Consumer medicine information

Zostavax

Varicella zoster vaccine, live attenuated

BRAND INFORMATION

Brand name

Zostavax

Active ingredient

Varicella zoster vaccine, live attenuated

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Zostavax.

What is in this leaflet

This leaflet answers some common questions about ZOSTAVAX. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines and vaccines have risks and benefits. Your doctor has weighed the risks of you being given ZOSTAVAX against the expected benefits it will have for you.

If you have any concerns about being given this vaccine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What ZOSTAVAX is used for

ZOSTAVAX is a vaccine used to help prevent shingles (zoster). It can be given to adults 50 years of age and older.

ZOSTAVAX boosts your immune system to help protect you from shingles and its complications. ZOSTAVAX cannot be used to treat existing shingles or the pain associated with existing shingles.

ZOSTAVAX can reduce the intensity and length of time your pain from shingles will last. If you are 70 years of age or older and you get shingles even though you have been vaccinated, ZOSTAVAX can help prevent the long-lasting nerve pain that can follow shingles.

Symptoms of shingles include a painful, blistering rash that may result in scarring. The blisters can persist for several weeks. They often break out in one part of the body. The nerve pain that comes from shingles can last for months or even years after the rash heals.

Shingles is caused by the same virus that causes chickenpox (varicella-zoster virus). After your chickenpox blisters heal, the virus that caused them stays in your body in nerve cells. The virus may be there for many years and not cause a problem. Sometimes, though, it may become active again. If this happens, it can cause a blistering and painful rash that may result in scarring. The blisters can persist for several weeks. They often break out in one part of the body.

Shingles can be serious. Sometimes the nerve pain caused by shingles can be severe and last for months or years. For some people, this nerve pain can get in the way of normal day-to-day activities such as walking, sleeping, and social activities.

The pain from shingles can also lead to emotional distress. People who suffer from shingles have described their pain in many ways. Some say the pain burns or throbs. Others say it feels like stabbing, shooting pain, and/or that it feels sharp. Severe pain can result from things as minor as a breeze or the touch of clothing against the skin.

In addition to severe pain, people with shingles may have other complications. These include:

  • scarring
  • bacterial skin infections
  • weakness
  • muscle paralysis
  • loss of hearing or vision.

Almost every adult has had chickenpox and so is at risk for shingles. The risk increases as you get older. This is especially true if you are over 50 years of age.

How it works

ZOSTAVAX boosts your immune system to help protect you from shingles.

As with any vaccine, ZOSTAVAX may not protect all people who receive the vaccine.

Before you are given ZOSTAVAX

When you must not be given it

Do not receive ZOSTAVAX if you:

  • are allergic to any of its ingredients listed at the end of this leaflet. This includes allergies to gelatin or neomycin.
    Symptoms of an allergic reaction may include swelling of the face, lips, tongue, throat, difficulty in breathing, or hives.
  • are pregnant
    ZOSTAVAX is not recommended to be given to pregnant women.
  • have a blood disorder or any type of cancer that weakens your immune system.
  • have been told by your doctor that you have a weakened immune system as a result of a disease, medications, (including high-dose corticosteroids or cancer medicines), or other treatment.
  • have active tuberculosis (TB) which is not being currently treated
  • the expiry date on the pack has passed.
    If the vaccine is used after the expiry date has passed, it may not work.

If you are not sure whether you should be given ZOSTAVAX, talk to your doctor.

Before you are given it

Tell your doctor if you:

  1. you have or have had any medical problems
  2. are taking or have taken any medications that might weaken your immune system
  3. have any allergies including allergies to gelatin or neomycin
  4. have a fever
  5. have HIV infection
  6. become pregnant or plan to become pregnant in the next three months, are breast-feeding, or plan to start breast-feeding
Your doctor will decide if ZOSTAVAX should be given
  1. have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.

If you have not told your doctor about any of the above, tell them before you are given an injection of ZOSTAVAX

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Use with other vaccines

ZOSTAVAX can be administered at the same time as inactivated influenza vaccine using a separate syringe.

ZOSTAVAX should not be given at the same time as PNEUMOVAX 23, a vaccine used to help prevent infections caused by certain types of germs or bacteria called pneumococcus. For more information about these vaccines, talk to your doctor, because it may be better to get these vaccines at least 4 weeks apart.

How ZOSTAVAX is given

ZOSTAVAX is given as a single dose (0.65 ml) by injection just under the skin (subcutaneously) of the upper arm by a doctor or trained nurse.

The vaccine should not be injected directly into a blood vessel (intravascularly).

After you have been given ZOSTAVAX

Things you must do

If you are a woman of child-bearing age, avoid falling pregnant for 3 months after vaccination.

Things to be careful of

There is no information to suggest that ZOSTAVAX affects the ability to drive or operate machinery.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well during or after having received a dose of ZOSTAVAX

ZOSTAVAX helps protect most people, but it may have unwanted side effects in a few people. All medicines and vaccines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following if they worry you:

  • redness, pain, swelling, hard lump, itching, warmth, or bruising, at the site you had the injection
  • headache
  • pain in your arm or leg

These were the most common side effects reported during studies.

The following additional side effects have been reported in general use with ZOSTAVAX:

  • allergic reactions which may be serious and may include difficulty in breathing or swallowing ( see also Allergic Reaction below)
  • chicken pox
  • fever
  • hives at the injection site
  • joint pain
  • muscle pain
  • nausea
  • rash
  • rash at the injection site
  • shingles
  • swollen glands near the injection site (that may last a few days to a few weeks).
  • Guillain-Barré syndrome (muscle weakness, abnormal sensations, tingling in the arms, legs and upper body)
  • Loss of facial muscle movements

Tell your doctor promptly about any unusual or severe symptoms that develop after you receive ZOSTAVAX. If the condition persists or gets worse, seek medical attention.

