Vaccines against hepatitis B surface antigen (HBsAg) are produced utilizing recombinant technology designed for intramuscular or subcutaneous (Engerix-B and Recombivax HB only) administration. The recombinant hepatitis B vaccines contain no human blood products. Engerix-B and Heplisav-B reportedly contain not more than 5% yeast proteins while Recombivax HB contains not more than 1%; Prehevbrio is developed in Chinese Hamster Ovary cells and does not contain yeast proteins. Engerix-B and Recombivax HB are indicated for hepatitis B prophylaxis in all ages and can be used in conjunction with hepatitis B immune globulin (HBIG) for postexposure prophylaxis. Heplisav-B and Prehevbrio are indicated for hepatitis B prophylaxis in adults 18 years of age and older. The first dose of the hepatitis B vaccine (Engerix-B or Recombivax HB) should be given to all neonates within 24 hours of birth. For infants born to hepatitis B surface antigen (HBsAg) positive mothers, the hepatitis B vaccine and hepatitis B immune globulin (HBIG) should be administered within 12 hours of birth. If the mother's HBsAg status is unknown, the hepatitis B vaccine should be administered to all neonates within 12 hours of birth. Additionally, HBIG should be administered within 12 hours to all neonates weighing less than 2 kg and within 7 days if the mother is determined to be HBsAg positive in neonates weighing more than 2 kg.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Inform the patient or parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the parent or guardian before each immunization. This action is required by the National Childhood Vaccine Injury Act of 1986.
-Record the manufacturer, lot number, administration date, and the name and address of the person administering the vaccine in the patient's permanent record. These actions are required by the National Childhood Vaccine Injury Act of 1986.
-Health care professionals administering vaccines should take appropriate precautions to prevent allergic reactions in vaccine recipients.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Administer as soon as possible after removal from refrigeration.
-Use as supplied; no dilution or reconstitution is necessary. The full recommended dose of the vaccine should be used.
-Hepatitis B vaccine is administered intramuscularly (preferred; administer Heplisav-B and Prehevbrio intramuscularly only) or subcutaneously (only for those who are at risk). Do not administer intravenously or intradermally.
-Prior to withdrawing a dose from the vial, shake vial or pre-filled syringe thoroughly to obtain a uniform suspension.
-Hepatitis B vaccine should not be given in the same syringe nor injected at the same site as hepatitis B immune globulin; inactivation of the vaccine can occur.
-Do not mix with any other vaccine.
-A separate syringe and needle should be used for each person receiving the hepatitis B vaccine.
-Preservative-free formulations: Once the single-dose vial has been penetrated, the withdrawn vaccine should be used promptly, and the vial must be discarded.
-Storage: Store refrigerated at 2 to 8 degrees C (36 to 46 degrees F); do not freeze. Storage at room temperature for up to 72 hours may be acceptable; however, confirmation of acceptable duration of storage at room temperature directly from the manufacturer for the specific vaccine being administered is recommended.
Intramuscular Administration
-For vials, use a sterile syringe and needle to withdraw suspension from the vial. For prefilled syringes, attach a sterile needle.
-Adults, adolescents, and older children: Inject into the deltoid muscle of the upper arm. Do NOT administer in the gluteal muscle; gluteal administration has resulted in lower hepatitis B seroconversion rates.
-Neonates, infants, and young children: Inject into the anterolateral aspect of the mid-thigh.
-Injection must be accomplished with a needle long enough to ensure IM deposition of the vaccine.
--For adults, the needle size required for deltoid injection ranges from 5/8- to 1 1/2-inches, depending on patient size.
-For pediatric patients 3 years and older, the needle size required for deltoid injection ranges from 5/8- to 1-inch.
-For children 1 to 2 years, a needle at least 1 inch long is preferred for administration into the thigh; a 5/8 inch needle is sufficient for administration into the deltoid if the skin is stretched flat and the needle is inserted at a 90-degree angle.
-For the majority of infants younger than 1 year, a 1-inch, 22- to 25-gauge needle is sufficient to penetrate thigh muscle.
Subcutaneous Administration
-Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after intramuscular injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including irritation, inflammation, nodules, or skin discoloration.
-For vials, use a sterile syringe and needle to withdraw suspension from the vial. For prefilled syringes, attach a sterile needle. A 5/8-inch, 23- to 25-gauge needle is appropriate.
-Administer at a 45-degree angle into the subcutaneous tissue.
--Adults, adolescents, and older children: Inject into the deltoid area.
-Infants and young children: Inject into the anterolateral thigh.
Most adverse reactions reported with hepatitis B vaccine, recombinant have been mild, self-limiting, and did not last for more than 48 hours. An injection site reaction (0.2% to 38.5%) may occur in patients receiving hepatitis B vaccine, recombinant and is manifested as pain (58.6% or less), tenderness (30.2% to 59.9%), soreness (22%), erythema (0.2% to 10%), swelling (0.2% to 10%), bruising (less than 1%), induration (1% to 10%), warmth, or a nodule at the injection site. Injection site pruritus has been reported during postmarketing surveillance.
