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Clinical Policy Bulletin:
Varicella and Herpes Zoster Vaccines
Number: 0115


Policy

  1. Aetna considers varicella (chicken pox) vaccine a medically necessary preventive service according to the recommendations of the Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP).

  2. Aetna considers combination measles, mumps, rubella, and varicella vaccine (MMRV) (ProQuad) a medically necessary preventive service alternative to individual measles, mumps and rubella (MMR) and varicella vaccines for children 12 months to 12 years of age where simultaneous administration of MMR and varicella vaccines is indicated. 

  3. Aetna considers zoster vaccine (Zostavax) a medically necessary preventive service to reduce the risk of herpes zoster (shingles) in members 60 years of age and older.  Aetna considers repeat (booster) zoster vaccination as experimental and investigational.

    Aetna considers Zostavax experimental and investigational for all other indications (e.g., autologous and allogeneic hematopoietic transplant recipients, individuals with chronic lymphocytic leukemia) because its effectiveness for these indications has not been established.



Background

Varicella vaccine (Varivax, Merck & Co., Whitehouse Station, NJ) immunization is recommended for children over 12 months of age who do not have a history of having had varicella (chicken pox).  The Advisory Committee on Immunization Practices (ACIP) recommends that children be immunized with 2 doses of varicella vaccine, with the 1st dose administered between 12 and 15 months of age, and a 2nd dose administered between 4 and 6 years of age.  In addition, the ACIP recommends that other persons who have not been immunized and have no history of varicella receive 2 doses of vaccine.  Children, adolescents and adults who previously received 1 dose of varicella vaccine should receive a 2nd one.

Healthy adolescents past their 13th birthday and adults who have not been immunized and have no history of varicella may also be immunized and require 2 doses of vaccine.  The Centers for Disease Control's (CDC) recommends vaccination of adolescents greater than or equal to 13 years of age and adults at high risk for exposure or transmission.  Groups at high risk include:

  • Adolescents and adults living in households with children; and
  • International travelers*; and
  • Non-pregnant women of childbearing age; and
  • Persons who live or work* in environments where transmission of chicken pox can occur (e.g., college students, inmates and staff members of correctional institutions, and military personnel); and
  • Persons who live or work* in environments where transmission of chicken pox is likely (e.g., teachers of young children, day care employees, and residents and staff members in institutional settings).

*Note: Some Aetna plans exclude coverage of vaccinations for work or for travel.  Please check benefit plan descriptions for details.

Very few people escape childhood without contracting chicken pox.  The recommendation is that all individuals under 21 years of age who do not have a clear history of chicken pox should be assumed to be susceptible and can be immunized.  Adults over 21 who have no history of chicken pox should be tested for immunity and, if they are susceptible, should be immunized.  Five to 10 % of the adult population is probably susceptible; 70 % of 18 year olds have been found to be immune, even if they have no clear history of having had chicken pox.

Children 12 months to 12 years of age should receive a 0.5-ml dose of varicella vaccine administered subcutaneously.  A 2nd dose of varicella vaccine should be given a minimum of 3 months later.  Adolescents and adults 13 years of age and older should receive a 0.5-ml dose administered subcutaneously at an elected date and a 2nd 0.5-ml dose 4 to 8 weeks later.

Varicella vaccine is contraindicated in certain individuals, including persons with an immunodeficient condition or receiving immunosuppressive therapy, persons with active untreated tuberculosis, and women who are pregnant.

The Food and Drug Administration (FDA) has approved a combined attenuated live virus vaccine containing measles, mumps, rubella, and varicella viruses (MMRV) (ProQuad injection, Merck & Co., Whitehouse Station, NJ) for use in children aged 12 months to 12 years.  It is also approved for use in this population if a 2nd dose of measles, mumps, and rubella vaccine is to be administered.

The approval was based on study data showing the immunogenicity, antibody persistence, and safety of the combination vaccine to be similar with that of its previously approved components (measles, mumps, and rubella (MMR) and varicella).  The incidence of adverse events including those most commonly reported (injection site reactions, nasopharyngitis, cough) was similar between the treatment groups.

