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Zostavax

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Summary for the public


What is ZOSTAVAX?

ZOSTAVAX is a vaccine. It is a powder and solvent to be made up into a suspension for injection. The active substance is the attenuated (weakened) varicella-zoster virus.


What is ZOSTAVAX used for?

ZOSTAVAX is used to vaccinate people aged 60 years or older, to prevent herpes zoster (also known as zoster or shingles) and the long-lasting nerve pain that may follow the disease (post-herpetic neuralgia). The medicine can only be obtained with a prescription.


How is ZOSTAVAX used?

ZOSTAVAX is provided as two separate components: a powder that must be kept frozen, and a solvent, in a vial or pre-filled syringe, that is kept in a refrigerator or at room temperature. Immediately before administration, the doctor or nurse will need to make up the suspension for injection by dissolving the frozen powder with the solvent. They will then inject the suspension subcutaneously (just under the skin) preferably into the upper arm.


How does ZOSTAVAX work?

Herpes zoster, or shingles, is a disease caused by the varicella-zoster virus, the same virus that causes chickenpox. Shingles develops in people who have had chickenpox earlier in life, generally as a child. After chickenpox, the varicella-zoster virus stays in the body, in the nervous system, in a ‘dormant’ (inactive) state. Sometimes, generally in older people, and for reasons which are not fully understood, the virus becomes active again, and the patient develops shingles, a painful, blistering rash typically in one part of the body. The rash takes usually several weeks to clear, and afterwards, there may also be pain, which can be severe and may be lasting months (post-herpetic neuralgia) in the area where the rash was.

The risk to develop shingles seems to be linked to a decline in the specific immunity (the way the body defends itself) against varicella-zoster virus. ZOSTAVAX is a vaccine that was shown to “boost” this specific immunity, which is thought to be the mechanism by which it protects against shingles and the pain the disease is associated with.


How has ZOSTAVAX been studied?

The main study of ZOSTAVAX compared the medicine to a placebo (a dummy vaccine) in over 38,500 patients aged between 59 and 99 years of age. The study was a double-blind trial, which means that neither the doctor nor the patient knew what treatment the patient was receiving. The patients were followed for 2 to 4.5 years after vaccination. The measure of the effectiveness of ZOSTAVAX was based on the number of people who developed shingles and post-herpetic pain during the study.


What benefit has ZOSTAVAX shown during the studies?

ZOSTAVAX was more effective than placebo in preventing the development of shingles. Less people developed shingles after vaccination with ZOSTAVAX than after receiving a placebo injection: 315 of the 19,254 patients who received the medicine had shingles during the study, against 642 of the 19,247 who received a placebo. This means that vaccinating 1,000 people with ZOSTAVAX will cut the number of cases of shingles seen over one year from about 11 to 6. ZOSTAVAX was also more effective than placebo in its effect on post-herpetic neuralgia: 27 of the ZOSTAVAX patients had post-herpetic neuralgia, against 80 in the placebo group.


What is the risk associated with ZOSTAVAX?

In studies, the most common side effects (seen in more than 1 patient in 10) are reactions at the site of the injection (redness, pain, swelling, itching, warmth and bruising). For the full list of all side effects reported with ZOSTAVAX, see the Package Leaflet.

ZOSTAVAX should not be used in people who may be hypersensitive (allergic) to any of the ingredients of the vaccine , including neomycin (an antibiotic). The vaccine should not be used in people who have problems with their immune system, either because they have a disease such as leukaemia, lymphoma, AIDS, or because they are taking medicines that affect the immune system. It should also not be used in patients with active untreated tuberculosis and in pregnant women. For the full list of restrictions, see the Package Leaflet.


Why has ZOSTAVAX been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that ZOSTAVAX’s benefits are greater than its risks for the prevention of herpes zoster (“zoster” or shingles) and post-herpetic neuralgia in individuals from 60 years of age. They recommended that ZOSTAVAX be given marketing authorisation.


Which measures are being taken to ensure the safe use of ZOSTAVAX?

The company that makes ZOSTAVAX will look at the use of the vaccine in patients whose immune system is weakened. They will also study the duration of the protection that the vaccine gives.


Other information about ZOSTAVAX

The European Commission granted a marketing authorisation valid throughout the European Union for ZOSTAVAX to Sanofi Pasteur MSD SNC on 19 May 2006.

Authorisation details
Name: Zostavax
EMEA Product number: EMEA/H/C/000674
Active substance: varicella-zoster virus (live, attenuated)
INN or common name: zoster vaccine (live)
Therapeutic area: ImmunizationHerpes Zoster
ATC Code: J07BK02
Marketing Authorisation Holder: Sanofi Pasteur MSD, SNC
Revision: 11
Date of issue of Market Authorisation valid throughout the European Union: 19/05/2006
Contact address:
Sanofi Pasteur MSD SNC
8 rue Jonas Salk
F-69007 Lyon
FRANCE



