Source: FDA, National Drug Code (US) Revision Year: 2020
Do not administer RECOMBIVAX HB to individuals with a history of severe allergic or hypersensitivity reactions (e.g., anaphylaxis) after a previous dose of any hepatitis B-containing vaccine or to any component of RECOMBIVAX HB, including yeast [see Description (11)].
The vial stopper and the syringe plunger stopper and tip cap contain dry natural latex rubber, which may cause allergic reactions in latex-sensitive individuals.
Apnea following intramuscular vaccination has been observed in some infants born prematurely. Decisions about when to administer an intramuscular vaccine, including RECOMBIVAX HB, to infants born prematurely should be based on consideration of the individual infant’s medical status and the potential benefits and possible risks of vaccination. For RECOMBIVAX HB, this assessment should include consideration of the mother’s hepatitis B antigen status and the high probability of maternal transmission of hepatitis B virus to infants born to mothers who are HBsAg positive if vaccination is delayed.
Hepatitis B vaccination should be delayed until 1 month of age or hospital discharge in infants weighing <2000 g if the mother is documented to be HBsAg negative at the time of the infant’s birth. Infants weighing <2000 g born to HBsAg positive or HBsAg unknown mothers should receive vaccine and hepatitis B immune globulin (HBIG) in accordance with ACIP recommendations if HBsAg status cannot be determined{3} [see Dosage and Administration (2)].
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration [see Contraindications (4)].
Hepatitis B virus has a long incubation period. RECOMBIVAX HB may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccination. Additionally, vaccination with RECOMBIVAX HB may not protect all individuals.
In healthy infants and children (up to 10 years of age), the most frequently reported systemic adverse reactions (>1% injections), in decreasing order of frequency, were irritability, fever, diarrhea, fatigue/weakness, diminished appetite, and rhinitis. In healthy adults, injection site reactions and systemic adverse reactions were reported following 17% and 15% of the injections, respectively.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.
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 adverse reactions 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 adverse reactions were reported following 17% and 15% of the injections, respectively. The following adverse reactions were reported:
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Injection site reactions consisting principally of soreness, and including pain, tenderness, pruritus, erythema, ecchymosis, swelling, warmth, nodule formation.
The most frequent systemic complaints include fatigue/weakness; headache; fever (≥100°F); malaise.
GASTROINTESTINAL DISORDERS: Nausea; diarrhea
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: Pharyngitis; upper respiratory infection
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Sweating; achiness; sensation of warmth; lightheadedness; chills; flushing
GASTROINTESTINAL DISORDERS: Vomiting; abdominal pains/cramps; dyspepsia; diminished appetite
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: Rhinitis; influenza; cough
NERVOUS SYSTEM DISORDERS: Vertigo/dizziness; paresthesia
SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Pruritus; rash (non-specified); angioedema; urticaria
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS: Arthralgia including monoarticular; myalgia; back pain; neck pain; shoulder pain; neck stiffness
BLOOD AND LYMPHATIC DISORDERS: Lymphadenopathy
PSYCHIATRIC DISORDERS: Insomnia/disturbed sleep
EAR AND LABYRINTH DISORDERS: Earache
RENAL AND URINARY DISORDERS: Dysuria
CARDIAC DISORDERS: Hypotension
The following additional adverse reactions have been reported with use of the marketed vaccine. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to a vaccine exposure.
Hypersensitivity reactions including anaphylactic/anaphylactoid reactions, bronchospasm, and urticaria 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 (5.1)]. Autoimmune diseases including systemic lupus erythematosus (SLE), lupus-like syndrome, vasculitis, and polyarteritis nodosa have also been reported.
Gastrointestinal Disorders: Elevation of liver enzymes; constipation
Nervous System Disorders: 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
Skin and Subcutaneous Disorders: Stevens-Johnson syndrome; alopecia; petechiae; eczema
Musculoskeletal and Connective Tissue Disorders: Arthritis, Pain in extremity
Blood and Lymphatic System Disorders: Increased erythrocyte sedimentation rate; thrombocytopenia
Psychiatric Disorders: Irritability; agitation; somnolence
*Eye Disorders:*Optic neuritis; tinnitus; conjunctivitis; visual disturbances; uveitis
Cardiac Disorders: Syncope; tachycardia
The following adverse reaction has been reported with another Hepatitis B Vaccine (Recombinant) but not with RECOMBIVAX HB: keratitis.
