Consumer medicine information

Shingrix

Varicella zoster virus glycoprotein E antigen recombinant vaccine

BRAND INFORMATION

Brand name

Shingrix

Active ingredient

Varicella zoster virus glycoprotein E antigen recombinant vaccine

Schedule

What is in this leaflet

Please read this leaflet carefully before you start using SHINGRIX. This leaflet answers some common questions about SHINGRIX. It does not contain all the available information. It does not take the place of talking to your doctor, nurse or pharmacist.

All medicines and vaccines have risks and benefits. Your doctor has weighed the risks of you receiving SHINGRIX against the benefits they expect it will have for you.

If you have any concerns about taking SHINGRIX, ask your doctor, nurse or pharmacist.

Keep this leaflet with the vaccine You may need to read it again.

What SHINGRIX is used for

SHINGRIX is a vaccine that helps to protect adults against herpes zoster (also called shingles) as well as the long-lasting nerve pain that can follow shingles called post-herpetic neuralgia or PHN.

SHINGRIX can be given to adults from the age of 50 years and above.

What is shingles and what are the complications related to shingles?

Shingles is caused by the same virus that causes chickenpox. After you have had chickenpox (primary varicella infection), the virus that caused it stays in your body in nerve cells. Sometimes, after many years, the virus can become active again and causes shingles (secondary varicella infection).

SHINGRIX cannot be used to prevent chickenpox (primary varicella infection).

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 complications such as long-lasting pain (PHN) and scarring. Less commonly, bacterial skin infections, weakness, muscle paralysis, loss of hearing or vision can occur.

What is post-herpetic neuralgia (PHN)?

After the shingles blisters heal, pain can last for months or years and may be severe. This long-lasting nerve pain is called PHN. PHN is the most common complication of shingles.

How does the vaccine work?

SHINGRIX helps your body to build its own protection against shingles and its complications.

SHINGRIX cannot be used to treat shingles or the pain associated with shingles. It is for the protection against shingles only.

As with all vaccines, SHINGRIX may not fully protect all people who are vaccinated.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

This medicine is available only with a doctor's prescription.

Before you are given SHINGRIX

When you must not be given SHINGRIX

Do not have SHINGRIX if you are allergic (hypersensitive) to any of the ingredients contained in SHINGRIX. Signs of an allergic reaction may include itchy skin rash, shortness of breath and swelling of the face or tongue. Tell your doctor if you have experienced any of these symptoms with a previous dose of SHINGRIX or any other vaccine or medicine.

Do not use this vaccine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should receive SHINGRIX, talk to your doctor.

Before being given SHINGRIX

Tell your doctor or nurse before you receive SHINGRIX:

if you have an infection with a high temperature. In these cases, the vaccination may be postponed until recovery. A minor infection such as a cold should not be a problem, but talk to your doctor first.
if you have a bleeding problem or bruise easily.
if you fainted with a previous injection. Fainting can occur following, or even before, any needle injection.
if you 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.

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you receive SHINGRIX.

Taking other medicines

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop. Some medicines and SHINGRIX may interfere with each other.

Having other vaccines

Tell your doctor or nurse if you have received another vaccine recently.

Some vaccines may be affected by other vaccines.

SHINGRIX can be given at the same time as the yearly influenza (flu) vaccine. If SHINGRIX is given at the same time as the influenza vaccine, a different injection site will be used for each vaccine.

How SHINGRIX is given

The doctor or nurse will give SHINGRIX as an injection.

If you have any concerns about how this vaccine is to be given, talk to your doctor, nurse or pharmacist.

How it is given

SHINGRIX is given as an injection of 0.5 ml into a muscle (usually in the upper arm).

When it is given

You will receive 2 injections with an interval of 2 to 6 months.

The first injection can be given from the age of 50 years. You will be informed when you should come back for the second dose of SHINGRIX.

Make sure you finish the complete vaccination course. This will maximise the protection offered by SHINGRIX.

If a dose is missed

If you miss a scheduled dose, talk to your doctor or nurse and arrange another visit as soon as possible.

If you are not sure what to do, ask your doctor, nurse or pharmacist.

While being given SHINGRIX

Things you must do

Keep the follow up visits with the doctor or clinic. Make sure you finish the complete vaccination course. This will maximise the protection offered by SHINGRIX.

Things to be careful of

There is no information on whether SHINGRIX affects the ability to drive or use machines.

However, do not drive or use machines if you are feeling unwell.

Side effects

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

This vaccine helps protect most people from shingles, but it may have unwanted side effects in some people. All medicines and vaccines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

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

The following side effects may occur after receiving SHINGRIX:

Very common (these may occur with more than 1 in 10 doses of the vaccine):

headache
stomach and digestive complaints (including nausea, vomiting, diarrhoea and/or stomach pain)
muscle pain (myalgia)
pain, redness and swelling at the injection site
tiredness, chills, fever

Common (these may occur with up to 1 in 10 doses of the vaccine):

injection site itching (pruritus)
generally feeling unwell

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

As with all vaccines given by injection there is a very small risk of serious allergic reaction. Contact your doctor immediately or go to the casualty department of your nearest hospital if any of the following happens:

swelling of limbs, face, eyes, inside of nose, mouth or throat
shortness of breath, breathing or swallowing difficulties
hives, itching (especially of the hands or feet), reddening of skin (especially around the ears), or severe skin reactions
unusual tiredness or weakness that is sudden and severe

Allergy to SHINGRIX is rare (may occur with up to 1 in 1,000 doses of the vaccine). Any such severe reactions will usually occur within the first few hours of vaccination. Tell your doctor or pharmacist if you notice anything that is making you feel unwell during or after a dose of vaccine.