Allergic Reaction

As with all vaccines given by injection, there is a very small risk of a serious allergic reaction.

Tell your doctor immediately or go to accident and emergency at your nearest hospital if you notice any of the following:

  • swelling of the face, lips, mouth, throat or neck which may cause difficulty in swallowing or breathing
  • wheezing or shortness of breath
  • severe skin reactions
  • pinkish, itchy swellings on the skin, also called hives or nettlerash

These are serious side effects. If you have them, you may have had a serious allergic reaction to ZOSTAVAX. You may need urgent medical attention or hospitalisation. Most of these side effects occur within the first few hours of vaccination.

Other side effects not listed above may also occur in some patients.

Storage

ZOSTAVAX is usually stored in the doctor's surgery or clinic or at the pharmacy.

However, if you need to store ZOSTAVAX.

  • Keep it where children cannot reach it.
  • Keep it in the refrigerator where the temperature is 2°C to 8°C.

Protect from light by keeping it in the original pack until it is time for it to be given.

Product description

What it looks like

ZOSTAVAX comes as a white to off-white powder in glass vials. It is reconstituted with a special diluent to make a solution suitable for injection. ZOSTAVAX when reconstituted is a semi-hazy to translucent, off white to pale yellow liquid.

Ingredients

Each 0.65-mL dose of ZOSTAVAX contains a minimum of 19,400 PFU (plaque-forming units) of Oka/Merck strain of varicella-zoster virus when reconstituted with the diluent and stored at room temperature for 30 minutes.

Inactive ingredients:

  • sucrose
  • urea
  • hydrolyzed gelatin (porcine)
  • sodium chloride
  • monosodium glutamate monohydrate
  • dibasic sodium phosphate
  • monobasic potassium phosphate
  • potassium chloride
  • residual components of MRC-5 cells including DNA and protein
  • trace quantities of neomycin and bovine calf serum.

The diluent contains water for injections.

During initial passage of the virus, tissue culture materials sourced from human embryonic stem cells may have been used in the research undertaken in the development of this vaccine.

The manufacture of this product includes exposure to bovine derived materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

Supplier

ZOSTAVAX is supplied in Australia by:

Seqirus (Australia) Pty Ltd
63 Poplar Road
PARKVILLE VIC 3052

This leaflet was prepared on
22 June 2020

Australian Registration Numbers:

AUST R 130225: vaccine vial

AUST R 130229: vaccine vial + diluent syringe

AUST R 130241: vaccine vial + diluent vial

Not all presentations and pack sizes may be marketed.

WPPI-V211-R-I-052018

Published by MIMS August 2020

BRAND INFORMATION

Brand name

Zostavax

Active ingredient

Varicella zoster vaccine, live attenuated

Schedule

S4

 

1 Name of Medicine

Live varicella vaccine.

2 Qualitative and Quantitative Composition

Each 0.65 mL dose contains a minimum of 19,400 PFU (plaque forming units) of Oka/Merck strain of varicella-zoster virus (VZV) when reconstituted and stored at room temperature for up to 30 minutes.

List of excipients with known effect.

Sulfites (present as a residue of hydrolyzed porcine gelatin).
For the full list of excipients, see Section 6.1 List of Excipients.
Zostavax is a lyophilized preparation of the Oka/Merck strain of live, attenuated varicella-zoster virus (VZV). The virus was initially obtained from a child with naturally-occurring varicella, then introduced into human embryonic lung cell cultures, adapted to and propagated in embryonic guinea pig cell cultures and finally propagated in human diploid cell cultures (WI-38). During initial passage of the virus, tissue culture materials sourced from human embryonic stem cells may have been used in the research undertaken in the development of the vaccine. Further passage of the virus was performed at Merck Research Laboratories (MRL) in human diploid cell cultures (MRC-5) that were free of adventitious agents. This live, attenuated zoster vaccine is a lyophilized preparation containing sucrose, phosphate, glutamate, and processed gelatin as stabilizers.

3 Pharmaceutical Form

Powder for injection.
Powder and solvent for injection.
The powder is a white compact, crystalline pellet.
The solvent is a clear, colourless solution.
Zostavax, when reconstituted as directed, is a sterile preparation that is a semi-hazy to translucent, off white to pale yellow liquid for subcutaneous administration.

4 Clinical Particulars

4.1 Therapeutic Indications

Zostavax is indicated for the prevention of herpes zoster (shingles) in individuals 50 years of age and older.
Zostavax is indicated for the prevention of postherpetic neuralgia (PHN) and for reduction of acute and chronic zoster-associated pain in individuals 60 years of age and older.

4.2 Dose and Method of Administration

For subcutaneous administration.
Do not inject intravascularly.
Individuals 50 years of age and older should receive a single dose (0.65 mL) of the vaccine.
Zostavax is not a treatment for zoster or PHN.
Reconstitute immediately upon removal from the refrigerator.
Product is for single use in one patient only.
To reconstitute the vaccine, use only the diluent supplied since it is free of preservatives or other antiviral substances which might inactivate the vaccine virus.

Vial of diluent.

