March 24, 2021
Audience: Consumer, Patient, Health Professional, Pharmacy
March 24, 2021 — FDA Safety Communication
Purpose: To inform the public and healthcare providers that FDA has required and approved safety labeling changes to the Prescribing Information for Shingrix (Zoster Vaccine Recombinant, Adjuvanted) to include a new warning about the risk for Guillain-Barré Syndrome (GBS) following administration of Shingrix. FDA required GlaxoSmithKline (GSK), the manufacturer of Shingrix, to revise the Prescribing Information to include the following language in the Warnings and Precautions section:
In a postmarketing observational study, an increased risk of GBS was observed during the 42 days following vaccination with Shingrix.
FDA evaluated data from a postmarketing observational study that assessed the risk of GBS following vaccination with Shingrix. Based on this evaluation, FDA has determined that the results of this observational study show an association of GBS with Shingrix, but that available evidence is insufficient to establish a causal relationship.
New Warning about Risk for GBS following Shingrix
FDA has required a new warning about GBS in the Prescribing Information for Shingrix as a result of new safety data from a postmarketing observational study. In the study, an increased risk of GBS was observed during the 42 days following vaccination with Shingrix.
Shingrix received FDA approval on October 20, 2017, for prevention of herpes zoster (shingles) in adults aged 50 years and older. Shingrix is administered as a two-dose series, with the second dose given anytime between 2 and 6 months after the first dose. In one clinical trial, compared to placebo, Shingrix reduced the incidence of shingles by 97% in individuals 50 years and older. In another clinical trial, compared to placebo, Shingrix reduced the incidence of shingles by 90% in individuals 70 years of age and older. Prior to approval of Shingrix, FDA evaluated safety data from 17 clinical studies. Approximately 17,000 adults aged 50 years and older enrolled in these studies received at least one dose of Shingrix. Across the two largest studies, the safety of Shingrix was evaluated by comparing approximately 14,600 individuals who received at least one dose of Shingrix to approximately 14,600 individuals who received saline placebo.
Summary of Safety Issue
The Centers for Disease Control and Prevention (CDC) conducted postmarketing safety surveillance of Shingrix in the Vaccine Safety Datalink (VSD) by monitoring prespecified adverse events, including GBS, among individuals 50 years of age and older who received Shingrix. The VSD analyses identified a preliminary statistical signal suggesting an increased risk of GBS among individuals who received Shingrix compared to a historical control group of individuals who had received Zostavax (Zoster Vaccine Live), another FDA-approved vaccine for the prevention of shingles. To evaluate this statistical signal, FDA, the Centers for Medicare & Medicaid Services (CMS), and CDC investigated GBS risk following administration of Shingrix in the Medicare claims database. This is the largest postmarket study evaluating GBS risk following vaccination with Shingrix.
The association between vaccination with Shingrix and GBS was evaluated among Medicare beneficiaries aged 65 years or older. Using Medicare claims data, from October 2017 through February 2020, 3,729,863 vaccinations with Shingrix (administered to 2,113,758 Medicare beneficiaries) were identified through National Drug Codes, and potential cases of hospitalized GBS among recipients of Shingrix were identified through International Classification of Diseases codes.
The risk of GBS following vaccination with Shingrix was assessed in self-controlled case series analyses using a risk window of 1 to 42 days post-vaccination and a control window of 43 to 183 days post-vaccination. The primary analysis (claims-based, all doses) found an increased risk of GBS during the 42 days following vaccination with Shingrix, with an estimated 3 excess cases of GBS per million doses administered to adults aged 65 years or older. In secondary analyses, an increased risk of GBS was observed during the 42 days following the first dose of Shingrix, with an estimated 6 excess cases of GBS per million doses administered to adults aged 65 years or older, and no increased risk of GBS was observed following the second dose of Shingrix. These analyses of GBS diagnoses in claims data were supported by analyses of GBS cases confirmed by medical record review.
FDA evaluated data from the above study, and based on this evaluation, FDA has determined that the results of this observational study show an association of GBS with Shingrix, but that available evidence is insufficient to establish a causal relationship. FDA has concluded that revision to the Warnings and Precautions section of the Prescribing Information for Shingrix to include a warning about GBS is warranted.
FDA has determined that the benefits of vaccination with Shingrix continue to outweigh its risks.
Shingles presents as a painful rash consisting of blisters that typically develop on one side of the body. The blisters typically scab over in 7 to 10 days and fully clear up within 2 to 4 weeks. An estimated 1 million people get shingles each year in the U.S. Anyone who has had chickenpox is at risk for developing shingles. Your risk of getting shingles and having serious complications increases as you get older. The most common complication of shingles is long-term nerve pain called postherpetic neuralgia or PHN. PHN occurs in the areas where the shingles rash was, even after the rash clears up. It can last for months or years after the rash goes away. For some people, this pain can be so severe and debilitating that it interferes with daily life.
Questions and Answers
What is Guillain-Barré Syndrome (GBS)?
Guillain-Barré syndrome (GBS) is a rare disorder in which the body’s immune system damages nerve cells, causing muscle weakness and sometimes paralysis. While its cause is not fully understood, the syndrome often follows infection with a virus or bacteria. Each year in the United States, an estimated 3,000 to 6,000 people develop GBS. This is about 10 to 20 cases of GBS per million people each year. Anyone can develop GBS, but it is more common among adults than children. The incidence of GBS increases with age, and people over age 50 are at greatest risk for developing GBS. Most people fully recover from GBS, but some have permanent nerve damage.
Was an increased risk for GBS observed in the Shingrix clinical trials?
FDA did not identify an increased risk for GBS in its evaluation of the clinical trials data regarding Shingrix, which FDA evaluated prior to the vaccine’s approval in 2017. Rare adverse events, some of which may be serious, may become apparent with more widespread use of the vaccine.
Is Shingrix a safe vaccine?
Yes. Although no medical product, such as vaccines or drugs, is 100 percent safe or effective, Shingrix has a strong safety record. Clinical trials conducted to support approval of Shingrix included approximately 17,000 adults ages 50 years and older who received at least one dose of Shingrix. There is also postmarketing experience with millions of Shingrix recipients. As it does for all vaccines it has approved for use in the United States, FDA will continue to monitor the safety of Shingrix.
How can I report a suspected adverse event after vaccination?
Suspected adverse events may be reported to the Vaccine Adverse Event Reporting System (VAERS) (https://vaers.hhs.gov/reportevent.html), which is co-managed by the FDA and the CDC.