Other side effects not listed above, can also occur during or soon after a dose of SHINGRIX.

Check with your doctor or nurse if you have any other side effects.

How to store SHINGRIX

Storage

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2°C – 8°C) Do not freeze.
Store in the original package in order to protect from light.
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.

Disposal

Ask your pharmacist what to do with any SHINGRIX that has expired or has not been used.

Product description

What it looks like

The powder is white.

The suspension is an opalescent, colourless to pale brownish liquid.

One pack of SHINGRIX consists of:

Powder for 1 dose in a vial
Suspension for 1 dose in a vial

SHINGRIX is available in pack sizes of:

1 vial of powder plus 1 vial of suspension
10 vials of powder plus 10 vials of suspension.

Ingredients

1 dose (0.5 ml) of SHINGRIX contains 50 micrograms of glycoprotein E (gE) powder mixed with AS01B adjuvant suspension.

gE is a protein present in the Varicella Zoster Virus. This protein is not infectious.

The adjuvant is composed of a plant extract (Quillaja saponaria saponin (QS-21) (50 micrograms) and a bacterial extract (3-O-desacyl-4’- monophosphoryl lipid A (MPL) (50 micrograms)) and is used to improve the body’s response to the vaccine.

The other ingredients are:

Powder

Sucrose
Polysorbate 80
Monobasic sodium phosphate dihydrate
Dibasic potassium phosphate

Suspension

Dioleoylphosphatidylcholine
Cholesterol
Sodium chloride
Dibasic sodium phosphate
Monobasic potassium phosphate
Water for injections

Supplier

GlaxoSmithKline Australia Pty Ltd
Level 4, 436 Johnston Street
Abbotsford, Victoria 3067 Australia.

Registration numbers: AUST R 289257

Date of preparation: 06 December 2018

Version 2.0

Trade marks are owned by or licensed to the GSK group of companies

Published by MIMS June 2021

BRAND INFORMATION

Brand name

Shingrix

Active ingredient

Varicella zoster virus glycoprotein E antigen recombinant vaccine

Schedule

1 Name of Medicine

Recombinant varicella zoster virus glycoprotein E antigen (AS01_B adjuvanted vaccine).

2 Qualitative and Quantitative Composition

After reconstitution, 1 dose (0.5 mL) contains 50 micrograms of gE antigen¹ adjuvanted with AS01_B².
¹ Varicella zoster virus (VZV) glycoprotein E (gE) produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cells.
² The GlaxoSmithKline proprietary AS01_B Adjuvant System is composed of the plant extract Quillaja saponaria saponin (QS-21) (50 micrograms) and 3-O-desacyl-4'-monophosphoryl lipid A (MPL) from Salmonella minnesota (50 micrograms).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder and suspension for suspension for injection.
The powder is white.
The suspension is an opalescent, colourless to pale brownish liquid.

4 Clinical Particulars

4.1 Therapeutic Indications

Shingrix is indicated for the prevention of herpes zoster (HZ) and post-herpetic neuralgia in:
adults 50 years of age or older;
adults 18 years of age or older at increased risk of HZ.

4.2 Dose and Method of Administration

The immunisation schedules for Shingrix should be based on official recommendations.
Further guidance regarding the use of vaccines can be found in the Australian Immunisation Handbook.

Dosage.

The primary vaccination schedule consists of two doses of 0.5 mL each; an initial dose followed by a second dose 2 to 6 months later.
For subjects who are immunodeficient, immunosuppressed or likely to become immunosuppressed due to known disease or therapy, and who would benefit from a shorter vaccination schedule, the second dose can be given 1 to 2 months after the initial dose (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
The need for booster doses has not been established.
Shingrix can be given with the same schedule in individuals previously vaccinated with live attenuated herpes zoster (HZ) vaccine, in accordance with local recommendations (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
Shingrix is not indicated for prevention of primary varicella infection (chickenpox) or for treatment of herpes zoster or post-herpetic neuralgia (PHN).

Method of administration.

Shingrix is for intramuscular injection only, preferably in the deltoid muscle.

Instructions for use and handling.

The powder and suspension should be inspected visually for any particulate matter and/or variation to the expected appearance (i.e. white powder and opalescent, colourless to pale brownish liquid). If either is observed, do not reconstitute the vaccine.

How to prepare Shingrix.

Shingrix must be reconstituted prior to administration.
1. Withdraw the entire contents of the vial containing the suspension into a syringe with a suitable needle (21G to 25G).
2. Add the entire contents of the syringe into the vial containing the powder.
3. Shake gently until the powder is completely dissolved.
The reconstituted vaccine is an opalescent, colourless to pale brownish liquid.
The reconstituted vaccine should be inspected visually for any foreign particulate matter and/or variation of appearance. If either is observed, do not administer the vaccine.
After reconstitution, the vaccine should be used promptly; if this is not possible, the vaccine should be stored in a refrigerator (2°C - 8°C). If not used within 6 hours it should be discarded.