Adverse reactions noted with hepatitis B vaccine, recombinant include myalgia (30.3% or less), fatigue (10% to 29.7%), fever (0.6% to 10%), chills (less than 1%), headache (1% to 33.8%), malaise (1% to 9.2%), lymphadenopathy (less than 1%), petechiae (less than 1%), hypotension (less than 1%), flushing (less than 1%), irritability (less than 1% with Engerix-B and 1% or more with Recombivax HB), agitation (less than 1%), back pain (less than 1%), and arthralgia (less than 1%). Postmarketing, Stevens-Johnson syndrome and vasculitis have been noted. Serum sickness-like syndrome has occurred days to weeks after hepatitis B vaccine, recombinant administration. The syndrome includes arthralgia or arthritis that is usually transient, as well as fever, hives, ecchymosis, erythema multiforme, and erythema nodosum.
Insomnia, paresthesias, and vertigo were all noted in less than 1% of hepatitis B vaccine, recombinant recipients. Dizziness was noted in 1% to 10% of Engerix-B recipients and in less than 1% of Recombivax HB recipients. Muscle weakness was noted in 1% or more of Recombivax HB recipients and in less than 1% of Engerix-B recipients. Within 7 months of the first dose of vaccine, granulomatosis with polyangiitis, lichen planus-like eruption, Guillain-Barre syndrome, and Grave's disease were each reported in 1 subject receiving Heplisav-B. Bell's palsy, Raynaud's phenomenon, and Grave's disease were each reported in 1 subject receiving Engerix-B. One additional Engerix-B recipient with a history of mixed connective tissue disease had p-ANCA-positive vasculitis. Postmarketing, tinnitus, encephalopathy, hypoesthesia, migraine, seizures, myelitis, peripheral neuropathy, encephalitis, neuritis, optic neuritis, paralysis, paresis, transverse myelitis, radiculopathy, and multiple sclerosis (MS) have been noted with the vaccine. Several well-designed epidemiologic studies have found no association with hepatitis B vaccine administration and the development of MS; hepatitis B vaccination does not appear to increase the risk of relapse in MS.
Rash, pruritus, angioedema, and urticaria were each noted in less than 1% of hepatitis B vaccine, recombinant recipients. Postmarketing, anaphylactoid reactions, anaphylactic shock, dyspnea, and bronchospasm were noted. Anaphylaxis and symptoms of immediate hypersensitivity reactions including rash, pruritus, urticaria, edema, angioedema, dyspnea, chest discomfort, bronchial spasm, palpitations, or symptoms consistent with a hypotensive episode have been reported within the first few hours after vaccination. Review the patient's immunization history for possible vaccine sensitivity and previous vaccination-related adverse reactions to help determine the benefits and risks of hepatitis B vaccine, recombinant receipt. If the vaccine is administered, have appropriate medical treatment and supervision available to manage possible anaphylactic reactions after vaccine administration.
Thrombocytopenia and purpura have been reported postmarketing with the hepatitis B vaccine, recombinant. The frequency of occurrence or causal relationship to the vaccine of postmarketing events cannot be reliably determined because events are reported voluntarily from a population of uncertain size.
Alopecia has been noted postmarketing with the hepatitis B vaccine, recombinant. Approximately 60 cases of alopecia occurring after vaccination have been reported (in most cases, patients received vaccination for hepatitis B). Although some people lost all of their hair, including eyelashes, in most instances, some or all of the hair grew back. A positive rechallenge was reported in 16 cases. Alopecia has been estimated to occur in roughly 5 people a year out of about 1 billion vaccinations.
Syncope has been noted postmarketing with the hepatitis B vaccine, recombinant. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Have procedures in place to avoid falling injury and to restore cerebral perfusion after syncope.
Adverse reactions to hepatitis B vaccine, recombinant include anorexia (less than 1%), abdominal pain (less than 1%), diarrhea (less than 1% with Engerix-B and 1% or more with Recombivax HB), vomiting (less than 1%), constipation (less than 1%), dyspepsia (less than 1%), and nausea (less than 1% with Engerix-B and 1% or more with Recombivax HB).
Acute myocardial infarction (AMI) was reported in 0.25% (n = 14) of Heplisav-B recipients and 0.04% (n = 1) of Engerix-B recipients. Five additional Heplisav-B recipients and 2 additional Engerix-B recipients were identified when using the standard Medical Dictionary for Regulatory Activities (MedDRA) query (SMQ) for MI. Additional evidence, including information on temporal relationship and baseline risk factors, did not support a causal relationship between Heplisav-B administration and AMI. Among the 19 MI events occurring in Heplisav-B recipients, 3 occurred within 4 days, 9 occurred within 53 to 180 days, and 7 occurred more than 180 days after any dose of Heplisav-B. Among the 3 MI events occurring in Engerix-B recipients, one each occurred 13, 115, and 203 days after any dose. All vaccine recipients reported one or more baseline risk factors for cardiovascular disease.
Prior to the administration of hepatitis B vaccine, health care personnel should inform the patient, parent, guardian, or responsible adult of the vaccine's benefits and risks. This should include the provision of the hepatitis B vaccine information statement from the manufacturer. The responsible adult should report any adverse reaction after vaccine administration to the health care provider. The US Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine. This includes, but is not limited to, the reporting of events required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 1-800-822-7967.
Results from 2 clinical studies indicate that there is no association between hepatitis B vaccination and the development of multiple sclerosis, and vaccination with hepatitis B vaccine does not appear to increase the short-term risk of relapse in multiple sclerosis.
Due to the long hepatitis B incubation period, the hepatitis B vaccine, recombinant vaccine may not prevent hepatitis B infection in patients with unrecognized hepatitis B infection at the time of vaccination. Additionally, vaccination with hepatitis B, recombinant vaccine may not protect all patients.