Herpes zoster (HZ) is the consequence of re-activation of the varicella zoster virus (VZV) that remains latent since primary infection (varicella).  The overall incidence of HZ is about 3 per 1,000 of the population per year increasing to 10 per 1,000 per year by age 80.  Approximately 50 % of persons reaching age 90 years will have had HZ.  In approximately 6 %, a second episode of HZ may occur; usually several decades after the first attack.  The most common complication of HZ is post-herpetic neuralgia (PHN), defined as significant pain or dysaesthesia present 3 months or more following HZ.  More than 5 % of the elderly have PHN at 1 year after acute HZ.  Reduced cell-mediated immunity to HZ occurs with aging, which may be responsible for the increased incidence in the elderly and from other causes such as tumors, human immunodeficiency virus infection as well as immunosuppressant drugs.  Diagnosis of PHN is usually clinical from typical unilateral dermatomal pain and rash.  Prodromal symptoms, pain, itching and malaise, are common (Johnson and Whitton, 2004).

There is reliable evidence that zoster vaccine significantly reduces morbidity from HZ and PHN among older adults.  In a randomized, controlled, multi-center study, Oxman and colleagues (2005) examined if vaccination against VZV would decrease the incidence, severity, or both of HZ and PHN among older adults.  A total of 38,546 adults aged 60 years or older were enrolled in this study.  The vaccine used was a live attenuated Oka/Merck VZV vaccine.  Herpes zoster (shingles) was diagnosed according to clinical and laboratory criteria.  The pain and discomfort associated with HZ were measured repeatedly for 6 months.  The primary end point was the burden of illness due to HZ, a measure affected by the incidence, severity, and duration of the associated pain and discomfort.  The secondary end point was the incidence of PHN.  More than 95 % of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for HZ.  A total of 957 confirmed cases of HZ (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of PHN (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis.  The use of the zoster vaccine reduced the burden of illness due to HZ by 61.1 % (p < 0.001), reduced the incidence of PHN by 66.5 % (p < 0.001), and reduced the incidence of HZ by 51.3 % (p < 0.001).  Reactions at the injection site were more frequent among vaccine recipients but were generally mild.  These researchers concluded that the zoster vaccine significantly reduced morbidity from HZ and PHN among older adults.

In May 2006, the FDA approved Zostavax (Merck & Co., Inc., Whitehouse Station, NJ), a vaccine for use to reduce the risk of HZ in people aged 60 years and older.  Zostavax is administered subcutaneously in one single injection, preferably in the upper arm.  The most common adverse effects in individuals who received Zostavax were redness, pain and tenderness, swelling at the site of injection, itching, as well as headache.

The FDA approved prescribing information indicates that zoster vaccine is not indicated for the treatment of herpes zoster or PHN.  Zoster vaccine is a live attenuated virus vaccine, and the labeling states that zoster vaccine is contraindicated in the following persons:

  • Persons with active untreated tuberculosis;
  • Persons on immunosuppressive therapy, including high-dose corticosteroids;
  • Those with a history of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine;
  • Those with a history of primary or acquired immunodeficiency states including leukemia; lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system; or AIDS or other clinical manifestations of infection with human immunodeficiency viruses;
  • Women who are or may be pregnant.

Zostavax is a live attenuated virus vaccine and is contraindicated in immunosuppressed persons, including persons with a history of primary or acquired immunodeficiency states including leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system; with AIDS or other clinical manifestations of infection with human immunodeficiency viruses; and with active untreated tuberculosis.  Zostavax is also contraindicated in persons on immunosuppressive therapy, including high-dose corticosteroids, and in women who are or may be pregnant.

Wutzler (2010) stated that although the efficacy of zoster vaccine against HZ declined with advancing age of the vaccinees, subjects older than 70 years also benefited from vaccination because the burden of illness was considerably reduced.  The protective effect of zoster vaccine persists for at least 7 years post-vaccination.  The author stated that the need for, or timing of, re-vaccination has not yet been determined.  Zostavax has been well-tolerated.  It can be concomitantly administered with inactivated influenza vaccine at separate sites.  The author stated that zoster and pneumococcal vaccines should not be given concomitantly.

According to the CDC (2011), zoster vaccine is administered subcutaneously as a single dose.  The vaccine should not be injected intra-muscularly.  However, it is not necessary to repeat vaccination if the shingles vaccine is administered intra-muscularly.  Studies are ongoing to assess the duration of protection from 1 dose of zoster vaccine and the need, if any, for booster doses.