Before administration.

1. Withdraw the entire contents of the vial containing the reconstituted vaccine into the syringe.
2. Change the needle so that you are using a new needle to administer the vaccine.
3. Administer 0.5 mL intramuscularly.
Shingrix is for single use in one patient only.

4.3 Contraindications

Hypersensitivity to the active substances or to any component of the vaccine.

4.4 Special Warnings and Precautions for Use

Prior to immunisation.

It is good clinical practice to precede vaccination by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events) and a clinical examination.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.
As with other vaccines, vaccination with Shingrix should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor infection, such as a cold, should not result in the deferral of vaccination.
As with any vaccine, a protective immune response may not be elicited in all vaccinees.
An increased risk of Guillain-Barré syndrome has been observed following vaccination with Shingrix.

Precautions for use.

Do not administer the vaccine intravascularly, intradermally or subcutaneously.
Maladministration via the subcutaneous route may lead to an increase in transient local reactions.
Shingrix should be given with caution to individuals with thrombocytopenia or any coagulation disorder since bleeding may occur following intramuscular administration to these subjects.
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. It is important that procedures are in place to prevent injury from faints and to manage syncopal reactions.
There are no safety, immunogenicity or efficacy data to support interchangeability of Shingrix with other HZ vaccines.
There are limited data to support the use of Shingrix in individuals with a history of HZ and in frail individuals including those with multiple comorbidities. Healthcare professionals therefore need to weigh the benefits and risks of HZ vaccination on an individual basis.
The administration of Shingrix to immunocompromised subjects should be based on careful consideration of potential benefits and risks. As with other vaccines, an adequate immune response may not be elicited in these individuals.

Use in the elderly.

There are no special precautions for use in the elderly.

Paediatric use.

The safety and efficacy of Shingrix have not been established in children and adolescents.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Use with other vaccines.

The first dose of Shingrix can be given concomitantly with either unadjuvanted seasonal influenza vaccine, 23-valent pneumococcal polysaccharide vaccine (PPV23), pneumococcal conjugate vaccine (PCV), reduced antigen diphtheria-tetanus-acellular pertussis vaccine (dTpa) or coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) booster vaccine (see Section 5.1 Pharmacodynamic Properties, Clinical trials). Data are not available for co-administration with the second dose of Shingrix. Data are not available for coadministration of Shingrix with the primary (100 microgram dose) course of COVID-19 mRNA vaccine. Incidence of arthralgia, chills, fatigue, gastrointestinal symptoms, headache, and myalgia were more frequent when Shingrix was co-administered with COVID-19 mRNA-1273 50 micrograms booster vaccine compared to when Shingrix was given alone (see Section 4.8 Adverse Effects (Undesirable Effects)).
The adverse reactions of fever and shivering were more frequent when PPV23 vaccine was co-administered with Shingrix compared to when Shingrix was given alone (see Section 4.8 Adverse Effects (Undesirable Effects)).
The vaccines should always be administered at different injection sites.
No data are currently available regarding concomitant use with other vaccines, including the adjuvanted seasonal influenza vaccine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Repeated exposure of male and female rats to Shingrix (0.1 and 0.2 mL respectively) by IM injection on 42, 28 and 14 days prior to mating (male) and 28 and 14 days prior to mating (female) had no effects on mating or fertility.
(Category B2)
There are no data on the use of Shingrix in pregnant women.
In a reproductive and developmental toxicity study, female rats were administered Shingrix or the AS01_B adjuvant alone by intramuscular injection 28 and 14 days prior to mating, on gestation Days 3, 8, 11, and 15, and on lactation Day 7. The total dose was 0.2 mL on each occasion (a single human dose of Shingrix is 0.5 mL). No adverse effects on preweaning development up to post-natal Day 25 were observed. There were no vaccine related foetal malformations or variations.
The effect on breast-fed infants of administration of Shingrix to their mothers has not been studied.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects of Shingrix on the ability to drive and use machines have been performed.
However, some of the undesirable effects mentioned in Section 4.8 Adverse Effects (Undesirable Effects), may temporarily influence the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

More than 17,000 adults aged 50 through 96 years of age received at least one dose of Shingrix in 17 clinical studies. The incidence of solicited local and general symptoms was higher in subjects who received Shingrix than in subjects who received control (placebo or other vaccines). Shingrix was generally well tolerated.
Additionally, in clinical studies, 1,587 subjects ≥ 18 years of age who are immunodeficient or immunosuppressed due to disease or therapy (referred to as immunocompromised (IC)), were vaccinated with at least 1 dose of Shingrix. The reported adverse reactions were consistent with those reported clinical trial adverse reactions of adults 50 years of age and older.
Overall, there was a higher incidence of some adverse reactions in younger age groups. However, the overall frequency and severity of these events did not indicate a clinically meaningful different reactogenicity profile in the younger age strata. In IC adult studies, there was a higher incidence of pain at the injection site, fatigue, myalgia, headache, shivering and fever in subjects aged 18 to 49 years compared with those aged 50 years and older. In older adult studies, there was a higher incidence of pain and swelling at the injection site, fatigue, myalgia, headache, shivering, fever and gastrointestinal symptoms in subjects aged 50 to 69 years compared with those aged 70 years and older.