Hepatitis B vaccine, recombinant is contraindicated for use by persons with known yeast hypersensitivity or hypersensitivity to any component of the vaccine and in patients with a severe allergic reaction such as anaphylaxis after a previous dose of any hepatitis B-containing vaccine. Anaphylaxis has been reported with the use of the hepatitis B vaccine, recombinant. Review the patient's immunization history for possible vaccine sensitivity and previous vaccination-related adverse reactions to allow an assessment of benefits and risks before administering the vaccine. As with any biologic product, the prescriber or health care professional should take precautions to prevent allergic reactions. The health care professional should have immediate availability of epinephrine (1 mg/mL) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the vaccine.
Defer receipt of Engerix-B for neonates who weigh less than 2 kg if the mother is documented to be HBsAg negative at the time of the infant's birth. Vaccination can commence at chronological age 1 month or hospital discharge. For infants who weigh less than 2 kg and who are born to HBsAg-positive mothers or to mothers of unknown HBsAg status, administer Engerix-B and hepatitis B immune globulin (HBIG) within 12 hours of birth. Do not count the birth dose as the first dose in the vaccine series; administer the full 3 dose standard regimen (total of 4 doses). Apnea after intramuscular vaccination has been observed in some premature neonates. Base the decision about when to administer an intramuscular vaccine to neonates born prematurely on the newborn's medical status and the potential benefits and possible risks of hepatitis B vaccine, recombinant vaccination. For example, consider the mother's hepatitis B antigen status and the high probability of maternal transmission of hepatitis B virus to infants born of mothers who are HBsAg positive if vaccination is delayed.
Do not give hepatitis B vaccine via intradermal administration or intravenous administration. Patients with thrombocytopenia, vitamin K deficiency, a coagulopathy (e.g., hemophilia) or receiving anticoagulant therapy should be monitored closely when given hepatitis B vaccine, recombinant because bleeding can occur at the IM injection site. In some of these patients, the vaccine may be administered via subcutaneous administration. However, the risk of local reactions may be greater with subcutaneous administration of aluminum adsorbed vaccines. Subcutaneous dosing may also result in lower GMTs.
In general, postpone hepatitis B vaccine administration to a patient with a moderate or severe acute infection or illness unless they are at immediate risk of hepatitis B infection such as neonates born to HBsAg-positive mothers. Any serious active infection including an illness with a fever is a reason for delaying use of the hepatitis B vaccine, recombinant except when in the opinion of the prescriber, withholding the vaccination entails a greater risk. Postponing the vaccine receipt can help avoid diagnostic confusion between manifestations of an acute illness and possible vaccine adverse effects. Use caution and appropriate care when administering the vaccine to individuals with severely compromised cardiopulmonary status such as some patients with cardiac disease or to others in whom a febrile or systemic reaction could pose a significant risk.
Patients with immunosuppression may respond to hepatitis B vaccine, recombinant with lower antibody titers than non-immunosuppressed patients. This is particularly a concern in patients receiving chemotherapy or in patients with human immunodeficiency virus (HIV) infection. Since a second infection in HIV-positive patients further weakens their immune system, it is still preferable to administer the vaccine. The seroconversion (SC) rate to hepatitis A vaccine is higher than the seroprotection (SP) rate to hepatitis B in these patients. Following vaccination with hepatitis A vaccine, inactivated the SC rates ranged between 77% to 88% for HIV-positive individuals and was 100% for HIV-negative individuals. Following vaccination with hepatitis B vaccine, recombinant the seroprotection rates ranged between 24% to 46% in HIV-positive individuals and was 93% in HIV-negative individuals. The guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV recommend vaccinating patients with a CD4 count less than 200 cells/mm3 if they have ongoing risks for hepatitis B. For HIV patients without risk factors, waiting to vaccinate until CD4 count is 200 cells/mm3 or higher is an option. Assess the antibody response (anti-HBs) to the vaccine 1 to 2 months after completing the series. If a primary immunization course fails to confer immunity, repeat doses may be required. Deferral of vaccination for at least 3 months after immunosuppressive therapy may also be considered.
Patients with renal disease or renal failure requiring hemodialysis may require larger doses to achieve adequate serum antibody titers (see Dosage). Hepatitis B vaccine products containing 10 mcg/ml of HBsAg should be avoided in these patients because of the inconvenience of large-volume IM administration as well as the potential problems associated with exceeding the recommended amount of aluminum hydroxide per dose of vaccine. A formulation containing 40 mcg/ml of antigen is available for use in dialysis patients, but has not been tested for safety in the pediatric population and should be avoided in children.
No adequate and well controlled studies have been conducted with hepatitis B vaccine, recombinant during pregnancy. In pre- and post-licensure clinical studies, 58 pregnant women who were inadvertently administrated hepatitis B vaccine, recombinant had rates of miscarriage and major birth defects that were consistent with estimated background rates. A pregnancy exposure registry of 245 women who received hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant (a bivalent vaccine containing the same hepatitis B surface antigen component and quantity as used in the hepatitis B vaccine, recombinant) during pregnancy or within 28 days prior to conception found that the rates of miscarriage and major birth defects were consistent with estimated background rates. Reproductive and developmental toxicity studies performed in rats administered Heplisav-B or Prehevbrio revealed no vaccine-related fetal malformations or variations. Animal reproduction studies have not been conducted with Engerix-B or Recombivax HB. According to the Advisory Committee on Immunization Practices (ACIP), administration of recombinant virus vaccines to pregnant women has not resulted in adverse effects in the fetus. The ACIP recommends vaccination during pregnancy when the likelihood of disease exposure is high, potential infection would cause harm to mother or fetus, and when the vaccine is unlikely to cause harm. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to Heplisav-B (1-844-443-7734) and Prehevbrio (1-888-421-8808).
