Zostavax

Zostavax

vaccine, varicella-zoster

Manufacturer:

Merck Sharp & Dohme

Distributor:

Zuellig
Full Prescribing Info
Contents
Live attenuated varicella-zoster virus (Oka/Merck strain).
Description
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) (Refrigerated) is a lyophylized preparation of the Oka/Merck strain of live, attenuated varicella-zoster virus (VZV).
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX), when reconstituted as directed, is a sterile preparation for subcutaneous administration. Each 0.65-mL dose contains a minimum of 19,400 PFU (plaque-forming units) of Oka/Merck VZV when reconstituted and stored at room temperature for up to 30 minutes.
Excipients/Inactive Ingredients: Each 0.65-mL dose contains: 41.05 mg of sucrose, 20.53 mg of hydrolyzed porcine gelatin, 8.55 mg of urea, 5.25 mg of sodium chloride, 0.82 mg of monosodium L-glutamate, 0.75 mg of sodium phosphate dibasic, 0.13 mg of potassium phosphate monobasic, 0.13 mg of potassium chloride; residual components of MRC-5 cells including DNA and protein; and trace quantities of neomycin and bovine calf serum. The product contains no preservative.
Action
Pharmacotherapeutic group: Viral Vaccine. ATC code: J07BK02.
Pharmacology: Pharmacodynamics: Herpes Zoster: Herpes zoster (HZ), known also as shingles or simply "zoster", is a manifestation of reactivation of VZV, which, as a primary infection, produces chickenpox (varicella).
Zoster is usually characterized by a unilateral, painful, vesicular cutaneous eruption with a dermatomal distribution. Although the blistering rash is the most distinctive feature of zoster, the most frequently debilitating symptom is pain, which may occur during the prodrome, the acute eruptive phase, and the postherpetic phase of the infection. During the acute eruptive phase, local pain has been reported to occur in up to 90% of immunocompetent individuals.
Anyone who has been infected with VZV, including those without a clinical history of varicella, is at risk for developing zoster, which is considered to be due to waning immunity to VZV. Nearly all adults are at risk for zoster in Europe (585 million population in 2005), where an estimated 2.1 million cases occur every year. This number is expected to rise with the aging of the population. The incidence and severity of zoster, as well as the frequency and severity of its complications, increase markedly with age, with two-thirds of the cases occurring in individuals older than 50 years of age. In recent studies, the lifetime risk of zoster has been estimated to be as high as 30% in the general population. It is estimated that by 85 years of age, 50% of individuals will have experienced an episode of zoster. Available hospitalization data for zoster are limited in Europe. Zoster-associated hospitalization rates vary across countries and are estimated to range from 5 to 10 per 100,000 population for an average length of stay of 10 to 13 days. The proportion of zoster patients hospitalized increases with age, up to more than 10% in individuals over 65 years of age. Seventy to 80% of hospitalizations for zoster occur among immunocompetent individuals.
Zoster may be associated with serious complications such as postherpetic neuralgia (PHN), scarring, bacterial superinfection, motor neuron palsies, pneumonia, encephalitis, Ramsay Hunt Syndrome, visual impairment, hearing loss, and death.
Zoster-associated pain and discomfort can be prolonged and disabling and can diminish quality of life and functional capacity to a degree comparable to such debilitating diseases as congestive heart failure, myocardial infarction, type II diabetes mellitus, and major depression.
Postherpetic Neuralgia: Postherpetic neuralgia (PHN) constitutes the most common serious complication and cause of zoster-associated morbidity in the immunocompetent host. Based on extrapolation of published prevalence data, the prevalence of PHN is estimated to be 1 to 2 million cases in Europe (585 million population). The frequency and severity of PHN increase with age, and may complicate 25 to 50% of zoster cases among patients over 50 years of age. PHN has been described as tender, burning, throbbing, stabbing, shooting and/or sharp pain that can persist for months or even years and can also lead to emotional distress. Allodynia (pain from an innocuous stimulus) is present in at least 90% of patients with PHN and is typically described as the most distressing and debilitating types of pain. Several definitions of PHN are widely used in the medical community, including pain persisting longer than 90 days after the onset of the rash.
