1. Name Of The Medicinal Product
VAQTA® Adult
Hepatitis A Vaccine, Purified Inactivated, for Adults
2. Qualitative And Quantitative Composition
Each 1 millilitre dose contains approximately 50U of hepatitis A virus antigen adsorbed onto approximately 0.45 milligram of aluminium provided as aluminium hydroxide, and 70 micrograms of sodium borate as a pH stabiliser, in 0.9% sodium chloride. Neomycin and formaldehyde are used in the manufacturing process.
3. Pharmaceutical Form
VAQTA® Adult is a sterile suspension for intramuscular use.
4. Clinical Particulars
4.1 Therapeutic Indications
VAQTA® Adult is indicated for active pre-exposure prophylaxis against disease caused by hepatitis A virus. Vaccination is recommended in healthy adults who are at risk of contracting or spreading infection or who are at risk of life-threatening disease if infected.
Subjects at high risk of hepatitis A infection include those travelling to, or living in, medium or high endemicity areas. Other high risk groups include recent close contacts of infected individuals and potential contacts of cases such as childcare or healthcare workers. In the event of a case contact, human normal immunoglobulin should be given simultaneously with VAQTA® Adult at different sites. Individuals who potentially play a key role in transmitting infection, e.g. food-handlers, might also be considered for vaccination.
VAQTA® Adult will not prevent hepatitis caused by infectious agents other than hepatitis A virus.
4.2 Posology And Method Of Administration
VAQTA® Adult should be injected INTRAMUSCULARLY in the deltoid region. The vaccine should not be administered subcutaneously or intradermally since administration by these routes may result in a less than optimal antibody response.
VAQTA® Adult should never be administered intravenously.
The vaccination series consists of one primary dose and one booster dose given according to the following schedule:
Adults, 18 years of age and older, should receive a single 1.0 millilitre (~50U) dose of vaccine at an elected date and a booster dose of 1.0 millilitre (~50U) 6 to 12 months later.
Interchangeability of the Booster Dose
A booster dose of VAQTA®Adult may be given at 6 to 12 months following the initial dose of other inactivated hepatitis A vaccines.
Use with Other Vaccines
VAQTA®Adult may be given concomitantly with yellow fever and polysaccharide typhoid vaccines. Data on concomitant use with other vaccines are limited. Separate injection sites and syringes should be used for concomitant administration of injectable vaccines.
Known or Presumed Exposure to HAV/Travel to Endemic Areas /Use with Immunoglobulin
VAQTA® Adult may be administered concomitantly with immunoglobulin using separate sites and syringes. The vaccination regimen for VAQTA® Adult should be followed as stated above. Consult the appropriate Summary of Product Characteristics/Data Sheet for the dosage of immunoglobulin. A booster dose of VAQTA® Adult should be administered at the appropriate time as outlined above (see 4.5 Interaction with other Medicinal Products and other forms of Interaction).
4.3 Contraindications
Hypersensitivity to any component of the vaccine.
Vaccination should be delayed in subjects with current severe febrile infections.
VAQTA® Adult is not to be used in individuals under 18 years of age.
4.4 Special Warnings And Precautions For Use
Individuals who develop symptoms suggestive of hypersensitivity after an injection of VAQTA® Adult should not receive further injections of the vaccine (see 4.3 Contraindications).
Duration of antibodies:
The long-term duration of serum antibodies to hepatitis A virus is unknown. In cases of doubt, the serum anti-hepatitis A antibody titre should be determined. However, immune memory persists in seroconverted vaccinees even if antibody titres wane to undetectable levels, and such individuals generally respond anamnestically to a booster.
Testing for antibodies to hepatitis A prior to a decision on immunisation should be performed in patients born in areas of high endemicity and/or with a history of jaundice.
VAQTA® Adult does not cause immediate protection against hepatitis A, and there may be a period of 2 to 4 weeks before antibody induction occurs.