Data are limited regarding use of the hepatitis B vaccine, recombinant during breast feeding and its' excretion in human milk is unknown. According to the Advisory Committee on Immunization Practices (ACIP), recombinant vaccines pose no risk to breast-feeding mothers or their infants. The manufacturer recommends caution when administering to nursing mothers. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Recombivax HB may be inappropriate for use by patients with latex hypersensitivity, as the vial stopper and the syringe plunger stopper and tip cap contain dry natural latex rubber that may cause allergic reactions.
Laboratory test interference may occur between the hepatitis B vaccine, recombinant and hepatitis B surface antigen (HBsAg) in blood samples. HBsAg has been transiently detected in blood samples after vaccination. Serum HBsAg may not have diagnostic value within 28 days after receipt of a hepatitis B vaccine.
General Dosing Information
-Immunization with hepatitis B vaccine, recombinant is recommended for all neonates, infants, children, and adolescents.
-Use monovalent hepatitis B vaccine rather than combination vaccines in patients younger than 6 weeks; a total of 4 doses of hepatitis B vaccines is recommended if a combination vaccine is used after a birth dose.
-Different brands of hepatitis B vaccines are interchangeable with the exception of the 2-dose hepatitis B vaccination series for adolescents 11 to 15 years of age; only Recombivax HB should be used in this schedule or the 2-dose Heplisav-B vaccination series. Series consisting of 1 dose of Heplisav-B and a vaccine from a different manufacturer should consist of 3 total vaccine doses with a minimum interval of 4 weeks between dose 1 and 2, 8 weeks between dose 2 and 3, and 16 weeks between dose 1 and 3.
-Interruption of the recommended schedule with a delay between doses should not interfere with the final immunity achieved with the hepatitis B vaccine. There is no need to start the primary series over again, regardless of the time between doses.
-Routine booster doses are not recommended as the duration of protective effect is unknown; however, revaccination may be recommended for the following populations: infants born to hepatitis B virus surface antigen (HBsAg)-positive mothers, predialysis or maintenance hemodialysis patients, and other immunocompromised patients. Post serologic testing 1 to 2 months after the final dose of vaccine is recommended to assess response to vaccination and the need for revaccination for certain patients (e.g., infants born to hepatitis B virus surface antigen (HBsAg)-positive mothers, predialysis or maintenance hemodialysis patients, HIV-infected and other immunocompromised patients, health care personnel, and sex partners of HBsAg-positive patients). In hemodialysis patients, the Advisory Committee on Immunization Practices (ACIP) recommends annual antibody testing and revaccination when HBsAg antibody concentrations decline to less than 10 milli-International units/mL.
-Hepatitis B vaccination is recommended for all infants, patients younger than 19 years, unvaccinated adults aged 19 to 59 years, and adults 60 years and older with risk factors for hepatitis B; adults 60 years and older without known risk factors may receive hepatitis B vaccination. Risk factors include being sexually active but not in a long-term, mutually monogamous relationship; seeking evaluation or treatment for a sexually transmitted disease; current or recent injection drug users; men who have sex with men; health-care and public safety workers who are exposed to blood or to other potentially infectious body fluids; adults with end-stage renal disease (ESRD) including those on hemodialysis; adults with HIV infection; patients with chronic liver disease; household contacts and sex partners of persons with chronic HBV infection; clients and staff members of institutions for persons with developmental disabilities; international travelers to countries with high or intermediate prevalence of chronic HBV infection. Adults with chronic liver disease including, but not limited to, hepatitis C virus infection, cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an ALT or AST more than twice the upper limit of normal should receive the vaccine series. Hepatitis B vaccination is also recommended for all adults in STD treatment facilities, HIV testing and treatment facilities, facilities providing drug abuse treatment and prevention services, health care settings targeting services to injection-drug users or men who have sex with men, correctional facilities, end-stage renal disease programs and facilities for chronic hemodialysis patients, and institutions and nonresidential daycare facilities for persons with developmental disabilities. Patients with diabetes may be at risk; need for Hepatitis B vaccination is determined by the treating clinician.
For hepatitis B prophylaxis:
-for prophylaxis of hepatitis B using Recombivax HB:
Intramuscular or Subcutaneous dosage (Recombivax HB):
Adults 20 years and older: 10 mcg IM or subcutaneously at initial visit; repeat at 1 and 6 months after initial dose. Administer the second dose 1 month after the first dose, and administer the third dose at least 2 months after the second dose and at least 4 months after the first dose.
Adults 18 to 19 years: 5 mcg IM or subcutaneously at initial visit. Repeat at 1 and 6 months after the initial dose.
Adult predialysis or dialysis patients: 40 mcg IM or subcutaneously at initial visit; repeat at 1 and 6 months after initial dose. For predialysis or dialysis patients, a booster dose or revaccination with 40 mcg IM or subcutaneously may be considered if the anti-HBs concentration is less than 10 milli-International Units/mL 1 to 2 months after the third dose. Assess the need for booster doses by annual antibody testing. Give booster dose when antibody concentrations decline to less than 10 milli-International Units/mL.