To reconstitute the vaccine, first withdraw the entire contents of the diluent vial into a syringe. Inject all of the diluent in the syringe into the vial of lyophilized vaccine and gently agitate to mix thoroughly. Withdraw the entire contents into a syringe and inject the total volume of reconstituted vaccine subcutaneously, preferably into the upper arm (preferably in the deltoid region).

Prefilled syringe of diluent.

To reconstitute the vaccine, inject all the diluent in the syringe into the vial of lyophilized vaccine and gently agitate to mix thoroughly. Withdraw the entire contents into a syringe and inject the total volume of reconstituted vaccine subcutaneously, preferably into the upper arm (preferably in the deltoid region).
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.
Do not freeze reconstituted vaccine.

Caution.

A sterile syringe free of preservatives, antiseptics, and detergents should be used for each injection and/or reconstitution of Zostavax because these substances may inactivate the vaccine virus.
A separate sterile needle and syringe should be used for administration of Zostavax to prevent transfer of infectious diseases.
Needles should be disposed of properly and should not be recapped.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Zostavax, when reconstituted is a semi-hazy to translucent, off white to pale yellow liquid.
Zostavax can be administered concurrently with inactivated influenza vaccine using separate syringes.

4.3 Contraindications

Zostavax is contraindicated in any patients with the following:
History of hypersensitivity to any component of the vaccine, including gelatin.
History of anaphylactic/ anaphylactoid reaction to neomycin (each dose of reconstituted vaccine contains trace quantities of neomycin). 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.
Primary and acquired immunodeficiency states due to conditions such as: acute and chronic leukemias; lymphoma; other conditions affecting the bone marrow or lymphatic system; immunosuppression due to HIV/AIDS (see Section 5.1, Clinical trials; Section 4.8 Adverse Effects (Undesirable Effects)); cellular immune deficiencies.
Immunosuppressive therapy (including high-dose corticosteroids) (see Section 4.8 Adverse Effects (Undesirable Effects)); 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 (see Section 5.1, Clinical trials, Immunogenicity in subjects on chronic/ maintenance systemic corticosteroids).
Zostavax is a live, attenuated varicella-zoster vaccine and administration may result in disseminated disease including systemic organ involvement and death in individuals who are immunosuppressed or immunodeficient.
Active untreated tuberculosis.
Pregnancy (see Section 4.6, Use in pregnancy).

4.4 Special Warnings and Precautions for Use

The health care provider should question the patient about reactions to a previous dose of any VZV-containing vaccines (see Section 4.3 Contraindications).
As with any vaccine, adequate treatment provisions, including adrenaline (epinephrine) injection (1:1000), should be available for immediate use should an anaphylactic/anaphylactoid reaction occur.
Deferral of vaccination should be considered in the presence of fever > 38.5°C (> 101.3°F).
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. A phase II safety and immunogenicity study in HIV-infected adults with conserved immune function has been completed (see Section 5.1, Clinical trials; Section 4.8 Adverse Effects (Undesirable Effects)).
As with any vaccine, vaccination with Zostavax may not result in protection of all vaccine recipients.

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. Transmission of vaccine virus from varicella vaccine recipients without a VZV-like rash has been reported but has not been confirmed. 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 zoster that could be transmitted to a susceptible individual.

Use in the elderly.

The mean age of subjects enrolled in the largest (N=38,546) clinical study of Zostavax was 69 years (range 59-99 years). Of the 19,270 subjects who received Zostavax, 10,378 were 60 69 years of age, 7,629 were 70 79 years of age, and 1,263 were 80 years of age or older. The safety and efficacy data presented (see Section 5 Pharmacological Properties; Section 5.1, Clinical trials; Section 4.8 Adverse Effects (Undesirable Effects)) were obtained from these subjects. Zostavax was demonstrated to be generally safe and effective in this population.

Paediatric use.

Zostavax is not recommended for use in this age group.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Zostavax must not be mixed with any other medicinal product in the same syringe. Other medicinal products must be given as separate injections and at different body sites.
Concurrent administration of Zostavax and antiviral medications known to be effective against VZV has not been evaluated.

Use with other vaccines.

Zostavax can be administered concurrently with inactivated influenza vaccine (see Section 4.2 Dose and Method of Administration; Section 5.1, Clinical trials).
Zostavax and Pneumovax 23 should not be given concomitantly because concomitant use resulted in reduced immunogenicity of Zostavax (see Section 5.1, Clinical trials). Consider administration of the two vaccines separated by at least 4 weeks.
No data are currently available regarding the concomitant use of Zostavax with vaccines other than inactivated influenza vaccine and Pneumovax 23.

Immunocompromise.

The use of Zostavax has not been studied in subjects suffering any form of severe immunocompromise.

Revaccination.

The duration of protection beyond 4 years after vaccination with Zostavax is unknown. The need for revaccination has not been defined.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no data on the potential of Zostavax to impair fertility.
(Category B2)
Pregnancy Category B2: Animal reproduction studies have not been conducted with Zostavax. It is also not known whether Zostavax can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. However, naturally-occurring VZV infection is known to sometimes cause fetal harm. Therefore, Zostavax should not be administered to pregnant females; furthermore, pregnancy should be avoided for three months following vaccination (see Section 4.3 Contraindications).
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 nursing woman.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Clinical studies.

In clinical trials, Zostavax has been evaluated for general safety in more than 32,000 adults 50 years of age or older. Zostavax was generally well tolerated.

Zostavax Efficacy and Safety Trial (ZEST) in subjects 50 to 59 years of age.

