Attenuated varicella-zoster virus

Attenuated varicella-zoster vaccine is a live vaccine and administration to individuals who are immunosuppressed or immunodeficient may result in disseminated varicella-zoster virus disease, including fatal outcomes. Patients who previously received immune suppressive therapy should be carefully evaluated for the reconstitution of the immune system prior to receiving the varicella-zoster vaccine.

Immunisation should be postponed in individuals suffering from moderate to severe acute febrile illness or infection.

There are no data on the use of varicella-zoster virus vaccine in pregnant women. Traditional non-clinical studies are insufficient with respect to reproductive toxicity. However naturally-occurring varicella-zoster virus infection is known to sometimes cause foetal harm. Varicella-zoster virus vaccine is not recommended to be administered to pregnant women. In any case, pregnancy should be avoided for one month following vaccination.

It is unknown whether VZV is secreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to not administer varicella-zoster virus vaccine taking into account the benefit of breast-feeding for the child and the benefit of vaccination for the woman.

Fertility

Varicella-zoster virus vaccine has not been evaluated in fertility studies.

No studies on the effects on the ability to drive or use machines have been performed. However, varicella-zoster virus vaccine is expected to have no or negligible influence on ability to drive and use machines.

a. Summary of the safety profile

The most common adverse reactions reported in pivotal clinical trials were injection-site reactions. Headache and pain in the extremity were the most common systemic adverse reactions. Most of these local and systemic adverse reactions were reported as mild in intensity. Vaccine-related serious adverse reactions were reported for 0.01% subjects vaccinated with varicella-zoster virus vaccine and subjects who received placebo.

Data from a clinical trial (n=368) demonstrated that the current refrigerated formulation has a safety profile comparable to that of the frozen formulation.

b. Summary of adverse events

In clinical trials, general safety has been evaluated in more than 57,000 adults vaccinated.

The list below presents vaccine-related injection-site and systemic adverse reactions reported at a significantly greater incidence in the vaccine group versus the placebo group within 42 days postvaccination in the varicella-zoster virus vaccine Efficacy and Safety trial study and in the Adverse Event Monitoring Substudy of Shingles Prevention Study (SPS).

Additional adverse reactions, spontaneously reported through post-marketing surveillance, are also included in the list below. As these events are reported voluntarily from a population of uncertain size, it is not possible to reliably calculate their frequency or establish a causal relationship to vaccine exposure. Consequently, the frequencies of these adverse reactions have been estimated based on the adverse events reported in SPS and ZEST (regardless of vaccine relationship assigned by the investigator).

The adverse reactions are assigned frequency categories using the following convention: Very Common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000).

Adverse Reactions from Clinical Trial Experience and Post-Marketing Surveillance:

¹ Clinical trials experience.
² Solicited adverse reaction within 5 days post-vaccination.

c. Description of selected adverse reactions

Injection site reactions

Vaccine-related injection-site adverse reactions were significantly greater for subjects vaccinated with varicella-zoster virus vaccine versus subjects who received placebo. In SPS, the overall incidence of vaccine-related injection-site adverse reactions were 48% for varicella-zoster virus vaccine and 17% for placebo in subjects 60 years of age and older.

In the varicella-zoster virus vaccine trial study, the overall incidence of vaccine-related injection site adverse reactions were 63.9% for varicella-zoster virus vaccine and 14.4% for placebo in subjects 50 to 59 years of age. Most of these adverse reactions were reported as mild in intensity.

In other clinical trials evaluating varicella-zoster virus vaccine in subjects 50 years of age or older, including a study of concomitantly administered inactivated influenza vaccine, a higher rate of injection-site adverse experiences of mild-to-moderate intensity was reported among subjects 50-59 years of age compared with subjects ≥60 years of age.

Varicella-zoster virus vaccine was administered either subcutaneously (SC) or intramuscularly (IM) in subjects 50 years of age or older. The general safety profiles of the SC and IM routes were otherwise comparable, but injection-site adverse reactions were significantly less frequent in the IM group (34%) compared with the SC group (64%).

Herpes zoster/herpes zoster-like rashes and Varicella/varicella-like rashes in clinical trials

In clinical trials the number of herpes zoster/herpes zoster-like rashes within the 42-day postvaccination was low in both varicella-zoster virus vaccine and placebo groups. The majority of rashes have been rated as mild to moderate; no complications from rash have been observed in the clinical setting. Most of the reporting rashes that were VZV positive by PCR analysis were associated with wild-type VZV.

In both trial studies, the number of subjects who reported herpes zoster/herpes zoster-like rashes was less than 0.2% for varicella-zoster virus vaccine and placebo groups, with no significant difference observed between the two groups. The number of subjects who reported varicella/varicella-like rashes was less than 0.7% for varicella-zoster virus vaccine and placebo.

The Oka/Merck strain of VZV was not detected from any specimens in SPS or ZEST. VZV was detected in one (0.01%) specimen from a varicella-zoster virus vaccine recipient reporting a varicella/varicella-like rash; however, the virus strain (wild type or Oka/Merck strain) could not be determined. Across all other clinical trials, the Oka/Merck strain was identified by PCR analysis from the lesion specimens of only two subjects who reported varicella-like rashes (onset on Day 8 and 17).

d. Special populations

Adults with a history of herpes zoster (HZ) prior to vaccination

Varicella-zoster virus vaccine was administered to subjects 50 years of age or older with a history of herpes zoster (HZ) prior to vaccination. The safety profile was generally similar to that seen in the Adverse Event Monitoring Substudy of the SPS.

Adults on chronic/maintenance systemic corticosteroids

In subjects 60 years of age or older who were receiving chronic/maintenance systemic corticosteroid therapy at a daily dose equivalent of 5 to 20 mg of prednisone for at least 2 weeks prior to enrollment, and 6 weeks or more following vaccination, the safety profile was generally comparable to that seen in the Adverse Event Monitoring Substudy of the SPS.

HIV-infected adults with conserved immune function

In a clinical trial, varicella-zoster virus vaccine was administered to HIV-infected adults (18 years of age or older, CD4+ T cell count ≥200 cells/µL). The safety profile was generally similar to the Adverse Event Monitoring Substudy of the SPS. Adverse events were followed up to Day 42 post vaccination and serious adverse events throughout the entire study period (i.e. through Day 180). Of the 295 varicella-zoster virus vaccine recipients, one case of serious vaccine related maculo-papular rash was reported on Day 4 following Dose 1 of varicella-zoster virus vaccine.

VZV-seronegative adults

Based on limited data from 2 clinical trials that enrolled VZV-seronegative or low seropositive subjects (30 years of age or older) receiving live attenuated zoster vaccine, injection site and systemic adverse experiences were generally similar to those reported by other subjects who received varicella-zoster virus vaccine in clinical trials, with 2 of the 27 subjects reporting fever. No subjects reported varicella-like or herpes zoster-like rashes. No serious vaccine-related adverse experiences were reported.

e. Other studies

Adults receiving additional doses/revaccination

In a clinical study, adults 60 years of age or older received a second dose of varicella-zoster virus vaccine 42 days following the initial dose. The frequency of vaccine-related adverse experiences after the second dose of varicella-zoster virus vaccine was generally similar to that seen with the first dose.

In another study, varicella-zoster virus vaccine was administered as a booster dose to HZ history-negative subjects 70 years of age or older who had received a first dose approximately 10 years previously, and as a first dose to HZ history-negative subjects 70 years of age or older. The frequency of vaccine-related adverse experiences after the booster dose of varicella-zoster virus vaccine was generally similar to that seen with the first dose.