Zoster Vaccine (Live/Attenuated)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Reconstituted, Subcutaneous [preservative free]:

Zostavax: 19,400 units/0.65 mL (1 ea) [contains albumin bovine, beef extract (bovine), gelatin (pork), neomycin]

Pharmacology

Mechanism of Action

A decline in VZV-specific immunity increases the risk of developing zoster infection. As a live, attenuated vaccine (Oka/Merck strain of varicella-zoster virus), zoster virus vaccine stimulates active immunity to disease caused by the varicella-zoster virus. Administration has been demonstrated to protect against the development of herpes zoster. It may also reduce the severity of complications, including postherpetic neuralgia, in patients who develop zoster following vaccination.

Zoster vaccine live reduced the incidence of zoster by ~70% in those 50 to 59 years of age, 64% in those 60-69 years of age, and 38% in those ≥70 years of age (CDC/ACIP [Dooling 2018]). Additional benefit was afforded to vaccine recipients who developed zoster by reduction in the incidence of PHN: 5% for those 60-69 years of age, 55% for those 70-79 years of age, and 26% for those 80 years and older. Other prespecified zoster-related complications were reported less frequently in subjects who received zoster vaccine compared with subjects who received placebo.

Pharmacokinetics/Pharmacodynamics

Onset of Action

Seroconversion: ~6 weeks (CDC/ACIP [Harpaz, 2008])

Duration of Action

Duration of protection decreases over time with substantial decrease after 1 year. Effectiveness of ZVL in preventing herpes zoster decreased to 32% after 8 years in individuals ≥50 years (Baxter 2017; CDC/ACIP [Dooling 2018]).

Use: Labeled Indications

Herpes zoster prevention: Prevention of herpes zoster (shingles) in patients ≥50 years of age

The Advisory Committee on Immunization Practices (ACIP) recommends zoster vaccine for the prevention of herpes zoster and related complications in immunocompetent adults. Recombinant zoster vaccine (RZV) is preferred for adults ≥50 years. However, zoster vaccine live (ZVL) remains an option for immunocompetent adults ≥60 years (CDC/ACIP [Dooling 2018]).

Limitations of use: Not indicated for treatment of active herpes zoster infection or postherpetic neuralgia (PHN); not indicated for prophylaxis of primary varicella infection (chickenpox).

Contraindications

History of anaphylactic/anaphylactoid reaction to gelatin, neomycin (excluding contact dermatitis to neomycin), or any other component of the vaccine; immunosuppression or immunodeficiency, including individuals with leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic systems; primary and acquired immunodeficiency states; AIDS or clinical manifestations of HIV; those receiving immunosuppressive therapy (including high-dose corticosteroids); pregnancy

In addition, ACIP recommends that the following immunocompromised patients should not receive zoster vaccine live (CDC/ACIP [Harpaz 2008]):

Patients undergoing hematopoietic stem cell transplant (limited data; assess risk:benefit, if needed, administer ≥24 months after transplantation).

Patients receiving recombinant human immune modulators, particularly antitumor necrosis factor agents (eg, adalimumab, infliximab, etanercept). Safety and efficacy of concurrent administration is unknown and not recommended. Defer vaccination for ≥1 month after discontinuation.

Patients with unspecified cellular immunodeficiency (exception, patients with impaired humoral immunity may receive vaccine).

Canadian labeling: Additional contraindications (not in US labeling): Active untreated tuberculosis

Dosage and Administration

Dosing: Adult

Shingles prevention:

Manufacturer labeling: Adults ≥50 years: SubQ: 0.65 mL administered as a single dose

ACIP recommendation: Adults ≥60 years: SubQ: 0.65 mL administered as a single dose; there are no data to support readministration of the vaccine (CDC/ACIP [Harpaz, 2008])

Dosage adjustment for concomitant chronic use of acyclovir, famciclovir, or valacyclovir: Discontinue acyclovir, famciclovir, or valacyclovir ≥24 hours before administration of zoster vaccine live. Do not use acyclovir, famciclovir, or valacyclovir for ≥14 days after vaccination (CDC/ACIP [Harpaz 2008]).