No changes were made to the current recommendation of herpes zoster vaccination for adults aged 60 years and older, the CDC's ACIP reported at its latest meeting.  The FDA licensed Zostavax for use in adults aged 50 to 59 years in March 2011, said Dr. Paul Cieslak, chair of the zoster working group.  However, the working group does not currently propose changes to the current recommendations.  Data from studies conducted by Merck have shown vaccine efficacy in the 50 to 59 age group, but there is insufficient evidence regarding the duration of vaccine protection when it is given well before the peak age for zoster incidence.  Also, "it might be inappropriate to expand recommendations while the vaccine remains in short supply," he said, adding that the incidence could increase "if limited supply is used at time of low incidence".  He also pointed out, however, that "the decision of the working group at this time is not intended to prejudice future deliberations".  The ACIP currently recommends Zostavax for all adults aged 60 years and older with no contraindications and for adults older than 80 years with chronic illnesses (Splete, 2011).

Guidelines for preventing infections in hematopoietic cell transplant (HCT) recipients by the Center for International Blood & Marrow Transplant Research, National Marrow Donor Program, European Group for Blood and Marrow Transplantation, American Society for Blood and Marrow Transplantation, Canadian Blood and Marrow Transplant Group, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, Association of Medical Microbiology and Infectious Disease, and the CDC (Ljungman et al, 2009) indicated that zoster vaccine (Zostavax, live) should not be given to HCT recipients.

The British Society for Haematology’s guidelines on “The diagnosis, investigation and management of chronic lymphocytic leukaemia” (Oscier et al, 2012) states that “live vaccines such as polio, herpes zoster, and yellow fever should be avoided”.

Zhang et al (2012) stated that methotrexate (MTX) has become the foundation disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA).  However, concern exists regarding its possible association with infectious complications including VZV and HZ.  Furthermore, no consensus exists regarding pre-MTX VZV screening or the use of VZV vaccine.  These researchers undertook systematic literature review (SLR) investigating the relationship between the use of MTX in patients with RA and VZV and HZ infection.  Additionally, the European Centre for Disease Prevention and Control, HPA, the CDC, Rheumatology societies and WHO web sites and publications were consulted.  A total of 35 studies fulfilled the inclusion criteria comprising 29 observational studies and 6 case reports.  The case reports and 13 observation studies considered the association between MTX and HZ.  Three of the observational studies reported a positive association although in 5 cases, patients were concurrently treated with prednisolone.  Five studies concluded that there was no association between HZ and MTX.  Three studies comparing the infection rates of MTX with other RA therapies found that MTX did not result in higher HZ infection rates.  Three studies examining the association between HZ and MTX treatment duration failed to show a link.  The authors concluded that no evidence exists to support an association between MTX and VZV infection in RA patients and the data regarding the role of MTX in HZ development is conflicting.  The role of pre-MTX VZV screening is controversial and, as it may delay initiation of RA treatment, these investigators suggested against VZV screening in this context.

Guthridge et al (2013) noted that patients with systemic lupus erythematosus (SLE) are at increased risk of HZ.  Although Zostavax has been approved by the FDA, its use in immunocompromised individuals remains controversial because it is a live-attenuated virus vaccine.  In a pilot study, these researchers examined the immunogenicity of Zostavax in patients with SLE.  A total of 10 patients with SLE and 10 control subjects aged 50 years or older participated in this open-label vaccination study.  All were sero-positive for VZV.  Patients with SLE were excluded for SLE Disease Activity Index (SLEDAI) greater than 4, or use of mycophenolate mofetil, cyclophosphamide, biologics, or greater than 10 mg prednisone daily.  Follow-up visits occurred at 2, 6, and 12 weeks.  Clinical outcomes included the development of adverse events, particularly HZ or vesicular lesions, and SLE flare.  Immunogenicity was assessed with VZV-specific interferon-gamma-producing enzyme-linked immunospot (ELISPOT) assays and with antibody concentrations.  All subjects were women.  Patients with SLE were slightly older than controls (60.5 versus 55.3 years, p < 0.05).  Median baseline SLEDAI was 0 (range of 0 to 2) for patients with SLE.  No episodes of HZ, vesicular rash, serious adverse events, or SLE flares occurred.  Three injection site reactions occurred in each group: mild erythema or tenderness.  The proportion of subjects with a greater than 50 % increase in ELISPOT results following vaccination was comparable between both groups, although absolute SLE responses were lower than controls.  Antibody titers increased only among controls following vaccination (p < 0.05).  The authors concluded that HZ vaccination yielded a measurable immune response in this cohort of patients with mild SLE taking mild-moderate immunosuppressive medications; no herpetiform lesions or SLE flares were seen in this small cohort of patients.  This was a pilot study testing the immunogenicity of Zostavax in SLE patients; the clinical value of Zostavax in these patients needs to be further-evaluated in well-designed studies.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
Varicella (chicken pox) and combination varicella and measles, mumps and rubella vaccine (MMRV):
CPT codes covered if selection criteria are met:
90710
90716
Other CPT codes related to the CPB:
90707
ICD-9 codes covered if selection criteria are met:
V05.4 Need for other prophylactic vaccination and inoculation against varicella
V06.8 Need for other prophylactic vaccination and inoculation against other combinations of diseases
Other ICD-9 codes related to the CPB:
052.0 - 052.9 Chickenpox
V06.4 Need for other prophylactic vaccination and inoculation against measles-mumps-rubella [MMR]
Zoster vaccine:
CPT codes covered if selection criteria are met:
90736
ICD-9 codes covered if selection criteria are met:
V05.8 Need for other prophylactic vaccination and inoculation against other specified disease
ICD-9 codes not covered for indications listed in the cPB:
204.10 - 204.12 Chronic lymphoid leukemia
Other ICD-9 codes related to the CPB:
053.0 - 053.9 Herpes zoster
ICD-9 codes contraindicated for this CPB:
011.0 - 011.9 Pulmonary tuberculosis
042 Human immunodeficiency Virus [HIV] disease
200.00 - 204.02, 204.20 - 208.91 Malignant neoplasm of lymphatic and hematopoietic tissue
630 - 669.94 Complications of pregnancy and childbirth
V08 Asymptomatic human immunodeficiency virus [HIV] infection status
V10.79 Personal history of other lymphatic and hematopoietic neoplasms
V14.7 Personal history of allergy to serum or vaccine
V22.0 - V23.9 Supervision of normal or high-risk pregnancy
V42.81 - V 42.82 Organ or tissue replaced by transplant, bone marrow or peripheral stem cells
V58.65 Long-term (current) use of steroids


