Side Effects of Recombivax HB (hepatitis B vaccine)

Recombivax HB (hepatitis B vaccine) is used to prevent hepatitis B infection, a serious liver infection caused by the hepatitis B virus (HBV).

Recombivax HB is made from noninfectious parts of HBV using recombinant DNA technology. The vaccine is a sterile preparation for intramuscular injection and contains purified inactive proteins from the surface of HBV.

The proteins can activate the immune system but cannot give rise to a replicating virus. Viral proteins used in Recombivax HB are manufactured in yeast cells (S. cerevisiae) using recombinant technology. Recombivax HB works by stimulating the immune system to attack the viral proteins.

When Recombivax HB is administered, the body's immune system recognizes the viral proteins in the vaccine as foreign, and develops antibodies against them, thus providing immunity from future infections. In the event of HBV exposure following vaccination, the body will already be primed to fight the infection.

Common side effects of Recombivax HB include

• irritability,
• fever,
• diarrhea,
• fatigue,
• weakness,
• reduced appetite,
• cold symptoms,
• headache,
• injections site reactions,
• flushing,
• back pain,
• muscle pain,
• joint pain,
• rash,
• difficulty sleeping,
• dizziness,
• ringing in the ears,
• constipation, and
• taste changes.

Serious side effects of Recombivax HB include

• low blood pressure,
• seizures, and
• hair loss.

Drug interactions of Recombivax HB include fingolimod, belimumab, anakinra, adalimumab, infliximab, antineoplastic agents (anti-cancer medications), and other immunosuppressives, which may decrease the effectiveness of Recombivax HB.

There are no adequate or well-controlled trials of Recombivax HB use in pregnant women. Recombivax HB should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is unknown if Recombivax HB is excreted into breast milk after administration to the mother. The manufacturer recommends caution when given to breastfeeding mothers.

Common side effects of HBV vaccines include:

• Irritability
• Fever
• Diarrhea
• Fatigue/weakness
• Reduced appetite
• Cold symptoms

Other reported side effects include:

• Headache
• Injections site reactions
• Low blood pressure
• Flushing
• Back pain
• Muscle pain
• Joint pain
• Rash
• Difficulty sleeping
• Dizziness
• Ringing in the ears
• Seizures
• Hair loss
• Constipation
• Taste changes

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.

Clinical Trials Experience

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:

Incidence Equal To or Greater Than 1% of Injections

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

Incidence Less Than 1% of Injections

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 5

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

Post-Marketing Experience

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.

Immune System Disorders

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.
• 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.

Concomitant Administration With Other Vaccines

• 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, Comvax [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine], 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.
• Comvax 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.

Concomitant Administration With Immune Globulin

• 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.