Kenneth McCall, PharmD, BCGP, RPh, FAPhAAssociate Professor

Getting to the Point: Strategies to Prevent Zoster

Zoster Prevention - Objectives

• Discuss the presentation and complications of herpes zoster• Recognize the ACIP recommendations for zoster vaccines• Describe the differences between the GSK zoster vaccine and

the Merck zoster vaccine in terms of FDA indication, storage, preparation, administration, dosing, and contraindications

Clinical Presentation of Herpes Zoster1–3

Abnormal Skin Sensations

Headache

Photophobia

Malaise

Unilateral Dermatomal Rash

Maculopapules/Vesicles

Altered Sensitivity to Touch

Unbearable Itching

Cessation of New Vesicles

Pustulation

Scabbing

Cutaneous Healing

Neurologic

Cutaneous

Ophthalmic

Visceral (rare)

Prodrome Acute HZ Rash Evolution of Rash Complications?

Pain (varying severity)

“Aching”, “burning”, “stabbing”, “shock-like”

1. Oxman MN. In: Arvin AM et al, eds. Varicella-Zoster Virus: Virology and Clinical Management. Cambridge, UK: Cambridge University Press; 2000:246–275.

2. Weaver BA. J Am Osteopath Assoc. 2007;107(suppl 1):S2–S7. 3. Harpaz R et al. MMWR Morb Mortal Wkly Rep. 2008;57(RR-5):1–30.

© Phototake. © Dr. P. Marazzi / Photo Researchers, Inc.

Herpes Zoster Rash Follows a Dermatomal Distribution

© Phototake.

551. Insinga RP et al. J Gen Intern Med. 2005;20:748–753.

Zoster Incidence by Age Group1

0

200

400

600

800

1,000

1,200

1,400

1,600

1,800

2,000

0-14 15-29 30-39 40-49 50-59 60-69 70-79 80+

0

2

4

6

8

10

12Number of Cases

Rate per person-years

Age

Rat

e p

er 1

,000

Per

son

-Yea

rs

Nu

mb

er o

f C

ases

of

Zo

ster

(n

= 9

,152

)

Herpes Zoster is the reactivation of which virus?

25%

25%

25%

25% 1. Measles

2. Mumps

3. Rubella

4. Varicella

What is the most common long-term complication of herpes zoster?

25%

25%

25%

25% 1. Bell’s palsy

2. Postherpetic neuralgia

3. Vision loss

4. Myocarditis

ZOSTAVAX® (Zoster Vaccine Live)

7

ZEST & Shingles Prevention Study (SPS) Results

0 10 20 30 40 50 60 70 80

50-59 yrs (n=11,211)

60-69 yrs (n=10,370)

70-79 yrs (n=7,621)

>80 yrs (n=1,263)

Vaccine Efficacy (%)95% CI

1

2

1. Oxman et al. New England Journal of Medicine. 2005. 352 (22): 2271

2. Zostavax® [package insert]. Whitehouse Station, NJ: Merck; April 2011.

(54 to 81)

(56 to 71)

(28 to 52)

(-29 to 48)

70%

64%

41%

18%1

1

ZOSTAVAX® Indication

ACIP recommends routine vaccination of all persons aged >60 years with 1 dose of zoster vaccine.

NEW FDA LABELING: “ZOSTAVAX is a live attenuated virus vaccine indicated for prevention of herpes zoster (shingles) in individuals 50 years of age and older.”

Persons who report a previous episode of zoster and persons with chronic medical conditions can be vaccinated unless those conditions are contraindications or precautions.

Zoster vaccination is not indicated to treat acute zoster.

9

Recommendations of the Advisory Committee on Immunization Practices (ACIP)

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5705a1.htm?s_cid=rr5705a1_e

Zostavax® [package insert]. Whitehouse Station, NJ: Merck; April 2011.

ZOSTAVAX® Contraindications

Allergy to neomycin or any vaccine component

Pregnancy

Immunocompromised status

AIDS or other clinical manifestations of HIV, including persons with CD4+ T-lymphocyte values <200 per mm3

malignant neoplasms affecting the bone marrow

chemotherapy or radiation within the last 3 months

Persons on immunosuppressive therapy, including high-dose corticosteroids (>20 mg/day of prednisone or equivalent) lasting two or more weeks

10

ZOSTAVAX® Storage and Handling

Zoster vaccine must be stored frozen

The vaccine must be discarded if not used within 30 minutes after reconstitution.