VAQTA® Adult will not prevent hepatitis caused by infectious agents other than hepatitis A virus. Because of the long incubation period (approximately 20 to 50 days) for hepatitis A, it is possible for unrecognised hepatitis A infection to be present at the time the vaccine is given. The vaccine may not prevent hepatitis A in such individuals.
As with any vaccine, adequate treatment provisions, including epinephrine (adrenaline), should be available for immediate use should an anaphylactic or anaphylactoid reaction occur.
As with any vaccine, vaccination with VAQTA® Adult may not result in a protective response in all susceptible vaccinees.
As no studies have been performed with VAQTA® Adult in subjects with liver disease the use of this vaccine in such subjects should be considered with care.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
If VAQTA® Adult is used in individuals with malignancies or those receiving immunosuppressive therapy or who are otherwise immunocompromised, the expected immune response may not be obtained.
Use with Immunoglobulin
For individuals requiring either post exposure prophylaxis or combined immediate and longer term protection (e.g. travellers departing on short notice to endemic areas), VAQTA® Adult may be administered concomitantly with immunoglobulin using separate sites and syringes (see 4.2 Posology and Method of Administration).
Use with Other Vaccines
VAQTA®Adult may be given concomitantly at separate injection sites with yellow fever and polysaccharide typhoid vaccines (see 4.2 Posology and Method of Administration and 5. Pharmacological Properties).
Interaction studies other than with yellow fever and polysaccharide typhoid vaccines are not yet available; however, interactions with other vaccines are not anticipated when vaccines are administered at different injection sites.When concurrent administration is necessary, VAQTA® Adult must not be mixed with other vaccines in the same syringe, and other vaccines should be administered at different sites.
4.6 Pregnancy And Lactation
Animal reproduction studies have not been conducted with VAQTA® Adult.
It is not known whether VAQTA® Adult can cause foetal harm when administered to a pregnant woman, or can affect reproduction capacity. VAQTA® Adult is not recommended in pregnancy unless there is a high risk of hepatitis A infection, and the attending physician judges that the possible benefits of vaccination outweigh the risks to the foetus.
It is not known whether VAQTA® Adult is excreted in human milk, and the effect on breastfed infants following administration of VAQTA® Adult to mothers has not been studied. Hence, VAQTA® Adult should be used with caution in women who are breastfeeding.
4.7 Effects On Ability To Drive And Use Machines
There are no specific data. However, asthenia/fatigue and headache have been reported following administration of VAQTA® Adult.
4.8 Undesirable Effects
Injection-site complaints, like tenderness, pain, warmth, swelling, and erythema were most frequently reported (>10%) and were generally mild and transient. Ecchymosis at the injection site was reported. Asthenia/fatigue, fever, myalgia, stiffness, headaches, arm pain, and back pain were observed. Gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhoea and isolated cases of elevated liver enzymes were reported. Allergic reactions, i.e. pruritis, rash and urticaria were rarely reported. Should anaphylactic reactions occur, see section 4.4. Special Warnings and Precautions for Use.
As with other vaccines, single cases of central or peripheral affections of the nervous system including Guillain-Barré Syndrome and haematologic autoimmune diseases like thrombocytopaenia have been reported.
4.9 Overdose
There are no data with regard to overdose.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
VAQTA® Adult is derived from hepatitis A virus grown in cell culture in human MRC-5 diploid fibroblasts. It contains inactivated virus of a strain which was originally derived by further serial passage of a proven attenuated strain. The virus is grown, harvested, highly purified, formalin inactivated and then adsorbed onto aluminium hydroxide. Within the limits of the current assay variability, the 50U dose of VAQTA®Adult contains less than 0.1 microgram of non-viral protein, less than 4 x 10-6 microgram of DNA, less than 10-4 microgram of bovine albumin and less than 0.8 microgram of formaldehyde. Other process chemical residuals are less than 10 parts per billion (ppb).
5.2 Pharmacokinetic Properties
The onset of seroconversion following a single dose of VAQTA® Adult was shown to parallel the onset of protection against clinical hepatitis A disease.
Clinical studies showed seroconversion rates of 95% in adults within 4 weeks after the recommended primary dose.