In the ZEST study, subjects received a single dose of either Zostavax (n = 11,184) or placebo (n = 11,212) and were monitored for safety throughout the study. During the study, a vaccine related serious adverse experience was reported for 1 subject vaccinated with Zostavax (anaphylactic reaction).
All subjects received a vaccination report card (VRC) to record adverse events occurring from Days 1 to 42 postvaccination in addition to undergoing routine safety monitoring throughout the study.
The following very common (≥ 1/10) and common (≥ 1/100, < 1/10) vaccine related injection site and systemic adverse experiences were reported in the ZEST study. Several adverse experiences were solicited (Days 1-5 postvaccination) and are designated with the * symbol.

Nervous system disorder.

Common: headache.

General disorders and administration site conditions.

Very common: erythema*, pain*, swelling*, pruritus.
Common: haematoma, warmth, induration.

Musculoskeletal and connective tissue disorders.

Common: pain in extremity.
The overall incidence of vaccine-related injection-site adverse experiences was significantly greater for subjects vaccinated with Zostavax versus subjects who received placebo (63.9% for Zostavax and 14.4% for placebo).
Within the 42-day postvaccination reporting period in the ZEST, non-injection-site zoster-like rashes were reported by 34 subjects (19 for Zostavax and 15 for placebo). Of 24 specimens that were adequate for Polymerase Chain Reaction (PCR) testing, wild-type VZV was detected in 10 (3 for Zostavax, 7 for placebo) of these specimens. The Oka/Merck strain of VZV was not detected from any of these specimens.
Of reported varicella-like rashes (n = 124, 69 for Zostavax and 55 for placebo), 23 had specimens that were available and adequate for PCR testing. VZV was detected in one of these specimens from the group of subjects who received Zostavax; however, the virus strain (wild type or Oka/Merck strain) could not be determined.

Shingles Prevention Study (SPS) in subjects 60 years of age and older.

In the largest of these trials, the Shingles Prevention Study (SPS), 38,546 subjects received a single dose of either the frozen formulation of Zostavax (n = 19,270) or placebo (n = 19,276) and were monitored for safety throughout the study. During the study, vaccine-related serious adverse experiences 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 = 3,345 received Zostavax and n = 3,271 received placebo) were provided vaccination report cards to record adverse events 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 experiences were reported at an incidence ≥ 1% in the Adverse Event Monitoring Substudy. Most of these adverse experiences 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, < 1/1000); 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 experiences was significantly greater for subjects vaccinated with Zostavax versus subjects who received placebo (48% for Zostavax and 17% for placebo).
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 noninjection-site zoster-like rashes among all subjects was small (17 for Zostavax, 36 for placebo; p = 0.009). Of these 53 zoster-like 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.

Other studies.

In other clinical trials in support of the initial licensure of the frozen formulation of Zostavax, the reported rates of noninjection-site zoster-like and varicella-like rashes within 42 days postvaccination were also low in both zoster vaccine recipients and placebo recipients. Of the 17 reported varicella-like and noninjection-site zoster-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).
A clinical trial (N = 695) was specifically designed to examine the safety and tolerability of a vaccine lot formulated at the maximal release potency. In the 461 subjects who received the maximal release potency, the adverse experience profile was as follows:

Nervous system disorder.

Common: headache.

General disorders and administration site conditions.

Very common: erythema*, pain/ tenderness*, pruritus, swelling*.
Common: fatigue, haematoma, warmth.
In 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 as well as vaccine related systemic adverse experiences were reported among subjects 50-59 years of age compared with subjects ≥ 60 years of age. The most frequently reported vaccine related systemic adverse experience was headache (1% in both groups).
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 of Zostavax and the safety profile. In this clinical trial, the safety profile was generally similar to that seen in the Adverse Event Monitoring Substudy of the SPS.
In a double blind, placebo controlled, randomized clinical trial, Zostavax was administered to 206 subjects 60 years of age or older who were receiving chronic/ maintenance systemic corticosteroid therapy at a daily dose equivalent of 5 to 20 mg of prednisone for at least 2 weeks prior to enrolment, and 6 weeks or more following vaccination to assess the immunogenicity and safety profile of Zostavax. All vaccinated study patients were followed for adverse experiences. Vaccine relatedness was determined by the investigator based upon blinded data. To evaluate the adverse experiences temporally associated with study vaccination, patients were given a Vaccination Report Card (VRC) to record any injection site adverse experiences, systemic adverse experiences, elevated temperatures, and rashes from Days 1 to 42 postvaccination. Patients were followed for serious adverse experiences, regardless of whether the event was related to the study vaccine, throughout the course of the study (through Day 182 postvaccination). In this clinical trial, the safety profile was generally similar to that seen in the Adverse Event Monitoring Substudy of the SPS (see Section 4.3 Contraindications regarding corticosteroids).
In a double blind, placebo controlled randomized clinical trial, Zostavax was administered as a two dose regimen to human immunodeficiency virus (HIV)-infected adults (18 years of age or older) on potent combination antiretroviral therapy with conserved immune function (CD4+ T cell count ≥ 200 cells/microlitre). Although a two dose regimen was used in this study, Zostavax is administered as a single dose regimen (see Section 4.2 Dose and Method of Administration). In this clinical trial, a total of 295 subjects received dose 1 and 286 subjects received dose 2. All vaccinated study patients were followed for adverse experiences. Vaccine relatedness was determined by the investigator based upon blinded data. To evaluate the adverse experiences temporally associated with study vaccination, patients were given a Vaccination Report Card (VRC) to record any injection-site adverse experiences, systemic adverse experiences, elevated temperatures, and rashes through Week 6 following each vaccination. Patients were followed for serious adverse experiences, regardless of whether the event was related to the study vaccine, throughout the course of the study (through Week 24 following dose 1). In this clinical trial, the safety profile was generally similar to that seen in the Adverse Event Monitoring Substudy of the SPS. (See Section 4.3 Contraindications regarding immunosuppression due to HIV/AIDS.)
To address concerns for individuals with an unknown history of vaccination with Zostavax, the safety and tolerability of a second dose of Zostavax was evaluated. 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.
The clinical safety of refrigerator stable Zostavax (n = 182) was compared with that of a frozen formulation of Zostavax (n = 187) for 28 days postvaccination. The safety profiles were comparable for the two different formulations and were similar to those seen in the AE Monitoring Substudy of the SPS. At week 4, the overall incidence of vaccine related injection site adverse experiences was 36% for the refrigerator stable formulation vs 46% for the frozen formulation of Zostavax. The overall incidence of vaccine related systemic adverse experiences was 6% for both groups.

