NDC 58160-823 Shingrix

Zoster Vaccine Recombinant, Adjuvanted

NDC Product Code 58160-823

NDC CODE: 58160-823

Proprietary Name: Shingrix What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Zoster Vaccine Recombinant, Adjuvanted What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This vaccine is used by adults 50 years and older to prevent zoster (shingles). Zoster is caused by the same virus that causes chickenpox. After you have been infected with chickenpox (usually in childhood), the virus can live in your body's nerve roots in an inactive form. For reasons that are not fully understood, the virus may become active again. This causes shingles with symptoms of rash, blisters, and pain. This vaccine works by boosting the body's natural defense (immunity) against the zoster virus so that symptoms of shingles do not develop. It should not be used for treating active shingles, nerve pain caused by shingles, or for the prevention of chickenpox. Vaccines may not fully protect everyone who receives them. This vaccine should not be used by children.

NDC Code Structure

  • 58160 - Glaxosmithkline Biologicals Sa

NDC 58160-823-11

Package Description: 1 KIT in 1 CARTON * .5 mL in 1 VIAL (58160-828-03) * .5 mL in 1 VIAL (58160-829-03)

NDC Product Information

Shingrix with NDC 58160-823 is a a vaccine lable product labeled by Glaxosmithkline Biologicals Sa. The generic name of Shingrix is zoster vaccine recombinant, adjuvanted. The product's dosage form is kit and is administered via form.

Labeler Name: Glaxosmithkline Biologicals Sa

Dosage Form: Kit - A packaged collection of related material.

Product Type: Vaccine What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SUCROSE (UNII: C151H8M554)
  • POLYSORBATE 80 (UNII: 6OZP39ZG8H)
  • SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE (UNII: 5QWK665956)
  • DIBASIC POTASSIUM PHOSPHATE (UNII: CI71S98N1Z)
  • 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)
  • SUCROSE (UNII: C151H8M554)
  • POLYSORBATE 80 (UNII: 6OZP39ZG8H)
  • SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE (UNII: 5QWK665956)
  • DIBASIC POTASSIUM PHOSPHATE (UNII: CI71S98N1Z)
  • 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)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Glaxosmithkline Biologicals Sa
Labeler Code: 58160
FDA Application Number: BLA125614 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 10-20-2017 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Shingrix Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

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

Prepare SHINGRIX by reconstituting the lyophilized varicella zoster virus glycoprotein E (gE) antigen component with the accompanying AS01B adjuvant suspension component. 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 1. Cleanse both vial stoppers. Using a sterile needle and sterile syringe, withdraw the entire contents of the vial containing the adjuvant suspension component by slightly tilting the vial (blue-green cap). Vial 1 of 2.Figure 2. Slowly transfer entire contents of syringe into the lyophilized gE antigen component vial (brown cap). 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)].

5.1 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.

6.1 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 one 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 EventsIn 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 YearsAged 60 - 69 YearsAged ≥70 Years SHINGRIX %Placeboc% SHINGRIX%Placeboc% SHINGRIX %Placeboc%Local Adverse Reactionsn = 1,315n = 1,312n = 1,311n = 1,305n = 2,258n = 2,263Pain88.414.482.811.169.28.8Pain, Grade 3d10.30.56.90.54.00.2Redness38.71.238.41.637.71.2Redness, >100 mm2.80.02.60.03.10.0Swelling30.50.826.51.023.01.1Swelling, >100 mm1.10.00.50.01.30.0General Adverse Eventsn = 1,315n = 1,312n = 1,309n = 1,305n =2,252n = 2,264Myalgia56.915.249.011.235.19.9Myalgia, Grade 3e8.90.95.30.82.80.4Fatigue57.019.845.716.836.614.4Fatigue, Grade 3e8.51.85.00.83.50.8Headache50.621.639.615.629.011.8Headache, Grade 3e6.01.73.70.21.50.4Shivering35.87.430.35.719.54.9Shivering, Grade 3e6.80.24.50.32.20.3Fever 27.83.023.93.414.32.7Fever, Grade 3f0.40.20.50.20.10.1GIg24.310.716.78.713.57.6GI, Grade 3e2.10.70.90.61.20.4Total 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 EventsUnsolicited 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.DeathsFrom 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 DiseasesIn 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 ScheduleIn 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.

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.

8.1 Pregnancy

Risk SummaryAll 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).DataAnimal 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 SummaryIt 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.

12.1 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)].

13.1 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.

14.1 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 ZosterCompared 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)SHINGRIXPlacebo% Efficacy (95% CI)NnIncidence Rate of HZ per 1,000 Person-YearsNnIncidence Rate of HZ per 1,000 Person-YearsOverall (≥50)c7,34460.37,4152109.197.2(93.7, 99.0)50 - 59 3,49230.33,525877.896.6(89.6, 99.3)60 - 69 2,14120.32,1667510.897.4(90.1, 99.7)≥70 1,71110.21,724489.497.9(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 PHNAmong 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 ZosterVaccine 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)SHINGRIXPlacebo% Efficacy (95% CI)NnIncidence Rate of HZ per 1,000 Person-YearsNnIncidence Rate of HZ per 1,000 Person-YearsOverall (≥70)c6,541230.96,6222239.289.8(84.3, 93.7)70 - 795,114170.95,1891698.890.0(83.5, 94.3)≥801,42761.21,4335411.089.1(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 PHNAmong 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 MedicationAmong 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 ZosterCompared 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)SHINGRIXPlacebo% Efficacy (95% CI)NnIncidence Rate of HZ per 1,000 Person-YearsNnIncidence Rate of HZ per 1,000 Person-YearsOverall (≥70)c8,250250.88,3462849.391.3(86.9, 94.5)70 - 79 6,468190.86,5542168.991.3(86.0, 94.9)≥80 1,78261.01,7926811.191.4(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 PHNTable 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)SHINGRIXPlacebo% Efficacy (95% CI)NnIncidence Rate of PHNc per 1,000 Person-YearsNnIncidence Rate of PHN per 1,000 Person-YearsOverall (≥70) 8,25040.18,346361.288.8(68.7, 97.1)70 - 79 6,46820.16,554291.293.0(72.5, 99.2)≥80 1,78220.31,79271.171.2(-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 (brown cap) and a single-dose vial of adjuvant suspension component (blue-green cap) (packaged without syringes or needles).An outer package of 1 dose (NDC 58160-819-12) contains: •Adjuvant Suspension Component (Vial 1 of 2) NDC 58160-829-01 •Lyophilized gE Antigen Component (Vial 2 of 2) NDC 58160-828-01An outer package of 10 doses (NDC 58160-823-11) contains: •Adjuvant Suspension Component (10 vials) NDC 58160-829-03 •Lyophilized gE Antigen Component (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

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. 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.

Other

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