New labeling: Zostavax may be stored and/or transported at fridge temp for up to 72 hours prior to reconstitution. Any unused vaccine at fridge temp should be discarded.

11

Zostavax® [package insert]. Whitehouse Station, NJ: Merck; April 2011.

ZOSTAVAX® Administration Zostavax: SINGLE 0.65-mL dose (reconstituted)

SQ – upper, outer tricep

5/8 inch, 25 gauge needle

12

What is the maximum length of time between reconstitution and administration of Zostavax?

25%

25%

25%

25% 1. 10 minutes

2. 30 minutes

3. 1 hour

4. 1 day

Shingrix®(Herpes Zoster Adjuvanted Subunit Vaccine)

14

Now Approved: Shingrix® Inactivated, recombinant zoster subunit vaccine

Manufactured by GlaxoSmithKline

Shingrix® Storage and Preparation Stored in the refrigerator at 4o C

Suspension that must be reconstituted (o.5 ml)*

*For use within 6 hours

Shingrix®(Herpes Zoster Adjuvanted Subunit Vaccine)

Shingrix® Trials Trials:

ZOE-50: Shingrix reduced risk of herpes zoster by 97.2% in patients 50-59 year olds

(Zostavax had only 70% efficacy for the same population group)

ZOE-70: Shingrix reduced risk of herpes zoster by 90% in patients ≥70 years old

(Zostavax had only 38% efficacy for the same population group)

Zoster-048: Shingrix demonstrates appropriate immunogeneicity and safety data in all approved populations regardless of if the patient has received a previous Zostavaxvaccine greater than 5 years earlier

Efficacy of Shingrix on incidence of zoster compared to placebo: ZOE-50

Efficacy of Shingrix on incidence of zoster compared to placebo: ZOE-70

Recommendations of the ACIP for Use of Herpes Zoster Vaccines

Recombinant zoster vaccine (RZV) is recommended for the prevention of herpes zoster and related complications for immunocompetent adults aged ≥50 years.

Whereas RZV is licensed for all persons aged ≥50 years, immunocompromised persons and those on moderate to high doses of immunosuppressive therapy were excluded from the efficacy studies (ZOE-50 and ZOE-70), and thus, ACIP has not made recommendations regarding the use of RZV in these patients.

https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a5.htm?s_cid=mm6703a5_w

Recommendations of the ACIP for Use of Herpes Zoster Vaccines

RZV is recommended for the prevention of herpes zoster and related complications for immunocompetent adults who previously received zoster vaccine live (ZVL).

Based on expert opinion, RZV should not be given <2 months after receipt of ZVL.

MMWR / January 26, 2018 / 67(3);103–108

https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a5.htm?s_cid=mm6703a5_w

Recommendations of the ACIP for Use of Herpes Zoster Vaccines

RZV may be used in adults aged ≥50 years, irrespective of prior receipt of varicella vaccine or ZVL.

RZV is preferred over ZVL for the prevention of herpes zoster and related complications.

MMWR / January 26, 2018 / 67(3);103–108

https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a5.htm?s_cid=mm6703a5_w

Summary

Zostavax® Shingrix®

Formulation Powder for reconstitution

Suspension for reconstitution

Storage Freezer Refrigerator

Administration SQSingle Dose

IM2 doses

Efficacy 38-70% 90-97%

Type LIVE INACTIVATED

What is the maximum length of time between reconstitution and administration of Shingrix?

25%

25%

25%

25% 1. 10 minutes

2. 30 minutes

3. 1 hour

4. 6 hours

A 55 yo woman requests a zoster vaccine. Select the best option to prevent shingles as recommended by ACIP.

A. Shingrix SQ x 1 dose

B. Shingrix IM x 2 doses

C. Zostavax SQ x 1 dose

D. Zostavax IM x 2 doses

A 72 yo man previously received Zostavax 7 years ago. Despite being vaccinated, he experienced a shingles attack in January 2018. Select the best option to prevent shingles.

A. Shingrix SQ x 1 dose

B. Shingrix IM x 2 doses

C. Zostavax booster SQ x 1 dose

D. Both Shingrix and Zostavax are contraindicated

kmccall@une.edu