TWINRIX SIDE EFFECTS

SIDE EFFECTS

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 with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

Following any dose of TWINRIX, the most common (≥10%) solicited injection site reactions were injection site soreness (35% to 41%) and redness (8% to 11%); the most common solicited systemic adverse reactions were headache (13% to 22%) and fatigue (11% to 14%).

The safety of TWINRIX has been evaluated in clinical trials involving the administration of approximately 7,500 doses to more than 2,500 individuals.

In a U.S. study, 773 subjects (aged 18 to 70 years) were randomized 1:1 to receive TWINRIX (0-, 1-, and 6-month schedule) or concurrent administration of ENGERIX-B (0-, 1-, and 6-month schedule) and HAVRIX (0- and 6-month schedule). Solicited local adverse reactions and systemic adverse events were recorded by parents/guardians on diary cards for 4 days (Days 0 to 3) after vaccination. Unsolicited adverse events were recorded for 31 days after vaccination. Solicited reactions reported following the administration of TWINRIX or ENGERIX-B and HAVRIX are presented in Table 1.

Table 1: Rates of Local Adverse Reactions and Systemic Adverse Reactions within 4 Days of Vaccination^a with TWINRIX^b or ENGERIX-B and HAVRIX^c

Most solicited local adverse reactions and systemic adverse reactions seen with TWINRIX were considered by the subjects as mild and self-limiting and did not last more than 48 hours.

In a clinical trial in which TWINRIX was given on a 0-, 7-, and 21- to 30-day schedule followed by a booster dose at 12 months, solicited local adverse reactions or systemic adverse reactions were comparable to those seen in other clinical trials of TWINRIX given on a 0-, 1-, and 6-month schedule.

Among 2,299 subjects in 14 clinical trials, the following adverse reactions were reported to occur within 30 days following vaccination:

Incidence 1% To 10% Of Injections, Seen In Clinical Trials With TWINRIX

Infections and Infestations: Upper respiratory tract infections.

General Disorders and Administration Site Conditions: Injection site induration.

Incidence <1% Of Injections, Seen In Clinical Trials With TWINRIX

Infections and Infestations: Respiratory tract illnesses.

Metabolism and Nutrition Disorders: Anorexia.

Psychiatric Disorders: Agitation, insomnia.

Nervous System Disorders: Dizziness, migraine, paresthesia, somnolence, syncope.

Ear and Labyrinth Disorders: Vertigo.

Vascular Disorders: Flushing.

Gastrointestinal Disorders: Abdominal pain, vomiting.

Skin and Subcutaneous Tissue Disorders: Erythema, petechiae, rash, sweating, urticaria.

Musculoskeletal and Connective Tissue Disorders: Arthralgia, back pain, myalgia.

General Disorders and Administration Site Conditions: Injection site ecchymosis, injection site pruritus, influenza-like symptoms, irritability, weakness.

Incidence <1% Of Injections, Seen In Clinical Trials With HAVRIX And/Or ENGERIX-B

Blood and Lymphatic System Disorders: Lymphadenopathy.^a+b

Nervous System Disorders: Dysgeusia,^a hypertonia,^a tingling.^b

Eye Disorders: Photophobia.^a

Vascular Disorders: Hypotension.^b

Gastrointestinal Disorders: Constipation.^b

Investigations: Creatine phosphokinase increased.^a

^a+b Following either HAVRIX or ENGERIX-B.
^a Following HAVRIX.
^b Following ENGERIX-B.

Adverse reactions within 30 days of vaccination in the U.S. clinical trial of TWINRIX given on a 0-, 7-, and 21- to 30-day schedule followed by a booster dose at 12 months were comparable to those reported in other clinical trials.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of TWINRIX, HAVRIX, or ENGERIX-B. 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 the vaccine.

Postmarketing Experience With TWINRIX

Infections and Infestations: Herpes zoster, meningitis.

Blood and Lymphatic System Disorders: Thrombocytopenia, thrombocytopenic purpura.

Immune System Disorders: Allergic reaction, anaphylactoid reaction, anaphylaxis, serum sickness-like syndrome days to weeks after vaccination (including arthralgia/arthritis, usually transient; fever; urticaria; erythema multiforme; ecchymoses; and erythema nodosum).

Nervous System Disorders: Bell’s palsy, convulsions, encephalitis, encephalopathy, Guillain-Barre syndrome, hypoesthesia, myelitis, multiple sclerosis, neuritis, neuropathy, optic neuritis, paralysis, paresis, transverse myelitis.

Eye Disorders: Conjunctivitis, visual disturbances.

Ear and Labyrinth Disorders: Earache, tinnitus.

Cardiac Disorders: Palpitations, tachycardia.

Vascular Disorders: Vasculitis.

Respiratory, Thoracic, and Mediastinal Disorders: Bronchospasm, including asthma-like symptoms; dyspnea.

Gastrointestinal Disorders: Dyspepsia.

Hepatobiliary Disorders: Hepatitis, jaundice.

Skin and Subcutaneous Tissue Disorders: Alopecia, angioedema, eczema, erythema multiforme, erythema nodosum, hyperhidrosis, lichen planus.

Musculoskeletal and Connective Tissue Disorders: Arthritis, muscular weakness.

General Disorders and Administration Site Conditions: Chills; immediate injection site pain, stinging, and burning sensation; injection site reaction; malaise.

Investigations: Abnormal liver function tests.

Postmarketing Experience With HAVRIX And/Or ENGERIX-B

The following list includes adverse reactions for HAVRIX and/or ENGERIX-B not already reported above for TWINRIX.

Eye Disorders: Keratitis.^a

Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome.^a

Congenital, Familial, and Genetic Disorders: Congenital abnormality.^b

SRC: NLM .