Pharmaceutical Name

Trade (marketing or proprietary) name: Engerix-B, RECOMBIVAX HB®

Generic (nonproprietary or active ingredient) name: Hepatitis B Vaccine (Recombinant) injectable suspension for intramuscular use.

Indication and Usage

Reason the product has been approved for sale on the market.

The FDA has approved this vaccine for immunization against infection caused by all known subtypes of hepatitis B virus.

Manufacturer Insert

Ingredients

Also known as “excipients” for vaccines.

RECOMBIVAX HB Hepatitis B Vaccine (Recombinant) is a sterile suspension of non-infectious subunit viral vaccine derived from HBsAg produced in yeast cells. A portion of the hepatitis B virus gene, coding for HBsAg, is cloned into yeast, and the vaccine for hepatitis B is produced from cultures of this recombinant yeast strain according to methods developed in the Merck Research Laboratories. All formulations contain approximately 0.5 mg of aluminum (provided as amorphous aluminum hydroxyphosphate sulfate, previously referred to as aluminum hydroxide) per mL of vaccine. In each formulation, hepatitis B surface antigen is adsorbed onto approximately 0.5 mg of aluminum (provided as amorphous aluminum hydroxyphosphate sulfate) per mL of vaccine. The vaccine contains <15 mcg/mL residual formaldehyde.

• Pediatric/Adolescent Formulation (Without Preservative), 10 mcg/mL: each 0.5 mL dose contains 5 mcg of hepatitis B surface antigen.
• Adult Formulation (Without Preservative), 10 mcg/mL: each 1 mL dose contains 10 mcg of hepatitis B surface antigen.
• Dialysis Formulation (Without Preservative), 40 mcg/mL: each 1 mL dose contains 40 mcg of hepatitis B surface antigen.

ENGERIX-B [Hepatitis B Vaccine (Recombinant)] is a sterile suspension of noninfectious HBsAg for intramuscular administration. It contains purified surface antigen of the virus obtained by culturing genetically engineered Saccharomyces cerevisiae cells, which carry the surface antigen gene of the hepatitis B virus. Each 0.5-mL pediatric/adolescent dose contains 10 mcg of HBsAg adsorbed on 0.25 mg aluminum as aluminum hydroxide. Each 1-mL adult dose contains 20 mcg of HBsAg adsorbed on 0.5 mg aluminum as aluminum hydroxide. ENGERIX-B contains the following excipients: Sodium chloride (9 mg/mL) and phosphate buffers (disodium phosphate dihydrate, 0.98 mg/mL; sodium dihydrogen phosphate dihydrate, 0.71 mg/mL).

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

Engerix-B: Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B-containing vaccine, or to any component of ENGERIX-B, including yeast, is a contraindication to administration of ENGERIX-B.

RECOMBIVAX HB: 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.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

Engerix-B

Syncope: Syncope (fainting) can occur in association with administration of injectable vaccines, including ENGERIX-B. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.

Infants Weighing Less than 2,000 g at Birth: Hepatitis B vaccine should be deferred for infants with a birth weight <2,000 g 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. Infants born weighing <2,000 g to HBsAg positive mothers should receive vaccine and HBIG within 12 hours after birth. Infants born weighing <2,000 g to mothers of unknown HBsAg status should receive vaccine and HBIG within 12 hours after birth if the mother’s HBsAg status cannot be determined within the first 12 hours of life. The birth dose in infants born weighing <2,000 g should not be counted as the first dose in the vaccine series and it should be followed with a full 3-dose standard regimen (total of 4 doses).

Apnea in Premature Infants: Apnea following intramuscular vaccination has been observed in some infants born prematurely. Decisions about when to administer an intramuscular vaccine, including ENGERIX-B, to infants born prematurely should be based on consideration of the infant’s medical status, and the potential benefits and possible risks of vaccination. For ENGERIX-B, 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 of mothers who are HBsAg positive if vaccination is delayed.

Preventing and Managing Allergic Vaccine Reactions: Prior to immunization, the healthcare provider should review the immunization history for possible vaccine sensitivity and previous vaccination-related adverse reactions to allow an assessment of benefits and risks. Epinephrine and other appropriate agents used for the control of immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur.

Moderate or Severe Acute Illness: To avoid diagnostic confusion between manifestations of an acute illness and possible vaccine adverse effects, vaccination with ENGERIX-B should be postponed in persons with moderate or severe acute febrile illness unless they are at immediate risk of hepatitis B infection (e.g., infants born of HBsAg-positive mothers).

Altered Immunocompetence: Immunocompromised persons may have a diminished immune response to ENGERIX-B, including individuals receiving immunosuppressant therapy.

