Zoster vaccine, recombinant is an adjuvant vaccine for the prevention of herpes zoster (shingles) in adults at least 50 years of age or adults 18 years and older who are or will be at increased risk of herpes zoster due to immunodeficiency or immunosuppression caused by known disease or therapy. Herpes zoster (a vesicular rash) and postherpetic neuralgia (a neuropathic pain syndrome which accompanies the vesicular rash) occurs after reactivation of the varicella-zoster virus; therefore, healthy adults 50 years of age and older should be vaccinated with zoster vaccine, recombinant to prevent shingles and related complications. The CDC recommends that all adults 50 years of age and older and without a contraindication receive herpes zoster vaccination with zoster vaccine, recombinant (Shingrix), even those adults who previously received varicella-zoster virus vaccine, live (Zostavax).
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The reconstituted vaccine should be an opalescent, colorless to pale brownish liquid. If discoloration or visible particulate matter are present, discard the vaccine dose.
-Do not mix with any other vaccine or product in the same syringe.
Intramuscular Administration
Reconstitution
-Prepare zoster vaccine, recombinant by reconstituting the lyophilized varicella zoster virus glycoprotein E (gE) antigen component with the accompanying AS01B adjuvant suspension component.
-Using a sterile needle and sterile syringe, withdraw the entire contents of the vial of the adjuvant suspension component (vial 1 of 2) by slightly tilting the vial.
-Slowly transfer entire contents of syringe into the lyophilized gE antigen component vial (vial 2 of 2).
-Gently swirl the vial until contents are thoroughly mixed and powder is completely dissolved. Do not shake vigorously.
-Withdraw 0.5 mL of reconstituted product for the dose.
-Storage of reconstituted vaccine: If possible, administer immediately after reconstitution; however, reconstituted vaccine may be stored refrigerated between 36 and 46 degrees F (2 and 8 degrees C) for up to 6 hours.
Intramuscular Injection
-Prior to administration, clean skin over the injection site with a suitable cleansing agent.
-The preferred injection site is the deltoid region of the upper arm. Do NOT inject into the gluteal area or other areas where there may be a major nerve trunk.
Overall, 17,041 adults aged 50 years and older received at least 1 dose of zoster vaccine, recombinant in 17 clinical studies. Safety was evaluated by pooling data from 2 placebo-controlled clinical studies involving 29.305 subjects aged 50 years and older who received at least 1 dose of zoster vaccine, recombinant (n = 14,645) or placebo (n = 14,660). The incidence of solicited local and general symptoms was lower in patients aged 70 years and older compared with those aged 50 to 69 years. Most of solicited local adverse reactions and general adverse events seen with zoster vaccine, recombinant had a median duration of 2 to 3 days.
During the zoster vaccine, recombinant clinical trials, injection site reaction was commonly reported. The most frequently reported localized reactions were pain at the injection site (overall incidence 69% to 88%; grade 3 incidence 4% to 11%), edema or swelling (overall incidence 10% to 31%; swelling greater than 100 mm 0.1% to 2%), and erythema or redness (overall incidence 20% to 39%; redness greater than 100 mm 1% to 3%). Injection site pruritus (2.2% vs. 0.2% placebo) was an unsolicited adverse event reported during clinical trials within 30 days of vaccination. During postmarketing surveillance, patients reported decreased mobility of the injected arm, persisting for 1 or more weeks.
Myalgia (overall incidence 35% to 57%; grade 3 incidence 2% to 9%), fatigue (overall incidence 37% to 57%; grade 3 incidence 3% to 10%), headache (overall incidence 15% to 51%; grade 3 incidence 0.1% to 6%), shivering (overall incidence 11% to 36%; grade 3 incidence 0.4% to 7%), fever (overall incidence 6% to 28%; grade 3 incidence 0% to 1%), and gastrointestinal symptoms (i.e., nausea, vomiting, diarrhea, and/or abdominal pain) (overall incidence 13% to 24%; grade 3 incidence 0.9% to 2%) are among the most frequent adverse effects reported after zoster vaccine, recombinant vaccination. Headache and shivering were reported more frequently after Dose 2 (25% to 38% and 21% to 26%, respectively) compared with Dose 1 (15% to 23% and 11% to 20%, respectively). Grade 3 general adverse events (headache, shivering, myalgia, and fatigue) were reported more frequently by subjects after Dose 2 (2% to 5%, 3% to 6%, 4% to 8%, and 4% to 10%, respectively) compared with Dose 1 (0.1% to 1.4%, 0.4% to 1.4%, 2% to 4%, and 2.4% to 6%, respectively). Nausea (1.4% vs. 0.5% placebo) was an unsolicited adverse event reported during clinical trials within 30 days of vaccination. Fever greater than 39 degrees C was reported by 1% or less of patients.
Unsolicited adverse events associated with the use of zoster vaccine, recombinant during the 30 days following vaccination include chills (3.5% vs. 0.2% placebo), malaise (1.7% vs. 0.3% placebo), arthralgia (1.7% vs. 1.2% placebo), dizziness (1.2% vs. 0.8% placebo), and gout (0.18% vs. 0.05%). Lymphadenitis was reported by one patient (less than 0.01%) within 30 days after vaccination and optic ischemic neuropathy was reported in 3 patients (0.02%) within 50 days after vaccination.
Hypersensitivity reactions, including angioedema, rash, and urticaria, have been reported during postmarketing surveillance.
