Shingrix's First Eight Months: What U.S. Safety Monitoring Found, 2017–2018

Recombinant zoster vaccine (RZV), sold as Shingrix, is a highly effective shingles vaccine. The Food and Drug Administration licensed it, and the Advisory Committee on Immunization Practices recommended it for adults 50 and older, in October 2017. It is given as two intramuscular doses, 2–6 months apart. (The older live vaccine, Zostavax, is recommended from age 60 and given under the skin.)

In clinical trials, reactions were common: 85% of 6,773 vaccinated participants had a local or whole-body reaction, and about 17% had a grade 3 reaction — redness or swelling over 3.5 inches, or symptoms bad enough to interfere with normal activity. But serious adverse events were no more common than with placebo. Once it was licensed, CDC and the FDA began watching its safety in the Vaccine Adverse Event Reporting System (VAERS).

The first eight months

From October 20, 2017, to June 30, 2018, about 3.2 million doses were distributed.

Most reported: fever (1,034; 23.6%), injection-site pain (985; 22.5%) and injection-site redness (880; 20.1%), along with chills, headache, fatigue and muscle aches. Symptoms were similar whether Shingrix was given alone or with other vaccines.

Serious events and deaths

Seven deaths after vaccination were confirmed. The median age was 65 (range 61–86), and deaths came between 6 hours and 6 weeks after vaccination:

• 4 from cardiovascular disease — 3 of them in people with several cardiac risk factors;
• 2 from septic shock, both in people who were immunosuppressed;
• 1, a woman aged 86, after a fall.

Physicians reviewed reports for 22 outcomes chosen in advance — conditions of general vaccine-safety interest and possible concerns raised in the trials. The commonest were shingles itself (196 reports; 6.1 per 100,000 doses; 14 mentioned earlier shingles) and postherpetic neuralgia (49; 1.5 per 100,000 doses; 6 mentioned earlier neuralgia). Every other outcome was under 0.5% of reports. A statistical search for vaccine–event pairs reported at least twice as often as with other vaccines found no safety signal.

Mistakes in giving it

230 reports described vaccination errors (some more than one):

• Administration errors — 143 (62.2%), most often the wrong route: 108 people were injected under the skin instead of into the muscle — which could reflect confusion with Zostavax, which is given that way.
• Preparation errors — 19. Shingrix comes as two vials that must be mixed: a freeze-dried antigen and a liquid adjuvant (AS01B). 8 reports described giving only the adjuvant; 11 described mixing the antigen with the wrong liquid — sterile water (6), Zostavax diluent (4) or something unspecified (1).
• Under-age recipients — 26 reports of people under 50; 15 were not coded as errors and may have been deliberate off-label use.
• "Incomplete course" — 12 of 24 "incorrect dose" reports, including 6 where a provider told a patient to skip the second dose after common, expected reactions to the first — injection-site reactions, arm swelling, fever, fatigue — though there was no clear reason not to give it.

What it means

• The early findings match the clinical trials. No reported adverse event was out of proportion to reports for other vaccines, and the pre-chosen outcomes looked like events that happen anyway in the general population around the time of vaccination.
• Compared with Zostavax in VAERS, Shingrix reports featured fever and chills more, Zostavax shingles and rash; both had many injection-site reactions. Reporting rates were 136 and 4.0 per 100,000 (all and serious) for Shingrix, against 106 and 4.4 for Zostavax — though passive reports don't allow direct comparisons.
• Warn patients to expect short-lived reactions — pain, swelling and redness at the injection site, fever, chills, body aches. In trials, grade 3 reactions cleared within a few days. Counselling may ease concerns and help people finish both doses; how well a single dose works has not been studied.
• CDC and the FDA will keep monitoring, including through near-real-time checks in CDC's Vaccine Safety Datalink.

Limits. VAERS is passive: anyone can report, reports are not necessarily medically confirmed, and it often lacks which dose in the series someone received, so first and second doses couldn't be told apart.

Sources

Based on Hesse EM, Shimabukuro TT, Su JR, et al., "Postlicensure Safety Surveillance of Recombinant Zoster Vaccine (Shingrix) — United States, October 2017–June 2018," MMWR volume 68, number 4, Centers for Disease Control and Prevention, with authors from CDC and the Food and Drug Administration; a work of the United States government in the public domain.