Product Characteristics

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS


1.
NAME OF THE MEDICINAL PRODUCT
ZOSTAVAX powder and solvent for suspension for injection
shingles (herpes zoster) vaccine (live)
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
After reconstitution, 1 dose (0.65 ml) contains:
Varicella-zoster virus 1 , Oka/Merck strain, (live, attenuated) not less than 19400 PFU 2
1 produced in human diploid (MRC-5) cells
2 PFU = Plaque-forming units
For a full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Powder and solvent for suspension for injection.
Before reconstitution, the powder is a white to off-white compact crystalline plug, and the solvent is a
clear, colourless fluid.
4.
CLINICAL PARTICULARS
4.1 Therapeutic indications
ZOSTAVAX is indicated for prevention of herpes zoster (“zoster” or shingles) and herpes zoster-related
post-herpetic neuralgia (PHN).
ZOSTAVAX is indicated for immunization of individuals 50 years of age or older.
4.2 Posology and method of administration
Individuals should receive a single dose administered subcutaneously.
The need for a second dose is currently unknown. See section 5.1.
The vaccine is to be injected SUBCUTANEOUSLY, preferably in the deltoid region.
See section 6.6 for preparation instructions.
DO NOT INJECT INTRAVASCULARLY.
4.3 Contraindications
Hypersensitivity to the active substance, to any of the excipients or trace residuals (e.g., neomycin)
(see sections 4.4 and 6.1).
2
Primary and acquired immunodeficiency states due to conditions such as: acute and chronic
leukaemias; lymphoma; other conditions affecting the bone marrow or lymphatic system;
immunosuppression due to HIV/AIDS; cellular immune deficiencies.
Immunosuppressive therapy (including high-dose corticosteroids); however, ZOSTAVAX is not
contraindicated for use in individuals who are receiving topical/inhaled corticosteroids or low-dose
systemic corticosteroids or in patients who are receiving corticosteroids as replacement therapy,
e.g., for adrenal insufficiency.
Active untreated tuberculosis.
Pregnancy (see sections 4.4 and 4.6).
4.4 Special warnings and precautions for use
Appropriate medical treatment and supervision should always be readily available in case of a rare
anaphylactic/anaphylactoid reaction following the administration of the vaccine, as there is a possibility of
hypersensitivity reactions, not only to the active substances, but also to the excipients and trace residuals
(e.g., neomycin) present in the vaccine (see sections 4.3 and 6.1).
Neomycin allergy generally manifests as a contact dermatitis. However, a history of contact dermatitis due
to neomycin is not a contraindication to receiving live virus vaccines.
Before vaccination of women of child-bearing potential, pregnancy must be excluded and effective
contraception must be used for 3 months following vaccination (see sections 4.3 and 4.6).
ZOSTAVAX is not indicated for treatment of zoster or PHN.
Deferral of vaccination should be considered in the presence of fever.
Vaccination with ZOSTAVAX may not result in protection in all vaccine recipients. See section 5.1.
The safety and efficacy of ZOSTAVAX have not been established in adults who are known to be infected
with HIV with or without evidence of immunosuppression (see section 4.3).
Transmission
In clinical trials with ZOSTAVAX, transmission of the vaccine virus has not been reported. However;
post-marketing experience with varicella vaccines suggests that transmission of vaccine virus may occur
rarely between vaccinees who develop a varicella-like rash and susceptible contacts (for example, VZV-
susceptible infant grandchildren). Transmission of vaccine virus from varicella vaccine recipients who do
not develop a varicella-like rash has also been reported. This is a theoretical risk for vaccination with
ZOSTAVAX. The risk of transmitting the attenuated vaccine virus to a susceptible individual should be
weighed against the risk of developing natural herpes zoster that could be transmitted to a susceptible
individual.
4.5 Interaction with other medicinal products and other forms of interaction
ZOSTAVAX can be administered concomitantly with inactivated influenza vaccine as separate injections
and at different body sites (see section 5.1).
ZOSTAVAX and 23-valent pneumococcal polysaccharide vaccine should not be given concomitantly
because concomitant use in a clinical trial resulted in reduced immunogenicity of ZOSTAVAX (see
section 5.1).
No data are currently available regarding concomitant use with other vaccines.
3
Concurrent administration of ZOSTAVAX and anti-viral medications known to be effective against VZV
has not been evaluated.
4.6
Pregnancy and lactation
There are no studies in pregnant women. It is also not known whether ZOSTAVAX can cause foetal harm
when administered to a pregnant woman or can affect reproduction capacity. However naturally-occurring
varicella-zoster virus infection is known to sometimes cause foetal harm. As ZOSTAVAX is not indicated
in individuals less than 50 years of age, ZOSTAVAX is not intended to be administered to pregnant
women. In any case, pregnancy should be avoided for three months following vaccination (see sections
4.3 and 4.4).
It is not known whether VZV is secreted in human milk. Therefore, because some viruses are secreted in
human milk, caution should be exercised if ZOSTAVAX is administered to a breast-feeding woman.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive or use machines have been performed .
4.8 Undesirable effects
In clinical trials, ZOSTAVAX has been evaluated for safety in more than 20000 adults.
In the largest of these trials, the Shingles Prevention Study (SPS), 38546 subjects received a single dose of
either the frozen formulation of ZOSTAVAX (n=19270) or placebo (n=19276) and were monitored for
safety throughout the study. During the study, vaccine-related serious adverse reactions were reported for
2 subjects vaccinated with ZOSTAVAX (asthma exacerbation and polymyalgia rheumatica) and 3
subjects who received placebo (Goodpasture’s syndrome, anaphylactic reaction, and polymyalgia
rheumatica).
In the Adverse Event Monitoring Substudy, a subgroup of individuals from the SPS (n=3345 received
ZOSTAVAX and n=3271 received placebo) were provided vaccination report cards to record adverse
reactions occurring from Days 0 to 42 postvaccination in addition to undergoing routine safety monitoring
throughout the study.
The following vaccine-related injection-site and systemic adverse reactions were reported at a
significantly greater incidence in the vaccine group versus the placebo group in the Adverse Event
Monitoring Substudy. Most of these adverse reactions were reported as mild in intensity. Several adverse
reactions were solicited (Days 0-4 postvaccination) and are designated with the * symbol.
[Very Common (≥1/10); Common (≥1/100, <1/10); Uncommon (≥1/1000, <1/100); Rare (≥1/10,000,
<1/1,000); Very rare (<1/10,000) including isolated cases]
Nervous system disorder
Common: headache
General disorders and administration site conditions
Very common: erythema, * pain/tenderness, * swelling *
Common: haematoma, pruritus, warmth
The overall incidence of vaccine-related injection-site adverse reactions was significantly greater for
subjects vaccinated with ZOSTAVAX versus subjects who received placebo (48% for ZOSTAVAX and
17% for placebo).
4
The remainder of subjects in the SPS received routine safety monitoring, but were not provided report
cards. The types of events reported in these patients were generally similar to the subgroup of patients in
the Adverse Event Monitoring Substudy.
Within the 42-day postvaccination reporting period in the SPS, the number of reported zosteriform rashes
among all subjects was small (17 for ZOSTAVAX, 36 for placebo; p=0.009). Of these 53 zosteriform
rashes, 41 had specimens that were available and adequate for PCR testing. Wild-type VZV was detected
in 25 (5 for ZOSTAVAX, 20 for placebo) of these specimens. The Oka/Merck strain of VZV was not
detected from any of these specimens.
Within the same 42-day postvaccination reporting period in the SPS, the number (n=59) of reported
varicella-like rashes was also small. Of these varicella-like rashes, 10 had specimens that were available
and adequate for PCR testing. VZV was not detected in any of these specimens.
In other clinical trials in support of the initial licensure of the frozen formulation of ZOSTAVAX, the
reported rates of noninjection-site zosteriform and varicella-like rashes within 42 days postvaccination
were also low in both zoster vaccine recipients and placebo recipients. Of the 17 reported noninjection-site
zosteriform and varicella-like rashes, 10 specimens were available and adequate for PCR testing. The
Oka/Merck strain was identified by PCR analysis from the lesion specimens of only two subjects who
reported varicella-like rashes (onset on Day 8 and 17).
In other clinical trials evaluating ZOSTAVAX in subjects 50 years of age or older, including a study of
concomitantly administered inactivated influenza vaccine, the safety profile was generally similar to that
seen in the Adverse Event Monitoring Substudy of the SPS. However, in these trials, a higher rate of
injection-site adverse experiences of mild-to-moderate intensity was reported among subjects 50-59 years
of age compared with subjects ≥60 years of age (see section 5.1).
Data from a clinical trial (n=368) demonstrated that the current refrigerated formulation is generally well
tolerated with a safety profile comparable to that of the frozen formulation.
In a double-blind, placebo-controlled, randomized clinical trial, in which ZOSTAVAX was administered
to 100 subjects 50 years of age or older with a history of herpes zoster (HZ) prior to vaccination, the safety
profile was generally similar to that seen in the Adverse Event Monitoring Substudy of the SPS.
Based on limited data from 2 clinical trials that enrolled VZV-seronegative or low seropositive subjects
(27 subjects 30 years of age or older received live attenuated zoster vaccine), injection site and systemic
adverse experiences were generally similar to those reported by other subjects who received ZOSTAVAX
in clinical trials, with 2 of the 27 subjects reporting fever. No subjects reported varicella-like or herpes
zoster-like rashes. No serious vaccine-related adverse experiences were reported.
Post-marketing Experience
During post-marketing experience, the following additional adverse events have been reported
spontaneously:
Skin and subcutaneous tissue disorders: rash
Musculoskeletal and connective tissue disorder: arthralgia; myalgia
General disorders and administration site conditions: injection-site rash; injection-site urticaria; pyrexia
Blood and lymphatic system disorders : lymphadenopathy (cervical, axillary)
Immune system disorders: hypersensitivity reactions including anaphylactic reactions
4.9 Overdose
5
No case of overdose has been reported.
5.
PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Viral Vaccine; ATC code: J07BK02
Mechanism of Action
Anyone who has been infected with VZV, including those without a clinical history of varicella, is at risk
for developing zoster. This risk appears to be causally related to a decline in VZV-specific immunity.
ZOSTAVAX was shown to boost VZV-specific immunity, which is thought to be the mechanism by
which it protects against zoster and its complications. (See Immunogenicity .)
Evaluation of Clinical Efficacy Afforded by ZOSTAVAX
ZOSTAVAX significantly reduced the risk of developing zoster and PHN compared with placebo. In
addition, ZOSTAVAX significantly reduced zoster-associated pain as measured by the HZ pain Burden of
Illness (BOI) score (see results and definition in Table 1).
Table 1
Efficacy of ZOSTAVAX Compared with Placebo
in the Shingles Prevention Study
95% CI
Incidence of Zoster 51% 44 to 58%
Incidence of PHN** 67% 48 to 79%
HZ Pain BOI*** 61% 51 to 69%
*Vaccine efficacy = relative reduction in the endpoint measurement in the vaccine group compared with
the placebo group
**Clinically significant zoster-associated pain persisting or appearing at least 90 days after the onset of
rash.
***The HZ pain BOI score is a composite score that incorporates the incidence, severity, and duration of
acute and chronic zoster-associated pain over a 6-month follow-up period.
Vaccine
efficacy*
In the Shingles Prevention Study (SPS), a placebo-controlled, double-blind clinical trial of ZOSTAVAX,
38546 subjects 60 years of age or older were randomized to receive a single dose of either ZOSTAVAX
(n=19270) or placebo (n=19276).
ZOSTAVAX significantly decreased the incidence of zoster compared with placebo (315 [5.4/1000
person-years] vs. 642 cases [11.1/1000 person-years], respectively; p<0.001). The protective efficacy of
ZOSTAVAX against zoster was 51% (95% CI: [44 to 58%]). ZOSTAVAX reduced the incidence of
zoster by 64% (95% CI: [56 to 71%]) in individuals 60-69 years of age and by 38% (95% CI: [25 to 48%])
in individuals ≥70 years of age.
In the SPS, the reduction in zoster was seen in almost all dermatomes. Ophthalmic zoster occurred in 35
subjects vaccinated with ZOSTAVAX vs. 69 subjects who received placebo. Impaired vision occurred in
2 subjects vaccinated with ZOSTAVAX vs. 9 who received placebo.
ZOSTAVAX decreased the incidence of PHN compared with placebo [(27 cases [0.5/1000 person-years]
vs. 80 cases [1.4/1000 person-years], respectively; p<0.001). In this trial, the definition of PHN was
clinically significant zoster-associated pain persisting or appearing at least 90 days after the onset of rash.
The protective efficacy of ZOSTAVAX against PHN was 67% (95% CI: [48 to 79%]). Referring only to
6
Endpoint
 