Seropositivity was shown to persist up to 6 months in adults (studies ongoing). Persistence of immunologic memory was demonstrated with an anamnestic antibody response to a booster dose given 6 to 12 months after the primary dose.
A mathematical model predicts duration of protection lasting for many years after the booster.
Concurrent administration to healthy adults (18-39 years of age) of 50 U/1.0 millilitre of VAQTA® Adult with immunoglobulin (immunoglobulin, 0.06 millilitre/kilogram) was evaluated in a clinical study. The seroconversion rate at week 24 in the vaccine alone group (97%) was higher than in the vaccine plus immunoglobulin group (92% p = 0.050) but rose to 100% in both groups one month post booster.
In studies of healthy adults who received two doses (50U) of VAQTA®Adult at 0 and 6 months, the hepatitis A antibody response to date has been shown to persist for up to 4 years. The GMTs tend to decline over time.
Studies are ongoing to evaluate longer term persistence and the need, if any, for additional booster doses.
Interchangeability of the Booster Dose
A clinical study in 537 healthy adults, 18 to 83 years of age, evaluated the immune response to a booster dose of VAQTA®Adult and a comparable licensed inactivated hepatitis A vaccine given at 6 or 12 months following the initial dose of the comparator vaccine. When VAQTA®Adult was given as a booster dose in this case it produced an equivalent immune response and was generally well tolerated (see 4.2 Posology and Method of Administration).
Use with Other Vaccines
A controlled clinical study was conducted with 240 healthy adults, 18 to 54 years of age, who were randomised to receive either
• VAQTA®Adult, yellow fever and polysaccharide typhoid vaccines concomitantly at separate injection sites or
• yellow fever and polysaccharide typhoid vaccines concomitantly at separate injection sites or
• VAQTA®Adult alone
The seropositivity rate for hepatitis A when VAQTA®Adult, yellow fever and polysaccharide typhoid vaccines were administered concomitantly was generally similar to when VAQTA®Adult was given alone. The antibody response rates for yellow fever and typhoid were equivalent when yellow fever and polysaccharide typhoid vaccines were administered concomitantly with and without VAQTA®Adult. The concomitant administration of these three vaccines at separate injection sites was generally well tolerated (see 4.2 Posology and Method of Administration).
5.3 Preclinical Safety Data
None stated.
6. Pharmaceutical Particulars
6.1 List Of Excipients
VAQTA® Adult contains aluminium hydroxide, sodium borate, and sodium chloride.
6.2 Incompatibilities
Do not mix with other vaccines/drugs.
6.3 Shelf Life
36 months when stored between +2°C and +8°C.
Expiry date has been printed on the package (month followed by year) and is applicable only if the vaccine has been stored between +2°C and +8°C. Potency of this vaccine is not significantly affected after exposure to temperatures up to 28°C for up to 3 months. However this is NOT a storage recommendation and if kept longer than three months at this temperature it should not be used.
6.4 Special Precautions For Storage
Store vaccine between +2°C and +8°C (+36°F and +46°F).
DO NOT FREEZE since freezing destroys potency.
6.5 Nature And Contents Of Container
Single dose prefilled syringe is available as a single unit pack and a pack of 10.
6.6 Special Precautions For Disposal And Other Handling
The vaccine should be used as supplied; no reconstitution is necessary.
Shake well immediately before use. Thorough agitation is necessary to maintain suspension of the vaccine.
Parenteral drug products should be inspected visually for extraneous particulate matter and discoloration prior to administration. After thorough agitation, VAQTA® Adult is a slightly opaque white suspension.
7. Marketing Authorisation Holder
Aventis Pasteur MSD Limited
Mallards Reach
Bridge Avenue
Maidenhead
Berkshire
SL6 1QP
8. Marketing Authorisation Number(S)
PL 6745/0065
9. Date Of First Authorisation/Renewal Of The Authorisation
15 August 1996
10. Date Of Revision Of The Text
August 2000
11. LEGAL CATEGORY
POM
® Registered trademark
4006774/VAQ/RA331/0800/A
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