The above policy is based on the following references:
  1. American Academy of Pediatrics (AAP). 2003 Red Book. Report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: AAP; 2003.
  2. Centers for Disease Control and Prevention. Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 1996;45(RR-11):1-36.
  3. Centers for Disease Control and Prevention. Prevention of varicella. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 1999;48(RR6):1-5.
  4. American Academy of Pediatrics. Committee on Infectious Diseases. Varicella vaccine update. Pediatrics. 2000;105(1 Pt 1):136-141.
  5. National Advisory Committee on Immunization (NACI). NACI update to statement on varicella vaccine. An advisory committee statement (ACS). Can Commun Dis Rep. 2002;28:1-7.
  6. Canadian Task Force on Preventive Health Care. Varicella vaccination. Recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ. 2001;164(13):1888-1889.
  7. Skull SA, Wang EEL; Canadian Task Force on Preventive Health Care (CTFPHC). Use of varicella vaccine in healthy populations: Systematic review and recommendations. CTFPHC Technical Report #01-1. London, ON: CTFPHC; 2000:1-26.
  8. Skull SA, Wang EE. Varicella vaccination: A critical review of the evidence. Arch Dis Childhood. 2001;85(2):83-90.
  9. Kilgore PE, Kruszon-Moran D, Seward JF, et al. Varicella in Americans from NHANES III: Implications for control through routine immunization. J Med Virol. 2003;70 Suppl 1:S111-S118.
  10. Kuter B, Matthews H, Shinefield H, et al. Ten year follow-up of healthy children who received one or two injections of varicella vaccine. Pediatr Infect Dis J. 2004;23(2):132-137.
  11. Merck & Co., Inc. ProQuad [measles, mumps, rubella and varicella (Oka/Merck) virus vaccine live. Prescribing Information. 9633800. Whitehouse Station, NJ: Merck; August 2005. Available at: http://www.fda.gov/cber/label/mmrvmer090605LB.pdf. Accessed September 16, 2005.
  12. Shinefield H, Black S, Williams WR, Dose-response study of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children. Pediatr Infect Dis J. 2005;24(8):670-675.
  13. Canadian Coordinating Office for Health Technology Assessment (CCOHTA). Vaccine for herpes zoster. Emerging Drug List No. 67. Ottawa, ON: CCOHTA; January 2006:1-3.
  14. Johnson RW, Whitton TL. Management of herpes zoster (shingles) and postherpetic neuralgia. Expert Opin Pharmacother. 2004;5(3):551-559.
  15. Oxman MN, Levin MJ, Johnson GR, A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271-2284.
  16. U.S. Food and Drug Administration (FDA). FDA licenses new vaccine to reduce older Americans' risk of shingles. FDA News. P06-73. Rockville, MD: FDA; May 26, 2006. Available at: http://www.fda.gov/bbs/topics/NEWS/2006/NEW01378.html. Accessed May 26, 2006.
  17. Merck & Co., Inc. Zostavax (zoster vaccine live (Oka/Merck)). Prescribing Information. 9703300. Whitehouse Station, NJ: Merck; May 2006. Available at: http://www.zostavax.com/. Accessed June 6, 2006.
  18. Centers for Disease Control and Prevention (CDC). CDC's Advisory Committee recommends changes in varicella vaccinations. Second dose of varicella vaccine to offer more protection for children, adolescents, and adults. CDC Press Release. Atlanta, GA: CDC; June 29, 2006.
  19. Merck Vaccine Division. CDC Advisory Committee on Immunization Practices unanimously recommends addition of a second dose of chickenpox-containing vaccine to childhood immunization schedule. Press Release. West Point, PA: Merck & Co., Inc.; June 2006.