subjects who developed zoster, there was a decrease in the risk of subsequently developing PHN. In the
vaccine group, the risk of developing PHN after zoster was 9 % (27/315), while in the placebo group it
was 13 % (80/642). This effect was more prominent in the group of older subjects (≥70 years of age),
where the risk of developing PHN after zoster was reduced to 10% in the vaccine group vs. 19% for the
placebo group.
ZOSTAVAX reduced the HZ pain BOI score by approximately 61% (95% CI: [51 to 69%]), compared
with placebo. The effect was more pronounced in the younger age group (60 to 69 years) where the
efficacy of ZOSTAVAX on HZ pain BOI was 66% compared to 55% in patients ≥70 years of age;
however, this difference was not statistically significant (p=0.266).
Prevention of HZ cases with severe pain in the entire study population
ZOSTAVAX reduced the incidence of zoster with severe and long-lasting pain (severity-by-duration score
>600) by 73% (95% CI: [46 to 87%]) compared with placebo (11 vs. 40 cases, respectively).
Reduction of zoster pain severity-by-duration in vaccinated individuals who developed zoster
With regard to the acute pain (pain between 0-30 days) there was no statistically significant difference
between the vaccine group and the placebo group. The HZ pain severity-by-duration score was 89
(95%CI: [82 to 97%]) for the vaccine group vs. 92 (95% CI: [87 to 97%]) for the placebo group. The
overall use of analgesic medication was similar in both study groups.
Among vaccinated individuals who developed PHN, ZOSTAVAX significantly reduced PHN-associated
(chronic) pain compared with placebo. In the period from 90 days after rash onset to the end of follow-up,
there was a 57% reduction in the severity-by-duration score (average scores of 347 for ZOSTAVAX and
805 for placebo; p=0.016).
Among vaccinated individuals who developed zoster, ZOSTAVAX significantly reduced overall acute
and chronic zoster-associated pain compared with placebo. Over the 6-month (acute and chronic) follow-
up period, there was a 22% reduction (p =0.008) in the severity-by-duration score and a 52% (95% CI: [7
to 74%]) reduction (from 6.2% to 3.5%) in the risk of having HZ with severe and long-lasting pain
(severity-by-duration score of >600).
Immunogenicity of ZOSTAVAX
Within the Shingles Prevention Study (SPS), immune responses to vaccination were evaluated in a subset
of the enrolled subjects (N=1395). ZOSTAVAX elicited higher VZV-specific immune responses at 6
weeks postvaccination compared with placebo. Increases in both VZV antibody level, measured by
glycoprotein enzyme-linked immunosorbent assay (gpELISA) (1.7-fold difference, geometric mean titer
[GMT] of 479 vs. 288 gpELISA units/ml, p <0.001), and T-cell activity, measured by VZV interferon-
gamma enzyme-linked immunospot (IFN- ELISPOT) assay (2.2-fold difference, geometric mean count
[GMC] of 70 vs. 32 spot-forming cells per million peripheral blood mononuclear cells [SFC/10 6 PBMCs],
p<0.001) were demonstrated. When evaluated at 4 weeks postvaccination, the immunogenicity of the
current refrigerator-stable formulation was shown to be similar to the immunogenicity of the earlier frozen
formulation of ZOSTAVAX.
In an integrated analysis of two clinical trials evaluating immune response to ZOSTAVAX at 4 weeks
postvaccination, responses were generally similar in subjects 50 to 59 (N=389) compared to subjects ≥60
years of age (N=731) (GMT of 668 vs. 614 gpELISA units/ml, respectively). The geometric mean fold-
rise of immune response following vaccination as measured by gpELISA was 2.6-fold (95% CI: [2.4 to
2.9]) in subjects 50 to 59 years of age and 2.3-fold (95% CI: [2.1 to 2.4]) in subjects ≥60 years age.
Immunogenicity following concomitant administration
In a double-blind, controlled clinical trial, 762 adults 50 years of age and older were randomized to
receive a single dose of ZOSTAVAX administered either concomitantly (N=382) or nonconcomitantly
7
(N=380) with inactivated split influenza vaccine. The antibody responses to both vaccines at 4 weeks
postvaccination were similar, whether administered concomitantly or nonconcomitantly.
In a double-blind, controlled clinical trial, 473 adults, 60 years of age or older, were randomized to receive
a single dose of ZOSTAVAX either concomitantly (N=237), or nonconcomitantly with 23-valent
pneumococcal polysaccharide vaccine (N=236). At four weeks postvaccination, the VZV antibody levels
following concomitant use were not similar to the VZV antibody levels following nonconcomitant
administration (GMTs of 338 vs. 484 gpELISA units/mL, respectively; GMT ratio = 0.70 (95% CI: [0.61,
0.80])). VZV antibody levels 4 weeks postvaccination were increased 1.9-fold (95% CI: [1.7, 2.1];
meeting the pre-specified acceptance criterion) in the concomitant group vs. 3.1-fold (95% CI: [2.8, 3.5])
in the nonconcomitant group. The GMTs for 23-valent pneumococcal polysaccharide vaccine antigens
were similar between the two groups. There was no significant difference in the safety profile between
concomitant and nonconcomitant administration of ZOSTAVAX and 23-valent pneumococcal
polysaccharide vaccine, except for headache and pneumococcal vaccine injection site erythema and
swelling, which were more common in the concomitant group.
Immunogenicity in subjects with a history of herpes zoster (HZ) prior to vaccination
In a double-blind, placebo-controlled, randomized clinical trial, ZOSTAVAX was administered to 100
subjects 50 years of age or older with a history of herpes zoster (HZ) prior to vaccination to assess
immunogenicity and safety (see section 4.8) of ZOSTAVAX . ZOSTAVAX induced a significantly higher
VZV-specific immune response measured by gpELISA at 4 weeks postvaccination, compared with
placebo (2.1-fold difference (95% CI: [1.5 to 2.9]), p<0.001, GMT of 812 vs. 393 gpELISA units/ml).
VZV antibody responses were generally similar in subjects 50 to 59 compared to subjects 60 years of
age.
Revaccination
The need for, or timing of, revaccination with ZOSTAVAX has not yet been determined.
In a placebo-controlled, double-blind, study, 98 adults 60 years of age or older received a second dose of
ZOSTAVAX 42 days following the initial dose; the vaccine was generally well tolerated. The frequency
of vaccine-related adverse experiences after the second dose of ZOSTAVAX was generally similar to that
seen with the first dose.
Immunocompromised subjects
The vaccine has not been studied in subjects with impaired immunity.
5.2 Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not required for vaccines.
5.3 Preclinical safety data
Traditional non-clinical studies were not performed, but there are no non-clinical concerns considered
relevant to clinical safety beyond data included in other sections of the SPC.
6.
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Powder:
Sucrose
Hydrolysed gelatin
8
Sodium chloride
Potassium dihydrogen phosphate
Potassium chloride
Monosodium L-glutamate
Anhydrous disodium phosphate
Sodium hydroxide (to adjust pH)
Urea
Solvent:
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products in the same syringe.
6.3 Shelf life
18 months.
After reconstitution, the vaccine should be used immediately. However, the in-use stability has been
demonstrated for 30 minutes when stored at 20 o C - 25 o C.
6.4 Special precautions for storage
Store and transport refrigerated (2C - 8C). Do not freeze. Store in the original package in order to
protect from light.
For storage conditions of the reconstituted medicinal product, see section 6.3.
6.5 Nature and contents of container
Powder in a vial (Type I glass) with a stopper (butyl rubber) and flip off cap (aluminium) and solvent in a
vial (Type I glass) with a stopper (chlorobutyl rubber) and flip off cap (aluminium) in a pack size of 1 or
10.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Avoid contact with disinfectants.
To reconstitute the vaccine, use the solvent provided. When reconstituted, ZOSTAVAX is a semi-hazy to
translucent, off-white to pale yellow liquid.
It is important to use a separate sterile syringe and needle for each patient to prevent transmission of
infectious agents from one individual to another.
Reconstitution instructions
To reconstitute the vaccine, first withdraw the entire contents of the solvent vial into a syringe. Inject all
the solvent in the syringe into the vial of lyophilized vaccine and gently agitate to mix thoroughly.
Withdraw the entire contents into a syringe for injection.
9
IT IS RECOMMENDED THAT THE VACCINE BE ADMINISTERED IMMEDIATELY AFTER
RECONSTITUTION, TO MINIMIZE LOSS OF POTENCY. DISCARD RECONSTITUTED
VACCINE IF IT IS NOT USED WITHIN 30 MINUTES.
The reconstituted vaccine must not be used if any particulate matter is noted or if the appearance of the
vaccine differs from that described above.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
MARKETING AUTHORISATION HOLDER
SANOFI PASTEUR MSD, SNC
8, rue Jonas Salk
F-69007 Lyon
France
8. MARKETING AUTHORISATION NUMBER(S)
EU/1/06/341/ 001
EU/1/06/341/ 002
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
May 19, 2006
10. DATE OF REVISION OF THE TEXT
10
1.
NAME OF THE MEDICINAL PRODUCT
ZOSTAVAX powder and solvent for suspension for injection in a pre-filled syringe
shingles (herpes zoster) vaccine (live)
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
After reconstitution, 1 dose (0.65 ml) contains:
Varicella-zoster virus 1 , Oka/Merck strain, (live, attenuated) not less than 19400 PFU 2
1 produced in human diploid (MRC-5) cells
2 PFU = Plaque-forming units
For a full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Powder and solvent for suspension for injection in a pre-filled syringe.
Before reconstitution, the powder is a white to off-white compact crystalline plug, and the solvent is a
clear, colourless fluid.
4.
CLINICAL PARTICULARS
4.1 Therapeutic indications
ZOSTAVAX is indicated for prevention of herpes zoster (“zoster” or shingles) and herpes zoster-related
post-herpetic neuralgia (PHN).
ZOSTAVAX is indicated for immunization of individuals 50 years of age or older.
4.2 Posology and method of administration
Individuals should receive a single dose administered subcutaneously.
The need for a second dose is currently unknown. See section 5.1.
The vaccine is to be injected SUBCUTANEOUSLY, preferably in the deltoid region.
See section 6.6 for preparation instructions.
DO NOT INJECT INTRAVASCULARLY.
4.3 Contraindications
Hypersensitivity to the active substance, to any of the excipients or trace residuals (e.g., neomycin)
(see sections 4.4 and 6.1).
11
Primary and acquired immunodeficiency states due to conditions such as: acute and chronic
leukaemias; lymphoma; other conditions affecting the bone marrow or lymphatic system;
immunosuppression due to HIV/AIDS; cellular immune deficiencies.
Immunosuppressive therapy (including high-dose corticosteroids); however, ZOSTAVAX is not
contraindicated for use in individuals who are receiving topical/inhaled corticosteroids or low-dose
systemic corticosteroids or in patients who are receiving corticosteroids as replacement therapy,
e.g., for adrenal insufficiency.
Active untreated tuberculosis.
Pregnancy (see sections 4.4 and 4.6).
4.4 Special warnings and precautions for use
Appropriate medical treatment and supervision should always be readily available in case of a rare
anaphylactic/anaphylactoid reaction following the administration of the vaccine, as there is a possibility of
