Label: SHINGRIX- zoster vaccine recombinant, adjuvanted kit

  • NDC Code(s): 58160-819-12, 58160-823-11, 58160-828-01, 58160-828-03, view more
    58160-829-01, 58160-829-03
  • Packager: GlaxoSmithKline Biologicals SA
  • Category: VACCINE LABEL
  • DEA Schedule: None
  • Marketing Status: Biologic Licensing Application

Drug Label Information

Updated July 23, 2021

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  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use SHINGRIX safely and effectively. See full prescribing information for SHINGRIX.
    SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted), suspension for intramuscular injection
    Initial U.S. Approval: 2017

    RECENT MAJOR CHANGES

    Indications and Usage (1)

    07/2021

    Dosage and Administration, Dose and Schedule (2.3)

    07/2021

    Warnings and Precautions, Guillain-Barré syndrome (5.2)

    03/2021

    Warnings and Precautions, Syncope (5.3)

    07/2021

    INDICATIONS AND USAGE

    SHINGRIX is a vaccine indicated for prevention of herpes zoster (HZ) (shingles):

    in adults aged 50 years and older.
    in adults aged 18 years and older who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression caused by known disease or therapy.

    Limitations of Use (1):

    SHINGRIX is not indicated for prevention of primary varicella infection (chickenpox).

    DOSAGE AND ADMINISTRATION

    For intramuscular administration only.

    Two doses (0.5 mL each) administered intramuscularly according to the following schedules:

    A first dose at Month 0 followed by a second dose administered 2 to 6 months later. (2.3)
    For individuals who are or will be immunodeficient or immunosuppressed and who would benefit from a shorter vaccination schedule: A first dose at Month 0 followed by a second dose administered 1 to 2 months later. (2.3)

    DOSAGE FORMS AND STRENGTHS

    Suspension for injection supplied as a single-dose vial of lyophilized varicella zoster virus glycoprotein E (gE) antigen component to be reconstituted with the accompanying vial of AS01B adjuvant suspension component. After reconstitution, a single dose of SHINGRIX is 0.5 mL. (3)

    CONTRAINDICATIONS

    History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine or after a previous dose of SHINGRIX. (4)

    WARNINGS AND PRECAUTIONS

    In a postmarketing observational study, an increased risk of Guillain-Barré syndrome was observed during the 42 days following vaccination with SHINGRIX. (5.2, 6.2)
    Syncope (fainting) can be associated with the administration of injectable vaccines, including SHINGRIX. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope. (5.3)

    ADVERSE REACTIONS

    Solicited local adverse reactions reported in individuals aged 50 years and older were pain (78%), redness (38%), and swelling (26%). (6.1)
    Solicited general adverse reactions reported in individuals aged 50 years and older were myalgia (45%), fatigue (45%), headache (38%), shivering (27%), fever (21%), and gastrointestinal symptoms (17%). (6.1)
    Solicited local adverse reactions reported in autologous hematopoietic stem cell transplant recipients (aged 18 to 49 and ≥50 years of age) were pain (88% and 83%), redness (30% and 35%), and swelling (21% and 18%). (6.1)
    Solicited general adverse reactions reported in autologous hematopoietic stem cell transplant recipients (aged 18 to 49 and ≥50 years of age) were fatigue (64% and 54%), myalgia (58% and 52%), headache (44% and 30%), gastrointestinal symptoms (21% and 28%), shivering (31% and 25%), and fever (28% and 18%). (6.1)

    To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or VAERS at 1-800-822-7967 or www.vaers.hhs.gov.

    See 17 for PATIENT COUNSELING INFORMATION.

    Revised: 7/2021

  • Table of Contents
  • 1 INDICATIONS AND USAGE

    SHINGRIX is a vaccine indicated for prevention of herpes zoster (HZ) (shingles):

        •    in adults aged 50 years and older.

        •    in adults aged 18 years and older who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression caused by known disease or therapy.

    Limitations of Use:

    SHINGRIX is not indicated for prevention of primary varicella infection (chickenpox).
  • 2 DOSAGE AND ADMINISTRATION

    For intramuscular injection only.

    2.1 Reconstitution

    SHINGRIX is supplied in 2 vials that must be combined prior to administration. Prepare SHINGRIX by reconstituting the lyophilized varicella zoster virus glycoprotein E (gE) antigen component (powder) with the accompanying AS01B adjuvant suspension component (liquid). Use only the supplied adjuvant suspension component (liquid) for reconstitution. The reconstituted vaccine should be an opalescent, colorless to pale brownish liquid. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.

    Figure 1Figure 2bFigure 3Figure 4

    Figure 1. Cleanse both vial stoppers. Using a sterile needle and sterile syringe, withdraw the entire contents of the vial containing the adjuvant suspension component (liquid) by slightly tilting the vial. Vial 1 of 2.

    Figure 2. Slowly transfer entire contents of syringe into the lyophilized gE antigen component vial (powder). Vial 2 of 2.

    Figure 3. Gently swirl the vial until powder is completely dissolved. Do not shake vigorously.

    Figure 4. After reconstitution, withdraw 0.5 mL from the vial containing the reconstituted vaccine and administer intramuscularly.

    2.2 Administration Instructions

    For intramuscular injection only.

    After reconstitution, administer SHINGRIX immediately or store refrigerated between 2° and 8°C (36° and 46°F) and use within 6 hours. Discard reconstituted vaccine if not used within 6 hours.

    Use a separate sterile needle and sterile syringe for each individual. The preferred site for intramuscular injection is the deltoid region of the upper arm.

    2.3 Dose and Schedule

    Two doses (0.5 mL each) administered intramuscularly according to the following schedules:

        •    A first dose at Month 0 followed by a second dose administered 2 to 6 months later.

        •    For individuals who are or will be immunodeficient or immunosuppressed and who would benefit from a shorter vaccination schedule: A first dose at Month 0 followed by a second dose administered 1 to 2 months later.

  • 3 DOSAGE FORMS AND STRENGTHS

    SHINGRIX is a suspension for injection supplied as a single-dose vial of lyophilized gE antigen component to be reconstituted with the accompanying vial of AS01B adjuvant suspension component. A single dose after reconstitution is 0.5 mL.

  • 4 CONTRAINDICATIONS

    Do not administer SHINGRIX to anyone with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine or after a previous dose of SHINGRIX [see Description (11)].

  • 5 WARNINGS AND PRECAUTIONS

    5.1 Preventing and Managing Allergic Vaccine Reactions

    Prior to administration, the healthcare provider should review the immunization history for possible vaccine sensitivity and previous vaccination-related adverse reactions. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of SHINGRIX.

    5.2 Guillain-Barré Syndrome (GBS)

    In a postmarketing observational study, an increased risk of GBS was observed during the 42 days following vaccination with SHINGRIX [see Adverse Reactions (6.2)].

    5.3 Syncope

    Syncope (fainting) can be associated with the administration of injectable vaccines, including SHINGRIX. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.

  • 6 ADVERSE REACTIONS

    6.1 Clinical Trials Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice. There is the possibility that broad use of SHINGRIX could reveal adverse reactions not observed in clinical trials.

