Vaccine Information: TWINRIX
TWINRIX- hepatitis a virus strain hm175 antigen (formaldehyde inactivated) and hepatitis b virus subtype adw2 hbsag surface protein antigen injection, suspension
GlaxoSmithKline Biologicals SA
1 INDICATIONS AND USAGE
TWINRIX is indicated for active immunization against disease caused by hepatitis A virus and infection by all known subtypes of hepatitis B virus. TWINRIX is approved for use in persons 18 years of age or older.
2 DOSAGE AND ADMINISTRATION
2.1 Preparation for Administration
The vaccine should be re-suspended before use. When re-suspended, the vaccine will have a uniform hazy white appearance.
Upon storage, a fine white deposit with a clear colorless layer above may be present. Re-suspend the vaccine following the steps below.
1. Hold the syringe upright in a closed hand.
2. Shake the syringe by tipping it upside down and back upright again.
3. Repeat this action vigorously for at least 15 seconds.
4. Inspect the vaccine again:
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- If the vaccine appears as a uniform hazy white suspension, it is ready to use – the appearance should not be clear.
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- If the vaccine still does not appear as a uniform hazy white suspension, tip upside down and back upright again for at least another 15 seconds then inspect again.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.
Attach a sterile needle to the prefilled syringe and administer intramuscularly.
2.2 Administration
TWINRIX should be administered by intramuscular injection only as a 1-mL dose. Administer in the deltoid region. Do not administer in the gluteal region; such injections may result in a suboptimal response.
Do not administer this product intravenously, intradermally, or subcutaneously.
2.3 Recommended Dose and Schedule
Standard dosing schedule consists of 3 doses (1-mL each), given intramuscularly at 0, 1, and 6 months. Alternatively, an accelerated schedule of 4 doses (1-mL each), given intramuscularly on Days 0, 7, and 21 to 30 followed by a booster dose at Month 12 may be used.
3 DOSAGE FORMS AND STRENGTHS
Suspension for injection available in 1-mL prefilled TIP-LOK syringes [see Description (11), How Supplied/Storage and Handling (16)].
4 CONTRAINDICATIONS
Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis A-containing or hepatitis B-containing vaccine, or to any component of TWINRIX, including yeast and neomycin, is a contraindication to administration of TWINRIX [see Description (11)].
5 WARNINGS AND PRECAUTIONS
5.1 Latex
The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions.
5.2 Syncope
Syncope (fainting) can occur in association with administration of injectable vaccines, including TWINRIX. 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.
5.3 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. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine. [See Contraindications (4).]
5.4 Moderate or Severe Acute Illness
To avoid diagnostic confusion between manifestations of an acute illness and possible vaccine adverse effects, vaccination with TWINRIX should be postponed in persons with moderate or severe acute febrile illness unless they are at immediate risk of hepatitis A or hepatitis B infection.
5.5 Altered Immunocompetence
Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished immune response to TWINRIX.
5.6 Multiple Sclerosis
Results from 2 clinical studies indicate that there is no association between hepatitis B vaccination and the development of multiple sclerosis,1 and that vaccination with hepatitis B vaccine does not appear to increase the short-term risk of relapse in multiple sclerosis.2
5.7 Limitations of Vaccine Effectiveness
Hepatitis A and hepatitis B have relatively long incubation periods. The vaccine may not prevent hepatitis A or hepatitis B infection in individuals who have an unrecognized hepatitis A or hepatitis B infection at the time of vaccination. Additionally, vaccination with TWINRIX may not protect all individuals.
6 ADVERSE REACTIONS
6.1 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.
| Local | TWINRIX | ENGERIX-B | HAVRIX | |||||
| Dose 1 | Dose 2 | Dose 3 | Dose 1 | Dose 2 | Dose 3 | Dose 1 | Dose 2 | |
| (n = 385) % | (n = 382) % | (n = 374) % | (n = 382) % | (n = 376) % | (n = 369) % | (n = 382) % | (n = 369) % | |
| Soreness | 37 | 35 | 41 | 41 | 25 | 30 | 53 | 47 |
| Redness | 8 | 9 | 11 | 6 | 7 | 9 | 7 | 9 |
| Swelling | 4 | 4 | 6 | 3 | 5 | 5 | 5 | 5 |
| Systemic | TWINRIX | ENGERIX-B and HAVRIX | ||||||
| Dose 1 | Dose 2 | Dose 3 | Dose 1d | Dose 2e | Dose 3d | |||
| (n = 385) % | (n = 382) % | (n = 374) % | (n = 382) % | (n = 376) % | (n = 369) % | |||
| Headache | 22 | 15 | 13 | 19 | 12 | 14 | ||
| Fatigue | 14 | 13 | 11 | 14 | 9 | 10 | ||
| Diarrhea | 5 | 4 | 6 | 5 | 3 | 3 | ||
| Nausea | 4 | 3 | 2 | 7 | 3 | 5 | ||
| Fever | 4 | 3 | 2 | 4 | 2 | 4 | ||
| Vomiting | 1 | 1 | 0 | 1 | 1 | 1 | ||
- a Within 4 days of vaccination defined as day of vaccination and the next 3 days.
- b 389 subjects received at least 1 dose of TWINRIX.
- c 384 subjects received at least 1 dose each of ENGERIX-B and HAVRIX.
- d Doses 1 and 3 included ENGERIX-B and HAVRIX in the control group receiving separate vaccinations.
- e Dose 2 included only ENGERIX-B in the control group receiving separate vaccinations.
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.
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