hypersensitivity reactions, not only to the active substances, but also to the excipients and trace residuals
(e.g., neomycin) present in the vaccine (see sections 4.3 and 6.1).
Neomycin allergy generally manifests as a contact dermatitis. However, a history of contact dermatitis due
to neomycin is not a contraindication to receiving live virus vaccines.
Before vaccination of women of child-bearing potential, pregnancy must be excluded and effective
contraception must be used for 3 months following vaccination (see sections 4.3 and 4.6).
ZOSTAVAX is not indicated for treatment of zoster or PHN.
Deferral of vaccination should be considered in the presence of fever.
Vaccination with ZOSTAVAX may not result in protection in all vaccine recipients. See section 5.1.
The safety and efficacy of ZOSTAVAX have not been established in adults who are known to be infected
with HIV with or without evidence of immunosuppression (see section 4.3).
Transmission
In clinical trials with ZOSTAVAX, transmission of the vaccine virus has not been reported. However;
post-marketing experience with varicella vaccines suggests that transmission of vaccine virus may occur
rarely between vaccinees who develop a varicella-like rash and susceptible contacts (for example, VZV-
susceptible infant grandchildren). Transmission of vaccine virus from varicella vaccine recipients who do
not develop a varicella-like rash has also been reported. This is a theoretical risk for vaccination with
ZOSTAVAX. The risk of transmitting the attenuated vaccine virus to a susceptible individual should be
weighed against the risk of developing natural herpes zoster that could be transmitted to a susceptible
individual.
4.5 Interaction with other medicinal products and other forms of interaction
ZOSTAVAX can be administered concomitantly with inactivated influenza vaccine as separate injections
and at different body sites (see section 5.1).
ZOSTAVAX and 23-valent pneumococcal polysaccharide vaccine should not be given concomitantly
because concomitant use in a clinical trial resulted in reduced immunogenicity of ZOSTAVAX (see
section 5.1).
No data are currently available regarding concomitant use with other vaccines.
12
Concurrent administration of ZOSTAVAX and anti-viral medications known to be effective against VZV
has not been evaluated.
4.6
Pregnancy and lactation
There are no studies in pregnant women. It is also not known whether ZOSTAVAX can cause foetal harm
when administered to a pregnant woman or can affect reproduction capacity. However naturally-occurring
varicella-zoster virus infection is known to sometimes cause foetal harm. As ZOSTAVAX is not indicated
in individuals less than 50 years of age, ZOSTAVAX is not intended to be administered to pregnant
women. In any case, pregnancy should be avoided for three months following vaccination (see sections
4.3 and 4.4).
It is not known whether VZV is secreted in human milk. Therefore, because some viruses are secreted in
human milk, caution should be exercised if ZOSTAVAX is administered to a breast-feeding woman.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive or use machines have been performed .
4.8 Undesirable effects
In clinical trials, ZOSTAVAX has been evaluated for safety in more than 20000 adults.
In the largest of these trials, the Shingles Prevention Study (SPS), 38546 subjects received a single dose of
either the frozen formulation of ZOSTAVAX (n=19270) or placebo (n=19276) and were monitored for
safety throughout the study. During the study, vaccine-related serious adverse reactions were reported for
2 subjects vaccinated with ZOSTAVAX (asthma exacerbation and polymyalgia rheumatica) and 3
subjects who received placebo (Goodpasture’s syndrome, anaphylactic reaction, and polymyalgia
rheumatica).
In the Adverse Event Monitoring Substudy, a subgroup of individuals from the SPS (n=3345 received
ZOSTAVAX and n=3271 received placebo) were provided vaccination report cards to record adverse
reactions occurring from Days 0 to 42 postvaccination in addition to undergoing routine safety monitoring
throughout the study.
The following vaccine-related injection-site and systemic adverse reactions were reported at a
significantly greater incidence in the vaccine group versus the placebo group in the Adverse Event
Monitoring Substudy. Most of these adverse reactions were reported as mild in intensity. Several adverse
reactions were solicited (Days 0-4 postvaccination) and are designated with the * symbol.
[Very Common (≥1/10); Common (≥1/100, <1/10); Uncommon (≥1/1000, <1/100); Rare (≥1/10,000,
<1/1,000); Very rare (<1/10,000) including isolated cases]
Nervous system disorder
Common: headache
General disorders and administration site conditions
Very common: erythema, * pain/tenderness, * swelling *
Common: haematoma, pruritus, warmth
The overall incidence of vaccine-related injection-site adverse reactions was significantly greater for
subjects vaccinated with ZOSTAVAX versus subjects who received placebo (48% for ZOSTAVAX and
17% for placebo).
13
The remainder of subjects in the SPS received routine safety monitoring, but were not provided report
cards. The types of events reported in these patients were generally similar to the subgroup of patients in
the Adverse Event Monitoring Substudy.
Within the 42-day postvaccination reporting period in the SPS, the number of reported zosteriform rashes
among all subjects was small (17 for ZOSTAVAX, 36 for placebo; p=0.009). Of these 53 zosteriform
rashes, 41 had specimens that were available and adequate for PCR testing. Wild-type VZV was detected
in 25 (5 for ZOSTAVAX, 20 for placebo) of these specimens. The Oka/Merck strain of VZV was not
detected from any of these specimens.
Within the same 42-day postvaccination reporting period in the SPS, the number (n=59) of reported
varicella-like rashes was also small. Of these varicella-like rashes, 10 had specimens that were available
and adequate for PCR testing. VZV was not detected in any of these specimens.
In other clinical trials in support of the initial licensure of the frozen formulation of ZOSTAVAX, the
reported rates of noninjection-site zosteriform and varicella-like rashes within 42 days postvaccination
were also low in both zoster vaccine recipients and placebo recipients. Of the 17 reported noninjection-site
zosteriform and varicella-like rashes, 10 specimens were available and adequate for PCR testing. The
Oka/Merck strain was identified by PCR analysis from the lesion specimens of only two subjects who
reported varicella-like rashes (onset on Day 8 and 17).
In other clinical trials evaluating ZOSTAVAX in subjects 50 years of age or older, including a study of
concomitantly administered inactivated influenza vaccine, the safety profile was generally similar to that
seen in the Adverse Event Monitoring Substudy of the SPS. However, in these trials, a higher rate of
injection-site adverse experiences of mild-to-moderate intensity was reported among subjects 50-59 years
of age compared with subjects ≥60 years of age (see section5.1).
Data from a clinical trial (n=368) demonstrated that the current refrigerated formulation is generally well
tolerated with a safety profile comparable to that of the frozen formulation.
In a double-blind, placebo-controlled, randomized clinical trial, in which ZOSTAVAX was administered
to 100 subjects 50 years of age or older with a history of herpes zoster (HZ) prior to vaccination, the safety
profile was generally similar to that seen in the Adverse Event Monitoring Substudy of the SPS.
Based on limited data from 2 clinical trials that enrolled VZV-seronegative or low seropositive subjects
(27 subjects 30 years of age or older received live attenuated zoster vaccine), injection site and systemic
adverse experiences were generally similar to those reported by other subjects who received ZOSTAVAX
in clinical trials, with 2 of the 27 subjects reporting fever. No subjects reported varicella-like or herpes
zoster-like rashes. No serious vaccine-related adverse experiences were reported.
Post-marketing Experience
During post-marketing experience, the following additional adverse events have been reported
spontaneously:
Skin and subcutaneous tissue disorders: rash
Musculoskeletal and connective tissue disorder: arthralgia; myalgia
General disorders and administration site conditions: injection-site rash; injection-site urticaria; pyrexia
Blood and lymphatic system disorders : lymphadenopathy (cervical, axillary)
Immune system disorders: hypersensitivity reactions including anaphylactic reactions
4.9 Overdose
14
No case of overdose has been reported.
5.
PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Viral Vaccine; ATC code: J07BK02
Mechanism of Action
Anyone who has been infected with VZV, including those without a clinical history of varicella, is at risk
for developing zoster. This risk appears to be causally related to a decline in VZV-specific immunity.
ZOSTAVAX was shown to boost VZV-specific immunity, which is thought to be the mechanism by
which it protects against zoster and its complications. (See Immunogenicity .)
Evaluation of Clinical Efficacy Afforded by ZOSTAVAX
ZOSTAVAX significantly reduced the risk of developing zoster and PHN compared with placebo. In
addition, ZOSTAVAX significantly reduced zoster-associated pain as measured by the HZ pain Burden of
Illness (BOI) score (see results and definition in Table 1).
Table 1
Efficacy of ZOSTAVAX Compared with Placebo
in the Shingles Prevention Study
95% CI
Incidence of Zoster 51% 44 to 58%
Incidence of PHN** 67% 48 to 79%
HZ Pain BOI*** 61% 51 to 69%
*Vaccine efficacy = relative reduction in the endpoint measurement in the vaccine group compared with
the placebo group
**Clinically significant zoster-associated pain persisting or appearing at least 90 days after the onset of
rash.
***The HZ pain BOI score is a composite score that incorporates the incidence, severity, and duration of
acute and chronic zoster-associated pain over a 6-month follow-up period.
Vaccine
efficacy*
In the Shingles Prevention Study (SPS), a placebo-controlled, double-blind clinical trial of ZOSTAVAX,
38546 subjects 60 years of age or older were randomized to receive a single dose of either ZOSTAVAX
(n=19270) or placebo (n=19276).
ZOSTAVAX significantly decreased the incidence of zoster compared with placebo (315 [5.4/1000
person-years] vs. 642 cases [11.1/1000 person-years], respectively; p<0.001). The protective efficacy of
ZOSTAVAX against zoster was 51% (95% CI: [44 to 58%]). ZOSTAVAX reduced the incidence of
zoster by 64% (95% CI: [56 to 71%]) in individuals 60-69 years of age and by 38% (95% CI: [25 to 48%])
in individuals ≥70 years of age.
In the SPS, the reduction in zoster was seen in almost all dermatomes. Ophthalmic zoster occurred in 35
subjects vaccinated with ZOSTAVAX vs. 69 subjects who received placebo. Impaired vision occurred in
2 subjects vaccinated with ZOSTAVAX vs. 9 who received placebo.
ZOSTAVAX decreased the incidence of PHN compared with placebo [(27 cases [0.5/1000 person-years]
vs. 80 cases [1.4/1000 person-years], respectively; p<0.001). In this trial, the definition of PHN was
clinically significant zoster-associated pain persisting or appearing at least 90 days after the onset of rash.
The protective efficacy of ZOSTAVAX against PHN was 67% (95% CI: [48 to 79%]). Referring only to
15
Endpoint
 