    Adults Aged 50 Years and Older

    Overall, 17,041 adults aged 50 years and older received at least 1 dose of SHINGRIX in 17 clinical studies.

    The safety of SHINGRIX was evaluated by pooling data from 2 placebo-controlled clinical studies (Studies 1 and 2) involving 29,305 subjects aged 50 years and older who received at least 1 dose of SHINGRIX (n = 14,645) or saline placebo (n = 14,660) administered according to a 0- and 2-month schedule. At the time of vaccination, the mean age of the population was 69 years; 7,286 (25%) subjects were aged 50 to 59 years, 4,488 (15%) subjects were aged 60 to 69 years, and 17,531 (60%) subjects were aged 70 years and older. Both studies were conducted in North America, Latin America, Europe, Asia, and Australia. In the overall population, the majority of subjects were White (74%), followed by Asian (18%), Black (1.4%), and other racial/ethnic groups (6%); 58% were female.

    Solicited Adverse Reactions: In Studies 1 and 2, data on solicited local and general adverse reactions were collected using standardized 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 and general adverse reaction following administration of SHINGRIX (both doses combined) were pain (78%), redness (38%), and swelling (26%); and myalgia (45%), fatigue (45%), headache (38%), shivering (27%), fever (21%), and gastrointestinal symptoms (17%).

    The reported frequencies of specific solicited local adverse reactions and general adverse reactions (overall per subject), by age group, from the 2 studies are presented in Table 1.

    Table 1. Percentage of Subjects with Solicited Local and General Adverse Reactions within 7 Daysa of Vaccination in Adults Aged 50 to 59 Years, 60 to 69 Years, and 70 Years and Olderb (Total Vaccinated Cohort with 7-Day Diary Card)
    Total vaccinated cohort for safety included all subjects with at least 1 documented dose (n).
    a 7 days included day of vaccination and the subsequent 6 days.
    b Data for subjects aged 50 to 59 years and 60 to 69 years are based on Study 1. Data for subjects 70 years and older are based on pooled data from Study 1: NCT01165177 and Study 2: NCT01165229.
    c Placebo was a saline solution.
    d Grade 3 pain: Defined as significant pain at rest; prevents normal everyday activities.
    e Grade 3 myalgia, fatigue, headache, shivering, and GI: Defined as preventing normal activity.
    f Fever defined as ≥37.5°C/99.5°F for oral, axillary, or tympanic route, or ≥38°C/100.4°F for rectal route; Grade 3 fever defined as >39.0°C/102.2°F.
    g GI = Gastrointestinal symptoms including nausea, vomiting, diarrhea, and/or abdominal pain.

    Adverse Reactions

    Aged 50-59 Years

    Aged 60-69 Years

    Aged ≥70 Years

    SHINGRIX

    Placeboc

    SHINGRIX

    Placeboc

    SHINGRIX

    Placeboc

    Local Adverse Reactions

    n = 1,315

    %

    n = 1,312

    %

    n = 1,311

    %

    n = 1,305

    %

    n = 2,258

    %

    n = 2,263

    %

    Pain

    88

    14

    83

    11

    69

    9

    Pain, Grade 3d

    10

    1

    7

    1

    4

    0.2

    Redness

    39

    1

    38

    2

    38

    1

    Redness, >100 mm

    3

    0

    3

    0

    3

    0

    Swelling

    31

    1

    27

    1

    23

    1

    Swelling, >100 mm

    1

    0

    1

    0

    1

    0

    General Adverse Reactions

    n = 1,315

    %

    n = 1,312

    %

    n = 1,309

    %

    n = 1,305

    %

    n =2,252

    %

    n = 2,264

    %

    Myalgia

    57

    15

    49

    11

    35

    10

    Myalgia, Grade 3e

    9

    1

    5

    1

    3

    0.4

    Fatigue

    57

    20

    46

    17

    37

    14

    Fatigue, Grade 3e

    9

    2

    5

    1

    4

    1

    Headache

    51

    22

    40

    16

    29

    12

    Headache, Grade 3e

    6

    2

    4

    0.2

    2

    0.4

    Shivering

    36

    7

    30

    6

    20

    5

    Shivering, Grade 3e

    7

    0.2

    5

    0.3

    2

    0.3

    Fever

    28

    3

    24

    3

    14

    3

    Fever, Grade 3f

    0.4

    0.2

    1

    0.2

    0.1

    0.1

    GIg

    24

    11

    17

    9

    14

    8

    GI, Grade 3e

    2

    1

    1

    1

    1

    0.4

    The incidence of solicited local and general reactions was lower in subjects aged 70 years and older compared with those aged 50 to 69 years.

    The local and general adverse reactions 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% and 21%, respectively) compared with Dose 1 (24% and 14%, respectively). Grade 3 solicited general adverse reactions (headache, shivering, myalgia, and fatigue) were reported more frequently by subjects after Dose 2 (2.3%, 3%, 4%, and 4%, respectively) compared with Dose 1 (1.4%, 1.4%, 2.3%, and 2.4%, respectively).

    Unsolicited Adverse Events: Unsolicited adverse events that occurred within 30 days following each vaccination (Day 0 to 29) were recorded on a diary card by all subjects. In the 2 studies, unsolicited adverse events occurring within 30 days of vaccination were reported in 51% and 32% of subjects who received SHINGRIX (n = 14,645) or 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 (4% versus 0.2%), injection site pruritus (2.2% versus 0.2%), 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 or placebo, respectively, within 30 days of vaccination; available information is insufficient to determine a causal relationship with SHINGRIX.

    Serious Adverse Events (SAEs): In the 2 studies, SAEs were reported at similar rates in subjects who received SHINGRIX (2.3%) or placebo (2.2%) from the first administered dose up to 30 days post-last vaccination. SAEs were reported for 10.1% of subjects who received SHINGRIX and for 10.4% of subjects who received placebo from the first administered dose up to 1 year post-last vaccination. One subject (<0.01%) reported lymphadenitis and 1 subject (<0.01%) reported fever greater than 39°C; there was a basis for a causal relationship with SHINGRIX.

    Optic ischemic neuropathy was reported in 3 subjects (0.02%) who received SHINGRIX (all within 50 days after vaccination) and 0 subjects who received placebo; available information is insufficient to determine a causal relationship with SHINGRIX.

    Deaths: From the first administered dose up to 30 days post-last vaccination, deaths were reported for 0.04% of subjects who received SHINGRIX and 0.05% of subjects who received placebo in the 2 studies. From the first administered dose up to 1 year post-last vaccination, deaths were reported for 0.8% of subjects who received SHINGRIX and for 0.9% of subjects who received placebo. Causes of death among subjects were consistent with those generally reported in adult and elderly populations.

    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.

    Dosing Schedule: In an open-label clinical study, 238 subjects 50 years and older received SHINGRIX as a 0- and 2-month or 0- and 6-month schedule. The safety profile of SHINGRIX was similar when administered according to a 0- and 2-month or 0- and 6-month schedule and was consistent with that observed in Studies 1 and 2.

