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
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
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® 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
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