Clinical trial data.

Adults aged 50 years and older. The safety profile presented below is based on pooled data from 2 placebo-controlled clinical studies (ZOE-50 and ZOE-70) involving 29,305 subjects aged 50 years and older who received at least one dose of Shingrix (n = 14,645) or saline placebo (n = 14,660) administered according to a 0, 2-month schedule. These studies were conducted in Europe, North America, Latin America, Asia and Australia.

Solicited adverse events.

In both studies, data on solicited local and general adverse events were collected using standardised diary cards for 7 days following each vaccine dose or placebo (i.e. day of vaccination and the next 6 days) in a subset of subjects (n = 4,886 receiving Shingrix, n = 4,881 receiving placebo with at least 1 documented dose). Across both studies, the percentages of subjects aged 50 years and older reporting each solicited local adverse reaction and each solicited general adverse event following administration of Shingrix (both doses combined) were pain (78.0%), redness (38.1%), and swelling (25.9%); and myalgia (44.7%), fatigue (44.5%), headache (37.7%), shivering (26.8%), fever (20.5%), and gastrointestinal symptoms (17.3%), respectively.
The reported frequencies of specific solicited local adverse reactions and general adverse events (overall per subject), by age group, from the 2 studies are presented in Table 1.

The incidence of solicited local and general symptoms was lower in subjects aged 70 years and older compared with those aged 50 to 69 years.
The majority of solicited local adverse reactions and general adverse events seen with Shingrix had a median duration of 2 to 3 days.
There were no differences in the proportions of subjects reporting any or grade 3 solicited local reactions between Dose 1 and Dose 2. Headache and shivering were reported more frequently by subjects after Dose 2 (28.2% and 21.4%, respectively) compared with Dose 1 (24.4% and 13.8%, respectively). Grade 3 solicited general adverse events (headache, shivering, myalgia, and fatigue) were reported more frequently by subjects after Dose 2 (2.3%, 3.1%, 3.6%, and 3.5%, respectively) compared with Dose 1 (1.4%, 1.4%, 2.3%, and 2.4%, respectively).

Unsolicited adverse events.

In both studies, unsolicited adverse events occurring within 30 days of vaccination were reported in 50.5% and 32.0% of subjects who received Shingrix (n = 14,645) and placebo (n = 14,660), respectively (Total Vaccinated Cohort). Unsolicited adverse events that occurred in ≥ 1% of recipients of Shingrix and at a rate at least 1.5-fold higher than placebo included chills (3.5% versus 0.2%), injection site pruritus (2.2% versus 0.2%), and malaise (1.7% versus 0.3%), arthralgia (1.7% versus 1.2%), nausea (1.4% versus 0.5%), and dizziness (1.2% versus 0.8%).
Gout (including gouty arthritis) was reported by 0.18% (n = 27) versus 0.05% (n = 8) of subjects who received Shingrix and placebo, respectively, within 30 days of vaccination; available information is insufficient to determine a causal relationship with Shingrix.
In a clinical study where 119 subjects ≥ 50 years of age were vaccinated with Shingrix following a 0, 6-month schedule, the safety profile was similar to that observed in subjects vaccinated with Shingrix following a 0, 2-month schedule.

Potential immune-mediated diseases.

In the 2 studies, new onset potential immune-mediated diseases (pIMDs) or exacerbation of existing pIMDs were reported for 0.6% of subjects who received Shingrix and 0.7% of subjects who received placebo from the first administered dose up to 1 year post last vaccination. The most frequently reported pIMDs occurred with comparable frequencies in the group receiving Shingrix and the placebo group.

Long-term follow-up study.

In the long-term follow-up study (follow-up period of approximately 11 years) including more than 7,000 adults ≥ 50 years of age, no new adverse reactions were identified.
Immunocompromised (IC) adults aged 18 years and older. In early phase I/II clinical studies Zoster-001 and Zoster-015, the co-primary objectives were to evaluate the safety and reactogenicity of HZ vaccine formulations in subjects ≥ 18 years of age with a selected IC condition (autologous hematopoietic stem cell transplant (auHSCT) and HIV infection, respectively). More than half of the subjects who participated in Zoster-001 and Zoster-015 (54%) were ≥ 50 years of age. With the limited number of subjects (n = 164), no safety concerns were identified as evaluated one year post-vaccination (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
The safety of Shingrix was also evaluated in 4 placebo-controlled phase II/III clinical studies of subjects aged 18 years and older who were immunocompromised. Subjects in the total vaccinated cohort received at least 1 dose (administered according to a 0- and 1-2-month schedule) of Shingrix or placebo, as follows: auHSCT recipients (n = 922 or n = 924, respectively); renal transplant recipients on chronic immunosuppressive treatment (n = 132 or n = 132, respectively); subjects with hematologic malignancies during a cancer therapy course or after the full cancer therapy course (n = 283 or n = 279, respectively); and subjects with solid tumours undergoing chemotherapy (n = 117 or n = 115, respectively). The methodology for evaluating solicited adverse reactions, unsolicited adverse events, serious adverse events, deaths, and pIMDs across these studies was similar to those in the ZOE-50 and ZOE-70 studies.