    Immunocompromised Adults Aged 18 Years and Older

    The safety of SHINGRIX was evaluated in 6 placebo-controlled clinical studies that enrolled 3,116 subjects aged 18 years and older from 5 different immunodeficient or immunosuppressed (referred to as immunocompromised) populations, in which a total of 1,587 received SHINGRIX. In all studies, subjects received Doses 1 and 2 of SHINGRIX 1 to 2 months apart. Safety monitoring for these studies was similar to Studies 1 and 2. In addition, subjects were monitored for events relevant to their specific disease or condition.

    At the time of receipt of SHINGRIX or placebo, the mean age of the population was 55 years; 28% subjects were aged 18 to 49 years and 72% subjects were aged 50 years and older. Each of the studies was conducted in one or more of the following regions: North America, Latin America, Europe, Asia, Africa and Australia/New Zealand. The majority of subjects were White (77%), followed by Asian (17%), Black (2%), and other racial groups (3%); 4% were of American Hispanic or Latino ethnicity; 37% were female.

    Table 2. Clinical Studies with SHINGRIX in Immunocompromised Adults Aged ≥18 Years
    a The first dose was administered within 50 to 70 days after autologous hematopoietic stem cell transplantation.
    b Safety follow-up was driven by HZ case accrual and ranged from a minimum of 12 months post last vaccination to 4 years at subject level.
    c For subjects who were vaccinated during a cancer therapy course, each dose was administered with at least 10 days between vaccination and cancer therapy cycles.
    d For subjects who received the vaccination after a full cancer therapy course, the first dose was administered from 10 days to 6 months after cancer therapy had ended.
    e The first dose was administered between 4 to 18 months after renal transplantation.
    f In the PreChemo group (TVC: SHINGRIX [n = 90], placebo [n = 91]), the first dose was administered a maximum of 1 month to a minimum of 10 days before the start of a chemotherapy cycle, and the second dose was administered on the first day of a chemotherapy cycle.
    g In the OnChemo group (TVC: SHINGRIX [n = 27], placebo [n = 24]), each dose was administered on the first day of a chemotherapy cycle.

    Clinical Studies

    Number of Subjects Vaccinated

    Study Population

    Safety Follow-up Period

    SHINGRIX

    Placebo

    auHSCT (NCT01610414)

    922

    924

    Autologous hematopoietic stem cell transplant recipientsa

    29 months median safety follow-upb

    Hematologic Malignancies (NCT01767467)

    283

    279

    Hematologic malignanciesc,d

    12 months post last vaccination

    Renal Transplant

    (NCT02058589)

    132

    132

    Renal transplant recipientse

    12 months post last vaccination

    Solid Malignant
    Tumors (NCT01798056)

    117

    115

    Solid tumors receiving chemotherapyf,g

    12 months post last vaccination

    HIV (NCT01165203)

    74

    49

    HIV-infected subjects

    12 months post last vaccination

    auHSCT (NCT00920218)

    59

    30

    Autologous hematopoietic stem cell transplant recipientsa

    12 months post last vaccination

    In the auHSCT study (NCT01610414), at the time of receipt of SHINGRIX or placebo, the mean age of the population was 55 years; 25% of subjects were aged 18 to 49 years and 75% subjects were aged 50 years and older. The majority of subjects were White (78%), followed by Asian (16%), Black (2%), and other racial groups (3%); 3% were of American Hispanic or Latino ethnicity; 37% were female.

    Solicited Adverse Reactions: Solicited local adverse reactions reported within 7 days following administration of SHINGRIX (both doses combined) in auHSCT recipients (aged 18 to 49 and ≥50 years of age) were pain (88% and 83%), redness (30% and 35%), and swelling (21% and 18%). Solicited general adverse reactions reported within 7 days following administration of SHINGRIX (both doses combined) in auHSCT recipients (aged 18 to 49 and ≥50 years of age) were fatigue (64% and 54%), myalgia (58% and 52%), headache (44% and 30%), gastrointestinal symptoms (21% and 28%), shivering (31% and 25%), and fever (28% and 18%). The percentages of subjects aged 18 years and older reporting each solicited local and general adverse reaction following administration of each dose of SHINGRIX or placebo in the auHSCT study (NCT01610414) are presented in Table 3.

    Table 3. Adult auHSCT Recipients (NCT01610414): Percentage of Subjects with Solicited Local and General Adverse Reactions within 7 Daysa of Vaccination in Adults Aged 18 to 49 Years and 50 Years and Older by Dose (Total Vaccinated Cohort)
    Total vaccinated cohort (TVC) for safety included all subjects with at least 1 documented dose (n).
    % = Percentage of subjects reporting the symptom at least once.
    a 7 days included day of vaccination and the subsequent 6 days.
    b Placebo was sucrose reconstituted with saline solution.
    c Grade 3 pain: defined as significant pain at rest preventing normal everyday activities.
    d Grade 3 myalgia, fatigue, headache, shivering, and GI: defined as preventing normal activity.
    e GI = Gastrointestinal symptoms including nausea, vomiting, diarrhea, and/or abdominal pain.

    Adverse Reactions

    Aged 18-49 Years

    Aged ≥50 Years

    SHINGRIX

    Placebob

    SHINGRIX

    Placebob

    Dose 1

    Dose 2

    Dose 1

    Dose 2

    Dose 1

    Dose 2

    Dose 1

    Dose 2

    Local Adverse Reactions

    n = 223%

    n = 205%

    n = 217%

    n = 207%

    n = 673%

    n = 635%

    n = 673%

    n = 627%

    Pain

    81

    82

    8

    6

    75

    74

    6

    5

    Pain, Grade 3c

    11

    11

    1

    0

    5

    7

    0.3

    0

    Redness

    20

    25

    0

    0

    21

    28

    1

    1

    Redness, >100 mm

    1

    2

    0

    0

    1

    3

    0

    0

    Swelling

    14

    17

    0

    0

    10

    15

    1

    1

    Swelling, >100 mm

    0

    2

    0

    0

    0.1

    1

    0

    0

    General Adverse Reactions

    n = 222
    %

    n = 203

    %

    n = 218
    %

    n = 207
    %

    n = 674
    %

    n = 633
    %

    n = 674
    %

    n = 628
    %

    Myalgia

    41

    51

    22

    21

    37

    43

    18

    17

    Myalgia, Grade 3d

    4

    8

    2

    2

    2

    4

    1

    1

    Fatigue

    49

    51

    34

    25

    37

    46

    31

    26

    Fatigue, Grade 3d

    6

    10

    1

    2

    3

    4

    2

    3

    Headache

    23

    38

    17

    17

    15

    25

    13

    8

    Headache, Grade 3d

    1

    5

    0

    2

    0.1

    2

    0.4

    1

    Shivering

    20

    26

    12

    6

    11

    21

    7

    7

    Shivering, Grade 3d

    1

    6

    0

    0

    0.4

    3

    1

    0.2

    Fever, ≥37.5°C/99.5°F

    9

    28

    4

    2

    6

    15

    3

    4

    Fever, Grade 3 >39.5°C/103.1°F

    0

    1

    0

    0

    0.1

    0.2

    0

    0.2

    GIe

    14

    13

    13

    12

    18

    18

    16

    12

    GI, Grade 3d

    1

    1

    0

    1

    1

    2

    1

    2

    In general, the reported frequencies of solicited local and general adverse reactions in the other studies in immunocompromised populations were similar to that in the auHSCT study (NCT01610414). The local and general adverse reactions seen with SHINGRIX had a median duration of 1 to 3 days across all studies enrolling immunocompromised subjects.