Do not mix RECOMBIVAX HB with any other vaccine in the same syringe or vial. Use separate injection sites and syringes for each vaccine.
In clinical trials in children, RECOMBIVAX HB was concomitantly administered with one or more of the following US licensed vaccines: Diphtheria, Tetanus and whole cell Pertussis; oral Poliomyelitis vaccine; Measles, Mumps, and Rubella Virus Vaccine, Live; Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] or a booster dose of Diphtheria, Tetanus, acellular Pertussis. Safety and immunogenicity were similar for concomitantly administered vaccines compared to separately administered vaccines.
In another clinical trial, a related HBsAg-containing product, Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) combination product (no longer licensed), was given concomitantly with eIPV (enhanced inactivated Poliovirus vaccine) or VARIVAX [Varicella Virus Vaccine Live (Oka/Merck)], using separate sites and syringes for injectable vaccines. No serious vaccine-related adverse events were reported, and no impairment of immune response to these individually tested vaccine antigens was demonstrated.
The Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) combination product (no longer licensed) has also been administered concomitantly with the primary series of DTaP to a limited number of infants. No serious vaccine-related adverse events were reported.
RECOMBIVAX HB may be administered concomitantly with HBIG. The first dose of RECOMBIVAX HB may be given at the same time as HBIG, but the injections should be administered at different sites.
Hepatitis B surface antigen (HBsAg) derived from hepatitis B vaccines has been transiently detected in blood samples following vaccination. Serum HBsAg detection may not have diagnostic value within 28 days after receipt of a hepatitis B vaccine, including RECOMBIVAX HB.
All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively.
There are no adequate and well-controlled studies designed to evaluate RECOMBIVAX HB in pregnant women. Available post-approval data do not suggest an increased risk of miscarriage or major birth defects in women who received RECOMBIVAX HB during pregnancy.
Developmental toxicity studies have not been conducted with the vaccine in animals.
In post-licensure clinical studies of RECOMBIVAX HB, 26 pregnant women were inadvertently administered RECOMBIVAX HB following their last menstrual period. Among these pregnancies, after excluding elective terminations (n=3), there were 23 pregnancies with known outcomes all with exposure in the first trimester. Miscarriage was reported in 4 of 23 (17%) pregnancies and major birth defects were reported in 0 of 19 (0%) live births. The rates of miscarriage and major birth defects were consistent with estimated background rates.
Post-approval adverse reactions are reported voluntarily from a population of uncertain size. It is not always possible to reliably estimate their frequency or establish a causal relationship to the vaccine.
In prospectively reported spontaneous post-approval reports from 1986 to 2018, 105 women with known pregnancy outcomes were exposed to RECOMBIVAX HB during pregnancy following the last menstrual period. After excluding induced abortions (n=5), those with exposure in the third trimester (n=4), and those with an unknown exposure timing (n=6), there were 90 pregnancies with known outcomes with exposures in the first or second trimester. Miscarriage was reported for 7 of 90 (7.8%) pregnancies. Major birth defects were reported for 2 of 83 (2.4%) live born infants. The rates of miscarriage and major birth defects were consistent with estimated background rates.
It is not known whether RECOMBIVAX HB is excreted in human milk. Data are not available to assess the effects of RECOMBIVAX HB on the breastfed infant or on milk production/excretion.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RECOMBIVAX HB and any potential adverse effects on the breastfed child from RECOMBIVAX HB or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to the disease prevented by the vaccine.
Safety and effectiveness of RECOMBIVAX HB have been established in all pediatric age groups. Maternally transferred antibodies do not interfere with the active immune response to the vaccine. [See Adverse Reactions (6.1) and Clinical Studies (14.1 and 14.2)]. The safety and effectiveness of RECOMBIVAX HB Dialysis Formulation in children have not been established.
Clinical studies of RECOMBIVAX HB used for licensure did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects. However, in later studies it has been shown that a diminished antibody response can be expected in persons older than 60 years of age.
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