Zostavax

Zostavax

vaccine, varicella-zoster

Manufacturer:

Merck Sharp & Dohme

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Live attenuated varicella-zoster virus (Oka/Merck strain).
Description
Each 0.65 mL dose of lyophilized preparation of the Oka/Merck strain of live, attenuated varicella-zoster virus (VZV) for reconstitution contains not less than 19,400 plaque-forming units (PFU) supplied as single-dose vials.
Each dose of reconstituted vaccine contains trace quantities of neomycin. When reconstituted, Zostavax is a semi-hazy to translucent, off white to pale yellow liquid.
Action
Pharmacology: Pharmacodynamics: Herpes Zoster: Herpes zoster (HZ), also known as shingles or simply "zoster", is a manifestation of the reactivation of VZV, which, as a primary infection, produces chickenpox (varicella). Following initial infection, the virus remains latent in the dorsal root or cranial sensory ganglia until it reactivates, producing zoster. 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 (approximately 98%) in U.S. are susceptible to zoster, where an estimated 1 million cases occur annually. This number is expected to rise as the mean age group of the population increases. The incidence and severity of zoster, as well as the frequency and severity of its complications, increase markedly with age, with 2/3 of the cases occurring in individuals >50 years. 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, 50% of individuals will have experienced an episode of zoster.
Seventy (70) to 80% of hospitalizations for zoster occur among immunocompetent individuals. In U.S., approximately 50,000-60,000 zoster-associated hospitalizations, including 12,000-19,000 in which the primary diagnosis is zoster, occur each year.
Zoster may be associated with serious complications eg, 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 (PHN): PHN constitutes the most common serious complication and cause of zoster-associated morbidity in the immunocompetent host. Published literature estimates the prevalence of PHN in U.S. population to be 500,000-1,000,000 cases. The frequency and severity of PHN increase with age, and may complicate 25-50% of zoster cases among patients >50 years. 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 one of the most distressing and debilitating types of pain. Several definitions of PHN are widely used in the medical community, including pain persisting >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. 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 Clinical Studies: Immunogenicity of Zostavax as follows.)
Clinical Studies: Evaluation of Clinical Efficacy Afforded by Zostavax: Zostavax Efficacy and Safety Trial (ZEST) in Subject 50-59 Years: In the ZEST, a placebo-controlled, double-blind clinical trial in which 22,439 subjects 50-59 years were randomized to receive a single-dose of either 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 0-2 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%).
Zostavax significantly decreased the incidence of zoster compared with placebo [30 cases (2/1000 person-years) vs 99 cases (6.6/1000 person-years), respectively; p<0.001)]. The protective efficacy of Zostavax against zoster was 69.8% [95% CI: (54.1-80.6%)].
Evaluation of Clinical Efficacy Afforded by Zostavax: In the shingles prevention study (SPS) a placebo-controlled, double-blind clinical trial of Zostavax, 38,546 subjects ≥60 years were randomized to receive a single dose of either Zostavax (n=19,270) or placebo (n=19,276) and were followed for the development of zoster for an average of 3.1 years (1 day-4.9 years). Randomization was stratified by age, 60-69 and ≥70 years. 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 (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 0-10 scale, using the zoster brief pain inventory (ZBPI), a validated questionnaire. A score of ≥3 was considered clinically significant because it correlates with significant interference with activities of daily living (ADL).
Zostavax significantly reduced the risk of developing zoster and PHN compared with placebo. In addition, Zostavax significantly reduced acute and chronic zoster-associated pain as measured by the HZ pain burden of illness (BOI) score. (See Table 1).

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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 Zostavax against zoster was 51% [95% CI: (44-58%)]. Zostavax reduced the incidence of zoster by 64% [95% CI: (56-71%)] in individuals 60-69 years and by 38% [95% CI: (25-48%)] in individuals ≥70 years. The cumulative incidence of zoster over time among vaccine recipients was also significantly reduced (p<0.001). (See Figure 1).

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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 Zostavax against PHN was 67% [95% CI: (48-79%)] and the reduction was similar for the 2 age groups (60-69 and ≥70 years). In addition, the efficacy of Zostavax did not change appreciably when PHN was defined using alternative cutoff times (30, 60, 120 or 182 days) for duration of pain. Zostavax significantly reduced the cumulative incidence of PHN over time compared with placebo (p<0.001). (See Figure 2).

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Zostavax reduced the HZ pain BOI score by approximately 61% [95% CI: (51-69%)], compared with placebo. Zostavax reduced the HZ pain BOI score to a similar extent for the 2 age groups (60-69 and ≥70 years). 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.
Zostavax reduced the incidence of zoster with severe and long-lasting zoster-associated pain (severity-by-duration score >600) by 73% [95% CI: (46-87%)] compared with placebo. Eleven (11) subjects vaccinated with Zostavax had severity-by-duration scores >600 compared with 40 subjects who received placebo. (See Figure 3).
Among vaccinated individuals who developed zoster, 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 Zostavax and 181 for placebo, p=0.008).

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Among vaccinated individuals who developed PHN, 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 Zostavax and 805 for placebo; p=0.016).
To evaluate the impact of 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 0-10 scale (0 being no interference and 10 being maximum interference). Compared to placebo, Zostavax led to a favorable, but not statistically significant, reduction (8%) 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, 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 Zostavax and 83 for placebo; p=0.002).
The use of antiviral drugs within 72 hrs of zoster rash onset did not have a significant effect on the efficacy of 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.
Fewer complications were reported by subjects who received Zostavax compared with subjects who received placebo. The number of subjects with specific complications of zoster that were reported in the SPS at a frequency of ≥1% is shown in Table 2. (See Table 2).