    Unsolicited Adverse Events: Across all 6 studies enrolling immunocompromised subjects, unsolicited adverse events, including both serious and non-serious events, occurring within 30 days following each vaccination were reported in 46% and 44% of subjects who received SHINGRIX or placebo. Adverse events of arthralgia, infective pneumonia, and influenza-like illness occurred in ≥1% of recipients of SHINGRIX and at a rate at least 1.5-fold higher than placebo (1.5% versus 1.0%, 1.5% versus 0.9%, and 1.3% versus 0.6%, respectively).

    Serious Adverse Events: Across all 6 studies enrolling immunocompromised subjects, SAEs were reported at similar rates in subjects who received SHINGRIX (7%) or placebo (8%) from the first administered dose up to 30 days post-last vaccination. SAEs were reported for 26% of subjects who received SHINGRIX and for 27% of subjects who received placebo from the first administered dose up to 1 year post-last vaccination. SAEs of infective pneumonia were reported for 21 subjects (1.3%) who received SHINGRIX and for 11 subjects (0.7%) who received placebo up to 30 days post-last vaccination. Available information is insufficient to determine a causal relationship to vaccination.

    Deaths: Across all 6 studies enrolling immunocompromised subjects, from the first administered dose up to 30 days post-last vaccination, deaths were reported for 2 subjects (0.1%) who received SHINGRIX and 7 subjects (0.5%) who received placebo. From the first administered dose up to 1 year post-last vaccination, deaths were reported for 6% of subjects who received SHINGRIX and for 6% of subjects who received placebo. Causes of death among subjects were consistent with those expected in the populations evaluated.

    Potential Immune-Mediated Diseases: Across all 6 studies enrolling immunocompromised subjects, new onset pIMDs or exacerbation of existing pIMDs were reported for 1.3% of subjects who received SHINGRIX and 1.0% of subjects who received placebo from the first administered dose up to 1 year post-last vaccination. There were no notable imbalances in specific pIMDs between treatment groups.

    Other Medically Relevant Events: In the auHSCT study (NCT01610414), relapse or progression was reported by 315 of 922 subjects (34%) who received at least one dose of SHINGRIX and 331 of 924 subjects (36%) who received placebo from the first vaccination to study end.

    In the auHSCT study (NCT00920218), relapse or progression was reported by 17 of 59 subjects (29%) who received at least one dose of SHINGRIX and 8 of 30 subjects (27%) who received placebo from the first vaccination to study end.

    In the hematologic malignancy study, relapse or progression was reported by 45 of 283 subjects (16%) who received at least one dose of SHINGRIX and 58 of 279 subjects (21%) who received placebo from the first vaccination to study end.

    In the renal transplant study, biopsy-confirmed allograft rejection was reported by 4 of 132 (3%) of subjects who received SHINGRIX and by 7 of 132 (5%) of subjects who received placebo from the first vaccination to study end (approximately 13 months later). Creatinine as a measure of graft function and changes in alloimmunity post-vaccination were not systematically evaluated.

    In the HIV study, at least 1 event of worsening HIV condition was reported by 9 of 74 (12%) of subjects who received SHINGRIX and by 5 of 49 (10%) of subjects who received placebo from the first vaccination to study end.

    6.2 Postmarketing Experience

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

    General Disorders and Administration Site Conditions

    Decreased mobility of the injected arm which may persist for 1 or more weeks.

    Immune System Disorders

    Hypersensitivity reactions, including angioedema, rash, and urticaria.

    Nervous System Disorders

    Guillain-Barré syndrome.

    Postmarketing Observational Study of the Risk of Guillain-Barré Syndrome following Vaccination with SHINGRIX

    The association between vaccination with SHINGRIX and GBS was evaluated among Medicare beneficiaries aged 65 years or older. Using Medicare claims data, from October 2017 through February 2020, vaccinations with SHINGRIX among beneficiaries were identified through National Drug Codes, and potential cases of hospitalized GBS among recipients of SHINGRIX were identified through International Classification of Diseases codes.

    The risk of GBS following vaccination with SHINGRIX was assessed in self-controlled case series analyses using a risk window of 1 to 42 days post-vaccination and a control window of 43 to 183 days post-vaccination. The primary analysis (claims-based, all doses) found an increased risk of GBS during the 42 days following vaccination with SHINGRIX, with an estimated 3 excess cases of GBS per million doses administered to adults aged 65 years or older. In secondary analyses, an increased risk of GBS was observed during the 42 days following the first dose of SHINGRIX, with an estimated 6 excess cases of GBS per million doses administered to adults aged 65 years or older, and no increased risk of GBS was observed following the second dose of SHINGRIX. These analyses of GBS diagnoses in claims data were supported by analyses of GBS cases confirmed by medical record review. While the results of this observational study suggest a causal association of GBS with SHINGRIX, available evidence is insufficient to establish a causal relationship.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary

    All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The data are insufficient to establish if there is vaccine-associated risk with SHINGRIX in pregnant women.

    A developmental toxicity study was performed in female rats administered SHINGRIX or the AS01B adjuvant alone prior to mating, during gestation, and during lactation. The total dose was 0.2 mL on each occasion (a single human dose of SHINGRIX is 0.5 mL). This study revealed no adverse effects on fetal or pre-weaning development due to SHINGRIX (see Data).

    Data

    Animal Data: In a developmental toxicity study, female rats were administered SHINGRIX or the AS01B 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 pre-weaning development up to post-natal Day 25 were observed. There were no vaccine-related fetal malformations or variations.

    8.2 Lactation

    Risk Summary

    It is not known whether SHINGRIX is excreted in human milk. Data are not available to assess the effects of SHINGRIX on the breastfed infant or on milk production/excretion.

    The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SHINGRIX and any potential adverse effects on the breastfed child from SHINGRIX or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

    8.4 Pediatric Use

    Safety and effectiveness in individuals younger than 18 years have not been established. SHINGRIX is not indicated for prevention of primary varicella infection (chickenpox).

    8.5 Geriatric Use

    Adults Aged 60 Years and Older

    Of the total number of subjects who received at least 1 dose of SHINGRIX in Studies 1 and 2 (n = 14,645), 2,243 (15%) were aged 60 to 69 years, 6,837 (47%) were aged 70 to 79 years, and 1,921 (13%) were 80 years and older. There were no clinically meaningful differences in efficacy across the age groups [See Clinical Studies (14.1, 14.2, 14.3).]

    The frequencies of solicited local and general adverse reactions in subjects aged 70 years and older were lower than in younger adults (aged 50 through 69 years). [See Adverse Reactions (6.1).]

    Immunocompromised Adults Aged 65 Years and Older

    Of the total number of subjects who received at least 1 dose of SHINGRIX in the auHSCT study (n = 922), 172 (18.7%) were aged 65 years and older [see Clinical Studies (14.6)]. There were no clinically meaningful differences in efficacy between these subjects and younger adults (aged 18 through 64 years).