Multiple Sclerosis: Results from 2 clinical studies indicate that there is no association between hepatitis B vaccination and the development of multiple sclerosis,3 and that vaccination with hepatitis B vaccine does not appear to increase the short-term risk of relapse in multiple sclerosis.

Limitations of Vaccine Effectiveness: Hepatitis B has a long incubation period. ENGERIX-B may not prevent hepatitis B infection in individuals who had an unrecognized hepatitis B infection at the time of vaccine administration. Additionally, it may not prevent infection in individuals who do not achieve protective antibody titers.

RECOMBIVAX HB®

Hypersensitivity to Latex: 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 in Premature Infants: 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.

Infants Weighing Less Than 2000 g: 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.

Prevention and Management of Allergic Vaccine Reactions: Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration.

Limitations of Vaccine Effectiveness: 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.

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

Engerix-B can cause: Herpes zoster (Shingles), Meningitis, Thrombocytopenia, Allergic/anaphylactoid reaction, anaphylaxis, Hypersensitivity syndrome (serum sickness-like), Arthralgia/arthritis, Fever, Urticaria (hives), Erythema multiforme/nodosum, Ecchymoses, Encephalitis, Visual disturbances, Earache, Tinnitus, Vertigo, Palpitations, Tachycardia, Vasculitis, Apnea, Bronchospasm including asthma-like symptoms, Dyspepsia, Alopecia (baldness), Angioedema, Encephalopathy, Migraine, Multiple sclerosis, Neuritis, Paralysis, Paresis, Seizures, Syncope (fainting), Transverse myelitis, Conjunctivitis (pink eye), Keratitis, Eczema, Erythema multiforme including Stevens-Johnson syndrome, Lichen planus, Purpura, Arthritis, Muscular weakness, Injection site reaction, Abnormal liver function tests, Neuropathy: hypoesthesia, paresthesia, Guillain-Barré syndrome, Bell’s palsy, optic neuritis.

RECOMBIVAX HB® can cause: Anaphylactic/anaphylactoid reactions, Bronchospasm, Urticaria (Hives), Hypersensitivity syndrome (serum-sickness-like), Arthralgia/arthritis, Fever, Erythema multiforme, Ecchymoses and erythema nodosum, Systemic lupus erythematosus (SLE), Lupus-like syndrome, Vasculitis, Polyarteritis nodosa, Elevation of liver enzymes, Constipation, Guillain-Barré syndrome, Multiple sclerosis, Transverse myelitis, Seizure/febrile seizure, Radiculopathy, Herpes zoster (Shingles), Migraine, Muscle weakness, Hypesthesia, Encephalitis, Stevens-Johnson syndrome, Alopecia (baldness), Petechiae, Eczema, Pain in extremity, Increased erythrocyte sedimentation rate, Thrombocytopenia, Irritability, Agitation, Somnolence, Optic neuritis, Tinnitus (ringing ears), Conjunctivitis (Pink eye), Visual disturbances, Uveitis, Syncope (Fainting), Tachycardia, and Peripheral neuropathy including Bell’s Palsy.

Limitations of Vaccine Effectiveness

Hepatitis B has a long incubation period. ENGERIX-B/RECOMBIVAX HB may not prevent hepatitis B infection in individuals who had an unrecognized hepatitis B infection at the time of vaccine administration. Additionally, it may not prevent infection in individuals who do not achieve protective antibody titers.

Specific Populations

Pregnancy

There are no adequate and well-controlled studies of ENGERIX-B/RECOMBIVAX HB in pregnant women in the U.S.

Breastfeeding

There is no information regarding the presence of ENGERIX-B/RECOMBIVAX HB in human milk, the effects on the breastfed child, or the effects on milk production.

Fertility

ENGERIX-B/RECOMBIVAX HB has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility in animals.

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

Engerix-B

Infection with hepatitis B virus can have serious consequences including acute massive hepatic necrosis and chronic active hepatitis. Chronically infected persons are at increased risk for cirrhosis and hepatocellular carcinoma. Antibody concentrations greater than or equal to 10 mIU/mL against HBsAg are recognized as conferring protection against hepatitis B virus infection. Seroconversion is defined as antibody titers greater than or equal to 1 mIU/mL.

RECOMBIVAX HB®

RECOMBIVAX HB has been shown to elicit antibodies to hepatitis B virus as measured by ELISA. Antibody concentrations ≥10mIU/mL against HBsAg are recognized as conferring protection against hepatitis B infection. Infection with hepatitis B virus can have serious consequences including acute massive hepatic necrosis and chronic active hepatitis. Chronically infected persons are at increased risk for cirrhosis and hepatocellular carcinoma.

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