What are the side effects of the shingles (herpes zoster) vaccine?

Side Effects of the Shingles (Herpes Zoster) Vaccine

The recombinant zoster vaccine (Shingrix/RZV) is associated with significantly higher rates of injection-site reactions (up to 9.5% grade 3) and systemic symptoms (up to 11.4% grade 3) compared to placebo, though these side effects are generally mild to moderate and temporary. 1

Types of Shingles Vaccines and Their Side Effect Profiles

There are two types of herpes zoster vaccines available:

Recombinant Zoster Vaccine (RZV, Shingrix)

• Currently the preferred vaccine due to higher efficacy (91.3% against HZ in adults ≥70 years) and longer protection (>83.3% for up to 8 years) 1
• Common side effects include:
  • Injection site reactions: pain, redness, and swelling (significantly higher than placebo, with grade 3 reactions in 9.5% vs 0.4% for placebo) 1
  • Systemic symptoms: fatigue, myalgia, headache, fever, and gastrointestinal symptoms (grade 3 symptoms in 11.4% vs 2.4% for placebo) 1
• Despite higher reactogenicity, no significant difference in serious adverse events (SAEs) or deaths compared to placebo 1
• Concerns about tolerability are a significant barrier to both initiation and completion of the two-dose series 2

Zoster Vaccine Live (ZVL, Zostavax)

• Live attenuated virus vaccine with lower efficacy compared to RZV (70% vs 96%) 1
• Less reactogenic than RZV but still associated with more frequent systemic and injection-site adverse events than placebo 1
• Contraindicated in immunocompromised patients due to risk of vaccine-strain VZV infection 1
• No longer recommended in the US and some Western European countries 1

Frequency and Severity of Side Effects

• Local reactions:

  • RZV: Up to 6.89 times higher risk compared to placebo (risk difference 67%) 3
  • Most common is pain at the injection site 1

• Systemic reactions:

  • RZV: 2.23 times higher risk compared to placebo (risk difference 33%) 3
  • Most commonly include fatigue, myalgia, headache, shivering, fever, and gastrointestinal symptoms 1

• Duration:

  • Most side effects resolve within 2-3 days 1, 3
  • Tolerability concerns lead to approximately 1% higher dropout rate for second dose compared to placebo 3

Special Considerations

Age-Related Considerations

• Side effect profiles are similar across all age groups for RZV, unlike ZVL which had varying efficacy by age 1
• Despite higher reactogenicity, RZV is still recommended for adults ≥50 years due to superior efficacy 1

Immunocompromised Patients

• Live zoster vaccine (ZVL) is contraindicated in immunocompromised patients 1
• RZV (non-live vaccine) is suggested as the preferred vaccine for immunocompromised adults, including those with solid cancers 1
• Patients taking JAK inhibitors have increased risk of herpes zoster and should ideally be vaccinated before starting therapy 1

Practical Management of Side Effects

• Patients should be informed about potential side effects before vaccination to improve adherence to the two-dose schedule 2
• Over-the-counter analgesics may be used to manage post-vaccination symptoms 3
• Despite reactogenicity, the benefits of vaccination in preventing herpes zoster and its complications (particularly postherpetic neuralgia) outweigh the temporary side effects 1, 4

CDC Recommendations

• The CDC Advisory Committee on Immunization Practices recommends:
  • RZV for prevention of herpes zoster in immunocompetent adults aged ≥50 years 1
  • RZV for adults who previously received ZVL 1
  • RZV is preferred over ZVL for prevention of herpes zoster and related complications 1