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Reconstitute with supplied diluent only, immediately upon removal from the freezer; use only sterile syringes free of preservatives, antiseptics, and detergents. Withdraw entire contents of the vial containing the provided diluent to reconstitute vaccine. Gently agitate to mix thoroughly. Withdraw entire contents of reconstituted vaccine vial for administration. Discard if reconstituted vaccine is not used within 30 minutes.

Administration

SubQ: Inject SubQ into the deltoid region of the upper arm. Do not administer IV or IM; inject immediately after reconstitution. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (ACIP [Kroger 2017]). To prevent syncope related injuries, patients should be vaccinated while seated or lying down (ACIP [Kroger 2017]). US federal law requires that the name of medication, date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.

Storage

To maintain potency, the lyophilized vaccine must be stored frozen between -50°C to -15°C (-58°F to 5°F). Do not ship or store on dry ice as this may result in temperatures below -50°C (-58°F). Protect from light. Store diluent separately at room temperature of 20°C to 25°C (68°F to 77°F) or in refrigerator at 2°C to 8°C (36°F to 46°F). The lyophilized vaccine may also be stored and/or transported under refrigeration at temperatures of 2°C to 8°C (36°F to 46°F) for 72 continuous hours prior to reconstitution; discard if not used within 72 hours.

Drug Interactions

Acyclovir-Valacyclovir: May diminish the therapeutic effect of Zoster Vaccine (Live/Attenuated). Management: When possible, discontinue antiviral agents with anti-zoster activity (i.e., acyclovir, valacyclovir, famciclovir) for at least 24 hours prior to and 14 days after receiving a live attenuated zoster vaccine. Avoid combination

Axicabtagene Ciloleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Axicabtagene Ciloleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for at least 6 weeks prior to initiation of lymphodepleting therapy, during axicabtagene ciloleucel infusion, and after treatment until full immune recovery is achieved. Consider therapy modification

AzaTHIOprine: May enhance the adverse/toxic effect of Vaccines (Live). AzaTHIOprine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose azathioprine (3 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of azathioprine should be avoided. Consider therapy modification

Belimumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification

Daclizumab: May enhance the adverse/toxic effect of Vaccines (Live). Daclizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Dimethyl Fumarate: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Canadian labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. U.S. labeling does not mention this. Consider therapy modification

Dupilumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Famciclovir: May diminish the therapeutic effect of Zoster Vaccine (Live/Attenuated). Management: When possible, discontinue antiviral agents with anti-zoster activity (i.e., acyclovir, valacyclovir, famciclovir) for at least 24 hours prior to and 14 days after receiving a live attenuated zoster vaccine. Avoid combination

Fingolimod: May enhance the adverse/toxic effect of Zoster Vaccine (Live/Attenuated). The risk of herpes zoster infection may be increased. Fingolimod may diminish the therapeutic effect of Zoster Vaccine (Live/Attenuated). Management: Wait 1 month after zoster vaccine administration to initiate fingolimod therapy. Avoid the use of the zoster vaccine during fingolimod treatment, and for 2 months following treatment discontinuation. Consider therapy modification

Guselkumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Immunosuppressants: May enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: AzaTHIOprine; Beclomethasone (Oral Inhalation); Betamethasone (Systemic); Budesonide (Systemic); Corticotropin; Cortisone; Cytarabine (Liposomal); Deflazacort; DexAMETHasone (Systemic); Fludrocortisone; Fluticasone (Oral Inhalation); Hydrocortisone (Systemic); Leflunomide; Mercaptopurine; Methotrexate; MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE; Triamcinolone (Systemic). Avoid combination

Leflunomide: May enhance the adverse/toxic effect of Vaccines (Live). Leflunomide may diminish the therapeutic effect of Vaccines (Live). Management: The ACIP guidelines state that live-attenuated vaccines should generally be avoided for at least 3 months after cessation of immunosuppressant therapy. However, the ACR does not recommend avoiding live vaccines in patients being treated with leflunomide. Consider therapy modification