Mechanism of Action: The risk of developing zoster appears to be causally related to a decline in VZV-specific immunity. Varicella-Zoster Vaccine Live (Oka/Merck) (ZOSTAVAX) was shown to boost VZV-specific immunity, which is thought to be the mechanism by which it protects against zoster and its complications. (See Immunogenicity.)
Clinical Studies: Evaluation of Clinical Efficacy Afforded by Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX): Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) Efficacy and Safety Trial (ZEST) in Subjects 50 to 59 Years of Age: In the Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) Efficacy and Safety Trial (ZEST), a placebo-controlled, double-blind clinical trial in which 22,439 subjects 50 to 59 years of age were randomized to receive a single dose of either Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) (n=11,211) or placebo (n=11,228) and were followed for the development of zoster for a median of 1.3 years (range 0 to 2 years). All suspected zoster cases were adjudicated by a clinical evaluation committee. Final determination of zoster cases was made by Polymerase Chain Reaction (PCR) [86%], or in the absence of virus detection, as determined by a clinical evaluation committee [14%].
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) significantly decreased the incidence of zoster compared with placebo (30 cases [2.0/1000 person-years] vs. 99 cases [6.6/1000 person-years], respectively; p<0.001). The protective efficacy of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) against zoster was 69.8% (95% CI: [54.1 to 80.6%]).
Shingles Prevention Study (SPS) in Subjects 60 Years of Age and Older: In the Shingles Prevention Study (SPS), a placebo-controlled, double-blind clinical trial of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX), 38,546 subjects 60 years of age or older were randomized to receive a single dose of either Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) (n=19,270) or placebo (n=19,276) and were followed for the development of zoster for an average of 3.1 years (range 1 day to 4.9 years). Randomization was stratified by age, 60-69 and ≥70 years of age. All suspected zoster cases were adjudicated by a clinical evaluation committee. Final determination of zoster cases was made by PCR, local culture, or the decision of the clinical evaluation committee, in that order. In both vaccination groups [Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and placebo], subjects who developed zoster were given famciclovir, and as necessary, pain medications. Severity of pain was evaluated according to a "worst pain" score on a 0-to-10 scale, using the Zoster Brief Pain Inventory (ZBPI), a validated questionnaire. A score of 3 or higher was considered clinically significant because it correlates with significant interference with Activities of Daily Living (ADL).
As shown in the table, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) significantly reduced the risk of developing zoster and PHN compared with placebo. In addition, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) significantly reduced acute and chronic zoster-associated pain as measured by the HZ pain Burden of Illness (BOI) score (see definition in the table).

Click on icon to see table/diagram/image

Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) significantly decreased the incidence of zoster compared with placebo (315 [5.4/1000 person-years] vs. 642 cases [11.1/1000 person-years], respectively; p<0.001). The protective efficacy of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) against zoster was 51% (95% CI: [44 to 58%]). Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) reduced the incidence of zoster by 64% (95% CI: [56 to 71%]) in individuals 60-69 years of age and by 38% (95% CI: [25 to 48%]) in individuals ≥70 years of age. The cumulative incidence of zoster over time among vaccine recipients was also significantly reduced (p<0.001).
In the SPS, the reduction in zoster was seen in almost all dermatomes. Ophthalmic zoster occurred in 35 subjects vaccinated with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) vs. 69 subjects who received placebo. Impaired vision occurred in 2 subjects vaccinated with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) vs. 9 who received placebo.
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) decreased the incidence of PHN compared with placebo [(27 cases [0.5/1000 person-years] vs. 80 cases [1.4/1000 person-years], respectively; p<0.001). In this trial, the definition of PHN was clinically significant zoster-associated pain persisting or appearing at least 90 days after the onset of rash. The protective efficacy of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) against PHN was 67% (95% CI: [48 to 79%]), and the reduction was similar for the two age groups (60-69 and ≥70 years of age). In addition, the efficacy of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) did not change appreciably when PHN was defined using alternative cutoff times (30, 60, 120, or 182 days) for duration of pain. Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) significantly reduced the cumulative incidence of PHN over time compared with placebo (p<0.001).
