Twinrix: Vaccine against hepatitis A and B

2021-06-26 11:34 PM

Twinrix immunizes against hepatitis A and hepatitis B infections by generating specific antibodies to HAV and anti-HBs. Twinrix is indicated for immunocompromised individuals who are at risk for both hepatitis A and hepatitis B infection.

Producer

GlaxoSmithKline

Ingredient

Each dose 1.0mL

Hepatitis A virus (inactivated) 1,2:720 ELISA units.

Hepatitis B3,4 surface antigen: 20 micrograms.

1. Produced on diploid human cells (MRC-5).

2. Adsorbed on aluminum hydroxide, 0.05 milligram Al3+ hydration.

3. Produced on yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology.

4. Adsorbed on aluminum phosphate 0.4 milligram Al3+.

Describe

Twinrix is ​​a slightly opalescent, white liquid in a pre-filled glass syringe.

The amino acids for use in the injectable product, formaldehyde, neomycin sulfate, and polysorbate 20 present in the product are residues from the manufacturing process.

Pharmacodynamic

Pharmacotherapeutic group: hepatitis vaccine, ATC code: J07BC20.

Twinrix immunizes against hepatitis A and hepatitis B infections by generating specific antibodies to HAV and anti-HBs.

Children from 1 to 15 years old

According to clinical studies conducted in children 1 to 15 years of age, the seropositivity rate for anti-HAV antibodies was 99.1% one month after the first dose and 100% after the second dose was administered. 6th month (ie 7th month). The seropositive rate for anti-HBs antibodies was 74.2% one month after the first dose and 100% after the second dose administered at month 6 (ie, month 7). The rates of seroprotection against HBs (titer ≥10 mIU/mL) at these time points were 37.4% and 98.2%, respectively.

In a clinical study in children 12 to including 15 years of age who received a second dose at 12 months, the seropositivity rate for anti-HAV antibodies was 99.0% and the seropositivity rate was 99.0%. for anti-HBs antibodies was 99.0% at 13 months with a seroprotection rate of 97.0%.

In a comparative study conducted in adolescents (aged 12 to including 15 years), a 3-dose vaccination schedule compared with a combination vaccine containing 360 units of inactivated hepatitis A virus ELISA and 10 μg of HBsAg in a 0.5 mL dose, the seroprotection rate against HBs prior to the second dose of Twinrix was lower than that achieved with the 3-dose vaccination schedule, but not as more after completing the vaccination schedule (at month 7).

Anti-HAV and anti-HBs antibodies have been shown to persist for at least 10 years after initiation of Twinrix injection according to the 0.6-month regimen. After 10 years, the anti-HAV seroprevalence was 100% in both age groups 1-11 years old and 12-15 years old. The rate of seroprotection against HBs in these two groups was 77.3% and 85.9%, respectively.

In a study performed on 12-15-year-old subjects with the primary immunization schedule, the immune response to both antigenic components was similar to that obtained after a 3-dose regimen when using the vaccine. Use a combination vaccine containing 360 units of inactivated hepatitis A virus ELISA and 10 µg of recombinant hepatitis B surface antibody in a 0.5 mL dose.

In a 6-year follow-up study of 12-15-year-old subjects receiving the primary immunization schedule, the anti-HAV seroprevalence was 100% with the 0.6-month or 0.12-month regimen. The seroprotection rates for anti-HBs antibodies were 84.8% and 92.9%, respectively.

Adults and adolescents 16 years of age and older

In adults 16 years of age and older who received Twinrix as a 3-dose regimen, protection against hepatitis A and hepatitis B appeared within 2-4 weeks. In clinical studies, specific humoral antibodies to hepatitis A were observed in approximately 94% of adults at one month after the first dose and in 100% at one month after the third dose (at month 7). . 70% of adults after the first dose and about 99% after the third dose have developed specific humoral antibodies against hepatitis B.

Exceptions in adults using the 0.7, 21 primary immunization schedule and adding a 4th dose at 12 months showed that 82% and 85% of those vaccinated had protective seroprotective levels, respectively. anti-HBV at weeks 1 and 5 after the third dose. One month after the fourth dose, all vaccinated individuals reached seroprotective levels against HBV. The anti-HAV seroprevalence reached 100% and 99.5% at weeks 1 and 5, respectively, after the third dose and reached 100% one month after the fourth dose.

In a clinical study performed in a group of patients over 40 years of age, the rate of seropositive anti-HAV antibodies and the rate of seroprotection against hepatitis B when using Twinrix according to regimen 0, 1, 6 months are comparable to the seropositive rates and seroprotection rates when using each monovalent hepatitis A and B vaccine.

The seroprotection rates against hepatitis B after administration of Twinrix were 92% and 57%, respectively, 7 and 48 months after the first dose, compared with 80% and 40% after vaccination with Twinrix. GlaxoSmithKline Biologicals 20 µg hepatitis B vaccine, and compared with 71% and 27% after another licensed 10 µg hepatitis B vaccine. In all groups, anti-HBs antibody levels decreased with increasing age and body mass index; This concentration is lower in men than in women.