    Of the total number of subjects who received at least 1 dose of SHINGRIX across the 6 studies in immunocompromised subjects (n = 1,587), 337 (21.2%) were aged 65 years and older. The frequencies of solicited local and general adverse reactions in subjects aged 65 years and older were generally similar to or lower than those reported by younger adults (aged 18 through 64 years).

  • 11 DESCRIPTION

    SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted) is a sterile suspension for intramuscular injection. The vaccine is supplied as a vial of lyophilized recombinant varicella zoster virus surface glycoprotein E (gE) antigen component, which must be reconstituted at the time of use with the accompanying vial of AS01B adjuvant suspension component. The lyophilized gE antigen component is presented in the form of a sterile white powder. The AS01B adjuvant suspension component is an opalescent, colorless to pale brownish liquid supplied in vials.

    The gE antigen is obtained by culturing genetically engineered Chinese Hamster Ovary cells, which carry a truncated gE gene, in media containing amino acids, with no albumin, antibiotics, or animal-derived proteins. The gE protein is purified by several chromatographic steps, formulated with excipients, filled into vials, and lyophilized.

    The adjuvant suspension component is AS01B which is composed of 3-O-desacyl-4’-monophosphoryl lipid A (MPL) from Salmonella minnesota and QS-21, a saponin purified from plant extract Quillaja saponaria Molina, combined in a liposomal formulation. The liposomes are composed of dioleoyl phosphatidylcholine (DOPC) and cholesterol in phosphate-buffered saline solution containing disodium phosphate anhydrous, potassium dihydrogen phosphate, sodium chloride, and water for injection.

    After reconstitution, each 0.5‑mL dose is formulated to contain 50 mcg of the recombinant gE antigen, 50 mcg of MPL, and 50 mcg of QS-21. Each dose also contains 20 mg of sucrose (as stabilizer), 4.385 mg of sodium chloride, 1 mg of DOPC, 0.54 mg of potassium dihydrogen phosphate, 0.25 mg of cholesterol, 0.160 mg of sodium dihydrogen phosphate dihydrate, 0.15 mg of disodium phosphate anhydrous, 0.116 mg of dipotassium phosphate, and 0.08 mg of polysorbate 80. After reconstitution, SHINGRIX is a sterile, opalescent, colorless to pale brownish liquid.

    SHINGRIX does not contain preservatives. Each dose may also contain residual amounts of host cell proteins (≤3.0%) and DNA (≤2.1 picograms) from the manufacturing process.

    The vial stoppers are not made with natural rubber latex.

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    The risk of developing HZ, which increases with age and with immunosuppression due to disease and/or therapy, appears to be related to a decline in varicella zoster virus (VZV)-specific immunity. SHINGRIX was shown to boost VZV-specific immune response, which is thought to be the mechanism by which it protects against zoster disease [see Clinical Studies (14)].

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    SHINGRIX has not been evaluated for its carcinogenic or mutagenic potential. Vaccination of female rats with SHINGRIX had no effect on fertility [see Use in Specific Populations (8.1)]. In a male fertility study, rats were vaccinated with 0.1 mL of SHINGRIX (a single human dose is 0.5 mL) on 42, 28, and 14 days prior to mating. There were no effects on male fertility.

  • 14 CLINICAL STUDIES

    14.1 Efficacy in Subjects Aged 50 Years and Older

    Study 1 was a randomized, placebo-controlled, observer-blind clinical study conducted in 18 countries. Randomization was stratified (8:5:3:1) by age: 50 to 59 years, 60 to 69 years, 70 to 79 years, and ≥80 years. The study excluded, among others, subjects who were immunocompromised, had a history of previous HZ, were vaccinated against varicella or HZ, and patients whose survival was not expected to be at least 4 years or with conditions that might interfere with study evaluations. Subjects were followed for the development of HZ and postherpetic neuralgia (PHN) for a median of 3.1 years (range: 0 to 3.7 years). Suspected HZ cases were followed prospectively for the development of PHN, an HZ-related complication defined as HZ-associated pain (rated as 3 or greater on a 0- to 10-point scale by the study subject) occurring or persisting at least 90 days following the onset of rash in confirmed cases of HZ.

    The primary efficacy analysis population (referred to as the modified Total Vaccinated Cohort [mTVC]) included 14,759 subjects aged 50 years and older who received 2 doses (0 and 2 months) of either SHINGRIX (n = 7,344) or placebo (n = 7,415) and did not develop a confirmed case of HZ within 1 month after the second dose. In the mTVC population, 61% were female; 72% were White, 19% were Asian, 1.7% were Black, and 7% were of other racial/ethnic groups. The mean age of subjects was 62.3 years.

    Confirmed HZ cases were determined by either Polymerase Chain Reaction (PCR) (89.4%) or by a Clinical Evaluation Committee (10.6%).

    Efficacy against Herpes Zoster

    Compared with placebo, SHINGRIX significantly reduced the risk of developing HZ by 97.2% (95% CI: 93.7, 99.0) in subjects aged 50 years and older (Table 4).

    Table 4. Efficacy of SHINGRIX on Incidence of Herpes Zoster Compared with Placebo in Study 1a (mTVCb)
    N = Number of subjects included in each group; n = Number of subjects having at least 1 confirmed HZ episode; HZ = Herpes zoster; CI = Confidence Interval.
    a Study 1: NCT01165177.
    b mTVC = Modified Total Vaccinated Cohort defined as subjects who received 2 doses (0 and 2 months) of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose.
    c Primary study endpoint was based on confirmed HZ cases in subjects aged 50 years and older.

    Age Group

    (Years)

    SHINGRIX

    Placebo

    % Efficacy (95% CI)

    N

    n

    Incidence Rate of HZ per 1,000 Person-Years

    N

    n

    Incidence Rate of HZ per 1,000 Person-Years

    Overall (≥50)c

    7,344

    6

    0.3

    7,415

    210

    9.1

    97.2

    (93.7, 99.0)

    50-59

    3,492

    3

    0.3

    3,525

    87

    7.8

    96.6

    (89.6, 99.3)

    60-69

    2,141

    2

    0.3

    2,166

    75

    10.8

    97.4

    (90.1, 99.7)

    ≥70

    1,711

    1

    0.2

    1,724

    48

    9.4

    97.9

    (87.9, 100.0)

    In a descriptive analysis, vaccine efficacy against HZ in subjects aged 50 years and older was 93.1% (95% CI: 81.3, 98.2) in the fourth year post-vaccination.

    Occurrence of Postherpetic Neuralgia

    Among all subjects aged 50 years or older in the mTVC, no cases of PHN were reported in the vaccine group compared with 18 cases reported in the placebo group.

    14.2 Efficacy in Subjects Aged 70 Years and Older

    Study 2 was a randomized, placebo-controlled, observer-blind clinical study conducted in 18 countries. Randomization was stratified (3:1) by age: 70 to 79 years and ≥80 years. With the exception of age, the study exclusion criteria were the same as for Study 1. Subjects were followed for the development of HZ and PHN for a median of 3.9 years (range: 0 to 4.5 years). Suspected HZ cases were followed prospectively for the development of PHN as for Study 1.