Post-marketing experience.

The following additional adverse reactions have been identified during post-marketing use of Zostavax. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to the vaccine.

Infections and infestations.

Varicella (vaccine strain), herpes zoster (vaccine strain).

Gastrointestinal disorders.

Nausea.

Musculoskeletal and connective tissue disorders.

Arthralgia; myalgia.

General disorders and administration site conditions.

Injection-site rash; injection-site urticaria; pyrexia; transient injection-site lymphadenopathy.

Immune system disorders.

Hypersensitivity reactions including anaphylactic reactions.

Skin and subcutaneous tissue disorders.

Rash.

Eye disorders.

Necrotizing retinitis (patients on immunosuppressive therapy).

Nervous system disorders.

Guillain-Barré syndrome; facial paralysis.
There have been fatal cases of disseminated disease in immunocompromised patients.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There are no data with regard to overdose.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

Epidemiology.

Herpes zoster.

Herpes zoster (HZ), commonly known as shingles or simply 'zoster', is a manifestation of the reactivation of VZV, which, as a primary infection, produces chickenpox (varicella). Following initial infection, the virus remains latent in the dorsal root or cranial sensory ganglia until it reactivates, producing zoster. Anyone who has been infected with VZV, including those without a clinical history of varicella, is at risk for developing zoster, which is considered to be due to waning immunity to VZV. The incidence and severity of zoster, as well as the frequency and severity of its complications, increase markedly with age, with two-thirds of the cases occurring in individuals older than 50 years of age. Zoster is usually characterized by a unilateral, painful, vesicular cutaneous eruption with a dermatomal distribution. Although the blistering rash is the most distinctive feature of zoster, the most frequently debilitating symptom is pain, which may occur during the prodrome, the acute eruptive phase and the postherpetic phase of the infection. During the acute eruptive phase, local pain has been reported to occur in up to 90% of immunocompetent individuals.
Zoster may be associated with serious complications, such as postherpetic neuralgia (PHN) and scarring; less commonly, bacterial superinfection and motor neuron palsies; and rarely pneumonia, encephalitis, Ramsay Hunt syndrome, visual impairment, hearing loss and death.
Zoster associated pain and discomfort can be prolonged and disabling and can diminish quality of life and functional capacity to a degree comparable to debilitating diseases such as congestive heart failure, myocardial infarction, type II diabetes mellitus and major depression.

Postherpetic neuralgia.

Postherpetic neuralgia (PHN) constitutes the most common serious complication and cause of zoster associated morbidity in the immunocompetent host. The frequency and severity of PHN increase with age, and may complicate 25 to 50% of zoster cases among patients over 50 years of age.

5.1 Pharmacodynamic Properties

Mechanism of action.

The risk of developing zoster 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 Section 5.1, Clinical trials, Immunogenicity.)

Clinical trials.

Evaluation of clinical efficacy afforded by Zostavax.

Zostavax Efficacy and Safety Trial (ZEST) in subjects 50 to 59 years of age.

In the Zostavax Efficacy and Safety Trial (ZEST), a placebo controlled, double blind clinical trial, 22,439 subjects 50 to 59 years of age were randomized to receive a single dose of either Zostavax (n = 11,211) or placebo (n = 11,228). Subjects were followed for the development of zoster for a median of 1.3 years (range 0 to 2 years). All suspected zoster cases were adjudicated by a clinical evaluation committee. Final determination of zoster cases was made by Polymerase Chain Reaction (PCR) [86%], or in the absence of virus detection, as determined by a clinical evaluation committee [14%].
Zostavax significantly decreased the incidence of zoster compared with placebo (30 cases [2.0/1000 person years] vs. 99 cases [6.6/1000 person years], respectively; p < 0.001). The protective efficacy of Zostavax against zoster was 69.8% (95% CI: [54.1 to 80.6%]). The effect of Zostavax on post-herpetic neuralgia was not evaluated in the ZEST trial.

Shingles Prevention Study (SPS) in subjects 60 years of age and older.