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) reduced the HZ pain BOI score by approximately 61% (95% CI: [51 to 69%]), compared with placebo. Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) reduced the HZ pain BOI score to a similar extent for the two age groups (60-69 and ≥70 years of age). The HZ pain BOI score is a composite score that incorporates the incidence, severity, and duration of acute and chronic zoster-associated pain over a 6-month follow-up period.
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) reduced the incidence of zoster with severe and long-lasting pain (severity-by-duration score >600) by 73% (95% CI: [46 to 87%]) compared with placebo. Eleven subjects vaccinated with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) had severity-by-duration scores >600 compared with 40 subjects who received placebo. For example, a daily worst pain rated at the maximum score of 10 for >60 days would result in a severity-by-duration score of >600.
Among vaccinated individuals who developed zoster, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) significantly reduced zoster-associated pain compared with placebo. Over the 6-month follow-up period, there was a 22% reduction in the severity-by-duration score [average scores of 141 for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and 181 for placebo, p=0.008].
Among vaccinated individuals who developed PHN, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) significantly reduced PHN-associated pain compared with placebo. In the period from 90 days after rash onset to the end of follow-up, there was a 57% reduction in the severity-by-duration score [average scores of 347 for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and 805 for placebo; p=0.016].
To evaluate the impact of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) on ADL interference associated with zoster, a combined score was calculated for each subject based on interference with general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life. Each item was measured on a 0-to-10 scale (0 being no interference and 10 being maximum interference). Compared to placebo, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) led to a favorable, but not statistically significant, reduction (8.2%) in the risk of having substantial ADL interference (defined as having a combined ADL interference score ≥2 for ≥7 days) beyond the vaccine efficacy for zoster.
Among vaccinated individuals who developed zoster, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) significantly reduced ADL interference compared with placebo. Over the 6-month follow-up period, there was a 31% reduction in the severity-by-duration score for combined ADL interference (average scores of 57 for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and 83 for placebo; p=0.002).
The use of antiviral drugs within 72 hours of zoster rash onset did not have a significant effect on the efficacy of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) for zoster pain or PHN incidence. The proportions of subjects using medications with analgesic effects were balanced between vaccination groups. Therefore, the use of these medications was not likely to have contributed to the reduction of zoster pain or PHN incidence.
Immunogenicity of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX): Within the Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) Efficacy and Safety Trial (ZEST), immune responses to vaccination were evaluated in a random 10% subcohort (n=1,136 for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and n=1,133 for placebo) of the subjects enrolled in the ZEST. Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) elicited higher VZV-specific immune responses at 6 weeks postvaccination compared with placebo. Increases in VZV antibody level, measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were demonstrated (2.3-fold difference (95% CI [2.2, 2.4]), geometric mean titer [GMT] of 664 vs. 288 gpELISA units/mL, p <0.001).
Within the Shingles Prevention Study (SPS), immune responses to vaccination were evaluated in a subset of the enrolled subjects (N=1395). Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) elicited higher VZV-specific immune responses at 6 weeks postvaccination compared with placebo. Increases in both VZV antibody level, measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) (1.7 fold-difference, geometric mean titer [GMT] of 479 vs. 288 gpELISA units/ml, p <0.001), and T-cell activity, measured by VZV interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay (2.2 fold-difference, geometric mean count [GMC] of 70 vs. 32 spot-forming cells per million peripheral blood mononuclear cells [SFC/106 PBMCs], p<0.001) were demonstrated.
In an integrated analysis of two clinical trials evaluating immune response to Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) at 4 weeks postvaccination, responses were generally similar in subjects 50 to 59 (N=389) compared to subjects ≥60 years of age (N=731) (GMT of 668 vs. 614 gpELISA units/ml, respectively). The geometric mean fold-rise of immune response following vaccination as measured by gpELISA was 2.6-fold (95% CI: [2.4 to 2.9]) in subjects 50 to 59 years of age and 2.3-fold (95% CI: [2.1 to 2.4]) in subjects ≥60 years of age.