    The primary efficacy analysis population (mTVC) included 13,163 subjects aged 70 years and older who received 2 doses (0 and 2 months) of either SHINGRIX (n = 6,541) or placebo (n = 6,622) and did not develop a confirmed case of HZ within 1 month after the second dose. In the mTVC population, 55% were female; 78% were White, 17% were Asian, 1% were Black, and 4% were of other racial/ethnic groups. The mean age of subjects was 75.5 years.

    Confirmed HZ cases were determined by either PCR (92.3%) or by a Clinical Evaluation Committee (7.7%).

    Efficacy against Herpes Zoster

    Vaccine efficacy results against HZ in subjects aged 70 years and older are shown in Table 5.

    Table 5. Efficacy of SHINGRIX on Incidence of Herpes Zoster Compared with Placebo in Study 2a (mTVCb)
    N = Number of subjects included in each group; n = Number of subjects having at least 1 confirmed HZ episode; HZ = Herpes zoster; CI = Confidence Interval.
    a Study 2: NCT01165229.
    b mTVC = Modified Total Vaccinated Cohort defined as subjects who received 2 doses (0 and 2 months) of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose.
    c Primary study endpoint was based on confirmed HZ cases in subjects aged 70 years and older.

    Age Group (Years)

    SHINGRIX

    Placebo

    % Efficacy (95% CI)

    N

    n

    Incidence Rate of HZ per 1,000 Person-Years

    N

    n

    Incidence Rate of HZ per 1,000 Person-Years

    Overall (≥70)c

    6,541

    23

    0.9

    6,622

    223

    9.2

    89.8

    (84.3, 93.7)

    70-79

    5,114

    17

    0.9

    5,189

    169

    8.8

    90.0

    (83.5, 94.3)

    ≥80

    1,427

    6

    1.2

    1,433

    54

    11.0

    89.1

    (74.7, 96.2)

    In a descriptive analysis, vaccine efficacy against HZ in subjects aged 70 years and older was 85.1% (95% CI: 64.5, 94.8) in the fourth year after vaccination.

    Efficacy against Postherpetic Neuralgia

    Among all subjects aged 70 years or older in the mTVC, 4 cases of PHN were reported in the vaccine group compared with 28 cases reported in the placebo group. Vaccine efficacy against PHN was 85.5% (95% CI: [58.5; 96.3]). The benefit of SHINGRIX in the prevention of PHN can be attributed to the effect of the vaccine on the prevention of HZ.

    Reduction of Use of Pain Medication

    Among subjects with confirmed HZ, the use of HZ-associated pain medications was reported for 10 of 23 subjects (43.5%) who received SHINGRIX and for 160 of 223 subjects (71.7%) who received placebo.

    14.3 Pooled Efficacy Analyses across Studies 1 and 2

    The efficacy of SHINGRIX to prevent HZ and PHN in subjects aged 70 years and older was evaluated by combining the results from Studies 1 and 2 through a pre-specified pooled analysis in the mTVC. A total of 8,250 and 8,346 subjects who received SHINGRIX and placebo, respectively, were included in the pooled mTVC analysis.

    Efficacy against Herpes Zoster

    Compared with placebo, SHINGRIX significantly reduced the risk of developing HZ by 91.3% (95% CI: 86.9, 94.5) in subjects 70 years and older (Table 6).

    Table 6. Efficacy of SHINGRIX on Incidence of Herpes Zoster Compared with Placebo in Studies 1 and 2 (Pooled Dataa) (mTVCb)
    N = Number of subjects included in each group; n = Number of subjects having at least 1 confirmed HZ episode; HZ = Herpes zoster; CI = Confidence Interval.
    a Pooled data from Study 1: NCT01165177 (subjects ≥50 years) and Study 2: NCT01165229 (subjects ≥70 years).
    b mTVC = Modified Total Vaccinated Cohort defined as subjects who received 2 doses (0 and 2 months) of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose.
    c Primary endpoint of pooled analysis was based on confirmed HZ cases in subjects 70 years and older.

    Age Group (Years)

    SHINGRIX

    Placebo

    % Efficacy (95% CI)

    N

    n

    Incidence Rate of HZ per 1,000 Person-Years

    N

    n

    Incidence Rate of HZ per 1,000 Person-Years

    Overall (≥70)c

    8,250

    25

    0.8

    8,346

    284

    9.3

    91.3

    (86.9, 94.5)

    70-79

    6,468

    19

    0.8

    6,554

    216

    8.9

    91.3

    (86.0, 94.9)

    ≥80

    1,782

    6

    1.0

    1,792

    68

    11.1

    91.4

    (80.2, 96.9)

    Efficacy against Postherpetic Neuralgia

    Table 7 compares the overall rates of PHN in the vaccine and placebo groups across both studies.

    Table 7. Efficacy of SHINGRIX on Overall Incidence of Postherpetic Neuralgia Compared with Placebo in Studies 1 and 2 (Pooled Dataa) (mTVCb)
    N = Number of subjects included in each group; n = Number of subjects having at least 1 PHN; CI = Confidence Interval.
    a Pooled data from Study 1: NCT01165177 (subjects ≥50 years) and Study 2: NCT01165229 (subjects ≥70 years).
    b mTVC = Modified Total Vaccinated Cohort defined as subjects who received 2 doses (0 and 2 months) of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose.
    c PHN = Postherpetic neuralgia defined as HZ-associated pain rated as 3 or greater (on a 0- to 10-point scale) occurring or persisting at least 90 days following the onset of rash using Zoster Brief Pain Inventory questionnaire.

    Age Group (Years)

    SHINGRIX

    Placebo

    % Efficacy (95% CI)

    N

    n

    Incidence Rate of PHNc per 1,000 Person-Years

    N

    n

    Incidence Rate of PHN per 1,000 Person-Years

    Overall (≥70)

    8,250

    4

    0.1

    8,346

    36

    1.2

    88.8

    (68.7, 97.1)

    70-79

    6,468

    2

    0.1

    6,554

    29

    1.2

    93.0

    (72.5, 99.2)

    ≥80

    1,782

    2

    0.3

    1,792

    7

    1.1

    71.2

    (-51.5, 97.1)

    The benefit of SHINGRIX in the prevention of PHN can be attributed to the effect of the vaccine on the prevention of HZ. The efficacy of SHINGRIX in the prevention of PHN in subjects with confirmed HZ could not be demonstrated.

    14.4 Immunological Evaluation to Support Dosing Schedule

    A measure of the immune response that confers protection against HZ is unknown. Anti-gE antibody levels were measured by anti-gE enzyme-linked immunosorbent assay (gE ELISA) and were used to support the dosing schedule.

    In an open-label clinical study, 238 subjects 50 years and older received SHINGRIX on either a 0- and 2-month or 0- and 6-month schedule. Non-inferiority of the 0- and 6-month schedule compared with the 0- and 2-month schedule based on anti-gE ELISA GMCs 1 month after the second dose was demonstrated.

    14.5 Concomitant Administration with Influenza Vaccine

    In an open-label clinical study, subjects 50 years and older received 1 dose each of SHINGRIX and FLUARIX QUADRIVALENT (QIV) at Month 0 and 1 dose of SHINGRIX at Month 2 (n = 413), or 1 dose of QIV at Month 0 and 1 dose of SHINGRIX at Months 2 and 4 (n = 415). There was no evidence for interference in the immune response to any of the antigens contained in SHINGRIX or the coadministered vaccine.