The seropositivity rate for anti-HAV antibodies after administration of Twinrix was 97% at both 7 and 48 months after the first dose compared with 99% and 94% after hepatitis A vaccine. unit price of GlaxoSmithKline Biologicals and compared with 99% and 96% after other licensed monovalent hepatitis A vaccine.

Subjects received an additional dose of Twinrix to assess immunologic memory at 48 months after the first dose of the primary immunization regimen with the same vaccine. One month after this supplement, 95% of subjects achieved anti-HBV antibody levels ≥10 mIU/mL and mean antibody levels increased 179-fold (mean antibody levels were 7233.7 mIU/mL). , thereby suggesting an immune memory response.

In 2 clinical studies performed in adults, 15 years after primary vaccination with Twinrix, the anti-HAV seroprevalence rate was 100% in both studies and the seroprotection rate against HBs is 89.3% and 92.9%, respectively (n=56). The pharmacokinetics of anti-HAV and anti-HBs antibody depletion was similar to subjects receiving monovalent vaccines.

Preclinical safety data

Preclinical safety data do not indicate any special hazard for humans based on general safety studies.

Indications and uses

Twinrix is ​​indicated for use in non-immune adults, adolescents, and children 1 year of age and older who are at risk for both hepatitis A and hepatitis B infection.

Dosage and Administration

Dosage

A 1.0 mL dose of Twinrix is ​​recommended for adults, adolescents, and children 1 year of age and older.

Basic vaccination schedule

Adults and adolescents 16 years of age and older

The standard primary immunization schedule with Twinrix consists of 3 doses, the first dose on the day of your choice, the second dose 1 month after the first dose, and the third dose 6 months after the first dose.

In exceptional cases in adults, when traveling for about 1 month or more after the first dose and cannot follow the 0, 1, and 6-month immunization schedule, a 3-shot schedule may be used. corn at 0, 7, and 21 days. When using this injection schedule, the 4th dose should be given 12 months after the first dose.

Children from 1 to 15 years old

Twinrix's standard primary immunization schedule consists of 2 doses, the first dose on the day of your choice, the second dose approximately 6 to 12 months after the first dose. Protection against hepatitis B infection cannot be achieved in all vaccinated persons until after the second dose, it is important to receive the second dose to ensure protection against infection hepatitis B.

The recommended vaccination schedule should be followed. Once vaccination is started, the same vaccine should be given throughout the primary course of immunization.

Reminder dose

Following administration of Twinrix to adults with a 0, 1, 6-month immunization schedule, data suggest long-lasting antibodies for up to 15 years after vaccination.

Anti-HBs and anti-HAV antibody titers observed after primary vaccination with combination vaccines were similar to those observed with monovalent vaccines. Following administration of Twinrix to adults, the pharmacokinetics of antibody depletion were similar to those following immunization with monovalent vaccines.

General guidelines for booster schedules can be drawn from experience with monovalent vaccines.

Hepatitis B

It is not clear whether a booster dose of hepatitis B vaccine for healthy subjects who have had the full primary course of therapy is necessary; however, some official immunization programs now recommend booster doses of hepatitis B vaccine and this should be taken into account.

In certain populations of patients exposed to HBV (e.g. hemodialysis or immunocompromised patients), care should be taken to ensure that protective antibody levels 10 IU/L are achieved.

Hepatitis A

It is not yet clear whether immunocompetent individuals who respond to the hepatitis A vaccine will need booster doses as protection can still be guaranteed by immunological memory even without a booster dose. antibodies detected. The guidelines for booster doses are based on the assumption that antibody production is required to provide protection; Anti-HAV antibodies have been shown to persist for at least 10 years.

Where a booster dose is required for both hepatitis A and hepatitis B, Twinrix can be used. In addition, people who are first vaccinated with Twinrix can receive a booster dose of the monovalent vaccines. The safety and immunogenicity of Twinrix booster doses after two primary vaccinations have not been evaluated.

Using

Twinrix should be injected intramuscularly into the deltoid muscle in the upper arm in adults, adolescents, and children. It can be injected into the anterolateral side of the thigh in young children.

Intradermal or gluteal injection should be avoided as a suboptimal response to the vaccine may be produced. Exceptionally, Twinrix may be administered subcutaneously to individuals with thrombocytopenia or bleeding disorders because bleeding may occur after intramuscular injection in these subjects. However, this route of administration may induce a suboptimal immune response.

Instructions for use and preservation

Vaccines should be shaken well before use. After thorough shaking, the vaccine should appear as a uniform translucent white suspension.

During storage, a fine white layer and a colorless upper layer can be observed.

Shake the vaccine well to obtain a translucent white homogeneous suspension.

Vaccines can be homogenized following the steps below.