The SPS Short-term Persistence Substudy (STPS): The STPS was initiated to accrue additional information on the persistence of vaccine efficacy and to preserve a subset of subjects for the long-term persistence substudy (LTPS). The STPS included 7,320 subjects previously vaccinated with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and 6,950 subjects previously vaccinated with placebo in the SPS. The mean age at enrollment in STPS was 73.3 years. During the course of STPS, placebo recipients were offered Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX), at which time they were considered to have completed the STPS.
The STPS analyses for vaccine efficacy are based on data collected primarily 4 to 7 years postvaccination in the SPS. The median follow-up in the STPS was ~1.2 years (range is one day to 2.2 years). In the STPS, there were 84 evaluable HZ cases in the Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) group and 95 evaluable cases in the placebo group. The estimated vaccine efficacy for HZ incidence during the STPS follow-up period was 39.6% (18.2%, 55.5%). The estimated vaccine efficacy for PHN incidence was 60.1% (-9.8%, 86.7%).The estimated vaccine efficacy for HZ BOI was 50.1% (14.1%, 71.0%).
There were no vaccine-related serious adverse experiences reported in the STPS.
The SPS Long-term Persistence Substudy (LTPS): Following completion of the STPS, the open-label LTPS evaluated the duration of protection against HZ, PHN and HZ BOI of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) on subjects vaccinated in the SPS. A total of 6,687 subjects previously vaccinated with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) in the SPS participated in the LTPS. The mean age at enrollment into LTPS was 74.5 years.
Because placebo subjects were previously offered vaccine during the STPS, a concurrent placebo control group was not available for calculation of vaccine efficacy for the LTPS. Therefore, prior placebo recipients were used as a reference group for calculating vaccine efficacy in the LTPS.
The LTPS analyses for vaccine efficacy are based on data collected primarily from Year 7 through Year 10 following vaccination in the SPS. Median follow up during the LTPS was ~3.9 years (range is one week to 4.75 years). There were 263 evaluable HZ cases during the LTPS. The estimated vaccine efficacy for HZ incidence during the LTPS follow-up period was 21.1% (10.9%, 30.4%). The estimated vaccine efficacy for PHN incidence was 35.4% (8.8%, 55.8%). The estimated vaccine efficacy for HZ BOI was 37.3% (26.7%, 46.4%). The observed vaccine efficacy in the LTPS is generally consistent with the vaccine efficacy for HZ observed during the SPS 70-year-old age group, and is consistent with the current age of the study cohort.
There were no vaccine-related serious adverse experiences reported in the LTPS.
Immunogenicity following concomitant administration: In a double-blind, controlled clinical trial, 762 adults 50 years of age and older were randomized to receive a single dose of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) administered either concomitantly (N=382) or nonconcomitantly (N=380) with inactivated influenza vaccine. The antibody responses to both vaccines at 4 weeks postvaccination were similar, whether administered concomitantly or nonconcomitantly.
In a double-blind, controlled clinical trial, 473 adults, 60 years of age or older, were randomized to receive Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and PNEUMOVAX 23 concomitantly (N=237), or PNEUMOVAX 23 alone followed 4 weeks later by Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) alone (N=236). At four weeks postvaccination, the VZV antibody levels following concomitant use were significantly lower than the VZV antibody levels following nonconcomitant administration (GMTs of 338 vs. 484 gpELISA units/mL, respectively; GMT ratio = 0.70 (95% CI: [0.61, 0.80])). VZV antibody levels 4 weeks postvaccination were increased 1.9-fold (95% CI: [1.7, 2.1]; meeting the pre-specified acceptance criterion) in the concomitant group vs. 3.1-fold (95% CI: [2.8, 3.5]) in the nonconcomitant group. The GMTs for PNEUMOVAX 23 antigens were comparable between the two groups. Concomitant use of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and PNEUMOVAX 23 demonstrated a safety profile that was generally similar to that of the two vaccines administered nonconcomitantly.