Solicited adverse reactions.

Across the 4 studies, the majority of solicited local and general adverse reactions seen with Shingrix had a median duration of 3 to 4 days. The reported frequencies of specific solicited local and general adverse reactions (overall per subject) by age group across the 4 studies are presented in Table 2. In the auHSCT study, the percentages of subjects aged 18 years and older reporting each solicited local and general adverse reaction following administration of Shingrix (both doses combined) were pain (84%), redness (33%), swelling (19%); fatigue (56%), myalgia (54%), headache (34%), gastrointestinal symptoms (26%), shivering (26%), and fever (20%). In the other 3 studies, the percentages of subjects aged 18 years and older reporting each solicited local and general adverse reaction following administration of Shingrix (both doses combined) were pain (80-87%), redness (25-41%), and swelling (12-23%); fatigue (47-70%), myalgia (44-54%), headache (34-41%), gastrointestinal symptoms (18-46%), shivering (22-35%), and fever (16-25%).

In studies with immunocompromised adults aged 18 years and older, there was a higher incidence of pain at the injection site (90% and 82%), fatigue (65% and 56%), myalgia (61% and 50%), headache (49% and 32%), shivering (33% and 25%) and fever (30% and 19%) in subjects aged 18 to 49 years compared with those aged 50 years and older.

Unsolicited adverse events.

Unsolicited adverse events occurring within 30 days following each vaccination were reported for the total vaccinated cohort in each of the 4 studies: auHSCT, 39% and 38% of subjects who received Shingrix or placebo, respectively; renal transplantation, 39% and 33%; hematologic malignancies, 47% and 46%; solid malignant tumours, 86% and 90%. The unsolicited adverse event that occurred in ≥ 1% of recipients of Shingrix and at a rate at least 1.5-fold higher than placebo was arthralgia (1.5% versus 1.0%).

Potential immune-mediated diseases.

In the 4 studies (auHSCT, renal transplantation, hematologic malignancies, and solid malignant tumours), new onset pIMDs or exacerbation of existing pIMDs were reported for subjects who received Shingrix (1.4%, 3%, 1.1%, 0%, respectively) and subjects who received placebo (0.9%, 1.5%, 0.7%, 0.9%, respectively) from the first administered dose up to 1 year post-last vaccination. The most frequently reported pIMDs were comparable in the groups receiving Shingrix and the placebo groups.

Use with other vaccines.

The incidence of fever and shivering were more frequent when PPV23 was administered with Shingrix (16% and 21%, respectively) compared to when Shingrix was given alone (7% for both adverse reactions) (study Zoster-035 including 865 adults ≥ 50 years of age).
The incidence of myalgia, fatigue, headache, chills, arthralgia, and gastrointestinal symptoms were more frequent when Shingrix was co-administered with a monovalent COVID-19 mRNA-1273 50 micrograms booster (myalgia 64%, fatigue 51.7%, headache 39%, chills 31.5%, arthralgia 30.3%, gastrointestinal symptoms 24%) compared to when Shingrix was given alone (myalgia 37.8%, fatigue 32.1%, headache 21.4%, chills 14.9%, arthralgia 19.1%, gastrointestinal symptoms 12.6%) (study Zoster-091 including 539 adults ≥ 50 years of age).

Post-marketing data.

See Table 3.

Post-marketing observational studies of the risk of Guillain-Barré syndrome.

In 2 similar post-marketing observational studies in the US among individuals aged 65 years or older, an increased risk of Guillain-Barré syndrome (estimated 3 to 7 excess cases per million doses administered) was observed during the 42 days following any dose of Shingrix. In further analyses, the increased risk was observed following the first dose of Shingrix (estimated 6 to 12 excess cases of Guillain-Barré syndrome per million doses administered), but no increased risk was observed following the second dose.

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

Insufficient data are available.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Varicella zoster vaccines, ATC code: J07BK03 zoster, purified antigen.

Mechanism of action.

By combining the VZV specific antigen (gE) with an adjuvant system (AS01_B), Shingrix induces antigen-specific cellular and humoral immune responses in individuals with pre-existing immunity against VZV.
Non-clinical data show that AS01_B induces a local and transient activation of the innate immune system. This facilitates the recruitment and activation of antigen presenting cells carrying gE-derived antigens in the draining lymph node, which in turn leads to the generation of gE-specific CD4+ T cells and antibodies. The adjuvant effect of AS01_B is the result of interactions between MPL and QS-21 formulated in liposomes.

Clinical trials.

Efficacy of Shingrix.

Efficacy against herpes zoster (HZ) and post-herpetic neuralgia (PHN).

