalent [recombinant]) may be confused with hepatitis B vaccine (recombinant) and hepatitis B vaccine (recombinant [adjuvanted]).
HepB (hepatitis B vaccine) may be confused with HepA (hepatitis A vaccine).
HepB (hepatitis B vaccine) may be confused with Hib (Haemophilus b conjugate vaccine).
HepB (hepatitis B vaccine) may be confused with HPV4 (human papillomavirus vaccine [quadrivalent]; 4vHPV is the correct abbreviation).
HBV (previously used for hepatitis B vaccine; HepB is correct abbreviation) may be confused with HPV (human papilloma virus vaccine; 2vHPV, 4vHPV, or 9vHPV are the correct abbreviations).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetaminophen: May decrease therapeutic effects of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider Therapy Modification
Anti-CD20 B-Cell Depleting Therapies: May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation or 6 months after anti-CD20 B-cell depleting therapies. If vaccinated prior to B cell recovery, consider assessing immune response to vaccination. Risk D: Consider Therapy Modification
Atidarsagene Autotemcel: May increase adverse/toxic effects of Vaccines. Atidarsagene Autotemcel may decrease therapeutic effects of Vaccines. Risk X: Avoid
Cladribine: May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting cladribine when possible. Patients vaccinated less than 14 days before initiating or during cladribine should be revaccinated at least 3 months after therapy is complete Risk D: Consider Therapy Modification
Corticosteroids (Systemic): May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Administer vaccines at least 2 weeks prior to immunosuppressive corticosteroids if possible. If patients are vaccinated less than 14 days prior to or during such therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. Risk D: Consider Therapy Modification
Dinutuximab Beta: May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Risk X: Avoid
Elivaldogene Autotemcel: May increase adverse/toxic effects of Vaccines. Specifically, there may be a greater risk for contracting an infection from any live vaccine. Elivaldogene Autotemcel may decrease therapeutic effects of Vaccines. Management: Administration of vaccines is not recommended in the 6 weeks before myeloablative conditioning, and until hematologic recovery after elivaldogene autotemcel treatment. Risk X: Avoid
Fingolimod: May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). 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. Risk D: Consider Therapy Modification
Immunosuppressants (Cytotoxic Chemotherapy): May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Immunosuppressants (Miscellaneous Oncologic Agents): May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Immunosuppressants (Therapeutic Immunosuppressant Agents): May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider Therapy Modification
Methotrexate: May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Administer vaccines at least 2 weeks prior to methotrexate initiation, if possible. If patients are vaccinated less than 14 days prior to or during methotrexate therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. Risk D: Consider Therapy Modification
Propacetamol: May decrease therapeutic effects of Vaccines. Management: Consider avoiding routine prophylactic use of propacetamol before or during vaccine administration when possible. Propacetamol is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider Therapy Modification
Siponimod: May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Avoid administration of non-live/inactivated/non-replicating vaccines during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy. Risk D: Consider Therapy Modification
Teplizumab: May decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Vaccination with non-live/inactivated/non-replicating vaccines is not recommended in the 2 weeks prior to teplizumab therapy, during treatment, or for 6 weeks following completion of therapy. Risk D: Consider Therapy Modification
Pregnant patients were excluded from initial studies; limited data are available following inadvertent exposure (Vesikari 2021a; Vesikari 2021b).
The Advisory Committee on Immunization Practices (ACIP) recommends HBsAg testing for all pregnant patients (CDC/ACIP [Schillie 2018a]). In general, vaccination is recommended for pregnant patients at risk for hepatitis B infection. However, vaccination with PreHevbrio during pregnancy is not currently recommended. When vaccination is clinically indicated, the ACIP recommends use of a different hepatitis B vaccine (CDC/ACIP [Sandul 2024]). Refer to current immunization schedule for vaccinating pregnant patients.
Data collection to monitor pregnancy and infant outcomes following exposure to the hepatitis B trivalent vaccine is ongoing. Health care providers are encouraged to enroll patients exposed to the vaccine during pregnancy in the pregnancy registry (888-421-8808).
It is not known if the components of this vaccine are present in breast milk.
According to the manufacturer, the decision to breastfeed following immunization should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of vaccination to the mother. Nonlive vaccines have not been shown to affect the safety of breastfeeding for the breastfed infant or mother. Breastfeeding infants should be vaccinated according to the recommended schedules (ACIP [Kroger 2023]).
Monitor for hypersensitivity and syncope for 15 minutes following administration (ACIP [Kroger 2023]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.
Hepatitis B vaccine (trivalent [recombinant]) is a noninfectious viral vaccine containing 3 hepatitis B surface antigens, which confers active immunity via formation of antihepatitis B antibodies.