Immunogenicity in subjects with a history of herpes zoster (HZ) prior to vaccination: In a double-blind, placebo-controlled, randomized clinical trial, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) was administered to 100 subjects 50 years of age or older with a history of herpes zoster (HZ) prior to vaccination to assess immunogenicity of Virus Varicella-Zoster Vaccine Live (Oka/Merck) (ZOSTAVAX). Varicella-Zoster Vaccine Live (Oka/Merck) (ZOSTAVAX) induced a significantly higher VZV-specific immune response as measured by gpELISA at 4 weeks postvaccination, compared with placebo (2.1-fold difference (95% CI: [1.5 to 2.9], p<0.001), GMT of 812 vs. 393 gpELISA units/ml). VZV antibody responses were generally similar in subjects 50 to 59 compared to subjects ≥60 years of age.
Revaccination: The need for, or timing of, revaccination with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) has not yet been determined. In an efficacy study, the duration of protection was demonstrated through 48 months of follow-up.
Immunogenicity and Safety in Subjects Receiving a Booster Dose: In an open-label study, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) was administered as: (1) a booster dose to 201 HZ history-negative subjects 70 years of age or older who had received a first dose approximately 10 years previously as participants in the SPS, and (2) a first dose to 199 HZ history-negative subjects 70 years of age or older who had not received Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) previously. The antibody response to vaccine 6 weeks postvaccination as measured by gpELISA was similar in the booster dose and first dose group (GMT of 389.1 vs 368.8 gpELISA units/mL, respectively). The geometric mean fold-rise of the VZV antibody response, as measured by gpELISA, from prevaccination to Week 6 postvaccination was 1.5 (95% CI: [1.4 to 1.6]) in both groups.
To evaluate the adverse experiences temporally associated with study vaccination, subjects were given a Vaccination Report Card (VRC) to record any injection-site adverse experiences, systemic adverse experiences, elevated temperatures, and rashes from Days 1 to 42 postvaccination. Subjects were followed for serious adverse experiences, regardless of whether the event was related to the study vaccine, throughout the course of the study (through Day 365). The vaccine was generally well tolerated; the frequency of vaccine-related adverse experiences after the booster dose of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) was generally similar to that seen with the first dose.
Indications/Uses
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) (Refrigerated) is indicated for: prevention of herpes zoster (shingles), prevention of postherpetic neuralgia (PHN), reduction of acute and chronic zoster-associated pain.
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) is indicated for immunization of individuals 50 years of age or older.
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) can be administered concomitantly with inactivated influenza vaccine (see DOSAGE & ADMINISTRATION and PHARMACOLOGY under ACTIONS).
Dosage/Direction for Use
FOR SUBCUTANEOUS ADMINISTRATION.
Do not inject intravascularly.
Individuals should receive a single dose. At present, the duration of protection after vaccination with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) is unknown. In the Shingles Prevention Study (SPS), protection was demonstrated through 4 years of follow-up. The need for revaccination has not yet been defined.
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) is not a treatment for zoster or PHN.
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) can be administered concomitantly with inactivated influenza vaccine using separate syringes.
Reconstitute immediately upon removal from the refrigerator.
To reconstitute the vaccine, use only the diluent supplied, since it is free of preservatives or other antiviral substances which might inactivate the vaccine virus.
Prefilled syringe of diluent: To reconstitute the vaccine, inject all the diluent in the syringe into the vial of lyophilized vaccine and gently agitate to mix thoroughly. Withdraw the entire contents into a syringe and inject the total volume of reconstituted vaccine subcutaneously, preferably into the upper arm (preferably in the deltoid region).
It is recommended that the vaccine be administered immediately after reconstitution, to minimize loss of potency. Discard reconstituted vaccine if it is not used within 30 minutes.
Do not freeze reconstituted vaccine.
CAUTION: A sterile syringe free of preservatives, antiseptics, and detergents should be used for each injection and/or reconstitution of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) because these substances may inactivate the vaccine virus.