Two phase III, placebo-controlled, observer-blind efficacy studies of Shingrix were conducted in adults ≥ 50 years with 2 doses administered 2 months apart:
Zoster-006 (ZOE-50): total vaccinated cohort (TVC) of 15,405 subjects ≥ 50 who received at least one dose of either Shingrix (N=7,695) or placebo (N=7,710).
Zoster-022 (ZOE-70): TVC of 13,900 subjects ≥ 70 who received at least two doses of either Shingrix (N=6,950) or placebo (N=6,950).
Two phase III, placebo-controlled, observer-blind studies evaluating Shingrix efficacy were conducted in IC adults ≥ 18 years with 2 doses administered 1-2 months apart:
Zoster-002: TVC of 1,846 autologous hematopoietic stem cell transplants (aHSCT) recipients who received at least one dose of either Shingrix (N=922) or placebo (N=924) post-transplant.
Zoster-039: TVC of 562 subjects with hematologic malignancies who received at least one dose of either Shingrix (N=283) or placebo (N=279) during a cancer therapy course or after the full cancer therapy course.
Incidence of HZ and PHN cases as well as vaccine efficacy were evaluated in the modified Total Vaccinated Cohort (mTVC), i.e. excluding subjects who did not receive the second dose of vaccine or who had a confirmed diagnosis of HZ within one month after the second dose.
Shingrix significantly decreased the incidence of HZ and PHN compared with placebo in:
adults ≥ 50 years (Zoster-006): 6 vs. 210 HZ cases and 0 vs. 18 PHN cases;
adults ≥ 70 years (pooled analysis of Zoster-006 and Zoster-022): 25 vs. 284 HZ cases and 4 vs. 36 PHN cases;
adults ≥ 18 years with aHSCT (Zoster-002): 49 vs. 135 HZ cases and 1 vs. 9 PHN cases;
adults ≥ 18 years with hematologic malignancies (Zoster-039): 2 vs. 14 HZ cases (PHN was not assessed as study endpoint). Vaccine efficacy was calculated post hoc.
Vaccine efficacy results are presented in Table 4 and Table 5, respectively.

In the fourth year after vaccination, the efficacy against HZ was 93.1% (95% CI: 81.2; 98.2) and 87.9% (95% CI: 73.3; 95.4) in subjects ≥ 50 years (Zoster-006) and subjects ≥ 70 years, (pooled Zoster-006 and Zoster-022), respectively.
In Zoster-002, during a follow-up period starting 1 month post-dose 2 (i.e. corresponding to approximately 6 months after aHSCT) until 1 year after aHSCT, when the risk for HZ is the highest, the efficacy against HZ was 76.2% (95% CI: 61.1; 86.0).
The duration of protection beyond 4 years is currently under investigation.
Shingrix significantly decreased the incidence of PHN compared with placebo in subjects ≥ 50 years (0 vs. 18 cases in ZOE-50) and in subjects ≥ 70 years (4 vs. 36 cases in the pooled analysis of ZOE-50 and ZOE-70).

The benefit of Shingrix in the prevention of PHN can be attributed to the effect of the vaccine on the prevention of HZ. Due to the very low numbers of shingles occurring in the Shingrix group, the efficacy of Shingrix in the prevention of PHN in subjects with confirmed HZ could not be demonstrated.

Other HZ-related complications.

The evaluated HZ-related complications (other than PHN) were: HZ vasculitis, disseminated disease, ophthalmic disease, neurologic disease including stroke, and visceral disease.
In a post hoc analysis of the pooled data of ZOE-50 and ZOE-70, Shingrix reduced HZ-related complications (other than PHN) by 93.7% (95% CI: 59.5; 99.9) and 91.6% (95% CI:43.3; 99.8) in subjects ≥ 50 years (1 vs. 16 cases) and subjects ≥ 70 years (1 vs. 12 cases), respectively.
In Zoster-002, Shingrix significantly reduced HZ-related complications by 77.8% (95% CI: 19.0; 96.0) in aHSCT recipients ≥ 18 years (3 vs 13 cases).
In addition, in Zoster-002, Shingrix significantly reduced HZ-related hospitalisations by 84.7% (95% CI: 32.1; 96.6) (2 vs. 13 cases).

Long-term efficacy against HZ, PHN and HZ-related complications other than PHN.

A phase IIIb, open-label, long-term follow-up study of Shingrix (Zoster-049) was conducted in adults ≥ 50 years from Zoster-006 and Zoster-022. The TVC for efficacy included 7,408 subjects.
Vaccine efficacy was calculated descriptively against HZ, PHN and HZ-related complications other than PHN in the mTVC (i.e. excluding subjects who did not receive the second dose of vaccine in the primary studies, or who developed a confirmed case of HZ within one month after the second dose). Estimates of incidence rates in the control group to assess the vaccine efficacy during Zoster-049 study were historical, derived from the Zoster-006 and Zoster-022 placebo groups.
Shingrix long-term efficacy results against HZ, PHN and other HZ-related complications up to approximately 11 years post-vaccination are presented in Table 6.
The number of cases of HZ, PHN and other HZ-related complications in subjects who received Shingrix compared to controls (see Table 6 for details on controls used) were as follows (age at the time of vaccination):
Over the duration of Zoster-049:
in adults ≥ 50 years: 69 vs. 341 HZ cases, 4 vs. 32 PHN cases, 1 vs. 12 other HZ-related complication cases;
in adults ≥ 70 years: 48 vs. 179 HZ cases, 3 vs. 23 PHN cases, 1 vs. 9 other HZ-related complication cases.
From 1 month post-dose 2 in Zoster-006 and Zoster-022 until the end of Zoster-049:
in adults ≥ 50 years: 101 vs. 818 HZ cases, 8 vs. 78 PHN cases, 2 vs. 28 other HZ-related complication cases;
in adults ≥ 70 years: 73 vs. 463 HZ cases, 7 vs. 59 PHN cases, 2 vs. 21 other HZ-related complication cases.