Mercaptopurine: May enhance the adverse/toxic effect of Vaccines (Live). Mercaptopurine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose 6-mercaptopurine (1.5 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of mercaptopurine should be avoided. Consider therapy modification

Methotrexate: May enhance the adverse/toxic effect of Vaccines (Live). Methotrexate may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose methotrexate (0.4 mg/kg/week or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses of methotrexate should be avoided. Consider therapy modification

Ocrelizumab: May enhance the adverse/toxic effect of Vaccines (Live). Ocrelizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Pneumococcal Polysaccharide Vaccine (23-Valent): May diminish the therapeutic effect of Zoster Vaccine (Live/Attenuated). Monitor therapy

Risankizumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Tildrakizumab: May enhance the adverse/toxic effect of Vaccines (Live). The risk for contracting an infection from the vaccine may be increased. Tildrakizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Tisagenlecleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Tisagenlecleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for two weeks prior to initiation of lymphodepleting therapy, during tisagenlecleucel infusion, and after treatment until full immune recovery is achieved. Consider therapy modification

Tuberculin Tests: Vaccines (Live) may diminish the diagnostic effect of Tuberculin Tests. Management: If a parenteral live vaccine has been recently administered, a scheduled PPD skin test should not be administered for at least 4-6 weeks following the administration of the vaccine. Consider therapy modification

Vaccines (Live): May diminish the therapeutic effect of other Vaccines (Live). Management: Two or more injectable or nasally administered live vaccines not administered on the same day should be separated by at least 28 days (ie, 4 weeks). If not, the vaccine administered second should be repeated at least 4 week later. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Rotavirus Vaccine. Monitor therapy

Venetoclax: May enhance the adverse/toxic effect of Vaccines (Live). Venetoclax may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live, attenuated vaccines before, during, or after (prior to B-cell recovery) venetoclax treatment. Avoid combination

Adverse Reactions

>10%: Local: Pain at injection site (≤54%), erythema at injection site (36% to 48%), swelling at injection site (26% to 40%), localized tenderness (≤34%), injection site pruritus (7% to 11%)

1% to 10%:

Cardiovascular: Cardiac failure (≤2%)

Central nervous system: Headache (1% to 9%)

Gastrointestinal: Diarrhea (2%)

Local: Warm sensation at injection site (2% to 4%), hematoma at injection site (2%), induration at injection site (1%)

Neuromuscular & skeletal: Asthenia (1%), limb pain (1%)

Respiratory: Pulmonary edema (≤2%), respiratory tract disease (1%)

<1%, postmarketing, and/or case reports: Anaphylaxis, arthralgia, exacerbation of asthma, facial nerve paralysis, fever, Guillain-Barre syndrome, herpes zoster infection, hypersensitivity reaction, lymphadenopathy (transient), myalgia, nausea, necrotizing retinitis (patients on immunosuppressive therapy), polymyalgia rheumatica, rash at injection site, skin rash, urticaria at injection site, varicella zoster infection (in immunocompromised patients)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Kroger 2017]).
• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2017]).

Disease-related concerns:

• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Defer administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (ACIP [Kroger 2017]).
• Tuberculosis: Defer treatment in patients with active untreated tuberculosis.
• Zoster infection: Not for use in the treatment of active zoster outbreak; delay vaccination until after acute stage of illness and symptoms are no longer present (CDC/ACIP [Dooling 2018]). May be used in patients with previous history of zoster unless other contraindications to the vaccine exist (CDC/ACIP [Harpaz 2008]).

Concurrent drug therapy issues:

• Antiviral drugs: Medications active against the herpesvirus family (eg, acyclovir, famciclovir, valacyclovir) may interfere with the zoster vaccine live (ZVL); avoid ZVL vaccination to a patient who has received these antivirals 24 hours before vaccination; avoid use of these antiviral agents for 14 days after ZVL vaccination (CDC/ACIP [Harpaz 2008]).
• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist (ACIP [Kroger 2017]).