  20. Holcomb K, Weinberg JM. A novel vaccine (Zostavax) to prevent herpes zoster and postherpetic neuralgia. J Drugs Dermatol. 2006;5(9):863-866.
  21. Heininger U, Seward JF. Varicella. Lancet. 2006;368(9544):1365-1376.
  22. American Academy of Pediatrics Committee on Infectious Diseases. Prevention of varicella: Recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule. Pediatrics. 2007;120(1):221-231.
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  24. Harpaz R, Ortega-Sanchez IR, Seward JF; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(RR-5):1-30.
  25. Levin MJ, Oxman MN, Zhang JH, et al; Veterans Affairs Cooperative Studies Program Shingles Prevention Study Investigators. Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine. J Infect Dis. 2008;197(6):825-835.
  26. Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices (ACIP). Update: Recommendations from the Advisory Committee on Immunization Practices (ACIP) regarding administration of combination MMRV vaccine. MMWR Morb Mortal Wkly Rep. 2008;57(10):258-260.
  27. Macartney K, McIntyre P. Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children and adults. Cochrane Database Syst Rev. 2008;(3):CD001833.
  28. Ljungman P, Cordonnier C, Einsele H, et al. Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2009;44(8):521-526.
  29. Prelog M, Zimmerhackl LB. Varicella vaccination in pediatric kidney and liver transplantation. Pediatr Transplant. 2010;14(1):41-47.
  30. Sanford M, Keating GM. Zoster vaccine (Zostavax): A review of its use in preventing herpes zoster and postherpetic neuralgia in older adults. Drugs Aging. 2010;27(2):159-176.
  31. Marin M, Broder KR, Temte JL, et al; Centers for Disease Control and Prevention (CDC). Use of combination measles, mumps, rubella, and varicella vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010;59(RR-3):1-12.
  32. Wutzler P. Zoster vaccine. Klin Monbl Augenheilkd. 2010;227(5):384-387.
  33. Centers for Disease Control and Prevention. Vaccines and preventable diseases: Herpes zoster vaccination for health care professionals. CDC: Atlanta, GA. Last reviewed January 10, 2011. Available at: http://www.cdc.gov/vaccines/vpd-vac/shingles/hcp-vaccination.htm. Accessed January 13, 2012.
  34. Splete H. ACIP keeps current recommendations for zoster vaccine. Family Practice News: Rockville, MD. July 5, 2011. Available at: http://www.familypracticenews.com/newsletter/family-practice-news-e-newsletter/singleview40731/acip-keeps-current-recommendations-for-zoster-vaccine/1a63f143f1.html. Accessed January 13, 2012.
  35. Gagliardi AM, Gomes Silva BN, Torloni MR, Soares BG. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev. 2012;10:CD008858.
  36. Oscier D, Dearden C, Erem E, et al. Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia. London (England): British Society for Haematology; 2012. Available at: http://www.guideline.gov/content.aspx?id=38251&search=zoster+vaccine+. Accessed January 7, 2013.
  37. Zhang N, Wilkinson S, Riaz M, et al. Does methotrexate increase the risk of varicella or herpes zoster infection in patients with rheumatoid arthritis? A systematic literature review. Clin Exp Rheumatol. 2012;30(6):962-971.
  38. Levin MJ, Schmader KE, Gnann JW, et al. Varicella-zoster virus-specific antibody responses in 50-59-year-old recipients of zoster vaccine. J Infect Dis. 2013;208(9):1386-1390.
  39. Guthridge JM, Cogman A, Merrill JT, et al. Herpes zoster vaccination in SLE: A pilot study of immunogenicity. J Rheumatol. 2013;40(11):1875-1880.


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