In the eleventh year after vaccination, the efficacy against HZ was 82.0% (95% CI: 63.0; 92.2) and 72.0% (95% CI: 33.4; 89.8) in subjects ≥ 50 years (Shingrix group: N=5,849) and subjects ≥ 70 years (Shingrix group: N=2,891), respectively.

Subjects with a history of HZ prior to vaccination.

In a phase III, randomised, placebo-controlled, observer-blind, multicentre clinical study (Zoster-062), subjects ≥ 50 years of age, with a prior history of HZ (resolved > 6 months prior to enrolment), received 2 doses of either Shingrix or placebo 2 months apart. The exposed set (ES) included 1426 subjects who received at least one dose of either Shingrix (N = 714) or placebo (N = 712). A total of 1286 subjects in the ES completed the study with a minimum follow-up period of 26 months.
The incidence of HZ recurrence (Shingrix vs. placebo) was evaluated in the modified exposed set (mES i.e. excluding subjects who did not receive the second dose of vaccine or who had a confirmed diagnosis of HZ within 30 days after the second dose). The mES included 1350 subjects [N = 668 (Shingrix), N = 682 (placebo)].
In subjects with a prior history of HZ, Shingrix vaccination did not increase the recurrence of HZ (0 HZ cases in the Shingrix group vs. 8 HZ cases in the placebo group). The incidence rate ratio of HZ recurrence (Shingrix vs. placebo) in the mES from 30 days post-dose 2 until end of Zoster-062 was 0.00 (95% CI: 0.00; 0.46).

Reduction of use of pain medication.

Among subjects ≥ 70 years with confirmed HZ, Shingrix reduced the use and the duration of HZ-related pain medication by 39.0% (95% CI: 11.9; 63.3) and 50.6% (95% CI: 8.8; 73.2), respectively.

Immunogenicity of Shingrix.

An immunological correlate of protection has not been established; therefore the level of immune response that provides protection against HZ is unknown.
In adults ≥ 50 years, the immune responses to Shingrix were evaluated in a subset of subjects from the phase III efficacy studies ZOE-50 [humoral immunity and cell-mediated immunity (CMI)] and ZOE-70 (humoral immunity). The gE-specific immune responses (humoral and CMI) elicited by Shingrix at 1 month post-dose 2 are presented in Tables 7 and 8, respectively.

At 3 years post-dose 2, the median fold increase over baseline was 9.3 (Q1: 4.9; Q3: 19.5) in adults ≥ 50 years (Zoster-006) and 7.2 (Q1: 3.5; Q3: 14.5) in adults ≥ 70 years (pooled Zoster-006 and Zoster-022).

At 3 years post-dose 2, in Zoster-006, the median fold increase over baseline was 7.9 (Q1: 2.7; Q3: 31.6) in adults ≥ 50 years and 7.3 (Q1: 1.7; Q3: 31.6) in adults ≥ 70 years.
In IC adults ≥ 18 years, the humoral and CMI responses to Shingrix were evaluated in:
one phase I/II study: Zoster-015 (HIV infected subjects);
one phase II/III study: Zoster-028 (patients with solid tumors undergoing chemotherapy);
three phase III studies: Zoster-002 (aHSCT recipients vaccinated post-transplant), Zoster-039 (patients with hematologic malignancies vaccinated during a cancer therapy course or after the full cancer therapy course) and Zoster-041 (renal transplant recipients on chronic immunosuppressive treatment at the time of vaccination).
The gE-specific immune responses (humoral and CMI) elicited by Shingrix at 1 month post-dose 2 in all IC populations studied are presented in Tables 9 and 10, respectively.

In Zoster-028, GMC 1-month post Dose 2 were 22,974.3 (19,080.0; 27,663.5) in the group that received the first dose of Shingrix at least 10 days prior to a chemotherapy cycle (PreChemo group) and 9,328.0 (4,492.5; 19,368.2) in the group that received the first dose of Shingrix simultaneously with chemotherapy cycle (OnChemo group). In Zoster-039, GMC 1-month post Dose 2 were 19,934.7 (14,674.1; 27,081.2) in the group that received the first dose of Shingrix after the full cancer therapy course and 5,777.4 (3,342.5; 9,985.9) in the group that received the first dose of Shingrix during a cancer therapy course. The clinical relevance in terms of impact on efficacy, on the short and long term, is unknown.
At 1 year post-dose 2, the median fold increase over baseline ranged from 2.7 to 6.5 in terms of anti-gE antibody concentration and from 2.0 to 43.6 in terms of gE-specific CD4[2+] T-cell frequencies (studies Zoster-002, Zoster-028, Zoster-039 and Zoster-041).
At 2 years post-dose 2, in Zoster-002, the median fold increase over baseline was 1.3 in terms of anti-gE antibody concentration and 50.9 in terms of gE-specific CD4[2+] T-cell frequencies.