Revaccination for Adult Vaccine Nonresponders: Revaccination with at least 1 dose of vaccine for nonresponse after the primary series increases the proportion of those achieving seroprotection. In a study (n = 178), 47% of nonresponders developed seroprotection after 1 additional dose. Of the 86 patients without seroprotection after the first revaccination, 42% developed seroprotection after 2 additional doses. A 3-dose revaccination (n = 17) with a higher dose of 40 mcg IM or subcutaneously improved the proportion of nonresponders achieving anti-HB levels of at least 10 milli-International Units/mL in a clinical trial; single dose revaccination with a higher dose has not been demonstrated in clinical trials.
Children and Adolescents 11 to 17 years: 5 mcg IM or subcutaneously at initial visit. Repeat dose ideally at 1 and 6 months after initial dose; a minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. For pediatric patients between 11 and 15 years of age, an alternative regimen using the Recombivax HB Adult Formulation is 10 mcg given IM or subcutaneously for 2 doses, given 4 to 6 months apart.
Infants and Children 1 month to 10 years: 5 mcg IM or subcutaneously at initial visit. Repeat dose ideally at 1 and 6 months after initial dose; the final dose (3rd or 4th dose) should be administered no earlier than age 24 weeks. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. In infants and children born to HBsAg-positive mothers, test for HBsAg and antibody to HBsAg at age 9 through 12 months or 1 to 2 months after completion of the hepatitis B series if the series was delayed. Revaccinate HBsAg-negative infants with anti-HBs less than 10 milli-International Units/mL with a single dose of hepatitis B vaccine; serologic testing should follow 1 to 2 months later. Infants whose anti-HBs remains less than 10 milli-International Units/mL should receive 2 additional doses of hepatitis B vaccine to complete the second series, followed by serologic testing 1 to 2 months after the final dose.
Neonates born to HBsAg-negative mothers: 5 mcg IM or subcutaneously within 24 hours of birth. Repeat doses ideally at 1 and 6 months after initial dose; the final dose (3rd or 4th dose) should be administered no earlier than age 24 weeks. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. If the neonate weighs less than 2 kg at birth, delay the initial vaccination until 1 month of age or hospital discharge (whichever is earlier and even if weight is still less than 2 kg).
Neonates born to HBsAg-positive mothers: 5 mcg IM or subcutaneously. Administer within 12 hours of birth with hepatitis B immune globulin (HBIG). In neonates weighing less than 2 kg at birth, give the birth dose plus the standard 3-dose regimen beginning at 1 month of age. Test for HBsAg and antibody to HBsAg at age 9 through 12 months, preferably at the next well-child visit, or 1 to 2 months after completion of the hepatitis B series if the series was delayed. Revaccinate HBsAg-negative infants with anti-HBs less than 10 milli-International Units/mL with a single dose of hepatitis B vaccine; serologic testing should follow 1 to 2 months later. Infants whose anti-HBs remains less than 10 milli-International Units/mL should receive 2 additional doses of hepatitis B vaccine to complete the second series, followed by serologic testing 1 to 2 months after the final dose.
Neonates born to mothers with unknown HBsAg status: 5 mcg IM or subcutaneously. Administer within 12 hours of birth. Give hepatitis B immune globulin (HBIG) concomitantly for neonates weighing less than 2 kg; give HBIG to infants weighing at least 2 kg only with positive maternal HBsAg test result (within age 1 week) or if evidence is suggestive of maternal HBV infection (e.g., presence of HBV DNA, HBeAg-positive, or mother known to be chronically infected with HBV). In neonates whom it is not possible to determine the mother's HBsAg status (e.g., when a neonate is surrendered confidentially), complete the vaccine series according to a recommended schedule for infants born to HBsAg-positive mothers with the final dose in the series administered after 24 weeks. Test for HBsAg and antibody to HBsAg at age 9 through 12 months; revaccinate if necessary. In neonates weighing less than 2 kg, give the birth dose plus the standard 3-dose regimen beginning at 1 month of age.
-for prophylaxis of hepatitis B using Engerix-B:
Intramuscular or Subcutaneous dosage (Engerix-B):
Adults 20 years and older: 20 mcg IM or subcutaneously at initial visit; repeat at 1 and 6 months after initial dose. Administer the second dose 1 month after the first dose, and administer the third dose at least 2 months after the second dose and at least 4 months after the first dose.
Adults 18 to 19 years: 20 mcg IM or subcutaneously at initial visit; repeat at 1 and 2 months after initial dose. Give additional 20 mcg IM or subcutaneously at 12 months for prolonged maintenance of titers.
Adults who have been recently exposed to the virus and certain travelers to high-risk areas: 20 mcg IM or subcutaneously at initial visit; repeat at 1 and 2 months after initial dose. Give additional 20 mcg IM or subcutaneously at 12 months for prolonged maintenance of titers.
Adult hemodialysis patients: 40 mcg IM or subcutaneously at initial visit; repeat at 1, 2, and 6 months after initial dose. Assess the need for booster doses by annual antibody testing. Give booster dose (40 mcg IM or subcutaneously) if antibody concentrations decline to less than 10 milli-International Units/mL.