In the Shingles Prevention Study (SPS)1, a placebo controlled, double blind clinical trial of the frozen formulation of Zostavax, 38,546 subjects 60 years of age or older were randomized to receive a single dose of either Zostavax (n = 19,270) or placebo (n = 19,276) and were followed for the development of zoster for an average of 3.1 years (range 1 day to 4.9 years). Randomization was stratified by age, 60-69 and ≥ 70 years of age. The racial distribution was as follows for the Zostavax and placebo groups: white (95%); black (2.0%); Hispanic-American (1.0%); and other (1.0%). The gender distribution was 59% male and 41% female in both vaccination groups. The age range of subjects enrolled was 59-99.
All suspected zoster cases were adjudicated by a clinical evaluation committee. Final determination of zoster cases was made by PCR, local culture, or the decision of the clinical evaluation committee, in that order. In both vaccination groups (Zostavax and placebo), subjects who developed zoster were offered famciclovir, and as necessary, pain medications. Severity of pain was evaluated according to a ‘worst pain’ score on a 0 to 10 scale, using the Zoster Brief Pain Inventory (ZBPI)2, a validated questionnaire. A score of 3 or higher was considered clinically significant because it correlates with significant interference with activities of daily living (ADL).
Zostavax significantly reduced the risk of developing zoster and PHN compared with placebo. In addition, Zostavax significantly reduced acute and chronic zoster associated pain as measured by the HZ pain burden of illness (BOI) score (see Table 1).
1 Oxman MN, Levin MJ, Johnson GR, et al. A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults. NEJM 2005;352:2271-84.
2 Coplan PM, Schmader K, Nikas A, et al. Development of a measure of the burden of pain due to herpes zoster and postherpetic neuralgia for prevention trials: Adaptation of the brief pain inventory. J Pain 2004;5(6):344-56.
Zostavax significantly decreased the incidence of zoster compared with placebo (315 cases [5.4/1,000 person years] vs. 642 cases [11.1/1,000 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. The cumulative incidence of zoster over time among vaccine recipients was also significantly reduced (p < 0.001; see Figure 1).
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 in the overall study population was 67% (95% CI: [48 to 79%]), and the reduction was similar for the two age groups (60 to 69 and ≥ 70 years of age). Among subjects 60 to 69 years of age, the benefit of Zostavax in the prevention of PHN can be primarily attributed to the effect of the vaccine on the prevention of zoster (64% efficacy against zoster, 66% efficacy against PHN, Table 1). In subjects ≥ 70 years of age, the prevention of PHN was achieved through a combination of the prevention of zoster and a reduction in the severity and duration of zoster associated pain, and thus PHN (38% efficacy against zoster and 67% efficacy against PHN, Table 1).
For the subset of subjects who developed zoster despite vaccination, an additional benefit in reduction of PHN was seen only in subjects 70 years of age and older.
The efficacy of Zostavax did not change appreciably when PHN was defined using alternative cutoff times (30, 60, 120, or 182 days) for duration of pain. Zostavax significantly reduced the cumulative incidence of PHN over time compared with placebo (p < 0.001; see Figure 2).
Zostavax reduced the HZ pain BOI score by approximately 61% (95% CI: [51 to 69%]), compared with placebo. Zostavax reduced the HZ pain BOI score to a similar extent for the two age groups (60-69 and ≥ 70 years of age). 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.
Zostavax reduced the incidence of severe and long lasting zoster associated pain (severity by duration score > 600) by 73% (95% CI: [46 to 87%]) compared with placebo. Eleven subjects vaccinated with Zostavax had severity by duration scores > 600, compared with 40 subjects who received placebo. (See Figure 3.)
Among vaccinated individuals who developed zoster, Zostavax significantly reduced zoster associated pain compared with placebo. Over the 6 month follow-up period, there was a 22% reduction in the severity by duration score (average scores of 141 for Zostavax and 181 for placebo; p = 0.008).
Among vaccinated individuals who developed PHN, Zostavax significantly reduced PHN associated 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).
To evaluate the impact of Zostavax on ADL interference associated with zoster, a combined score was calculated for each subject based on interference with general activity, mood, walking ability, normal work, relations with others, sleep and enjoyment of life. Each item was measured on a 0 to 10 scale (0 being no interference and 10 being maximum interference). Compared to placebo, Zostavax led to a reduction (8%) in the risk of having substantial ADL interference (defined as having a combined ADL interference score ≥ 2 for ≥ 7 days) beyond the vaccine efficacy for zoster. This reduction was not statistically significant. Among vaccinated individuals who developed zoster, Zostavax significantly reduced ADL interference compared with placebo. Over the 6 month follow-up period, there was a 31% reduction in the severity by duration score for combined ADL interference (average scores of 57 for Zostavax and 83 for placebo; p = 0.002).
The use of antiviral drugs within 72 hours of zoster rash onset did not have a significant effect on the efficacy of Zostavax for zoster pain or PHN incidence. The proportions of subjects using medications with analgesic effects were balanced between vaccination groups. Therefore, the use of these medications was not likely to have contributed to the reduction of zoster pain or PHN incidence.
Fewer complications were reported by subjects who received Zostavax compared with subjects who received placebo. The number of subjects with specific complications of zoster that were reported in the SPS at a frequency of ≥ 1% is shown in Table 2.
Visceral complications such as pneumonitis, hepatitis and meningoencephalitis were reported by fewer than 1% of subjects with zoster (3 cases of pneumonitis and 1 case of hepatitis in the placebo group; 1 case of meningoencephalitis in the vaccine group).

Immunogenicity of Zostavax.

Zostavax Efficacy and Safety Trial (ZEST) in subjects aged 50-59 years.

Within the Zostavax Efficacy and Safety Trial (ZEST), immune responses to vaccination were evaluated in a random 10% subcohort (n = 1,136 for Zostavax and n = 1,133 for placebo) of the subjects enrolled in the ZEST. Zostavax elicited higher VZV specific immune responses at 6 weeks postvaccination compared with placebo. Increases in VZV antibody level, measured by glycoprotein enzyme linked immunosorbent assay (gpELISA) were demonstrated (2.3-fold difference (95% CI [2.2, 2.4]), geometric mean titre [GMT] of 664 vs. 288 gpELISA units/mL, p < 0.001).

