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 October 4, 2019

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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

    INDICATIONS AND USAGE

    SHINGRIX is a vaccine indicated for prevention of herpes zoster (shingles) in adults aged 50 years and older.

    Limitations of Use (1):

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

    DOSAGE AND ADMINISTRATION

    For intramuscular administration only.

    Administer 2 doses (0.5 mL each) at 0 and 2 to 6 months. (2.2, 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)

    ADVERSE REACTIONS

    Solicited local adverse reactions in subjects aged 50 years and older were pain (78.0%), redness (38.1%), and swelling (25.9%). (6.1)
    Solicited general adverse reactions in subjects aged 50 years and older were myalgia (44.7%), fatigue (44.5%), headache (37.7%), shivering (26.8%), fever (20.5%), and gastrointestinal symptoms (17.3%). (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: 10/2019

  • Table of Contents
  • 1 INDICATIONS AND USAGE

    SHINGRIX is a vaccine indicated for prevention of herpes zoster (shingles) in adults aged 50 years and older.

    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 shake the vial to thoroughly mix contents until powder is completely dissolved.

    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 schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 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.

  • 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.

    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 (24.9%) subjects were aged 50 to 59 years, 4,488 (15.3%) subjects were aged 60 to 69 years, and 17,531 (59.8%) 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 (74.3%), followed by Asian (18.3%), black (1.4%), and other racial/ethnic groups (6.0%); 58% were female.

    Solicited Adverse Events

    In Studies 1 and 2, data on solicited local and general adverse events 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 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.

    Table 1. Percentage of Subjects with Solicited Local Adverse Reactions and General Adverse Events 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)

    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

    88.4

    14.4

    82.8

    11.1

    69.2

    8.8

    Pain, Grade 3d

    10.3

    0.5

    6.9

    0.5

    4.0

    0.2

    Redness

    38.7

    1.2

    38.4

    1.6

    37.7

    1.2

    Redness, >100 mm

    2.8

    0.0

    2.6

    0.0

    3.1

    0.0

    Swelling

    30.5

    0.8

    26.5

    1.0

    23.0

    1.1

    Swelling, >100 mm

    1.1

    0.0

    0.5

    0.0

    1.3

    0.0

    General Adverse Events

    n = 1,315

    n = 1,312

    n = 1,309

    n = 1,305

    n =2,252

    n = 2,264

    Myalgia

    56.9

    15.2

    49.0

    11.2

    35.1

    9.9

    Myalgia, Grade 3e

    8.9

    0.9

    5.3

    0.8

    2.8

    0.4

    Fatigue

    57.0

    19.8

    45.7

    16.8

    36.6

    14.4

    Fatigue, Grade 3e

    8.5

    1.8

    5.0

    0.8

    3.5

    0.8

    Headache

    50.6

    21.6

    39.6

    15.6

    29.0

    11.8

    Headache, Grade 3e

    6.0

    1.7

    3.7

    0.2

    1.5

    0.4

    Shivering

    35.8

    7.4

    30.3

    5.7

    19.5

    4.9

    Shivering, Grade 3e

    6.8

    0.2

    4.5

    0.3

    2.2

    0.3

    Fever

    27.8

    3.0

    23.9

    3.4

    14.3

    2.7

    Fever, Grade 3f

    0.4

    0.2

    0.5

    0.2

    0.1

    0.1

    GIg

    24.3

    10.7

    16.7

    8.7

    13.5

    7.6

    GI, Grade 3e

    2.1

    0.7

    0.9

    0.6

    1.2

    0.4

    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, 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.

    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

    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 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%), 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.

    Serious Adverse Events (SAEs)

    In the 2 studies, SAEs were reported at similar rates in subjects who received SHINGRIX (2.3%) and 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.

    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.

  • 7 DRUG INTERACTIONS

    7.1 Concomitant Vaccine Administration

    For concomitant administration of SHINGRIX with inactivated influenza vaccine [see Clinical Studies (14.5)].

    7.2 Immunosuppressive Therapies

    Immunosuppressive therapies may reduce the effectiveness of SHINGRIX.

  • 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. There are no available human data to establish whether there is vaccine-associated risk with SHINGRIX in pregnant women.

    A reproductive and 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 reproductive and 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

    Of the total number of subjects who received at least 1 dose of SHINGRIX in the 2 efficacy trials (n = 14,645), 2,243 (15.3%) were aged 60 to 69 years, 6,837 (46.7%) were aged 70 to 79 years, and 1,921 (13.1%) were 80 years and older. There were no clinically meaningful differences in efficacy across the age groups or between these subjects and younger subjects. [See Clinical Studies (14.1, 14.2, 14.3).]

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

  • 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 herpes zoster (HZ) increases with age and appears to be related to a decline in 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 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, 61.2% were female; 72.3% were white, 18.9% were Asian, 1.7% were black, and 7.0% 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 50 years and older (Table 2).

    Table 2. Efficacy of SHINGRIX on Incidence of Herpes Zoster Compared with Placebo in Study 1a (mTVCb)

    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)

    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.

    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 PHN

    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 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, 54.7% were female; 77.6% were white, 17.1% were Asian, 1.0% were black, and 4.2% 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 70 years and older are shown in Table 3.

    Table 3. Efficacy of SHINGRIX on Incidence of Herpes Zoster Compared with Placebo in Study 2a (mTVCb)

    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)

    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.

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

    Efficacy against PHN

    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 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 4).

    Table 4. Efficacy of SHINGRIX on Incidence of Herpes Zoster Compared with Placebo in Studies 1 and 2 (Pooled Dataa) (mTVCb)

    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)

    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.

    Efficacy against PHN

    Table 5 compares the overall rates of PHN in the vaccine and placebo groups across both studies.

    Table 5. Efficacy of SHINGRIX on Overall Incidence of Postherpetic Neuralgia Compared with Placebo in Studies 1 and 2 (Pooled Dataa) (mTVCb)

    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)

    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.

    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.

  • 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 6: 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

    ©2019 GSK group of companies or its licensor.

    SHX:4PI

  • 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

    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

    Antigen and Adjuvant Made in Belgium

    ©2019 GSK group of companies or its licensor.

     
    498197 Rev. 6/19
    Shingrix 1 count carton
  • PRINCIPAL DISPLAY PANEL

    One Count Adjuvant Vial Label

    NDC 58160-829-01

     
    490627 Rev. 10/17
    Shingrix 1 count Adjuvant vial label
  • PRINCIPAL DISPLAY PANEL

    One Count Antigen Vial Label

    NDC 58160-828-01

     
    490628 Rev. 10/17
    Shingirx 1 count 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

    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

    Antigen and Adjuvant Made in Belgium

    ©2018 GSK group of companies or its licensor.

     
    495520 Rev. 11/18
    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)