Revaccination for Adult Vaccine Nonresponders: Revaccination with at least 1 dose of vaccine for nonresponse after the primary series increases the proportion of those achieving seroprotection. In a study (n = 178), 47% of nonresponders developed seroprotection after 1 additional dose. Of the 86 patients without seroprotection after the first revaccination, 42% developed seroprotection after 2 additional doses. A 3-dose revaccination (n = 17) with a higher dose of 40 mcg IM or subcutaneously improved the proportion of nonresponders achieving anti-HB concentrations of at least 10 milli-International Units/mL in a clinical trial; single dose revaccination with a higher dose has not been demonstrated in clinical trials.
Children and Adolescents 11 to 17 years receiving primary vaccination: Give 3 doses of 10 mcg IM or subcutaneously. ACIP recommends the second and third doses ideally at 1 and 6 months after initial dose. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. Alternatively, a higher dose of 20 mcg may also be given at 0, 1, and 6 months. If prolonged duration of protective titers is desired, the higher dose of 20 mcg may be given at 0, 1, 2, and 12 months.
Children and Adolescents 11 to 16 years for whom an extended administration schedule is acceptable based on risk of exposure to the virus: Give a 3 dose-series of 10 mcg IM or subcutaneously with the second and third dose given 12 and 24 months after the first, respectively.
Children 5 to 10 years receiving primary vaccination: 10 mcg IM or subcutaneously at initial visit; repeat at 1 and 6 months after initial dose. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. If prolonged duration of protective titers is desired, doses may be given at 0, 1, 2, and 12 months.
Children 5 to 10 years for whom an extended administration schedule is acceptable based on risk of exposure to the virus: 10 mcg IM or subcutaneously at initial visit; repeat at 12 and 24 months after initial dose.
Infants and Children 1 month to 4 years: 10 mcg IM or subcutaneously at initial visit; repeat at 1 and 6 months after initial dose; the final dose (3rd or 4th dose) should be administered no earlier than age 24 weeks. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. In infants and children born to HBsAg-positive mothers, an alternative schedule of doses at 0, 1, 2, and 12 months may be used; the fourth dose is given at 12 months to prolong maintenance titers. In these infants and children, test for HBsAg and antibody to HBsAg at age 9 through 12 months, preferably at the next well-child visit, or 1 to 2 months after completion of the hepatitis B series if the series was delayed. Revaccinate HBsAg-negative infants with anti-HBs less than 10 milli-International Units/mL with a single dose of hepatitis B vaccine; serologic testing should follow 1 to 2 months later. Infants whose anti-HBs remains less than 10 milli-International Units/mL should receive 2 additional doses of hepatitis B vaccine to complete the second series, followed by serologic testing 1 to 2 months after the final dose.
Neonates born to HBsAg-negative mothers: 10 mcg IM or subcutaneously within 24 hours of birth. Repeat doses at 1 and 6 months after initial dose; the final dose (3rd or 4th dose) should be administered no earlier than age 24 weeks. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. If the neonate weighs less than 2 kg at birth, delay the initial vaccination until 1 month of age or hospital discharge (whichever is earlier and even if weight is still less than 2 kg).
Neonates born to HBsAg-positive mothers: 10 mcg IM or subcutaneously. Administer the vaccine within 12 hours of birth with hepatitis B immune globulin (HBIG). In neonates weighing less than 2 kg at birth, give the birth dose plus the standard 3-dose regimen beginning at 1 month of age. Test for HBsAg and antibody to HBsAg at age 9 through 12 months, preferably at the next well-child visit, or 1 to 2 months after completion of the hepatitis B series if the series was delayed. Revaccinate HBsAg-negative infants with anti-HBs less than 10 milli-International Units/mL with a single dose of hepatitis B vaccine; serologic testing should follow 1 to 2 months later. Infants whose anti-HBs remains less than 10 milli-International Units/mL should receive 2 additional doses of hepatitis B vaccine to complete the second series, followed by serologic testing 1 to 2 months after the final dose.
Neonates born to mothers with unknown HBsAg status: 10 mcg IM or subcutaneously. Administer the vaccine within 12 hours of birth. Give HBIG concomitantly for neonates weighing less than 2 kg; give HBIG to infants weighing at least 2 kg only with positive maternal HBsAg test result (within age 1 week) or if evidence is suggestive of maternal HBV infection (e.g., presence of HBV DNA, HBeAg-positive, or mother known to be chronically infected with HBV). In neonates whom it is not possible to determine the mother's HBsAg status (e.g., when a neonate is surrendered confidentially), complete the vaccine series according to a recommended schedule for infants born to HBsAg-positive mothers with the final dose in the series administered after 24 weeks. Test for HBsAg and antibody to HBsAg at age 9 through 12 months; revaccinate if necessary. In neonates weighing less than 2 kg born to mothers with unknown HBsAg status, give the birth dose plus the standard 3-dose regimen beginning at 1 month of age.
-for prophylaxis of hepatitis B using Heplisav-B:
Intramuscular dosage (Heplisav-B):
Adults: 20 mcg IM at initial visit; repeat at 1 month after initial dose.
-for prophylaxis of hepatitis B using Prehevbrio:
Intramuscular dosage (Prehevbrio):
Adults: 10 mcg IM at initial visit; repeat at 1 and 6 months after initial dose.
-for booster vaccination using Engerix-B:
Intramuscular and Subcutaneous dosage (Engerix-B):
Children and Adolescents 11 to 17 years: 20 mcg IM or subcutaneously, whenever administration of a booster dose is appropriate. Studies have demonstrated a substantial increase in antibody titers after booster vaccination with Engerix-B. Routine booster doses are generally not recommended as the duration of protective effect is unknown. In hemodialysis patients, ACIP recommends annual antibody testing and revaccination when HBsAg antibody concentrations decline to less than 10 milli-International units/mL.
