Introduction

Inactivated (recombinant) vaccine. Zoster vaccine recombinant contains recombinant varicella zoster virus (VZV) surface glycoprotein E (gE) and an adjuvant (i.e., AS01_B) and is used to boost active immunity to VZV.

Uses for Zoster Vaccine Recombinant

Prevention of Herpes Zoster

Prevention of herpes zoster (zoster, shingles) in adults ≥50 years of age.

Zoster is caused by reactivation of latent VZV infection in individuals who previously had varicella (chickenpox) infection. An estimated 500,000 to 1 million cases of zoster occur each year in the US; many patients develop postherpetic neuralgia (PHN) and require long-term management for refractory PHN. Risk of developing zoster increases with age and declining cell-mediated immunity to VZV. Zoster occurs principally in individuals >45 years of age; estimated lifetime risk of zoster is ≥32%, and 50% of individuals living until 85 years of age will develop zoster.

Zoster vaccine recombinant is used to boost active immunity to VZV, thereby reducing risk of VZV reactivation. May also reduce frequency and/or duration of PHN in those who develop zoster despite vaccination.

Not indicated for treatment of zoster or PHN. Do not administer during an acute episode of zoster. Has no role in postexposure management of zoster.

Not indicated for prevention of primary varicella infection (chickenpox); do not use in children or adults <50 years of age. Has no role in postexposure management of chickenpox.

There are 2 different types of zoster vaccine commercially available in the US for immunization against zoster in adults ≥50 years of age: zoster vaccine recombinant (RZV; Shingrix) and zoster vaccine live (ZVL; Zostavax).

For prevention of zoster in immunocompetent adults ≥50 years of age, the US Public Health Service Advisory Committee on Immunization Practices (ACIP) states that zoster vaccine recombinant (not zoster vaccine live) is preferred and can be used in such individuals regardless of history of zoster or prior vaccination with varicella virus vaccine live or zoster vaccine live. The recombinant zoster vaccine also preferred in adults ≥50 years of age with certain chronic medical conditions (e.g., chronic renal failure, diabetes mellitus, rheumatoid arthritis, chronic pulmonary disease).

For prevention of zoster in immunocompetent adults ≥60 years of age, ACIP states that either zoster vaccine recombinant or zoster vaccine live can be used.

Zoster Vaccine Recombinant Dosage and Administration

Administration

Administer only by IM injection. Do not administer sub-Q, IV, or intradermally.

May be given concurrently with other age-appropriate vaccines. When multiple vaccines are administered during a single health-care visit, give each parenteral vaccine using separate syringes and different injection sites. Injection sites should be separated by ≥1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.

Be aware that 2 different types of zoster vaccine are commercially available in the US (zoster vaccine recombinant [RZV; Shingrix] and zoster vaccine live [ZVL; Zostavax]). These vaccines have different recommendations for dosage and administration (e.g., different routes of administration, different number of required doses) and different storage requirements.

FDA alerted healthcare professionals about multiple reports of medication errors related to confusion about the 2 different zoster vaccines (e.g., incorrect reconstitution, incorrect route of administration, incorrect interval or number of vaccine doses, inappropriate age of vaccinee, administration after incorrect storage). Follow dosage and administration recommendations for the specific zoster vaccine used.

IM Administration

Administer reconstituted zoster vaccine recombinant by IM injection, preferably into deltoid region of upper arm.

To ensure delivery into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for the individual’s age and body mass, thickness of adipose tissue and muscle at injection site, and injection technique. Consider anatomic variability, especially in deltoid, and use clinical judgment to avoid inadvertent underpenetration or overpenetration of muscle.

Reconstitution

Commercially available as a kit containing single-dose vials of lyophilized VZV gE antigen and single-dose vials of AS01_B adjuvant suspension.