Guillain-Barre syndrome (GBS) has been reported with zoster vaccine, recombinant. In a postmarketing observational study, an increased risk of GBS was observed during the 42 days after vaccination, with an estimated 3 excess cases of GBS per million doses administered to adults aged 65 years or older. In a secondary analysis, an increased risk of GBS was observed during the 42 days after the first dose of zoster vaccine, with an estimated 6 excess cases of GBS per million doses administered to adults aged 65 years or older. There was no increased risk of GBS after the second dose of zoster vaccine. These results suggest a causal association of GBS with zoster vaccine; however, available evidence is insufficient to establish a causal relationship.
During clinical trials, influenza-like illness was reported in 1.3% of zoster vaccine, recombinant patients vs. 0.6% placebo. Infective pneumonia was reported in 1.5% of zoster vaccine, recombinant patients vs. 0.9% placebo up to 30 days post-last vaccination..
Use of zoster vaccine, recombinant is contraindicated in patients with a previous allergic reaction to any component of the vaccine. With any biologic product, the prescriber or health care professional should take precautions to prevent allergic reactions. The health care professional should have immediate availability of epinephrine (1 mg/mL) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the vaccine.
Zoster vaccine, recombinant is only indicated for intramuscular (IM) administration. Administer the vaccine carefully to patients with an increased risk for bleeding. The vaccine should be given cautiously to patients receiving anticoagulant therapy, with thrombocytopenia, vitamin K deficiency, a coagulopathy (e.g., hemophilia), or other bleeding disorders. Monitor these patients closely for bleeding at the IM injection site.
Patients with significant immunosuppression may have a suboptimal antibody response to the zoster vaccine, recombinant. Immunosuppressed persons may include patients with human immunodeficiency virus (HIV) infection; severe combined immunodeficiency (SCID); hypogammaglobulinemia; agammaglobulinemia; altered immune states due to generalized neoplastic disease; or an immune system compromised by radiation therapy or drug therapy (e.g., chemotherapy or corticosteroid therapy with greater than physiologic doses). Short-term (less than 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. To maximize the immunologic response to the vaccine, consider delaying immunization of patients with HIV until virologic suppression on antiretroviral therapy is achieved or wait for immune reconstitution in those who had a CD4 count less than 200 cells/mm3.
Safety and efficacy of zoster vaccine, recombinant have not been established in neonates, infants, children, or adolescents. Zoster vaccine, recombinant is not indicated for use in pediatric patients and is not indicated for the prevention of primary varicella infection (chickenpox).
No adequate and well controlled studies have been conducted with zoster vaccine, recombinant during pregnancy. Reproductive and developmental toxicity studies performed in rats given doses of 0.2 mL revealed no vaccine-related fetal malformations or variations.
There are no data on the presence of zoster vaccine, recombinant in human milk, the effects on a breast-fed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Guillain-Barre syndrome (GBS) has been reported with zoster vaccine, recombinant. The results of a postmarketing observational study suggest a causal association of GBS with zoster vaccine; however, available evidence is insufficient to establish a causal relationship.
Syncope has been noted with the zoster vaccine, recombinant. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Have procedures in place to avoid falling injury and to restore cerebral perfusion after syncope.
For herpes zoster (shingles) infection prophylaxis:
-for herpes zoster (shingles) infection prophylaxis in immunocompetent adults:
Intramuscular dosage:
Adults 50 years and older: 0.5 mL IM initially, followed by a second dose of 0.5 mL IM 2 to 6 months later. Administer both doses regardless of past episodes of herpes zoster or receipt of zoster vaccine, live (Zostavax).
-for herpes zoster (shingles) infection prophylaxis in adults who are or will be at increased risk of herpes zoster due to immunodeficiency or immunosuppression:
Intramuscular dosage:
Adults: 0.5 mL IM initially, followed by a second dose of 0.5 mL IM 2 to 6 months later. The second dose may be given 1 to 2 months later in patients who would benefit from a shorter vaccination schedule. If the second dose is given sooner than 4 weeks after the first, a valid second dose should be repeated at least 4 weeks after the dose given too early.
Maximum Dosage Limits:
-Adults
0.5 mL/dose IM.
-Geriatric
0.5 mL/dose IM.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Zoster Vaccine, Recombinant products.
The risk of developing herpes zoster increases with age and appears to be related to a decline in varicella-zoster virus (VZV)-specific immunity. Boosting the VZV-specific immune response is thought to be the mechanism by which zoster vaccine, recombinant protects against herpes zoster and its complications.
-Route-Specific Pharmacokinetics
Intramuscular Route
The zoster vaccine, recombinant is administered intramuscularly.
Efficacy of 2 doses of zoster vaccine, recombinant was studied in patients aged 50 years and older and 70 years and older. Efficacy was determined by the percentage of patients who did not develop a confirmed case of herpes zoster (HZ) within 1 month after the second dose of zoster vaccine, recombinant. Compared with placebo, zoster vaccine, recombinant reduced the risk of developing HZ by 97.2% (95% CI: 93.7; 99) in patients 50 years and older. Over a median of 3.1 years, patients were followed prospectively for the development of postherpetic neuralgia (PHN), a herpes zoster-related complication. No cases of PHN were reported in the vaccine group compared with 18 cases reported in the placebo group. In a second study of patients 70 years and older, zoster vaccine, recombinant reduced the risk of developing HZ by 89.8% (95% CI: 84.3; 93.7) compared to placebo. Over a median of 3.9 years, patients were followed prospectively for the development of postherpetic neuralgia (PHN). Four cases of PHN were reported in the vaccine group compared with 28 cases reported in the placebo group.