1. Hold the syringe upright in the clenched fist.

2. Shake the syringe by turning the syringe over and over.

3. Repeat the movement above for at least 15 seconds.

4. Test the vaccine again:

a) If the vaccine is a homogeneous translucent white suspension, the vaccine is ready for use.

b) If the vaccine still does not produce a uniform translucent white suspension, turn the syringe over and over again for at least 15 seconds and then recheck.

Vaccines should be visually inspected for foreign substances or unusual physical forms prior to administration. If so, the vaccine must be discarded.

Unused products or ingredients should be disposed of according to local regulations.

Warning

As with other vaccines, administration of Twinrix should be delayed in those who are experiencing acute high fever.

Due to the psychological reaction to the injection, the vaccinated person may faint after or even before the injection. It is important to select the appropriate unit for the injection to avoid injury from fainting.

It is possible that some people are in the incubation period of hepatitis A or B infection at the time of vaccination. It is not yet known whether Twinrix will prevent hepatitis A and B in these cases.

This vaccine does not prevent infection caused by other agents such as hepatitis C and hepatitis E and other known pathogens that cause hepatitis.

Twinrix is ​​not recommended for post-exposure (eg, needlestick) prevention. The vaccine has not been tested in immunocompromised patients. In patients on hemodialysis and those with weakened immune systems, adequate anti-HAV and HBs antibody titers may not be achieved after the primary immunization schedule and therefore doses of the vaccine may be required. Please supplement for these patients.

As with all parenteral vaccines, medical treatment and reasonable monitoring should be available to prevent the development of anaphylaxis, although rarely, following vaccination.

Under no circumstances should Twinrix be administered intravenously.

Effects on ability to drive and use machinery

This vaccine does not affect the ability to drive and use machines.

Overdose

Cases of overdose following Twinrix injection have been reported in post-marketing surveillance. Adverse events reported after overdose were similar to those reported after vaccination with the usual dose.

Contraindications

Twinrix should not be used in persons with known hypersensitivity to any component of the vaccine or who have demonstrated hypersensitivity following a previous dose of Twinrix or to monovalent hepatitis A or hepatitis B vaccines.

Use in pregnant and lactating women

Pregnancy

Twinrix should be used during pregnancy only when clearly needed and when the potential benefit outweighs the possible risk to the fetus.

The effects of Twinrix on survival and development during infancy, perinatal and postnatal periods have not been evaluated in clinical trials.

The effects of Twinrix on survival and development during infancy, perinatal and postnatal periods have been studied in rats. Animal studies have shown no direct or indirect harmful effects on fertility, pregnancy, embryo/fetal development, parturition or postnatal development.

Breastfeeding

There are no adequate human data on the use of Twinrix during lactation and animal reproduction studies. Therefore, caution should be exercised when Twinrix is ​​used in nursing mothers.

Interactive

There are no data on the concomitant use of Twinrix with hepatitis A-specific immunoglobulin or hepatitis B-specific immunoglobulin. However, when monovalent hepatitis A and hepatitis B vaccines were co-administered with specific immunoglobulins, no effect on seroconversion was observed, although antibody titers could be induced. lower body.

Clinical studies have shown that Twinrix can be administered concurrently with diphtheria, tetanus, acellular pertussis, inactivated polio, Haemophilus influenzae type b (DTPa-IPV/Hib), or measles vaccine. -mumps-rubella for 2-year-olds. In these trials, vaccinations were administered at different sites.

Although Twinrix has not been specifically studied with other vaccines, interactions are unlikely if different syringes were used and different sites were injected.

Patients on immunosuppressive therapy or immunocompromised patients may not achieve an adequate immune response.

Incompatibility

Twinrix should not be mixed with other vaccines in the same syringe.

Side effects

Systemic and local adverse reactions following a primary dose of Twinrix were classified by the frequency of occurrence.

The frequency of adverse events is classified as follows: Very common: ≥1/10, Common: ≥1/100 and <1/10, Uncommon: ≥1/1000 and <1/ 100, Rare: ≥1/10,000 and <1/1000, Very rare: <1/10,000.

Adults and adolescents 16 years of age and older

The safety data below are for more than 6000 subjects injected with the standard regimen 0, 1, 6 months or the rapid injection regimen 0, 7, 21 days.

A comparative study found that the frequency of adverse events was not different after administration of Twinrix than after administration of monovalent vaccines.

In a clinical trial where Twinrix was administered as a 0, 7, 21-day regimen, systemic symptoms were reported with the same frequency classification as above. After an additional fourth dose at 12 months, the incidence of systemic adverse events was similar to the incidence after the 0.7, 21-day regimen.

Children from 1 to 15 years old (including 15 years old)

Clinical trials were conducted using 1537 doses of Twinrix according to the 2-dose primary immunization schedule in 778 subjects aged 1 to 15 years.

Preservation

Twinrix should be stored between +2oC and +8oC.

Do not freeze; Discard if the vaccine is frozen.

Presentation and packaging

Suspension for injection: box of 1 pre-filled syringe containing 1 dose of 1.0mL (the pre-filled syringe is made of class 1 neutral glass, in accordance with the requirements of the European Pharmacopoeia).