Ask the Experts: Concurrent administration of zoster and pneumococcal vaccines

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Learn about the concurrent administration of the zoster and pneumococcal vaccines.

Question: I am getting mixed messages about the concurrent administration of zoster vaccine (Zostavax—Merck) and pneumococcal vaccine (Pneumovax—Merck). The Zostavax package insert says to not give them concurrently but instead to separate the injections by 4 weeks. The CDC Advisory Committee on Immunization Practices (ACIP) has not changed its general statement on giving a live vaccine and inactivated vaccine at the same time. What should we recommend?

Answer: Two messages are definitely being delivered. This was based on a nonpublished, Merck-sponsored, randomized clinical study to determine whether Pneumovax and Zostavax are safe and immunogenic when given together versus given alone in adults 60 years or older. A total of 470 patients (442 of whom completed the study) were either given the two vaccines together at separate injection sites (concomitant group) or the pneumococcal vaccine on day 1 followed by zoster vaccine on week 4 (nonconcomitant group). Geometric mean titer (GMT) was measured at 4 weeks postvaccination (gpELISA units/mL). In the nonconcomitant group, the GMT of varicella–zoster response was 448.5 (95% CI 400.3–502.4), while in the concomitant group, the GMT was 371.6 (328.7–420.0). This resulted in a geometric mean fold rise (GMFR) of 1.9 (1.7–2.1) in zoster antibody response from day 1 to 4 weeks postvaccination in the concomitant group compared with a GMFR of 3.1 in the nonconcomitant group. The study demonstrated no differences in the two groups in the GMT of pneumococcal polysaccharide serotypes 3, 14, 19A, and 22F. The safety and tolerability of both regimens were the same.1

The package insert described this study as follows: “In a double-blind, controlled clinical trial, 473 adults, 60 years of age or older, were randomized to receive ZOSTAVAX and PNEUMOVAX 23 concomitantly (N=237), or PNEUMOVAX 23 alone followed 4 weeks later by ZOSTAVAX alone (N=236). At four weeks postvaccination, the VZV antibody levels following concomitant use were significantly lower than the VZV antibody levels following nonconcomitant administration (GMTs of 338 vs. 484 gpELISA units/mL, respectively; GMT ratio = 0.70 (95% CI: [0.61, 0.80]).”2

These data were evaluated by an FDA review committee. The committee stated that the gpELIZA assay was considered acceptable and validated by FDA. They concluded: “Based on an immunogenicity endpoint using GMT, the results of this concomitant administration study of Zostavax and Pneumovax23 demonstrate that Pneumovax23 interferes with the immune response to Zostavax.”3 FDA ruled that the package insert must be changed to state: “ZOSTAVAX and PNEUMOVAX 23 should not be given concurrently because concomitant use resulted in reduced immunogenicity of ZOSTAVAX.”

This has been discussed by CDC and the ACIP zoster working group, and CDC does not agree with the conclusion made above. Several problems have been noted with this study (Rafael Harpaz, MD, chairman of ACIP zoster working group, oral communications, October 2010). First, no evidence exists that immunoglobulin G (IgG) titers have any role in zoster prevention or any role in protection. The experts on zoster dismiss this as an indicator of protection. Second, the baseline IgG titers were significantly different between the two groups, which could demonstrate fault with the study.4 CDC continues to stand by the ACIP general statement that inactivated vaccine can be administered simultaneously or at any time before or after a different inactivated vaccine or live vaccine.5 The following statement was provided by Dr. Bill Atkinson at CDC:

“In December 2009 Merck revised the package insert for herpes zoster vaccine (HZV) to advise that HZV and 23-valent pneumococcal polysaccharide vaccine (PPSV) should not be administered concurrently. This recommendation was based on a Merck study that showed the average titer against varicella zoster virus (VZV) was lower in persons who received zoster and PPSV at the same visit compared to persons who received these vaccines 4 weeks apart. However, the clinical relevance of this observation is unknown because there is no evidence to indicate that antibody titers against VZV are a measure of protection against HZ (results were additionally confounded by unexplained differences across comparison group in the baseline VZV antibody titers). Antibody levels to PPSV serotypes 3, 14, 19A, and 22F were assessed during this study and were unaffected by simultaneous administration, though significance of this observation is also unknown. Finally, the safety profile of HZV is unaffected by simultaneous administration of PPSV. Consequently, to avoid introducing barriers to patients and providers who are interested in these two important vaccines, CDC has not changed its recommendation for either vaccine, and continues to recommend that HZV and PPSV be administered at the same visit if the person is eligible for both vaccines.”

The zoster working group of the ACIP has been recently reinstated, and whether further discussion and/or recommendations are forthcoming is unknown. It would be awkward for CDC to come out with a statement that went against FDA. Pharmacists and other health professionals will need to decide whether Zostavax and Pneumovax can be given together. If the vaccines were given together in the past, repeating either vaccination is not necessary.

Stephan L. Foster, PharmD, FAPhA
Professor and Vice Chair
University of Tennessee College of Pharmacy
Memphis
APhA Liaison Representative to the Advisory Committee on Immunization Practices (ACIP)

References

  1. ClinTrials.gov. Zostavax administered concomitantly with Pneumovax 23. Accessed at http://clinicaltrials.gov/ct2/show/study/NCT00535730, October 20, 2010.
  2. Merck. Zostavax full prescribing information. Accessed at www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf, October 20, 2010.
  3. FDA. Summary basis for regulatory action. Accessed at www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM196007.pdf, October 20, 2010.
  4. MacIntyre CR, Egerton T, McCaughey, et al. Concomitant administration of zoster and pneumococcal vaccines in adults ≥60 years old. Poster presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy/Infectious Disease Society Annual Meeting. Washington, DC, October 25–28, 2008.
  5. Advisory Committee on Immunization Practices. General recommendations on immunization. MMWR Recomm Rep. 2006;55(RR-15):1–48.
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