Hepatitis B Vaccine (Recombinant)

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

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

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

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

Call your doctor for instructions if you miss a dose, or if you miss an appointment to have your injection given.

• If you have an allergy to any part of hepatitis B vaccine (recombinant).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have an infection or an illness with a fever.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

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]).

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

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.

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.

Hypersensitivity to yeast or any component of the vaccine.

Patients who develop symptoms suggestive of hypersensitivity after an injection should not receive further injections of the vaccine (see CONTRAINDICATIONS ).

Because of the long incubation period for hepatitis B, it is possible for unrecognized infection to be present at the time the vaccine is given. The vaccine may not prevent hepatitis B in such patients.

RECOMBIVAX HB and RECOMBIVAX HB Dialysis Formulation are generally well-tolerated. No serious adverse reactions attributable to the vaccine have been reported during the course of clinical trials. No adverse experiences were reported during clinical trials which could be related to changes in the titers of antibodies to yeast. As with any vaccine, there is the possibility that broad use of the vaccine could reveal adverse reactions not observed in clinical trials.

In three clinical studies, 434 doses of RECOMBIVAX HB, 5 mcg, were administered to 147 healthy infants and children (up to 10 years of age) who were monitored for 5 days after each dose. Injection site reactions and systemic complaints were reported following 0.2% and 10.4% of the injections, respectively. The most frequently reported systemic adverse reactions (>1% injections), in decreasing order of frequency, were irritability, fever (>/=101°F oral equivalent), diarrhea, fatigue/weakness, diminished appetite, and rhinitis.

In a study that compared the three-dose regimen (5 mcg) with the two-dose regimen (10 mcg) of RECOMBIVAX HB in adolescents, the overall frequency of adverse reactions was generally similar.

In a group of studies, 3258 doses of RECOMBIVAX HB, 10 mcg, were administered to 1252 healthy adults who were monitored for 5 days after each dose. Injection site reactions and systemic complaints were reported following 17% and 15% of the injections, respectively. The following adverse reactions were reported:

Incidence Equal to or

Greater Than 1% of Injections

LOCAL REACTION (INJECTION SITE)

Injection site reactions consisting principally of soreness, and including pain, tenderness, pruritus, erythema, ecchymosis, swelling, warmth, and nodule formation.

BODY AS A WHOLE

The most frequent systemic complaints include fatigue/weakness; headache; fever (>/=100°F); and malaise.

DIGESTIVE SYSTEM

Nausea; and diarrhea

RESPIRATORY SYSTEM

Pharyngitis; and upper respiratory infection

Incidence Less than 1% of Injections

BODY AS A WHOLE

Sweating; achiness; sensation of warmth; lightheadedness; chills; and flushing

DIGESTIVE SYSTEM

Vomiting; abdominal pains/cramps; dyspepsia; and diminished appetite

RESPIRATORY SYSTEM

Rhinitis; influenza; and cough

NERVOUS SYSTEM

Vertigo/dizziness; and paresthesia

INTEGUMENTARY SYSTEM

Pruritus; rash (non-specified); angioedema; and urticaria

MUSCULOSKELETAL SYSTEM

Arthralgia including monoarticular; myalgia; back pain; neck pain; shoulder pain; and neck stiffness

HEMIC/LYMPHATIC SYSTEM

Lymphadenopathy

PSYCHIATRIC/BEHAVIORAL

Insomnia/Disturbed sleep

SPECIAL SENSES

Earache

UROGENITAL SYSTEM

Dysuria

CARDIOVASCULAR SYSTEM

Hypotension

Marketed Experience

The following additional adverse reactions have been reported with use of the marketed vaccine. In many instances, the relationship to the vaccine was unclear.

Hypersensitivity

Anaphylaxis and symptoms of immediate hypersensitivity reactions including rash, pruritus, urticaria, edema, angioedema, dyspnea, chest discomfort, bronchial spasm, palpitation, or symptoms consistent with a hypotensive episode have been reported within the first few hours after vaccination. An apparent hypersensitivity syndrome (serum-sickness-like) of delayed onset has been reported days to weeks after vaccination, including: arthralgia/arthritis (usually transient), fever, and dermatologic reactions such as urticaria, erythema multiforme, ecchymoses and erythema nodosum (See WARNINGS and PRECAUTIONS ).

Digestive System

Elevation of liver enzymes; constipation

Nervous System

Guillain-Barré Syndrome; multiple sclerosis; exacerbation of multiple sclerosis; myelitis including transverse myelitis; seizure; febrile seizure; peripheral neuropathy including Bell's Palsy; radiculopathy; herpes zoster; migraine; muscle weakness; hypesthesia; encephalitis

Integumentary System

Stevens-Johnson Syndrome; petechiae

Musculoskeletal System

Arthritis

Hematologic

Increased erythrocyte sedimentation rate; thrombocytopenia

Immune System

Systemic lupus erythematosus (SLE); lupus-like syndrome; vasculitis

Psychiatric/Behavioral

Irritability; agitation; somnolence

Special Senses

Optic neuritis; tinnitus; conjunctivitis; visual disturbances

Cardiovascular System

Syncope; tachycardia.

The following adverse reaction has been reported with another Heaptitis B Vaccine (Recombinant) but not with RECOMBIVAX HB: keratitis.

Patients, parents and guardians should be instructed to report any serious adverse reactions to their healthcare provider, who in turn should report such events to the U.S. Department of Health and Human Services through the Vaccine Adverse Event Reporting System (VAERS), 1-800-822-7967.