A separate sterile needle and syringe should be used for administration of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) to prevent transfer of infectious diseases.
Needles should be disposed of properly and should not be recapped.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) when reconstituted is a semi-hazy to translucent, off white to pale yellow liquid.
Overdosage
There are no data with regard to overdose.
Contraindications
History of hypersensitivity to any component of the vaccine, including gelatin.
History of anaphylactic/anaphylactoid reaction to neomycin (each dose of reconstituted vaccine contains trace quantities of neomycin). Neomycin allergy generally manifests as a contact dermatitis. However, a history of contact dermatitis due to neomycin is not a contraindication to receiving live virus vaccines.
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) is a live, attenuated varicella-zoster vaccine and administration to individuals who are immunosuppressed or immunodeficient may result in disseminated varicella-zoster virus disease, including fatal outcomes.
Primary and acquired immunodeficiency states due to conditions such as: acute and chronic leukemias; lymphoma; other conditions affecting the bone marrow or lymphatic system; immunosuppression due to HIV/AIDS (see PHARMACOLOGY under ACTIONS and SIDE EFFECTS); cellular immune deficiencies.
Immunosuppressive therapy (including high-dose corticosteroids) (see SIDE EFFECTS); however, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) is not contraindicated for use in individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or in patients who are receiving corticosteroids as replacement therapy, e.g., for adrenal insufficiency.
Active untreated tuberculosis.
Pregnancy (see USE IN PREGNANCY & LACTATION).
Special Precautions
The health care provider should question the patient about reactions to a previous dose of any VZV-containing vaccines (see CONTRAINDICATIONS).
As with any vaccine, adequate treatment provisions, including epinephrine injection (1:1000), should be available for immediate use should an anaphylactic/anaphylactoid reaction occur.
Deferral of vaccination should be considered in the presence of fever >38.5°C (>101.3°F).
The safety and efficacy of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) have not been established in adults who are known to be infected with human immunodeficiency virus (HIV) with or without evidence of immunosuppression. A phase II safety and immunogenicity study in HIV-infected adults with conserved immune function has been completed (see PHARMACOLOGY under ACTIONS and SIDE EFFECTS).
As with any vaccine, vaccination with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) may not result in protection of all vaccine recipients.
Transmission: In clinical trials with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX), transmission of the vaccine virus has not been reported. However, post-marketing experience with varicella vaccines suggests that transmission of vaccine virus may occur rarely between vaccinees who develop a varicella-like rash and susceptible contacts. Transmission of vaccine virus from varicella vaccine recipients who do not develop a varicella-like rash has also been reported. This is a theoretical risk for vaccination with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX). The risk of transmitting the attenuated vaccine virus to a susceptible individual should be weighed against the risk of developing natural zoster that could be transmitted to a susceptible individual.
Effects on ability to drive and use machines: There are no data to suggest that Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) affects the ability to drive or operate machinery.
Use in Children: Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) is not recommended for use in this age group.
Use in Elderly: The mean age of subjects enrolled in the largest (N=38,546) clinical study of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) was 69 years (range 59-99 years). Of the 19,270 subjects who received Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX)), 10,378 were 60-69 years of age, 7,629 were 70-79 years of age, and 1,263 were 80 years of age or older. Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) was demonstrated to be generally safe and effective in this population.
Use In Pregnancy & Lactation
Pregnancy: Animal reproduction studies have not been conducted with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX). It is also not known whether Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. However, naturally-occurring VZV infection is known to sometimes cause fetal harm. Therefore, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) should not be administered to pregnant females; furthermore, pregnancy should be avoided for three months following vaccination (see CONTRAINDICATIONS).
Lactation: It is not known whether VZV is secreted in human milk. Therefore, because some viruses are secreted in human milk, caution should be exercised if Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) is administered to a nursing woman.
Side Effects
In clinical trials, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) has been evaluated for general safety in more than 32,000 adults 50 years of age or older. Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) was generally well tolerated.