Prior to administration, reconstitute a single-dose vial of lyophilized VZV gE antigen from the kit by adding entire contents of a single-dose vial of adjuvant suspension from the kit according to the manufacturer's directions. After adding the adjuvant suspension component to the VZV gE antigen component, gently agitate to ensure the powder is completely dissolved. Reconstituted vaccine is an opalescent, colorless to pale brown liquid; discard if it contains particulates or appears discolored. Consult manufacturer’s labeling for additional information regarding preparation of zoster vaccine recombinant.

Administer immediately after reconstitution or store at 2–8° for up to 6 hours. Discard if not used within 6 hours. (See Storage under Stability.)

Dosage

Adults

Prevention of Herpes Zoster

Adults ≥50 Years of Age

Give zoster vaccine recombinant in a series of 2 doses. Each dose is 0.5 mL.

Give second dose 2–6 months after first dose.

Minimum interval between the 2 doses is 4 weeks. ACIP states repeat second dose if it was inadvertently given <4 weeks after first dose.

If interruptions or delays result in an interval >6 months between the 2 doses, ACIP states vaccine series does not need to be restarted; however, efficacy of dosing interval >6 months not evaluated to date.

A 2-dose regimen recommended regardless of history of zoster or prior vaccination with varicella virus vaccine live or zoster vaccine live.

If used in those who previously received zoster vaccine live, give zoster vaccine recombinant ≥2 months after zoster vaccine live.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Contraindications

• History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine or to a previous dose of the vaccine. (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Take all known precautions to prevent adverse reactions, including a review of the patient’s history with respect to possible hypersensitivity to the vaccine or previous vaccine-associated adverse reactions.

Have appropriate medical treatment readily available in case an anaphylactic reaction occurs.

Individuals with Altered Immunocompetence

Individuals with altered immunocompetence were excluded from initial clinical trials evaluating safety and efficacy of zoster vaccine recombinant.

ACIP states that recombinant vaccines generally can be administered safely to individuals with altered immunocompetence.

Recommendations for use of recombinant vaccines in HIV-infected individuals usually are the same as those for individuals without HIV infection.

Immune response and efficacy may be reduced in individuals receiving immunosuppressive therapy. (See Specific Drugs under Interactions.)

Concomitant Illness

Base decision to administer or delay vaccination in an individual with a current or recent acute illness on severity of symptoms and etiology of the illness.

Do not administer zoster vaccine recombinant during an acute episode of zoster; defer vaccination until acute stage of the illness is over and symptoms have abated.

May be administered to age-appropriate adults with certain chronic medical conditions (e.g., chronic renal failure, diabetes mellitus, rheumatoid arthritis, chronic pulmonary disease).

ACIP states mild acute illness generally does not preclude vaccination.

ACIP states moderate or severe acute illness (with or without fever) is a precaution for vaccination; defer vaccine administration until individual has recovered from the acute phase of the illness. This avoids superimposing vaccine adverse effects on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccine administration.

Limitations of Vaccine Effectiveness

Does not prevent zoster in all vaccine recipients. In vaccinated individuals who develop zoster, duration of pain and discomfort may be reduced.

Duration of Immunity

Duration of protection against zoster following a 2-dose series of zoster vaccine recombinant not fully determined.

Data to date indicate duration of protection following a 2-dose series is at least 4 years; ACIP states that substantial protection against zoster is likely for >4 years.

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune responses in vaccinees.

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained. (See Storage under Stability.)

Do not administer vaccine that has been mishandled or has not been stored at the recommended temperature.

If there are concerns about mishandling, contact the manufacturer or state or local immunization or health departments for guidance on whether the vaccine is usable.

Specific Populations

Pregnancy

Data not available regarding use of zoster vaccine recombinant in pregnant women. In animal studies, no evidence that the vaccine or the AS01_B adjuvant component of the vaccine affects fetal development or causes fetal harm.

ACIP states consider deferring administration of zoster vaccine recombinant in pregnant women.

Lactation

Not known whether zoster vaccine recombinant vaccine is distributed into milk, affects milk production, or affects the breast-fed infant.

Consider benefits of breast-feeding and clinical importance of the vaccine to the woman along with potential adverse effects on the breast-fed child from the vaccine or the underlying maternal condition (i.e., susceptibility to reactivation of VZV infection).