subjects who developed zoster, there was a decrease in the risk of subsequently developing PHN. In the
vaccine group, the risk of developing PHN after zoster was 9 % (27/315), while in the placebo group it
was 13 % (80/642). This effect was more prominent in the group of older subjects (≥70 years of age),
where the risk of developing PHN after zoster was reduced to 10% in the vaccine group vs. 19% for the
placebo group.
ZOSTAVAX reduced the HZ pain BOI score by approximately 61% (95% CI: [51 to 69%]), compared
with placebo. The effect was more pronounced in the younger age group (60 to 69 years) where the
efficacy of ZOSTAVAX on HZ pain BOI was 66% compared to 55% in patients ≥70 years of age;
however, this difference was not statistically significant (p=0.266).
Prevention of HZ cases with severe pain in the entire study population
ZOSTAVAX reduced the incidence of zoster with severe and long-lasting pain (severity-by-duration score
>600) by 73% (95% CI: [46 to 87%]) compared with placebo (11 vs. 40 cases, respectively).
Reduction of zoster pain severity-by-duration in vaccinated individuals who developed zoster
With regard to the acute pain (pain between 0-30 days) there was no statistically significant difference
between the vaccine group and the placebo group. The HZ pain severity-by-duration score was 89
(95%CI: [82 to 97%]) for the vaccine group vs. 92 (95% CI: [87 to 97%]) for the placebo group. The
overall use of analgesic medication was similar in both study groups.
Among vaccinated individuals who developed PHN, ZOSTAVAX significantly reduced PHN-associated
(chronic) pain compared with placebo. In the period from 90 days after rash onset to the end of follow-up,
there was a 57% reduction in the severity-by-duration score (average scores of 347 for ZOSTAVAX and
805 for placebo; p=0.016).
Among vaccinated individuals who developed zoster, ZOSTAVAX significantly reduced overall acute
and chronic zoster-associated pain compared with placebo. Over the 6-month (acute and chronic) follow-
up period, there was a 22% reduction (p =0.008) in the severity-by-duration score and a 52% (95% CI: [7
to 74%]) reduction (from 6.2% to 3.5%) in the risk of having HZ with severe and long-lasting pain
(severity-by-duration score of >600).
Immunogenicity of ZOSTAVAX
Within the Shingles Prevention Study (SPS), immune responses to vaccination were evaluated in a subset
of the enrolled subjects (N=1395). ZOSTAVAX elicited higher VZV-specific immune responses at 6
weeks postvaccination compared with placebo. Increases in both VZV antibody level, measured by
glycoprotein enzyme-linked immunosorbent assay (gpELISA) (1.7-fold difference, geometric mean titer
[GMT] of 479 vs. 288 gpELISA units/ml, p <0.001), and T-cell activity, measured by VZV interferon-
gamma enzyme-linked immunospot (IFN- ELISPOT) assay (2.2-fold difference, geometric mean count
[GMC] of 70 vs. 32 spot-forming cells per million peripheral blood mononuclear cells [SFC/10 6 PBMCs],
p<0.001) were demonstrated. When evaluated at 4 weeks postvaccination, the immunogenicity of the
current refrigerator-stable formulation was shown to be similar to the immunogenicity of the earlier frozen
formulation of ZOSTAVAX.
In an integrated analysis of two clinical trials evaluating immune response to ZOSTAVAX at 4 weeks
postvaccination, responses were generally similar in subjects 50 to 59 (N=389) compared to subjects ≥60
years of age (N=731) (GMT of 668 vs. 614 gpELISA units/ml, respectively). The geometric mean fold-
rise of immune response following vaccination as measured by gpELISA was 2.6-fold (95% CI: [2.4 to
2.9]) in subjects 50 to 59 years of age and 2.3-fold (95% CI: [2.1 to 2.4]) in subjects ≥60 years age.
Immunogenicity following concomitant administration
In a double-blind, controlled clinical trial, 762 adults 50 years of age and older were randomized to
receive a single dose of ZOSTAVAX administered either concomitantly (N=382) or nonconcomitantly
16
(N=380) with inactivated split influenza vaccine. The antibody responses to both vaccines at 4 weeks
postvaccination were similar, whether administered concomitantly or nonconcomitantly.
In a double-blind, controlled clinical trial, 473 adults, 60 years of age or older, were randomized to receive
a single dose of ZOSTAVAX either concomitantly (N=237), or nonconcomitantly with 23-valent
pneumococcal polysaccharide vaccine (N=236). At four weeks postvaccination, the VZV antibody levels
following concomitant use were not similar to the VZV antibody levels following nonconcomitant
administration (GMTs of 338 vs. 484 gpELISA units/mL, respectively; GMT ratio = 0.70 (95% CI: [0.61,
0.80])). VZV antibody levels 4 weeks postvaccination were increased 1.9-fold (95% CI: [1.7, 2.1];
meeting the pre-specified acceptance criterion) in the concomitant group vs. 3.1-fold (95% CI: [2.8, 3.5])
in the nonconcomitant group. The GMTs for 23-valent pneumococcal polysaccharide vaccine antigens
were similar between the two groups. There was no significant difference in the safety profile between
concomitant and nonconcomitant administration of ZOSTAVAX and 23-valent pneumococcal
polysaccharide vaccine, except for headache and pneumococcal vaccine injection site erythema and
swelling, which were more common in the concomitant group.
Immunogenicity in subjects with a history of herpes zoster (HZ) prior to vaccination
In a double-blind, placebo-controlled, randomized clinical trial, ZOSTAVAX was administered to 100
subjects 50 years of age or older with a history of herpes zoster (HZ) prior to vaccination to assess
immunogenicity and safety (see section 4.8) of ZOSTAVAX. ZOSTAVAX induced a significantly higher
VZV-specific immune response measured by gpELISA at 4 weeks postvaccination, compared with
placebo (2.1-fold difference (95% CI: [1.5 to 2.9]), p<0.001), GMT of 812 vs. 393 gpELISA units/ml.
VZV antibody responses were generally similar in subjects 50 to 59 compared to subjects 60 years of
age.
Revaccination
The need for, or timing of, revaccination with ZOSTAVAX has not yet been determined.
In a placebo-controlled, double-blind, study, 98 adults 60 years of age or older received a second dose of
ZOSTAVAX 42 days following the initial dose; the vaccine was generally well tolerated. The frequency
of vaccine-related adverse experiences after the second dose of ZOSTAVAX was generally similar to that
seen with the first dose.
Immunocompromised subjects
The vaccine has not been studied in subjects with impaired immunity.
5.2 Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not required for vaccines.
5.3 Preclinical safety data
Traditional non-clinical studies were not performed, but there are no non-clinical concerns considered
relevant to clinical safety beyond data included in other sections of the SPC.
6.
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Powder:
Sucrose
Hydrolysed gelatin
17
Sodium chloride
Potassium dihydrogen phosphate
Potassium chloride
Monosodium L-glutamate
Anhydrous disodium phosphate
Sodium hydroxide (to adjust pH)
Urea
Solvent:
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products in the same syringe.
6.3 Shelf life
18 months.
After reconstitution, the vaccine should be used immediately. However, the in-use stability has been
demonstrated for 30 minutes when stored at 20 o C - 25 o C.
6.4 Special precautions for storage
Store and transport refrigerated (2C - 8C). Do not freeze. Store in the original package in order to
protect from light.
For storage conditions of the reconstituted medicinal product, see section 6.3.
6.5
Nature and contents of container
Powder in a vial (Type I glass) with a stopper (butyl rubber) and flip off cap (aluminium) and solvent in a
pre-filled syringe (Type I glass) with plunger stopper (chlorobutyl rubber) and tip cap (styrene-butadiene
rubber) with one or two unattached needles in a pack size of 1, 10 or 20.
Powder in a vial (Type I glass) with a stopper (butyl rubber) and flip off cap (aluminium) and solvent in a
pre-filled syringe (Type I glass) with plunger stopper (chlorobutyl rubber) and tip cap (styrene-butadiene
rubber) without needle in pack size of 1, 10 or 20.
Powder in a vial (Type I glass) with a stopper (butyl rubber) and flip off cap (aluminium) and solvent in a
pre-filled syringe (Type I glass) with plunger stopper (chlorobutyl rubber) and needle shield (natural
rubber), in a pack size of 1 or 10.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Avoid contact with disinfectants.
To reconstitute the vaccine, use the solvent provided. When reconstituted, ZOSTAVAX is a semi-hazy to
translucent, off-white to pale yellow liquid.
18
It is important to use a separate sterile syringe and needle for each patient to prevent transmission of
infectious agents from one individual to another.
Reconstitution instructions
To reconstitute the vaccine, inject all the solvent in the syringe into the vial of lyophilized vaccine and
gently agitate to mix thoroughly. Withdraw the entire contents into a syringe for injection. One or 2
separate needles may be available in the secondary packaging of the presentation containing the pre-filled
syringe without the attached needle. The needle should be pushed into the extremity of the syringe and
rotated a quarter of a turn (90) to secure the connection.
IT IS RECOMMENDED THAT THE VACCINE BE ADMINISTERED IMMEDIATELY AFTER
RECONSTITUTION, TO MINIMIZE LOSS OF POTENCY. DISCARD RECONSTITUTED
VACCINE IF IT IS NOT USED WITHIN 30 MINUTES.
The reconstituted vaccine must not be used if any particulate matter is noted or if the appearance of the
vaccine differs from that described above.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
MARKETING AUTHORISATION HOLDER
SANOFI PASTEUR MSD, SNC
8, rue Jonas Salk
F-69007 Lyon
France
8. MARKETING AUTHORISATION NUMBER(S)
EU/1/06/341/ 003
EU/1/06/341/ 004
EU/1/06/341/ 005
EU/1/06/341/ 006
EU/1/06/341/ 007
EU/1/06/341/ 008
EU/1/06/341/ 009
EU/1/06/341/ 010
EU/1/06/341/ 011
EU/1/06/341/ 012
EU/1/06/341/ 013
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
May 19, 2006
10. DATE OF REVISION OF THE TEXT
19
ANNEX II
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE
SUBSTANCE ANDMANUFACTURING AUTHORISATION
HOLDER RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
20
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer of the biological active substance
Merck Sharp & Dohme Corp.
Sumneytown Pike
West Point
Pennsylvania 19486
U.S.A.
Name and address of the manufacturer responsible for batch release
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands
B. CONDITIONS OF THE MARKETING AUTHORISATION
CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON
THE MARKETING AUTHORISATION HOLDER
Medicinal product subject to medical prescription.
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE
USE OF THE MEDICINAL PRODUCT
Not aplicable.
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in version 2.0 presented in
Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst
the product is on the market.
Official batch release: in accordance with Article 114 Directive 2001/83/EC as amended, the official batch
release will be undertaken by a state laboratory or a laboratory designated for that purpose.
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the
Pharmacovigilance Plan, as agreed in version 4 of the Risk Management Plan (RMP) presented in Module
1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the
CHMP.
21
ANNEX III
LABELLING AND PACKAGE LEAFLET
22
A. LABELLING
23
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
ZOSTAVAX - Powder in vial and solvent in vial - Pack of 1, 10
1.
NAME OF THE MEDICINAL PRODUCT
ZOSTAVAX powder and solvent for suspension for injection
shingles (herpes zoster) vaccine (live)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
After reconstitution, 1 dose (0.65 ml) contains:
Varicella-zoster virus, Oka/Merck strain, (live, attenuated) ≥19400 PFU*
*PFU = Plaque-forming units
3.
LIST OF EXCIPIENTS
Sucrose, hydrolysed gelatin, urea, sodium chloride, potassium dihydrogen phosphate, potassium chloride,
monosodium L-glutamate, anhydrous disodium phosphate, sodium hydroxide.
4.
PHARMACEUTICAL FORM AND CONTENTS
Powder and solvent for suspension for injection
Pack of 1 single dose vial (powder) + 1 single dose vial (solvent)
Pack of 10 single dose vials (powder) + 10 single dose vials (solvent)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Subcutaneous use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
24
 