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) Efficacy and Safety Trial (ZEST) in Subjects 50 to 59 Years of Age: In the ZEST study, subjects received a single dose of either Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) (n=11,184) or placebo (n=11,212) and were monitored for safety throughout the study. During the study, a vaccine-related serious adverse experience was reported for 1 subject vaccinated with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) (anaphylactic reaction).
All subjects received a vaccination report card (VRC) to record adverse events occurring from Days 1 to 42 postvaccination in addition to undergoing routine safety monitoring throughout the study.
The following very common (≥1/10) and common (≥1/100, <1/10) vaccine-related injection-site and systemic adverse experiences were reported in the ZEST study. Several adverse experiences were solicited (Days 1-5 postvaccination) and are designated with the * symbol.
Nervous system disorder: Common: headache.
General disorders and administration site conditions: Very common: erythema,* pain,* swelling*, pruritus. Common: hematoma, warmth, induration.
Musculoskeletal and connective tissue disorders: Common: pain in extremity.
The overall incidence of vaccine-related injection-site adverse experiences was significantly greater for subjects vaccinated with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) versus subjects who received placebo [63.9% for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and 14.4% for placebo].
Within the 42-day postvaccination reporting period in the ZEST, noninjection-site zosteriform rashes were reported by 34 subjects [19 for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and 15 for placebo]. Of 24 specimens that were adequate for Polymerase Chain Reaction (PCR) testing, wild-type VZV was detected in 10 [3 for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX), 7 for placebo] of these specimens. The Oka/Merck strain of VZV was not detected from any of these specimens.
Within the same 42-day postvaccination reporting period in the ZEST, varicella-like rashes were reported by 124 subjects [69 for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and 55 for placebo]. Of 23 specimens that were available and adequate for PCR testing, VZV was detected in one of these specimens from the group of subjects who received Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX); however, the virus strain (wild type or Oka/Merck strain) could not be determined.
Shingles Prevention Study (SPS) in Subjects 60 Years of Age and Older: In the largest of these trials, the Shingles Prevention Study (SPS), 38,546 subjects received a single dose of either Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) (n=19,270) or placebo (n=19,276) and were monitored for safety throughout the study. During the study, vaccine-related serious adverse experiences were reported for 2 subjects vaccinated with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) (asthma exacerbation and polymyalgia rheumatica) and 3 subjects who received placebo (Goodpasture's syndrome, anaphylactic reaction, and polymyalgia rheumatica).
In the Adverse Event Monitoring Substudy, a subgroup of individuals from the SPS (n=3,345 received Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and n=3,271 received placebo) were provided vaccination report cards to record adverse events occurring from Days 0 to 42 postvaccination in addition to undergoing routine safety monitoring throughout the study.
The following very common (≥1/10) and common (≥1/100, <1/10) vaccine-related injection-site and systemic adverse experiences were reported in the Adverse Event Monitoring Substudy. Most of these adverse experiences were reported as mild in intensity. Several adverse experiences were solicited (Days 0-4 postvaccination) and are designated with the * symbol.
Nervous system disorder: Common: headache.
General disorders and administration site conditions: Very common: erythema,* pain/tenderness,* swelling*. Common: hematoma, pruritus, warmth.
The overall incidence of vaccine-related injection-site adverse experiences was significantly greater for subjects vaccinated with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) versus subjects who received placebo (48% for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and 17% for placebo).
The remainder of subjects in the SPS received routine safety monitoring, but were not provided report cards. The types of events reported in these patients were generally similar to the subgroup of patients in the Adverse Event Monitoring Substudy.
Within the 42-day postvaccination reporting period in the SPS, the number of reported zosteriform rashes among all subjects was small [17 for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX), 36 for placebo; p=0.009]. Of these 53 zosteriform rashes, 41 had specimens that were available and adequate for PCR testing. Wild-type VZV was detected in 25 [5 for Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX), 20 for placebo] of these specimens. The Oka/Merck strain of VZV was not detected from any of these specimens.
Within the same 42-day postvaccination reporting period in the SPS, the number (n=59) of reported varicella-like rashes was also small. Of these varicella-like rashes, 10 had specimens that were available and adequate for PCR testing. VZV was not detected in any of these specimens.
