Vaccine Information: Shingrix

SHINGRIX- zoster vaccine recombinant, adjuvanted
GlaxoSmithKline Biologicals SA

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 1
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Figure 2bFigure 3
Figure 4
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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.

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