Children 1 to 10 years: 10 mcg IM or subcutaneously, whenever administration of a booster dose is appropriate. Studies have demonstrated a substantial increase in antibody titers after booster vaccination with Engerix-B. Routine booster doses are generally not recommended as the duration of protective effect is unknown. In hemodialysis patients, ACIP recommends annual antibody testing and revaccination when HBsAg antibody concentrations decline to less than 10 milli-International units/mL.
Maximum Dosage Limits:
-Adults
20 years and older: 10 mcg/dose IM/subcutaneous for Recombivax HB; 20 mcg/dose IM/subcutaneous for Engerix-B; 20 mcg/dose IM for Heplisav-B; 10 mcg/dose IM for Prehevbrio.
18 to 19 years: 5 mcg/dose IM/subcutaneous for Recombivax HB; 20 mcg/dose IM/subcutaneous for Engerix-B; 20 mcg/dose IM for Heplisav-B; 10 mcg/dose IM for Prehevbrio.
-Geriatric
10 mcg/dose IM/subcutaneous for Recombivax HB; 20 mcg/dose IM/subcutaneous for Engerix-B; 20 mcg/dose IM for Heplisav-B; 10 mcg/dose IM for Prehevbrio.
-Adolescents
16 to 17 years: 5 mcg/dose IM/subcutaneous for Recombivax HB; 20 mcg/dose IM/subcutaneous for Engerix-B.
13 to 15 years: 5 mcg/dose IM/subcutaneous for Recombivax HB standard, 3-dose regimen or 10 mcg/dose IM/subcutaneous for Recombivax HB 2-dose regimen; 20 mcg/dose IM/subcutaneous for Engerix-B.
-Children
11 to 12 years: 5 mcg/dose IM/subcutaneous for Recombivax HB standard, 3-dose regimen or 10 mcg/dose IM/subcutaneous for Recombivax HB 2-dose regimen; 20 mcg/dose IM/subcutaneous for Engerix-B.
1 to 10 years: 5 mcg/dose IM/subcutaneous for Recombivax HB; 10 mcg/dose IM/subcutaneous for Engerix-B.
-Infants
5 mcg/dose IM/subcutaneous for Recombivax HB; 10 mcg/dose IM/subcutaneous for Engerix-B.
-Neonates
5 mcg/dose IM/subcutaneous for Recombivax HB; 10 mcg/dose IM/subcutaneous for Engerix-B.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
In adult predialysis and dialysis patients, a special formulation containing 40 mcg/mL of vaccine should be administered. For all other patients with renal impairment, it appears that no dosage adjustments are needed.
Intermittent hemodialysis
A dialysis formulation containing 40 mcg/mL of vaccine should be used. See dosage for specific regimens.
Continuous hemodialysis
A dialysis formulation containing 40 mcg/mL of vaccine should be used. See dosage for specific regimens.
Peritoneal dialysis
A dialysis formulation containing 40 mcg/mL of vaccine should be used. See dosage for specific regimens.
*non-FDA-approved indication
Albuterol; Budesonide: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Betamethasone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Bimekizumab: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to vaccines. When feasible, administer indicated vaccines at least two weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Budesonide: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Budesonide; Formoterol: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Corticosteroids (systemic): (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Corticotropin, ACTH: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Cortisone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Deflazacort: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Deucravacitinib: (Moderate) Patients receiving immunosuppressant medications may have a diminished vaccine response. When feasible, administer indicated vaccines at least two weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dexamethasone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Elivaldogene Autotemcel: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to non-live vaccines. When feasible, administer indicated vaccines at least six weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Hepatitis B Immune Globulin, HBIG: (Minor) Administration of hepatitis B virus vaccines (e.g., hepatitis B vaccine, recombinant) at the same site or in the same syringe as hepatitis B immune globulin, HBIG can result in neutralization. Hepatitis B Immune Globulin (human) may be administered at the same time (but at a different site) or up to one month preceding hepatitis B vaccination without impairing the active immune response to hepatitis B vaccine.
Hydrocortisone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Methylprednisolone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Ocrelizumab: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
Ofatumumab: (Major) Administer all needed non-live vaccines according to immunization guidelines at least 2 weeks before initiation of ofatumumab. Ofatumumab may interfere with the effectiveness of inactivated vaccines due to its actions, which cause B-cell depletion.
Prednisolone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Prednisone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Satralizumab: (Major) Administer all non-live vaccines according to immunization guidelines at least 2 weeks before initiation of satralizumab.
Siponimod: (Moderate) Administer all non-live vaccines at least 2 weeks before siponimod initiation, whenever possible. Vaccines may be less effective if given during siponimod treatment. Patients should be considered unimmunized if vaccinated within a 14-day period before starting immunosuppresive therapy or during immunosuppressive therapy, and should they be revaccinated at least 3 months after therapy is discontinued if immune competence is restored.
Triamcinolone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Ublituximab: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to non-live vaccines. When feasible, administer indicated vaccines at least two weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Vamorolone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Many epidemiological studies indicate that patients who develop anti-hepatitis B surface antigen antibodies (anti-HBs) following infection with hepatitis B are immune to the virus upon reexposure. Active immunization with hepatitis B vaccine stimulates the immune system to produce anti-HBs without exposing the patient to the risks of active infection. Infection with hepatitis D can occur only with concurrent hepatitis B infection, so vaccination with recombinant hepatitis B vaccine provides protection against hepatitis D as well.