ACIP states that recombinant vaccines generally do not pose any unusual risks for women who are breast-feeding or their breast-fed infants. However, these experts state consider deferring administration of zoster vaccine recombinant in women who are breast-feeding.

Pediatric Use

Safety and efficacy not established in pediatric patients. Not indicated for prevention of primary varicella infection (chickenpox).

Geriatric Use

Safety and efficacy established only in adults ≥50 years of age, including geriatric adults.

No clinically meaningful differences in efficacy among various age groups of adults ≥60 years of age or between those ≥60 years of age and those 50–59 years of age; adverse effects reported less frequently in vaccine recipients ≥70 years of age compared with those 50–69 years of age.

Common Adverse Effects

Injection site reactions (pain, erythema, swelling), myalgia, fatigue, headache, shivering, fever, GI symptoms (nausea, vomiting, diarrhea, abdominal pain).

Administration

Administer only by IM injection. Do not administer sub-Q, IV, or intradermally.

May be given concurrently with other age-appropriate vaccines. When multiple vaccines are administered during a single health-care visit, give each parenteral vaccine using separate syringes and different injection sites. Injection sites should be separated by ≥1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.

Be aware that 2 different types of zoster vaccine are commercially available in the US (zoster vaccine recombinant [RZV; Shingrix] and zoster vaccine live [ZVL; Zostavax]). These vaccines have different recommendations for dosage and administration (e.g., different routes of administration, different number of required doses) and different storage requirements.

FDA alerted healthcare professionals about multiple reports of medication errors related to confusion about the 2 different zoster vaccines (e.g., incorrect reconstitution, incorrect route of administration, incorrect interval or number of vaccine doses, inappropriate age of vaccinee, administration after incorrect storage). Follow dosage and administration recommendations for the specific zoster vaccine used.

IM Administration

Administer reconstituted zoster vaccine recombinant by IM injection, preferably into deltoid region of upper arm.

To ensure delivery into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for the individual’s age and body mass, thickness of adipose tissue and muscle at injection site, and injection technique. Consider anatomic variability, especially in deltoid, and use clinical judgment to avoid inadvertent underpenetration or overpenetration of muscle.

Reconstitution

Commercially available as a kit containing single-dose vials of lyophilized VZV gE antigen and single-dose vials of AS01_B adjuvant suspension.

Prior to administration, reconstitute a single-dose vial of lyophilized VZV gE antigen from the kit by adding entire contents of a single-dose vial of adjuvant suspension from the kit according to the manufacturer's directions. After adding the adjuvant suspension component to the VZV gE antigen component, gently agitate to ensure the powder is completely dissolved. Reconstituted vaccine is an opalescent, colorless to pale brown liquid; discard if it contains particulates or appears discolored. Consult manufacturer’s labeling for additional information regarding preparation of zoster vaccine recombinant.

Administer immediately after reconstitution or store at 2–8° for up to 6 hours. Discard if not used within 6 hours. (See Storage under Stability.)

Dosage

Adults

Prevention of Herpes Zoster

Adults ≥50 Years of Age

Give zoster vaccine recombinant in a series of 2 doses. Each dose is 0.5 mL.

Give second dose 2–6 months after first dose.

Minimum interval between the 2 doses is 4 weeks. ACIP states repeat second dose if it was inadvertently given <4 weeks after first dose.

If interruptions or delays result in an interval >6 months between the 2 doses, ACIP states vaccine series does not need to be restarted; however, efficacy of dosing interval >6 months not evaluated to date.

A 2-dose regimen recommended regardless of history of zoster or prior vaccination with varicella virus vaccine live or zoster vaccine live.

If used in those who previously received zoster vaccine live, give zoster vaccine recombinant ≥2 months after zoster vaccine live.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Vaccines

Concurrent administration with other age-appropriate vaccines or toxoids during the same health-care visit (using separate syringes and different injection sites) not expected to affect immunologic responses or adverse reactions to any of the vaccines.

Specific Drugs