Shingles Prevention Study (SPS) in subjects 60 years of age and older.

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 titre [GMT] of 479 vs. 288 gpELISA units/mL, p < 0.001), and T cell activity, measured by VZV interferon gamma enzyme linked immunospot (IFN-γ ELISPOT) assay (2.2-fold difference, geometric mean count [GMC] of 70 vs. 32 spot forming cells per million peripheral blood mononuclear cells [SFC/106 PBMCs], p < 0.001) were demonstrated.
The VZV antibody (gpELISA) titres were at the highest level 6 weeks after administration of the zoster vaccine and then gradually decreased over 36 months to a level slightly above the prevaccination level. The zoster vaccine recipients maintained a higher fold rise of IFN-γ ELISPOT counts compared with placebo recipients up to 36 months postvaccination.

Other studies.

The immunogenicity of a refrigerator stable formulation of Zostavax was shown to be similar to that of a frozen formulation of Zostavax in a single bridging study. The study enrolled 368 subjects randomized in a 1:1 ratio to receive a dose of either the refrigerator stable or frozen formulation of Zostavax. Subjects were stratified by age (50 to 59 years and ≥ 60 years) in a 1:2 ratio. Blood samples were collected at day 1 and week 4 postvaccination to assess VZV antibody responses. Zostavax refrigerator stable and frozen formulations elicited similar VZV antibody responses as measured by gpELISA (GMTs of 727 vs. 834 gpELISA units/mL, respectively at week 4).
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 of age.

The SPS short-term persistence substudy (STPS).

The STPS was initiated to accrue additional information on the persistence of vaccine efficacy and to preserve a subset of subjects for the long-term persistence substudy (LTPS). The STPS included 7,320 subjects previously vaccinated with Zostavax and 6,950 subjects previously vaccinated with placebo in the SPS. The mean age at enrollment in STPS was 73.3 years. During the course of STPS, placebo recipients were offered Zostavax, at which time they were considered to have completed the STPS.
The STPS analyses for vaccine efficacy are based on data collected primarily 4 to 7 years postvaccination in the SPS. The median follow-up in the STPS was ~1.2 years (range is one day to 2.2 years). In the STPS, there were 84 evaluable HZ cases in the Zostavax group and 95 evaluable cases in the placebo group. The estimated vaccine efficacy for HZ incidence during the STPS follow-up period was 39.6% (18.2%, 55.5%). The estimated vaccine efficacy for PHN incidence was 60.1% (-9.8%, 86.7%). The estimated vaccine efficacy for HZ BOI was 50.1% (14.1%, 71.0%).
There were no vaccine-related serious adverse experiences reported in the STPS.

The SPS long-term persistence substudy (LTPS).

Following completion of the STPS, the open-label LTPS evaluated the duration of protection against HZ, PHN and HZ BOI of Zostavax on subjects vaccinated in the SPS. A total of 6,867 subjects previously vaccinated with Zostavax in the SPS participated in the LTPS. The mean age at enrollment into LTPS was 74.5 years.
Because placebo subjects were previously offered vaccine during the STPS, a concurrent placebo control group was not available for calculation of vaccine efficacy for the LTPS. Therefore, prior placebo recipients were used as a reference group for calculating vaccine efficacy in the LTPS.
The LTPS analyses for vaccine efficacy are based on data collected primarily from Year 7 through Year 10 following vaccination in the SPS. Median follow up during the LTPS was ~3.9 years (range is one week to 4.75 years). There were 263 evaluable HZ cases during the LTPS. The estimated vaccine efficacy for HZ incidence during the LTPS follow-up period was 21.1% (10.9%, 30.4%). The estimated vaccine efficacy for PHN incidence was 35.4% (8.8%, 55.8%). The estimated vaccine efficacy for HZ BOI was 37.3% (26.7%, 46.4%). The observed vaccine efficacy in the LTPS is generally consistent with the vaccine efficacy for HZ observed during the SPS 70-year-old age group, and is consistent with the current age of the study cohort.
There were no vaccine-related serious adverse experiences reported in the LTPS.

Immunogenicity following concomitant administration with inactivated influenza vaccine.

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 (N = 380) with inactivated influenza vaccine. Subjects enrolled in the concomitant group received Zostavax and influenza vaccine on day 1 and placebo at week 4. Subjects enrolled in the nonconcomitant group received influenza vaccine and placebo on day 1 and Zostavax at week 4. The antibody responses at 4 weeks postvaccination to Zostavax were similar, whether administered concomitantly or nonconcomitantly (GMTs of 554 vs. 597 gpELISA units/mL). The geometric mean fold rise of immune response following vaccination was acceptable in the concomitant group as measured by gpELISA (2.1-fold (95% CI: [2.0 to 2.3]). Influenza antibody responses at 4 weeks postvaccination were similar and satisfactory, whether administered concomitantly or nonconcomitantly.
In another double-blind, controlled study, 882 adults in the US, 50 years of age and older (median age = 60 years), were randomized to receive quadrivalent inactivated influenza vaccine and Zostavax concurrently (N=440), or quadrivalent inactivated influenza vaccine alone followed 4 weeks later by Zostavax alone (N=442). The antibody responses to both vaccines at 4 weeks postvaccination were similar in both groups.

Immunogenicity following concomitant administration with pneumococcal vaccine.