    14.6 Efficacy in Immunocompromised Adults Aged 18 Years and Older

    The efficacy of SHINGRIX was evaluated in one Phase 3 randomized, placebo-controlled, observer-blind clinical study in immunocompromised adults aged ≥18 years who received an auHSCT 50 to 70 days prior to Dose 1 and who were expected to receive prophylactic antiviral therapy for ≤6 months post-transplant. The efficacy of SHINGRIX was calculated post-hoc in another randomized, placebo-controlled, observer-blind study in subjects with hematologic malignancies who received Dose 1 of SHINGRIX or placebo during or within 6 months of completing immunosuppressive chemotherapy. Each of these studies was conducted in the following regions: North America, Latin America, Europe, Asia, Africa (auHSCT study only), and Australia/New Zealand.

    Efficacy in Subjects Aged 18 Years and Older: auHSCT Recipients

    In the auHSCT study, subjects were followed for the development of HZ and PHN for a median of 21 months (range: 0 to 49.4 months). Suspected HZ cases were followed prospectively for the development of PHN as in Studies 1 and 2.

    The primary efficacy analysis population (mTVC) for the auHSCT study included 1,721 subjects who received 2 doses of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose. Confirmed HZ cases were determined by either PCR (83.7%) or by a Clinical Evaluation Committee (16.3%).

    Efficacy against Herpes Zoster: Compared with placebo, SHINGRIX significantly reduced the risk of developing HZ in auHSCT recipients aged 18 years and older (Table 8).

    Table 8. Efficacy of SHINGRIX on Incidence of Herpes Zoster Compared with Placebo in Immunocompromised Adults Aged ≥18 Years (mTVCa)
    auHSCT = Autologous, hematopoietic, stem cell transplant.
    N = Number of subjects included in each group; n = Number of subjects having at least 1 confirmed HZ episode; HZ = Herpes zoster; CI = Confidence Interval.
    a mTVC = Modified Total Vaccinated Cohort, defined as subjects who received 2 doses (0 and 1 to 2 months) of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose. Follow-up was censored at the time of treatment for relapse.
    b NCT01610414.
    c Primary study endpoint was based on confirmed HZ cases in subjects aged ≥18 years.

    Clinical Studies

    Age Group (Years)

    SHINGRIX

    Placebo

    % Efficacy (95% CI)

    N

    n

    Incidence Rate of HZ per 1,000 Person-Years

    N

    n

    Incidence Rate of HZ per 1,000 Person-Years

    auHSCTb

    Overall (≥18)c

    870

    49

    30.0

    851

    135

    94.3

    68.2

    (55.5, 77.6)

    18-49

    213

    9

    21.5

    212

    29

    76.0

    71.8

    (38.7, 88.3)

    ≥50

    657

    40

    33.0

    639

    106

    100.9

    67.3

    (52.6, 77.9)

    Efficacy in Subjects Aged 18 Years and Older with Hematologic Malignancies

    In the study of hematologic malignancies, the mean age was 57 years. The majority of subjects were White (71%), followed by Asian (25%), Black (0.4%), and other racial groups (4%); 5% were of American Hispanic or Latino ethnicity; and 41% were female. Subjects were followed for the development of HZ for a median of 11.1 months (range: 0 to 15.6 months). PHN was not assessed as a study endpoint.

    In the hematologic malignancy study, the population for the post hoc efficacy analysis included 515 subjects who received 2 doses of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose. Confirmed HZ cases were determined by either PCR (81.3%) or by a Clinical Evaluation Committee (18.7%). The post hoc analysis showed SHINGRIX was 87.2% (95% CI [44.2; 98.6]) effective against development of HZ. The incidence rate of HZ per 1,000 person-years was 8.5 versus 66.2 in the SHINGRIX and placebo groups, respectively.

    Additional Efficacy Endpoints Evaluated in the auHSCT Study

    Efficacy against Postherpetic Neuralgia: In a descriptive analysis, including all subjects aged ≥18 years in the mTVC, 1 case of PHN was reported in the vaccine group compared with 9 cases reported in the placebo group. Vaccine efficacy against PHN was 89.3% (95% CI: [22.5; 99.8]). The benefit of SHINGRIX in the prevention of PHN can be attributed to the effect of the vaccine on the prevention of HZ.

    Herpes Zoster-Associated Pain: Subjects with suspected HZ rated their “worst” HZ-associated pain on a 10-point scale. Among subjects with confirmed HZ, 37 out of 49 subjects (75.5%) receiving SHINGRIX and 120 out of 135 subjects (88.9%) receiving placebo rated their “worst” HZ-associated pain as 3 or greater. In this subset of subjects, the median duration of “worst” HZ associated pain was 14 and 24 days, among SHINGRIX and placebo recipients, respectively.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    SHINGRIX is supplied as 2 components: A single-dose vial of lyophilized gE antigen component (powder) and a single-dose vial of adjuvant suspension component (liquid) (packaged without syringes or needles).

    Table 9. Product Presentations for SHINGRIX

    Presentation

    Carton NDC Number

    Components

    Adjuvant Suspension Component (liquid)

    Lyophilized gE Antigen Component (powder)

    An outer carton of 1 dose

    58160-819-12

    Vial 1 of 2

    NDC 58160-829-01

    Vial 2 of 2

    NDC 58160-828-01

    An outer carton of 10 doses

    58160-823-11

    10 vials

    NDC 58160-829-03

    10 vials

    NDC 58160-828-03

    16.1 Storage before Reconstitution

    Adjuvant suspension component vials: Store refrigerated between 2° and 8°C (36° and 46°F). Protect vials from light. Do not freeze. Discard if the adjuvant suspension has been frozen.

    Lyophilized gE antigen component vials: Store refrigerated between 2° and 8°C (36° and 46°F). Protect vials from light. Do not freeze. Discard if the antigen component has been frozen.

    16.2 Storage after Reconstitution

    Administer immediately or store refrigerated between 2° and 8°C (36° and 46°F) for up to 6 hours prior to use.
    Discard reconstituted vaccine if not used within 6 hours.
    Do not freeze. Discard if the vaccine has been frozen.
  • 17 PATIENT COUNSELING INFORMATION

    Inform patients of the potential benefits and risks of immunization with SHINGRIX and of the importance of completing the 2-dose immunization series according to the schedule.
    Inform patients about the potential for adverse reactions that have been temporally associated with administration of SHINGRIX.
    Provide the Vaccine Information Statements, which are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines).
  • SPL UNCLASSIFIED SECTION

    Trademarks are owned by or licensed to the GSK group of companies.

    Manufactured by GlaxoSmithKline Biologicals

    Rixensart, Belgium, U.S. License 1617, and

    Distributed by GlaxoSmithKline

    Research Triangle Park, NC 27709

    ©2021 GSK group of companies or its licensor.