The recombinant hepatitis B vaccine is produced by injecting Saccharomyces cerevisiae (yeast) with a plasmid that codes for the adw subtype of HBsAg. The genetically altered yeast produce significant quantities of HBsAg, which are released by cell disruption, collected, and purified. The particulate matter present in the hepatitis B vaccine, recombinant contains large amounts of protein derived from HBsAg against which an immune response occurs, resulting in the formation of anti-HBs. Extensive study of the recombinant-stimulated antibodies reveals that they are remarkably similar to naturally occurring anti-HBs in variety, biochemistry, potency, and protective efficacy.
Engerix-B and Recombivax HB are intended for intramuscular administration, although both can be given subcutaneously in patients where IM injections are contraindicated. Heplisav-B is administered intramuscularly. The pharmacokinetics of hepatitis B vaccine recombinant are not well understood. The exact distribution of the recombinant hepatitis B vaccines is not clear, and it is not known if HBsAg crosses the placenta or is excreted in human milk. Similarly, the metabolism and elimination of these vaccines are not well characterized.
-Route-Specific Pharmacokinetics
Intramuscular Route
Studies evaluating plasma-derived hepatitis B vaccine reveal that anti-HBs appear in the serum 2 weeks after IM administration, peak within 6 months, and can remain detectable for 3 to 7 years. The minimum anti-HBs titer needed to provide protection against active viral infection is 10 milliunits/mL.
-Special Populations
Pediatrics
Infants 6 months or older, Children, and Adolescents
In infants and children who received hepatitis B vaccine, recombinant (Engerix) (10 mcg/dose) at 0, 1, and 6 months, the seroprotective rate 1 to 2 months after the third dose was 98%. The geometric mean titer of seroconverters was 4023 milli-international units/mL. Similar rates of protection were found in adolescents. In infants and children, 100% and 99% experienced a protective level of antibodies after the 3-dose Recombivax series. The immunogenicity of the 2 dose regimen (10 mcg at 0 and 4 to 6 months) of hepatitis B vaccine, recombinant (Recombivax) was compared to the standard 3 dose regimen (5 mcg at 0, 1, and 6 months) in an open-label, randomized clinical study. One month after the last dose in each series, 99% of 255 adolescents who received the 2 dose regimen developed protective HBsAg antibody concentrations compared to 98% of 121 adolescents who received the 3 dose regimen. After receipt of the first 10 mcg dose, 72% of recipients developed protective HBsAg antibody concentrations.
Neonates and Infants younger than 6 months
In neonates and infants given hepatitis B vaccine, recombinant (Engerix) (10 mcg/dose) at 0, 1, and 6 months of age (n = 52) or at 0, 1, and 2 months of age (n = 381), sera was obtained 1 month following the third dose. At 7 months, 97% of infants given the vaccine at 0, 1, and 6 months of age developed seroprotective hepatitis b virus surface antigen (HBsAg) antibody concentrations (10 milli-international units/mL or greater). At 4 months, 96% of infants given the vaccine at 0, 1, and 2 months of age developed seroprotective HBsAg antibody concentrations.. Additionally, 100% of infants given the 3-dose Recombivax series had protective antibody concentrations. In neonates born to HBsAg and HBeAg positive mothers, efficacy in the prevention of hepatitis B infection after 3 doses of Recombivax and HBIG was 95% as compared to historical controls who only received HBIG.
Alternative Dosing Strategies
In a clinical trial involving children older than 5 years and adolescents immunized with 10 mcg doses of hepatitis B vaccine, recombinant (Engerix) at 0, 1, and 6 months (n = 181) or 1, 12, and 24 months (n = 161), seroprotection occurred 1 month after the third dose in 99.5% and 98.1% of recipients in each group, respectively. Geometric mean titers were higher (p = 0.02) in children who received the vaccine on the 0, 1, 6 month schedule (5687.4 milli-international units/mL vs. 3158.7 milli-international units/mL).
Booster Vaccination
The immune response to a booster dose of the vaccine was evaluated among children 5 to 7 years and adolescents 10 to 15 years who completed the primary series and got the first vaccine dose within 7 days of birth. Among the children, 70 got Engerix-B and 96 got Recombivax HB; most adolescents (132 of 138) got Recombivax HB. Four weeks after a booster dose, an anamnestic response was obtained in 99% of the 166 children and in 88% of the 138 adolescents. An anamnestic response was defined as an HBsAg antibody concentration of at least 10 milli-international units/mL for patients with a baseline concentration below 10 milli-international units/ml and at least a 4-fold increase in the concentration for patients with a baseline concentration above 10 milli-international units/mL. Only 29% of the children and 14% of the adolescents had HBsAg antibody concentrations of at least 10 milli-international units/mL before booster dose receipt. However, 95 to 100% of the 116 children with a baseline HBsAg antibody concentration less than 10 milli-international units/mL had an anamnestic response whereas only 77 to 81% of the 118 adolescents with a baseline HBsAg antibody concentration less than 10 milli-international units/mL had an anamnestic response; all of the children and adolescents with a baseline HBsAg antibody concentration of at least 10 milli-international units/mL had an anamnestic response.