9.
SPECIAL STORAGE CONDITIONS
STORE AND TRANSPORT REFRIGERATED. Do not freeze. Keep the vial of powder in the outer
carton to protect from light.
After reconstitution, use immediately or within 30 minutes if stored at 20°C-25°C.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Read the package leaflet for disposal of medicines no longer required
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
12. MARKETING AUTHORISATION NUMBER(S)
EU/1/06/341/001 – pack of 1
EU/1/06/341/002 – pack of 10
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
25
 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL OF POWDER
1.
NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION
ZOSTAVAX powder for suspension for injection.
SC
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 dose
6.
OTHER
SANOFI PASTEUR MSD SNC
26
 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL OF SOLVENT
1.
NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION
Solvent for ZOSTAVAX
Water for injections
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 dose
6.
OTHER
SANOFI PASTEUR MSD SNC
27
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
ZOSTAVAX - Powder in vial and solvent in pre-filled syringe with attached needle Pack of 1, 10
1.
NAME OF THE MEDICINAL PRODUCT
ZOSTAVAX powder and solvent for suspension for injection in a pre-filled syringe
shingles (herpes zoster) vaccine (live)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
After reconstitution, 1 dose (0.65 ml) contains:
Varicella-zoster virus, Oka/Merck strain, (live, attenuated) ≥19400 PFU*
*PFU = Plaque-forming units
3.
LIST OF EXCIPIENTS
Sucrose, hydrolysed gelatin, urea, sodium chloride, potassium dihydrogen phosphate, potassium chloride,
monosodium L-glutamate, anhydrous disodium phosphate, sodium hydroxide.
4.
PHARMACEUTICAL FORM AND CONTENTS
Powder and solvent for suspension for injection in a pre-filled syringe
Pack of 1single dose vial (powder) + 1 pre-filled syringe with attached needle (solvent)
Pack of 10 single dose vials (powder) + 10 pre-filled syringes with attached needle (solvent)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Subcutaneous use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
28
 