Special populations:

• Adults: Not for use in patients <50 years of age.
• Altered immunocompetence: In patients where immunosuppressant therapy is anticipated, zoster vaccine live should be given at least 14 days to 1 month prior to beginning therapy when possible. Use is contraindicated in severely immunocompromised patients (eg, patients receiving chemo-/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination or may have an adverse event secondary to replication. Persons with AIDS or manifestations of HIV with CD4+ T-lymphocyte counts ≤200 cells/microliter or CD4+ T-lymphocyte percentages ≤15% should not be vaccinated. Patients receiving corticosteroids in low-to-moderate doses, topical (inhaled, nasal, skin), local injection (intra-articular, bursal, tendon) may receive vaccine. In general, household and close contacts of persons with altered immunocompetence may receive all age-appropriate vaccines (ACIP [Kroger 2017]); CDC/ACIP [Harpaz 2008]).
• Pediatric: Zoster vaccine live is not a substitute for varicella vaccine and should not be used in children and adolescents.
• Varicella vaccine recipients: The ACIP does not recommend zoster vaccine live for patients of any age who have received the varicella vaccine (CDC/ACIP [Harpaz 2008]). Patients can receive recombinant zoster vaccine (RZV) regardless of prior varicella vaccination (CDC/ACIP [Dooling 2018]).

Dosage form specific warnings:

• Gelatin: Contains gelatin; do not use in patients with a history of anaphylactic/anaphylactoid reaction to gelatin.
• Neomycin sensitivity: Contains neomycin; do not use in patients with a history of anaphylactic/anaphylactoid reaction to neomycin. Contact dermatitis to neomycin is not a contraindication to the vaccine.

Other warnings/precautions:

• Appropriate use: Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the annual ACIP Recommended Immunization Schedules (refer to CDC schedule for detailed information). Specific recommendations for use of this vaccine in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions as well as contacts of immunocompromised patients are available from the IDSA (Rubin 2014).
• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2017]).
• Transmission of virus: Although transmission of the vaccine virus may occur between vaccinees and susceptible contacts, vaccinated individuals do not need to take precautions against spreading varicella following vaccination; transmission of virus is rare following vaccination unless rash develops. In case of rash, standard contact precautions should be followed. Persons with rash should avoid contact with persons at high risk for severe varicella infection until lesions have crusted (CDC/ACIP [Harpaz 2008])

Monitoring Parameters

Fever, rash; monitor for anaphylaxis and syncope for 15 minutes following administration (ACIP [Kroger 2017]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Pregnancy

Pregnancy Considerations

Use during pregnancy is contraindicated.

Per the manufacturer, women should avoid becoming pregnant for 3 months after vaccination (4 weeks per CDC). Risk to the fetus following exposure to wild-type varicella zoster virus is small, and risk following exposure from the attenuated vaccine is probably even less (CDC/ACIP [Harpaz 2008]). Based on information collected from the manufacturer's pregnancy registry, of women who received a varicella-containing vaccine within 3 months of pregnancy or any time during pregnancy and who were available for analysis, there were no infants born with abnormalities consistent with congenital varicella syndrome. Information specific to exposure following zoster vaccine live was limited. Due to the rare incidence of congenital varicella syndrome and the low rates of varicella vaccine exposure in women of reproductive potential, the pregnancy registry has been closed. Although zoster vaccine live is not licensed for use in women within traditional reproductive ages, inadvertent exposures will still be monitored (Marin 2014).

Any exposures to the vaccine during pregnancy or within 3 months prior to pregnancy should continue to be reported to the manufacturer (Merck & Co, 877-888-4231) or to VAERS (800-822-7967) as suspected adverse reactions (Marin 2014).

Patient Education

What is this drug used for?

• It is used to prevent shingles.

Frequently reported side effects of this drug

• Injection site pain or irritation
• Itching
• Headache

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• A significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.