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 The leading web portal for pharmacy resources, news, education and careers February 22, 2018
Pharmacy Choice - Herpes Zoster Disease State Management - February 22, 2018

Herpes Zoster Disease State Management

Herpes Zoster (Shingles) Prevention

Darrell Hulisz, RPh, PhamD
and Jenna Mills, Pharmacy Intern, ONU College of Pharmacy

Herpes zoster (HZ), or shingles, is a reactivation of the varicella zoster virus (VZV or varicella). Shingles is characterized by a painful cutaneous rash of small blisters and can occur anywhere on the body. Occasionally, the pain may persist for a prolonged period well after the rash is gone causing a condition known as post herpetic neuralgia (PHN). The varicella virus causes chickenpox, usually in children who have not been vaccinated. VZV is an enveloped, double-stranded DNA virus, and it is the reactivation of VZV later in life produces shingles. In the US, 95-99.5% of adults have antibodies to VZV; thus many individuals are vulnerable to reactivation of infection, especially the elderly and immunocompromised patients. The annual number of herpes zoster cases in the US is approximately 1 million.

Reactivated VSV may involve sensory ganglia along with cutaneous nerves. The thoracic portions of the spine are most often affected, as well as the lumbar and cervical portions. Viral replication of HZ spreads both centrally and peripherally along the cutaneous neuron and dorsal root ganglia. When the virus reaches the skin, HZ replicates in the lower layers of the epidermis where it disrupts normal cellular processes.

The clinical features of HZ often progress through three stages: prodromal, active, and chronic. However, patients may not experience all three stages. The prodromal phase is common. During this phase, constant or intermittent burning, tingling, itching, or pain often precede rash by a few hours to several days. The acute phase follows the prodromal phase, which involves the development of characteristic skin lesions. Skin rash appears and is accompanied by mild fever, malaise, headache, and nausea. The active phase is initially characterized by erythematous papules and edema. Papules progress to vesicles in 12 to 24 hours and to pustules within one to seven days. The pustules eventually heal and disappear within 14 to 21 days, leaving behind erythematous lesions. The chronic phase is also known as post herpetic neuralgia (PHN), which mostly occurs in the elderly. Patients with PHN often have chronic burning or throbbing pain, or intermittent stabbing or shooting pain, or even allodynia.

A combination of nonpharmacologic therapy and medication is the most effective approach for managing shingles and PHN. Pharmacologic approaches include the use of antiviral therapy (e.g. acyclovir, valacyclovir, famciclovir), antidepressants (e.g. duloxetine, tricyclics), simple analgesics (e.g. acetaminophen, NSAIDs), anticonvulsants (pregabalin, gabapentin), and topical agents (capsaicin, transdermal lidocaine) individualized to each patient's needs.

The live, attenuated VZV vaccine (Varivax) has been available in the United States since 1995, and has been up to 99% effective in protecting against primary varicella infection (chickenpox). The higher-potency live, attenuated VZV vaccine (Zostavax), introduced in 2005, reduces the incidence rate of HZ substantially, but loses its effectiveness in more elderly patients. Shingrix (HZ/su) vaccine is a new herpes zoster vaccine recently approved by the FDA for the prevention of shingles in adults 50 years of age and older. Shingrix joins Zostavax as the second vaccine available in the United States for shingles prevention. The efficacy of Shingrix was established following two concurrent, multicenter, randomized, placebo-controlled, phase III trials: ZOE-50 and ZOE-70. The objective of ZOE-50 was to evaluate the efficacy of the HZ/su vaccine in reducing the risk of shingles in those 50 years of age, and ZOE-70 was similar, but was conducted in adults 70 years of age and older. In the ZOE-50 study, the vaccine's overall efficacy in reducing risk of HZ was 97.2% (p<0.001). In ZOE-70 study, the vaccine's overall efficacy was 89.8% (p<0.001).

Shingrix is a non-live vaccine for intramuscular administration only, and is administered in two 0.5ml doses at 0 and 2 to 6 months approved for shingles prevention in those 50 years and older. The current average wholesale cost of one dose of Shingrix is $168, where the estimated total cost of the vaccine series is $336. This compares to Zostavax, a live vaccine administered subcutaneously in one dose, which is priced at $267.74. The most common adverse effects of both Shingrix and Zostavax include pain, redness, and swelling at the injection site. Fatigue, headache, fever, gastrointestinal adverse effects, and myalgia have also been reported with Shingrix.

The CDC reports the Advisory Committee on Immunization Practices (ACIP) voted for Shingrix as the preferred vaccine for preventing shingles and its complications, and recommends Shingrix for adults previously vaccinated with Zostavax to prevent shingles and its complications. ACIP recommendations will be published in the Morbidity and Mortality Weekly Report and serve as official guidance once approved by the CDC director.
References
  • Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002 Aug 1. 347(5):340-6
  • Blein C, Gavazzi G, Paccalin M, Baptiste C, Berrut G, Vainchtock A. Burden of herpes zoster: the direct and comorbidity costs of herpes zoster events in hospitalized patients over 50 years in France. BMC Infect Dis. 2015 Aug 19;15:350.
  • Dworkin RH, Johnson RW, Breuer J, Gnann JW, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007 Jan 1. 44 Suppl 1:S1-26.
  • Lal H, Cunningham A, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28; 372(22): 2087-2096.
  • Cunningham A, Lal H, Kovac M, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016 Sept 15; 375(11): 1019-1032.
  • Oxman M, Levin M, Johnson G, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2; 352(22): 2271-2284.
  • Centers for Disease Control and Prevention [Internet]. Atlanta (GA). 2017 [cited 2018 Jan 29]. Available from: https://www.cdc.gov/vaccines/vpd/shingles/public/index.html
  • Shingrix (Zoster Vaccine Recombinant, Adjuvanted) [package insert on the Internet]. Research Triangle Park (NC): GlaxoSmithKline. 2017. Available from: https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM581605.pdf
  • Shingrix approved in the US for prevention of shingles in adults aged 50 and over [Internet]. GlaxoSmithKline; 2001-2017. Available from: https://www.gsk.com/en-gb/media/press-releases/shingrix-approved-in-the-us-for-prevention-of-shingles-in-adults-aged-50-and-over/
  • Bharucha T, Ming D, Breuer J. A critical appraisal of 'Shingrix', a novel herpes zoster subunit vaccine (HZ/Su or GSK1437173A) for varicella zoster virus. Hum Vaccin Immunother. 2017 Aug 3;13(8):1789-1797.


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