Other Studies: In other clinical trials in support of the initial licensure of the frozen formulation of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX), the reported rates of noninjection-site zosteriform and varicella-like rashes within 42 days postvaccination were also low in both zoster vaccine recipients and placebo recipients. Of 17 reported varicella-like rashes and non-injection site zoster-like rashes, 10 specimens were available and adequate for PCR testing, and 2 subjects had varicella (onset Day 8 and 17) confirmed to be Oka/Merck strain.
In clinical trials evaluating Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) in subjects 50 years of age or older, including a study of concomitantly administered inactivated influenza vaccine, the safety profile was generally similar to that seen in the Adverse Event Monitoring Substudy of the SPS. However, in these trials, 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.
In a double-blind, placebo-controlled, randomized clinical trial, Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) was administered to 100 subjects 50 years of age or older with a history of herpes zoster (HZ) prior to vaccination to assess immunogenicity of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and the safety profile. In this clinical trial, the safety profile was generally similar to that seen in the Adverse Event Monitoring Substudy of the SPS.
To address concerns for individuals with an unknown history of vaccination with Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX), the safety and tolerability of a second dose of Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) was evaluated. In a placebo-controlled, double-blind study, 98 adults 60 years of age or older received a second dose of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) 42 days following the initial dose; the vaccine was generally well tolerated. The frequency of vaccine-related adverse experiences after the second dose of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) was generally similar to that seen with the first dose.
Post-marketing Experience: The following additional adverse reactions have been identified during post-marketing use of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX). Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to the vaccine.
Gastrointestinal disorders: nausea.
Infections and infestations: herpes zoster (vaccine strain).
Skin and subcutaneous tissue disorders: rash.
Musculoskeletal and connective tissue disorders: arthralgia; myalgia.
General disorders and administration site conditions: injection-site rash; injection-site urticaria; pyrexia; transient injection-site lymphadenopathy.
Immune system disorders: hypersensitivity reactions including anaphylactic reactions.
Eye Disorders: Necrotizing retinitis (patients on immunosuppressive therapy).
Drug Interactions
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) must not be mixed with any other medicinal product in the same syringe. Other medicinal products must be given as separate injections and at different body sites.
Concurrent administration of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and antiviral medications known to be effective against VZV has not been evaluated.
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) and PNEUMOVAX* 23 should not be given concomitantly because concomitant use resulted in reduced immunogenicity of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) (see PHARMACOLOGY under ACTIONS). Consider administration of the two vaccines separated by at least 4 weeks.
Caution For Usage
Incompatibilities: See INTERACTIONS.
Storage
Storage: During shipment, to ensure that there is no loss of potency, the vaccine must be maintained at a temperature of 8°C (46°F) or colder, but not to exceed temperatures lower than -50°C (-58°F). Use of dry ice may subject Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) to temperatures colder than -50°C (-58°F).
Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX) SHOULD BE STORED REFRIGERATED at a temperature of 2 to 8°C (36 to 46°F) or colder until it is reconstituted for injection (see DOSAGE & ADMINISTRATION). The diluent should be stored separately at room temperature (20 to 25°C, 68 to 77°F) or in the refrigerator (2 to 8°C, 36 to 46°F).
Before reconstitution, protect from light.
DISCARD IF RECONSTITUTED VACCINE IS NOT USED WITHIN 30 MINUTES.
DO NOT FREEZE THE RECONSTITUTED VACCINE.
Patient Counseling Information
The health care provider should inform the patient of the benefits and risks of Varicella-Zoster Virus Vaccine Live (Oka/Merck) (ZOSTAVAX).
Patients should be instructed to report any adverse reactions to their health care provider.
Pregnancy should be avoided for three months following vaccination.
ATC Classification
J07BK01 - varicella, live attenuated ; Belongs to the class of varicella viral vaccines.
Presentation/Packing
Vaccine (inj) 19,400 PFU/dose (lyophilized powd; single-dose vial + pre-filled syringe diluent) x 0.65 mL x 1's.
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