    SHX:6PI

  • PRINCIPAL DISPLAY PANEL

    PRINCIPAL DISPLAY PANEL

    NDC 58160-819-12

    SHINGRIX

    Zoster Vaccine Recombinant, Adjuvanted

    Rx only

    NOTICE: One vial of lyophilized powder and one vial of liquid suspension MUST BE COMBINED BEFORE USE

    For 50 Years of Age and Older and For 18 Years of Age and Older who are Immunocompromised and at Increased Risk of Herpes Zoster

    Contents (a single dose of SHINGRIX):

    1 Vial containing Lyophilized gE Antigen Component

    1 Vial containing Adjuvant Suspension Component

    After reconstitution, a single dose of SHINGRIX is 0.5 mL

    SHINGRIX

    Antigen and Adjuvant Made in Belgium

    ©2021 GSK group of companies or its licensor.

     
    DFT-02815-5637442 Rev. 7/21
    Shingrix 1 count carton
  • PRINCIPAL DISPLAY PANEL

    One Count Adjuvant Vial Label

    NDC 58160-829-01

     
    496837 Rev. 2/19
    Adjuvant Vial Label
  • PRINCIPAL DISPLAY PANEL

    One Count Antigen Vial Label

    NDC 58160-828-01

     
    496835 Rev. 2/19
    Antigen Vial label
  • PRINCIPAL DISPLAY PANEL

    PRINCIPAL DISPLAY PANEL

    NDC 58160-823-11

    SHINGRIX

    Zoster Vaccine Recombinant, Adjuvanted

    Rx only

    For 50 Years of Age and Older and For 18 Years of Age and Older who are Immunocompromised and at Increased Risk of Herpes Zoster

    Contents (10 doses of SHINGRIX):

    10 Vials containing Lyophilized gE Antigen Component

    10 Vials containing Adjuvant Suspension Component

    After reconstitution, a single dose of SHINGRIX is 0.5 mL

    SHINGRIX

    Antigen and Adjuvant Made in Belgium

    ©2021 GSK group of companies or its licensor.

     
    DFT-02815-5637444 Rev. 7/21
     
    Shingrix 10 count carton
  • PRINCIPAL DISPLAY PANEL

    10 Count Adjuvant Vial Label

    NDC 58160-829-03

     
    490658 Rev. 10/17
    Shingrix 10 count adjuvant vial label
  • PRINCIPAL DISPLAY PANEL

    10 Count Antigen Vial Label

    NDC 58160-828-03

     
    490735 Rev. 10/17
    Shingrix 10 count antigen vial label
  • INGREDIENTS AND APPEARANCE
    SHINGRIX 
    zoster vaccine recombinant, adjuvanted kit
    Product Information
    Product TypeVACCINEItem Code (Source)NDC:58160-819
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:58160-819-121 in 1 CARTON; Type 0: Not a Combination Product
    Quantity of Parts
    Part #Package QuantityTotal Product Quantity
    Part 12 VIAL 1 mL
    Part 22 VIAL 1 mL
    Part 1 of 2
    SHINGRIX 
    ge recombinant varicella zoster virus (vzv) glycoprotein e injection, powder, lyophilized, for suspension
    Product Information
    Item Code (Source)NDC:58160-828
    Route of AdministrationINTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    RECOMBINANT VARICELLA ZOSTER VIRUS GLYCOPROTEIN E ANTIGEN (UNII: COB9FF6I46) (RECOMBINANT VARICELLA ZOSTER VIRUS GLYCOPROTEIN E ANTIGEN - UNII:COB9FF6I46) RECOMBINANT VARICELLA ZOSTER VIRUS GLYCOPROTEIN E ANTIGEN50 ug  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    SUCROSE (UNII: C151H8M554)  
    POLYSORBATE 80 (UNII: 6OZP39ZG8H)  
    SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE (UNII: 5QWK665956)  
    DIBASIC POTASSIUM PHOSPHATE (UNII: CI71S98N1Z)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:58160-828-010.5 mL in 1 VIAL; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    BLABLA12561410/20/2017
    Part 2 of 2
    AS01B 
    as01b suspension
    Product Information
    Item Code (Source)NDC:58160-829
    Route of AdministrationINTRAMUSCULAR
    Inactive Ingredients
    Ingredient NameStrength
    MONOPHOSPHORYL LIPID A (UNII: MWC0ET1L2P)  
    QS-21 (UNII: 61H83WZX3U)  
    DIOLEOYLPHOSPHATIDYLCHOLINE, DL- (UNII: EDS2L3ODLV)  
    CHOLESTEROL (UNII: 97C5T2UQ7J)  
    SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE (UNII: 5QWK665956)  
    POTASSIUM PHOSPHATE, MONOBASIC (UNII: 4J9FJ0HL51)  
    SODIUM CHLORIDE (UNII: 451W47IQ8X)  
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:58160-829-010.5 mL in 1 VIAL; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    BLABLA12561410/20/2017
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    BLABLA12561410/20/2017
    SHINGRIX 
    zoster vaccine recombinant, adjuvanted kit
    Product Information
    Product TypeVACCINEItem Code (Source)NDC:58160-823
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:58160-823-111 in 1 CARTON; Type 0: Not a Combination Product
    Quantity of Parts
    Part #Package QuantityTotal Product Quantity
    Part 120 VIAL 10 mL
    Part 220 VIAL 10 mL
    Part 1 of 2
    SHINGRIX 
    ge recombinant varicella zoster virus (vzv) glycoprotein e injection, powder, lyophilized, for suspension
    Product Information
    Item Code (Source)NDC:58160-828
    Route of AdministrationINTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    RECOMBINANT VARICELLA ZOSTER VIRUS GLYCOPROTEIN E ANTIGEN (UNII: COB9FF6I46) (RECOMBINANT VARICELLA ZOSTER VIRUS GLYCOPROTEIN E ANTIGEN - UNII:COB9FF6I46) RECOMBINANT VARICELLA ZOSTER VIRUS GLYCOPROTEIN E ANTIGEN50 ug  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    SUCROSE (UNII: C151H8M554)  
    POLYSORBATE 80 (UNII: 6OZP39ZG8H)  
    SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE (UNII: 5QWK665956)  
    DIBASIC POTASSIUM PHOSPHATE (UNII: CI71S98N1Z)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:58160-828-030.5 mL in 1 VIAL; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    BLABLA12561410/20/2017
    Part 2 of 2
    AS01B 
    as01b suspension
    Product Information
    Item Code (Source)NDC:58160-829
    Route of AdministrationINTRAMUSCULAR
    Inactive Ingredients
    Ingredient NameStrength
    MONOPHOSPHORYL LIPID A (UNII: MWC0ET1L2P)  
    QS-21 (UNII: 61H83WZX3U)  
    DIOLEOYLPHOSPHATIDYLCHOLINE, DL- (UNII: EDS2L3ODLV)  
    CHOLESTEROL (UNII: 97C5T2UQ7J)  
    SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE (UNII: 5QWK665956)  
    POTASSIUM PHOSPHATE, MONOBASIC (UNII: 4J9FJ0HL51)  
    SODIUM CHLORIDE (UNII: 451W47IQ8X)  
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:58160-829-030.5 mL in 1 VIAL; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    BLABLA12561410/20/2017
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    BLABLA12561410/20/2017
    Labeler - GlaxoSmithKline Biologicals SA (372748392)