In a double blind, controlled clinical trial, 473 adults 60 years of age or older were randomized to receive Zostavax and Pneumovax 23 concomitantly (N = 237), or Pneumovax 23 alone followed 4 weeks later by Zostavax alone (N = 236). At four weeks postvaccination, the VZV antibody levels following concomitant use were significantly lower than 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 prespecified acceptance criterion) in the concomitant group vs. 3.1-fold (95% CI: [2.8, 3.5]) in the nonconcomitant group. The GMTs for Pneumovax 23 antigens were comparable between the two groups. Concomitant use of Zostavax and Pneumovax 23 demonstrated a safety profile that was generally similar to that of the two vaccines administered nonconcomitantly.

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 of Zostavax. Zostavax induced a significantly higher VZV specific immune response as 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.

Immunogenicity in subjects on chronic/ maintenance systemic corticosteroids.

In a double blind, placebo controlled, randomized clinical trial, Zostavax was administered to 206 subjects 60 years of age or older who were receiving chronic/ maintenance systemic corticosteroid therapy at a daily dose equivalent of 5 to 20 mg of prednisone for at least 2 weeks prior to enrollment, and 6 weeks or more following vaccination to assess the immunogenicity and safety profile of Zostavax. Compared with placebo, Zostavax induced a higher VZV specific gpELISA antibody GMT at 6 weeks postvaccination (GMT of 531.1 vs. 224.3 gpELISA units/mL, respectively). The geometric mean fold rise of the VZV antibody response, as measured by gpELISA, from prevaccination to postvaccination was 2.3 (95% CI: [2.0 to 2.7]) in the Zostavax group compared to 1.1 (95% CI: [1.0 to 1.2]) in the placebo group (see Section 4.3 Contraindications regarding corticosteroids). Immunogenicity of Zostavax in patients taking chronic/ maintenance systemic corticosteroids has not been compared with subjects receiving Zostavax alone in the same study.

Immunogenicity in subjects with HIV infection.

In a double blind, placebo controlled randomized clinical trial, Zostavax was administered as a two dose regimen to human immunodeficiency virus (HIV) infected adults (18 years of age or older) on potent combination antiretroviral therapy with conserved immune function (CD4+ T cell count ≥ 200 cells/microlitre). Although a two dose regimen was used in this study, Zostavax is administered as a single dose regimen (see Section 4.2 Dose and Method of Administration). In this study, a total of 295 subjects received dose one and 286 subjects received dose two. Compared with placebo, Zostavax induced a higher VZV specific gpELISA antibody GMT at week 6 (6 weeks following dose one) and week 12 (6 weeks following dose two) (GMT of 534.4 and 530.3 vs. 263.7 and 250.3 gpELISA units/mL, respectively). The geometric mean fold rises of the VZV antibody response, as measured by gpELISA, from baseline to week 6 and week 12 were 1.78 (95% CI: [1.64 to 1.92]) and 1.80 (95% CI: [1.66 to 1.95]), respectively, in vaccine recipients and 1.05 (95% CI: [0.98 to 1.12]) and 1.04 (95% CI: [0.96 to 1.13]), respectively, in placebo recipients. (See Section 4.3 Contraindications regarding immunosuppression due to HIV/AIDS.)

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Genotoxicity.

Zostavax has not been evaluated for genotoxicity.

Carcinogenicity.

No animal carcinogenicity studies have been conducted with Zostavax.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sucrose, hydrolysed gelatin (porcine), urea, sodium chloride, monosodium glutamate monohydrate, dibasic sodium phosphate, monobasic potassium phosphate, potassium chloride, residual components of MRC 5 cells including DNA and protein, trace quantities of neomycin, and bovine calf serum.
The product contains no preservatives.
The manufacture of this product includes exposure to bovine derived material. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

6.2 Incompatibilities

Please see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions for further information.

6.3 Shelf Life

18 months.

6.4 Special Precautions for Storage

Zostavax should be stored refrigerated at an average temperature of 2 to 8°C (36 to 46°F) until it is reconstituted for injection. The diluent should be stored separately at room temperature (20 to 25°C, 68 to 77°F) or in the refrigerator (2 to 8°C, 36 to 46°F).
Do not freeze the reconstituted vaccine.
Discard reconstituted vaccine if it is not used within 30 minutes.
Before reconstitution, protect from light.
During shipment, to ensure that there is no loss of potency, the vaccine must be maintained at a temperature of 8°C (46°F) or colder, but not to exceed temperatures lower than -50°C (-58°F). Use of dry ice may subject Zostavax to temperatures colder than -50°C (-58°F).

6.5 Nature and Contents of Container

Zostavax is supplied as follows:
(1) a single-dose (glass) vial of lyophilized vaccine, in packs of 1 or 10.
(2) a single-dose (glass) vial of lyophilized vaccine, in packs of 1 or 10, supplied with a separate package of 1 or 10 single dose (glass) vials of sterile diluent.
(3) a single-dose (glass) vial of lyophilized vaccine, in packs of 1 or 10, supplied with a separate package of 1 or 10 needleless (glass) syringes of sterile diluent.
(4) a single-dose (glass) vial of lyophilized vaccine and single-dose (glass) vial of sterile diluent in composite packs of 1, 5 or 10.
(5) a single-dose (glass) vial of lyophilized vaccine and needleless (glass) syringe of sterile diluent in composite packs of 1 or 10.
Not all presentations and pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Not applicable.

CAS number.

Not applicable.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Medicine.

Summary Table of Changes