9.
SPECIAL STORAGE CONDITIONS
STORE AND TRANSPORT REFRIGERATED. Do not freeze. Keep the vial of powder in the outer
carton to protect from light.
After reconstitution, use immediately or within 30 minutes if stored at 20°C-25°C.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Read the package leaflet for disposal of medicines no longer required
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
12. MARKETING AUTHORISATION NUMBER(S)
EU/1/06/341/003 – pack of 1
EU/1/06/341/004 – pack of 10
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
29
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
ZOSTAVAX - Powder in vial and solvent in pre-filled syringe without needle - Pack of 1, 10, 20
1.
NAME OF THE MEDICINAL PRODUCT
ZOSTAVAX powder and solvent for suspension for injection in a pre-filled syringe
shingles (herpes zoster) vaccine (live)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
After reconstitution, 1dose (0.65 ml) contains:
Varicella-zoster virus, Oka/Merck strain, (live, attenuated) ≥19400 PFU*
*PFU = Plaque-forming units
3.
LIST OF EXCIPIENTS
Sucrose, hydrolysed gelatin, urea, sodium chloride, potassium dihydrogen phosphate, potassium chloride,
monosodium L-glutamate, anhydrous disodium phosphate, sodium hydroxide .
4.
PHARMACEUTICAL FORM AND CONTENTS
Powder and solvent for suspension for injection in a pre-filled syringe.
Pack of 1single dose vial (powder) + 1 pre-filled syringe without needle (solvent)
Pack of 10 single dose vials (powder) + 10 pre-filled syringes without needle (solvent)
Pack of 20 single dose vials (powder) + 20 pre-filled syringes without needle (solvent)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Subcutaneous use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
30
 
9.
SPECIAL STORAGE CONDITIONS
STORE AND TRANSPORT REFRIGERATED. Do not freeze. Keep the vial of powder in the outer
carton to protect from light.
After reconstitution, use immediately or within 30 minutes if stored at 20°C-25°C.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Read the package leaflet for disposal of medicines no longer required
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
12. MARKETING AUTHORISATION NUMBER(S)
EU/1/06/341/005 – pack of 1
EU/1/06/341/006 – pack of 10
EU/1/06/341/007 – pack of 20
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
31
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
ZOSTAVAX - Powder in vial and solvent in pre-filled syringe with one unattached needle - Pack of
1, 10, 20
1.
NAME OF THE MEDICINAL PRODUCT
ZOSTAVAX powder and solvent for suspension for injection in a pre-filled syringe
shingles (herpes zoster) vaccine (live)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
After reconstitution, 1dose (0.65 ml) contains:
Varicella-zoster virus Oka/Merck strain, (live, attenuated) ≥19400 PFU*
*PFU = Plaque-forming units
3.
LIST OF EXCIPIENTS
Sucrose, hydrolysed gelatin, urea, sodium chloride, potassium dihydrogen phosphate, potassium chloride,
monosodium L-glutamate, anhydrous disodium phosphate, sodium hydroxide.
4.
PHARMACEUTICAL FORM AND CONTENTS
Powder and solvent for suspension for injection in a pre-filled syringe.
Pack of 1single dose vial (powder) + 1 pre-filled syringe (solvent) + 1 needle unattached needle.
Pack of 10 single dose vials (powder) + 10 pre-filled syringes (solvent) + 10 unattached needles.
Pack of 20 single dose vials (powder) + 20 pre-filled syringes (solvent) + 20 unattached needles.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Subcutaneous use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
32
 
9.
SPECIAL STORAGE CONDITIONS
STORE AND TRANSPORT REFRIGERATED. Do not freeze. Keep the vial of powder in the outer
carton to protect from light.
After reconstitution, use immediately or within 30 minutes if stored at 20°C-25°C.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Read the package leaflet for disposal of medicines no longer required
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
12. MARKETING AUTHORISATION NUMBER(S)
EU/1/06/341/008 - pack of 1
EU/1/06/341/009 - pack of 10
EU/1/06/341/010 - pack of 20
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
33
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
ZOSTAVAX - Powder in vial and solvent in pre-filled syringe with 2 unattached needles - Pack of
1, 10, 20
1.
NAME OF THE MEDICINAL PRODUCT
ZOSTAVAX powder and solvent for suspension for injection in a pre-filled syringe
shingles (herpes zoster) vaccine (live)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
After reconstitution, 1 dose (0.65 ml) contains:
Varicella-zoster virus Oka/Merck strain, (live, attenuated) ≥19400 PFU*
*PFU = Plaque-forming units
3.
LIST OF EXCIPIENTS
Sucrose, hydrolysed gelatin, urea, sodium chloride, potassium dihydrogen phosphate, potassium chloride,
monosodium L-glutamate, anhydrous disodium phosphate, sodium hydroxide.
4.
PHARMACEUTICAL FORM AND CONTENTS
Powder and solvent for suspension for injection in a pre-filled syringe.
Pack of 1single dose vial (powder) + 1 pre-filled syringe (solvent) + 2 unattached needles.
Pack of 10 single dose vials (powder) + 10 pre-filled syringes (solvent) + 20 unattached needles.
Pack of 20 single dose vials (powder) + 20 pre-filled syringes (solvent) + 40 unattached needles.
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Subcutaneous use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
34
 
9.
SPECIAL STORAGE CONDITIONS
STORE AND TRANSPORT REFRIGERATED. Do not freeze. Keep the vial of powder in the outer
carton to protect from light.
After reconstitution, use immediately or within 30 minutes if stored at 20°C-25°C.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Read the package leaflet for disposal of medicines no longer required
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
SANOFI PASTEUR MSD SNC
8, rue Jonas Salk
F-69007 Lyon
France
12. MARKETING AUTHORISATION NUMBER(S)
EU/1/06/341/011– pack of 1
EU/1/06/341/012 – pack of 10
EU/1/06/341/013– pack of 20
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
35
 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL OF POWDER
1.
NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION
ZOSTAVAX powder for suspension for injection.
SC
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 dose
6.
OTHER
SANOFI PASTEUR MSD SNC
36
 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
PRE-FILLED SYRINGE OF SOLVENT
1.
NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION
Solvent for ZOSTAVAX
Water for injections
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 dose
6.
OTHER
SANOFI PASTEUR MSD SNC
37
 