Immunogenicity following concomitant vaccination.

In five phase III, controlled, open-label clinical studies, adults ≥ 50 years of age were randomized to receive 2 doses of Shingrix 2 months apart administered either concomitantly at the first dose or non-concomitantly with unadjuvanted seasonal influenza vaccine (N=828; Zoster-004), PPV23 vaccine (N=865; Zoster-035), PCV13 vaccine (N=912; Zoster-059), dTpa vaccine formulated with 0.3 milligrams Al³⁺ (N=830; Zoster-042) or monovalent COVID-19 mRNA-1273 50 micrograms booster vaccine (original SARS-CoV-2 strain) (N=458; Zoster-091). The vaccine response rate (in terms of anti-gE antibodies) was 95.8% (95% CI: 93.3; 97.6), 98.3% (95% CI: 96.4; 99.3), 99.1% (95% CI: 97.6; 99.7), 97.8% (95% CI: 95.8; 99.1) and 97.4% (95% CI: 94.4; 99.0) following co-administration of Shingrix with the influenza, PPV23, PCV13, dTpa and COVID-19 mRNA-1273 booster vaccine respectively. The immune responses of the co-administered vaccines were unaffected, with the exception of lower geometric mean concentrations (GMCs) for one of the pertussis antigens (pertactin) when Shingrix is co-administered with the dTpa vaccine. The clinical relevance of these data is not known.

Immunogenicity in subjects with a history of HZ prior to vaccination.

In adults ≥ 50 years with a prior history of HZ (resolved > 6 months prior to enrolment), the immune responses to Shingrix were evaluated in subjects from the phase III study Zoster-062. The gE-specific immune responses (humoral) elicited by Shingrix at 30 days post dose 2 are presented in Table 11.

Immunogenicity in subjects receiving 2 doses of Shingrix 6 months apart.

In a phase III, open-label clinical study (Zoster-026) where 238 subjects ≥ 50 years of age were equally randomised to receive 2 doses of Shingrix 2 or 6 months apart, the vaccine response rate (anti-gE antibodies) at 1 month post-vaccination following the 0, 6-month schedule was 96.5% (95% CI: 90.4; 99.2).
The humoral immune response (anti-gE antibodies concentration) following the 0, 6-month schedule was not inferior to the humoral immune response following the 0, 2-month schedule, as the 97.5% CI upper limit of the antibodies concentration ratio was below 1.50 [1.16 (97.5% CI: 0.98; 1.39)].

Immunogenicity and safety in individuals previously vaccinated with live attenuated herpes zoster (HZ) vaccine.

In a phase III, open-label, multicentre clinical study (Zoster-048), 430 adults ≥ 65 years of age with or without a previous history of vaccination with live attenuated HZ vaccine ≥ 5 years earlier were group-matched at a 1:1 ratio to receive 2 doses of Shingrix 2 months apart. The immune response to Shingrix was unaffected by prior vaccination with live attenuated HZ vaccine. The safety and reactogenicity profiles were comparable in subjects irrespective of previous vaccination with live attenuated HZ vaccine.

Persistence of immunogenicity.

Persistence of immunogenicity was evaluated in a subset of subjects in a phase IIIb, open-label, long-term follow-up study (Zoster-049) in adults ≥ 50 years from Zoster-006 and Zoster-022. At Year 12 post-vaccination, MGI (Mean Geometric Increase versus pre-vaccination) of anti-gE antibody concentrations in 435 evaluable subjects was 5.8 (95% CI: 5.2; 6.4). Median frequency of gE-specific CD4[2+] T cells at Year 12 post-vaccination in 73 evaluable subjects remained above pre-vaccination level.

5.2 Pharmacokinetic Properties

Not relevant to vaccines.

5.3 Preclinical Safety Data

Genotoxicity.

Shingrix was not tested for genotoxicity.

Carcinogenicity.

Shingrix was not tested for carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Powder (gE antigen).

Sucrose, polysorbate 80, monobasic sodium phosphate dihydrate, dibasic potassium phosphate.

Suspension (AS01_B adjuvant system).

Dioleoylphosphatidylcholine, cholesterol, sodium chloride, dibasic sodium phosphate, monobasic potassium phosphate, water for injections.

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
For shelf-life after reconstitution of the medicinal product, see Section 4.2 Dose and Method of Administration, Instructions for use and handling.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C - 8°C).
Do not freeze.
Store in the original package in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see Section 4.2 Dose and Method of Administration, Instructions for use and handling.

6.5 Nature and Contents of Container

Shingrix is presented as:
Powder for 1 dose in a vial (type I glass) with a stopper (butyl rubber).
Suspension for 1 dose in a vial (type I glass) with a stopper (butyl rubber).
Shingrix is available in a pack size of 1 vial of powder plus 1 vial of suspension or in a pack size of 10 vials of powder plus 10 vials of suspension.
Not all pack sizes and container types may be distributed in Australia.

6.6 Special Precautions for Disposal

Discard any residue. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

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Shingrix

Varicella zoster virus glycoprotein E antigen recombinant vaccine

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