B. PACKAGE LEAFLET
38
PACKAGE LEAFLET: INFORMATION FOR THE USER
ZOSTAVAX
Powder and solvent for suspension for injection
shingles (herpes zoster) vaccine (live)
Read all of this leaflet before you are vaccinated.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This vaccine has been prescribed for you. Do not pass it on to others.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
In this leaflet:
1.
What ZOSTAVAX is and what it is used for
2.
Before you receive ZOSTAVAX
3.
How to use ZOSTAVAX
4.
Possible side effects
5.
How to store ZOSTAVAX
6.
Further information
1. WHAT ZOSTAVAX IS AND WHAT IT IS USED FOR
ZOSTAVAX is a vaccine used to prevent shingles (zoster) and zoster-related post-herpetic neuralgia
(PHN), the long-lasting nerve pain that follows shingles.
ZOSTAVAX is used to vaccinate individuals 50 years of age or older.
ZOSTAVAX cannot be used to treat existing shingles or the pain associated with existing shingles.
Disease information on shingles:
What is shingles?
Shingles is a painful, blistering rash. It usually occurs in one part of the body and can last for several
weeks. It may lead to severe and long-lasting pain and scarring. Less commonly, bacterial skin infections,
weakness, muscle paralysis, loss of hearing or vision can occur. Shingles is caused by the same virus that
causes chickenpox. After you have had chickenpox, the virus that caused it stays in your body in nerve
cells. Sometimes, after many years, the virus becomes active again and causes shingles.
What is PHN?
After the shingles blisters heal, pain can last for months or years and may be severe. This long-lasting
nerve pain is called post-herpetic neuralgia or PHN.
2.
BEFORE YOU RECEIVE ZOSTAVAX
Do not receive ZOSTAVAX
if you are allergic (hypersensitive) to any of the components (for example, neomycin) of
ZOSTAVAX (including any of the ingredients listed under “the other ingredients are”- see section
6. Further information- what ZOSTAVAX contains)
if you have a blood disorder or any type of cancer that weakens your immune system
39
if you have been told by your doctor that you have a weakened immune system as a result of a
disease, medicines, or other treatment
if you have active untreated tuberculosis
if you are pregnant (see Pregnancy and breast-feeding )
Take special care with ZOSTAVAX
Talk to your doctor or pharmacist before being vaccinated with ZOSTAVAX:
if you have or have had any medical problems and about any allergies
if you have a fever
if you have HIV infection
if you are pregnant or think you could be pregnant, if you are planning to become pregnant, you
should consult your doctor as pregnancy must be excluded before vaccination. Women of child-
bearing potential must use effective birth control to avoid pregnancy for 3 months following
vaccination.
As with many vaccines, ZOSTAVAX may not completely protect all persons who are vaccinated.
ZOSTAVAX cannot be used to treat existing shingles or the pain associated with existing shingles.
Using other medicines and other vaccines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
ZOSTAVAX can be administered at the same time as inactivated influenza vaccine. The two vaccines
should be given as separate injections at different body sites.
ZOSTAVAX should not be given at the same time as the 23-valent pneumococcal polysaccharide vaccine.
For more information about these vaccines, talk to your doctor or health care provider.
Pregnancy and breast-feeding
ZOSTAVAX should not be given to pregnant women. Women of child-bearing potential should take the
necessary precautions to avoid pregnancy for 3 months following vaccination.
Inform your doctor if you are breast-feeding or intending to breast-feed. Your doctor will decide if
ZOSTAVAX should be given.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
There is no information to suggest that ZOSTAVAX affects the ability to drive or use machines.
Important information about the ingredients of ZOSTAVAX
Tell your doctor if you have ever had an allergic reaction to any of the ingredients (including neomycin or
any of the ingredients listed under “the other ingredients are”- see section 6. Further information- what
ZOSTAVAX contains) before you receive this vaccine.
3.
HOW TO USE ZOSTAVAX
ZOSTAVAX should be injected under the skin, preferably in the upper arm.
ZOSTAVAX is given as a single dose by injection.
40
Reconstitution instructions intended for medical and healthcare professionals are included at the
end of the leaflet.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, ZOSTAVAX can cause side effects, although not everybody gets them.
In studies, the most commonly reported side effects (occurring in at least 1 in 10 individuals) were at the
injection site. These side effects included redness, pain, swelling, itching, warmth, and bruising at the
injection site. Headache was also commonly reported (occurring in at least 1 of 100 and less than 1 of 10
individuals).
The following additional side effects have been reported in general use with ZOSTAVAX: joint pain;
muscle pain; fever; swollen gland (neck, armpit); rash; rash at the injection site; hives at the injection site;
allergic reactions, which may be serious and may include difficulty in breathing or swallowing. If you
have an allergic reaction, call your doctor right away.
Your doctor or pharmacist has a more complete list of side effects for ZOSTAVAX.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell
your doctor or pharmacist. If the condition persists or worsens, seek medical attention.
5. HOW TO STORE ZOSTAVAX
Keep out of the reach and sight of children.
Do not use ZOSTAVAX after the expiry date which is stated on the outer carton after EXP.
Store and transport refrigerated (2C - 8C). Do not freeze. Keep the vial in the outer carton in order to
protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help protect the environment.
6.
FURTHER INFORMATION
What ZOSTAVAX contains
After reconstitution, 1 dose (0.65 ml) contains:
The active substance is:
Varicella-zoster virus 1 , Oka/Merck strain, (live, attenuated) not less than 19400 PFU (plaque-forming
units).
1 Produced in human diploid (MRC-5) cells
The other ingredients are:
Powder
Sucrose, hydrolysed gelatin, sodium chloride, potassium dihydrogen phosphate, potassium chloride,
monosodium L-glutamate, anhydrous disodium phosphate, sodium hydroxide (to adjust pH), and urea.
Solvent
41
Water for injections
What ZOSTAVAX looks like and contents of the pack
The vaccine is a powder for suspension for injection contained in a single-dose vial, which should be
reconstituted with the solvent provided with the vial of powder.
The solvent is a clear and colourless liquid. Before mixing with the solvent, the powder is a white to off-
white compact crystalline plug.
ZOSTAVAX is available in packs of 1 or 10. Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: Sanofi Pasteur MSD SNC, 8 rue Jonas Salk, F-69007 Lyon, France
Manufacturer: Merck Sharp and Dohme, B.V., Waarderweg, 39, 2031 BN Haarlem, The Netherlands
For any information about this medicinal product, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien: Sanofi Pasteur MSD, Tél/Tel: +32.2.726.95.84
България: Мерк Шарп и Доум България ЕООД тел. + 359 2 8193740
Česká republika: Merck Sharp & Dohme, IDEA, Inc.,org. sl.,Tel.: +420.233.010.111
Danmark: Sanofi Pasteur MSD, Tlf: +45.23.32.69.29
Deutschland: Sanofi Pasteur MSD GmbH, Tel: +49.6224.5940
Eesti: Merck Sharp & Dohme OÜ, Tel: +372.613.9750
Ελλάδα: ΒΙΑΝΕΞ Α.Ε., Τηλ: +30.210.8009111
España: Sanofi Pasteur MSD S.A., Tel: +34.91.371.78.00
France: Sanofi Pasteur MSD SNC, Tél: +33.4.37.28.40.00
Ireland: Sanofi Pasteur MSD Ltd, Tel: +3531.468.5600
Ísland: Sanofi Pasteur MSD, Sími: +32.2.726.95.84
Italia: Sanofi Pasteur MSD Spa, Tel: +39.06.664.092.11
Kύπρος: Merck Sharp & Dohme Cyprus Limited, Τηλ: +357 22866700
Latvija: SIA Merck Sharp & Dohme Latvija, Tel: +371.67364.224
Lietuva: UAB Merck Sharp & Dohme, Tel.: +370.5.2780.247
Luxembourg/Luxemburg: Sanofi Pasteur MSD, Tél: +32.2.726.95.84
Magyarország: MSD Magyarország Kft, Tel.: + 36.1.888.5300
Malta: Merck Sharp & Dohme Cyprus Limited, Tel: +357 22866700
Nederland: Sanofi Pasteur MSD, Tel: +31.23.567.96.00
Norge: Sanofi Pasteur MSD, Tlf: +47.67.50.50.20
Österreich: Sanofi Pasteur MSD GmbH, Tel: +43.1.866.70.22.202
Polska: MSD Polska Sp. z o.o., Tel.: +48.22.549.51.00
Portugal : Sanofi Pasteur MSD, SA, Tel: +351 21 470 45 50
România : Merck Sharp & Dohme Romania S.R.L. Tel: + 4021 529 29 00
Slovenija: Merck Sharp & Dohme, inovativna zdravila d.o.o., Tel: +386.1.520.4201
Slovenská republika: Merck Sharp & Dohme IDEA, Inc., Tel: +421.2.58282010
Suomi/Finland: Sanofi Pasteur MSD, Puh/Tel: +358.9.565.88.30
Sverige: Sanofi Pasteur MSD, Tel: +46.8.564.888.60
United Kingdom: Sanofi Pasteur MSD Ltd, Tel: +44.1.628.785.291
This leaflet was last approved in:
42
The following information is intended for medical or healthcare professionals only:
Reconstitution instructions
The solvent is a clear and colourless liquid. Before mixing with the solvent, the powder is a white to off-
white compact crystalline plug. When completely reconstituted, the vaccine is a semi-hazy to translucent,
off-white to pale yellow liquid.
Withdraw the entire volume of solvent into a syringe. Inject the entire content of the syringe into the vial
containing the powder. Gently agitate to dissolve completely. Withdraw the entire content of the
reconstituted vaccine vial into a syringe for injection.
It is recommended that the vaccine be administered immediately after reconstitution to minimize loss of
potency. Discard if reconstituted vaccine is not used within 30 minutes.
Do not use the reconstituted vaccine if you notice any particulate matter or if the appearance of the solvent
or powder or of the reconstituted vaccine differs from that described above.
Any unused product or waste material should be disposed of in accordance with local requirements.
See also section 3. HOW TO USE ZOSTAVAX
43
PACKAGE LEAFLET: INFORMATION FOR THE USER
ZOSTAVAX
Powder and solvent for suspension for injection in a pre-filled syringe
shingles (herpes zoster) vaccine (live)
Read all of this leaflet before you are vaccinated.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This vaccine has been prescribed for you. Do not pass it on to others.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
In this leaflet:
1.
What ZOSTAVAX is and what it is used for
2.
Before you receive ZOSTAVAX
3.
How to use ZOSTAVAX
4.
Possible side effects
5.
How to store ZOSTAVAX
6.
Further information
1.
WHAT ZOSTAVAX IS AND WHAT IT IS USED FOR
ZOSTAVAX is a vaccine used to prevent shingles (zoster) and zoster-related post-herpetic neuralgia
(PHN), the long-lasting nerve pain that follows shingles.
ZOSTAVAX is used to vaccinate individuals 50 years of age or older.
ZOSTAVAX cannot be used to treat existing shingles or the pain associated with existing shingles.
Disease information on shingles:
What is shingles?
Shingles is a painful, blistering rash. It usually occurs in one part of the body and can last for several
weeks. It may lead to severe and long-lasting pain and scarring. Less commonly, bacterial skin infections,
weakness, muscle paralysis, loss of hearing or vision can occur. Shingles is caused by the same virus that
causes chickenpox. After you have had chickenpox, the virus that caused it stays in your body in nerve
cells. Sometimes, after many years, the virus becomes active again and causes shingles.
What is PHN?
After the shingles blisters heal, pain can last for months or years and may be severe. This long-lasting
nerve pain is called post-herpetic neuralgia or PHN.
2.
BEFORE YOU RECEIVE ZOSTAVAX
Do not receive ZOSTAVAX
if you are allergic (hypersensitive) to any of the components (for example, neomycin) of
ZOSTAVAX (including any of the ingredients listed under “the other ingredients are”- see section
6. Further information- what ZOSTAVAX contains)
if you have a blood disorder or any type of cancer that weakens your immune system
44
if you have been told by your doctor that you have a weakened immune system as a result of a
disease, medicines, or other treatment
if you have active untreated tuberculosis
if you are pregnant (see Pregnancy and breast-feeding )
Take special care with ZOSTAVAX
Talk to your doctor or pharmacist before being vaccinated with ZOSTAVAX:
if you have or have had any medical problems and about any allergies
if you have a fever
if you have HIV infection
if you are pregnant or think you could be pregnant, if you are planning to become pregnant, you
should consult your doctor as pregnancy must be excluded before vaccination. Women of child-
bearing potential must use effective birth control to avoid pregnancy for 3 months following
vaccination.
As with many vaccines, ZOSTAVAX may not completely protect all persons who are vaccinated.
ZOSTAVAX cannot be used to treat existing shingles or the pain associated with existing shingles.
Using other medicines and other vaccines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
ZOSTAVAX can be administered at the same time as inactivated influenza vaccine. The two vaccines
should be given as separate injections at different body sites.
ZOSTAVAX should not be given at the same time as the 23-valent pneumococcal polysaccharide vaccine.
For more information about these vaccines, talk to your doctor or health care provider.
Pregnancy and breast-feeding
ZOSTAVAX should not be given to pregnant women. Women of child-bearing age should take the
necessary precautions to avoid pregnancy for 3 months following vaccination.
Inform your doctor if you are breast-feeding or intending to breast-feed. Your doctor will decide if
ZOSTAVAX should be given.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
There is no information to suggest that ZOSTAVAX affects the ability to drive or use machines.
Important information about the ingredients of ZOSTAVAX
Tell your doctor if you have ever had an allergic reaction to any of the ingredients (including neomycin or
any of the ingredients listed under “the other ingredients are”- see section 6. Further information- what
ZOSTAVAX contains) before you receive this vaccine.
3.
HOW TO USE ZOSTAVAX
ZOSTAVAX should be injected under the skin, preferably in the upper arm.
ZOSTAVAX is given as a single dose by injection.
45
Reconstitution instructions intended for medical and healthcare professionals are included at the
end of the leaflet.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, ZOSTAVAX can cause side effects, although not everybody gets them.
In studies, the most commonly reported side effects (occurring in at least 1 in 10 individuals) were at the
injection site. These side effects included redness, pain, swelling, itching, warmth, and bruising at the
injection site. Headache was also commonly reported (occurring in at least 1 of 100 and less than 1 of 10
individuals).
The following additional side effects have been reported in general use with ZOSTAVAX: joint pain;
muscle pain; fever; swollen gland (neck, armpit); rash; rash at the injection site; hives at the injection site;
allergic reactions, which may be serious and may include difficulty in breathing or swallowing. If you
have an allergic reaction, call your doctor right away.
Your doctor or pharmacist has a more complete list of side effects for ZOSTAVAX.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell
your doctor or pharmacist. If the condition persists or worsens, seek medical attention.
5.
HOW TO STORE ZOSTAVAX
Keep out of the reach and sight of children.
Do not use ZOSTAVAX after the expiry date which is stated on the outer carton after EXP.
Store and transport refrigerated (2C - 8C). Do not freeze. Keep the vial in the outer carton in order to
protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help protect the environment.
6.
FURTHER INFORMATION
What ZOSTAVAX contains
After reconstitution, 1 dose (0.65 ml) contains:
The active substance is:
Varicella-zoster virus 1 , Oka/Merck strain, (live, attenuated) not less than 19400 PFU (plaque-forming
units).
1 Produced in human diploid (MRC-5) cells
The other ingredients are:
Powder
Sucrose, hydrolysed gelatin, sodium chloride, potassium dihydrogen phosphate, potassium chloride,
monosodium L-glutamate, anhydrous disodium phosphate, sodium hydroxide (to adjust pH), and urea.
Solvent
46
Water for injections
What ZOSTAVAX looks like and contents of the pack
The vaccine is a powder for suspension for injection contained in a single-dose vial, which should be
reconstituted with the solvent provided with the vial of powder.
The solvent is a clear and colourless liquid. Before mixing with the solvent, the powder is a white to off-
white compact crystalline plug.
One pack of ZOSTAVAX contains a vial and a prefilled syringe with or without attached needles. One or
2 separate needles may be available in the secondary packaging of the presentation containing the pre-
filled syringe without the attached needle
ZOSTAVAX is available in packs of 1, 10 or 20 with or without needles. Not all pack sizes may be
marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: Sanofi Pasteur MSD SNC, 8 rue Jonas Salk, F-69007 Lyon, France
Manufacturer: Merck Sharp and Dohme, B.V., Waarderweg, 39, 2031 BN Haarlem, The Netherlands
For any information about this medicinal product, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien: Sanofi Pasteur MSD, Tél/Tel: +32.2.726.95.84
България: Мерк Шарп и Доум България ЕООД тел. + 359 2 8193740
Česká republika: Merck Sharp & Dohme, IDEA, Inc., org. sl.,Tel.: +420.233.010.111
Danmark: Sanofi Pasteur MSD, Tlf: +45.23.32.69.29
Deutschland: Sanofi Pasteur MSD GmbH, Tel: +49.6224.5940
Eesti: Merck Sharp & Dohme OÜ, Tel: +372.613.9750
Ελλάδα: ΒΙΑΝΕΞ Α.Ε., Τηλ: +30.210.8009111
España: Sanofi Pasteur MSD S.A., Tel: +34.91.371.78.00
France: Sanofi Pasteur MSD SNC, Tél: +33.4.37.28.40.00
Ireland: Sanofi Pasteur MSD Ltd, Tel: +3531.468.5600
Ísland: Sanofi Pasteur MSD, Sími: +32.2.726.95.84
Italia: Sanofi Pasteur MSD Spa, Tel: +39.06.664.092.11
Kύπρος: Merck Sharp & Dohme Cyprus Limited, Τηλ: +357 22866700
Latvija: SIA Merck Sharp & Dohme Latvija, Tel: +371.67364.224
Lietuva: UAB Merck Sharp & Dohme, Tel.: +370.5.2780.247
Luxembourg/Luxemburg: Sanofi Pasteur MSD, Tél: +32.2.726.95.84
Magyarország: MSD Magyarország Kft, Tel.: + 36.1.888.5300
Malta: Merck Sharp & Dohme Cyprus Limited, Tel: +357 22866700
Nederland: Sanofi Pasteur MSD, Tel: +31.23.567.96.00
Norge: Sanofi Pasteur MSD, Tlf: +47.67.50.50.20
Österreich: Sanofi Pasteur MSD GmbH, Tel: +43.1.866.70.22.202
Polska: MSD Polska Sp. z o.o., Tel.: +48.22.549.51.00
Portugal : Sanofi Pasteur MSD, SA, Tel: +351 21 470 45 50
România : Merck Sharp & Dohme Romania S.R.L. Tel: + 4021 529 29 00
Slovenija: Merck Sharp & Dohme, inovativna zdravila d.o.o., Tel: +386.1.520.4201
Slovenská republika: Merck Sharp & Dohme IDEA, Inc., Tel: +421.2.58282010
Suomi/Finland: Sanofi Pasteur MSD, Puh/Tel: +358.9.565.88.30
Sverige: Sanofi Pasteur MSD, Tel: +46.8.564.888.60
United Kingdom: Sanofi Pasteur MSD Ltd, Tel: +44.1.628.785.291
47
This leaflet was last approved in:
The following information is intended for medical or healthcare professionals only:
Reconstitution instructions
The solvent is a clear and colourless liquid. Before mixing with the solvent, the powder is a white to off-
white compact crystalline plug. When completely reconstituted, the vaccine is a semi-hazy to translucent,
off-white to pale yellow liquid.
Inject the entire content of the pre-filled syringe into the vial containing the powder. Gently agitate to
dissolve completely. Withdraw the entire content of the reconstituted vaccine vial into a syringe for
injection. One or 2 separate needles may be available in the secondary packaging of the presentation
containing the pre-filled syringe without the attached needle. The needle should be pushed into the
extremity of the syringe and rotated a quarter of a turn (90) to secure the connection.
It is recommended that the vaccine be administered immediately after reconstitution to minimize loss of
potency. Discard if reconstituted vaccine is not used within 30 minutes.
Do not use the reconstituted vaccine if you notice any particulate matter or if the appearance of the solvent
or powder or of the reconstituted vaccine differs from that described above.
Any unused product or waste material should be disposed of in accordance with local requirements.
See also section 3. HOW TO USE ZOSTAVAX
48


Source: European Medicines Agency



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