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Visceral complications eg, pneumonitis, hepatitis, and meningoencephalitis were reported by <1% of subjects with zoster (3 cases of pneumonitis and 1 case of hepatitis in the placebo group; 1 case of meningoencephalitis in the vaccine group).
Immunogenicity of Zostavax: Within ZEST, immune responses to vaccination were evaluated in a random 10% subcohort (n=1136 for Zostavax and n=1133 for placebo) of the subjects enrolled in the ZEST. Zostavax elicited higher VZV-specific immune responses at 6 weeks post-vaccination compared with placebo. Increases in VZV antibody level, measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were demonstrated [2.3-fold difference (95% Cl: 2.2, 2.4), geometric mean titer (GMT) of 664 vs 228 gpELISA units/mL, p<0.001].
Within the SPS, immune responses to vaccination were evaluated in a subset of the enrolled subjects (N=1395). Zostavax elicited higher VZV-specific immune responses at 6 weeks post-vaccination compared with placebo. Increases in both VZV antibody level, measured by 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-γ 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 2 clinical trials evaluating immune response to Zostavax at 4 weeks post-vaccination, responses were generally similar in subjects 50-59 (N=389) compared to subjects ≥60 years (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: (2.4-2.9)] in subjects 50-59 years and 2.3-fold [95% CI: (2.1-2.4)] in subjects ≥60 years.
Immunogenicity following Concomitant Administration: In a double-blind, controlled clinical trial, 762 adults ≥50 years were randomized to receive a single dose of Zostavax administered either concomitantly (N=382) or nonconcomitantly (N=380) with inactivated influenza vaccine. Subjects enrolled in the concomitant group received Zostavax and influenza vaccine on day 1 and placebo at week 4. Subjects enrolled in the nonconcomitant group received influenza vaccine and placebo on day 1 and Zostavax at week 4. The antibody responses to both vaccines at 4 weeks post-vaccination were similar, whether administered concomitantly or nonconcomitantly.
In a double-blind, controlled clinical trial, 473 adults ≥60 years , were randomized to receive Zostavax and Pneumovax 23 concomitantly (N=237), or Pneumovax 23 alone followed 4 weeks later by Zostavax alone (N=236). At 4 weeks post-vaccination, 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=0.7 [95% CI: (0.61, 0.8)]. VZV antibody levels 4 weeks post-vaccination 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 2 groups. Concomitant use of Zostavax and Pneumovax 23 demonstrated a safety profile that was generally similar to that of the 2 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, Zostavax was administered to 100 subjects ≥50 years with a history of HZ prior to vaccination to assess immunogenicity of Zostavax. Zostavax induced a significantly higher VZV-specific immune response as measured by gpELISA at 4 weeks post-vaccination, compared with placebo [2.1-fold difference [95% CI: (1.5-2.9), p<0.001], GMT of 812 vs 393 gpELISA units/mL]. VZV antibody responses were generally similar in subjects 50-59 compared to subjects ≥60 years.
Immunogenicity in Subjects on Chronic/Maintenance Systemic Corticosteroids: In a double-blind, placebo-controlled, randomized clinical trial, Zostavax was administered to 206 subjects ≥60 years who were receiving chronic/maintenance systemic corticosteroid therapy at a daily dose equivalent of 5-20 mg of prednisone for at least 2 weeks prior to enrollment, and >6 weeks following vaccination to assess the immunogenicity and safety profile of Zostavax. Compared with placebo, Zostavax induced a higher VZV-specific gpELISA antibody GMT at 6 weeks post-vaccination (GMT of 531.1 vs. 224.3 gpELISA units/mL, respectively). The geometric mean fold-rise of the VZV antibody response, as measured by gpELISA, from prevaccination to post-vaccination was 2.3 [95% CI: (2-2.7) in the Zostavax group compared to 1.1 (95% CI: 1-1.2) in the placebo group (see Contraindications).
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 7320 subjects previously vaccinated with Zostavax and 6950 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 Zostavax, at which time they were considered to have completed the STPS.
The STPS analyses for vaccine efficacy are based on data collected primarily 4-7 years post-vaccination in the SPS. The median follow-up in the STPS was approximately 1.2 years (range is 1 day to 2.2 years). In the STPS, there were 84 evaluable HZ cases in the 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%).
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 Zostavax on subjects vaccinated in the SPS. A total of 6687 subjects previously vaccinated with 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 10 following vaccination in the SPS. Median follow up during the LTPS was approximately 3.9 years (range is 1 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%).
Indications/Uses
Prevention of herpes zoster (shingles) and postherpetic neuralgia (PHN); reduction of acute and chronic zoster-associated pain; immunization of individuals ≥50 yr.
Dosage/Direction for Use
Individuals should receive a single dose. At present, the duration of protection after vaccination with 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.
Zostavax is not a treatment for zoster or postherpetic neuralgia (PHN).
Administration: Zostavax is for SC administration. Do not inject intravascularly.
Zostavax can be administered concomitantly with inactivated influenza vaccine using separate syringes (see Pharmacology: Clinical Studies under Actions).
Reconstitution: Reconstitute immediately upon removal from the refrigerator.
Use only the diluent supplied, since it is free of preservatives or other antiviral substances which might inactivate the vaccine virus.
Vial of Diluent: To reconstitute the vaccine, first withdraw the entire contents of the diluent vial into a syringe. Inject all of 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 SC, preferably into the upper arm (deltoid region).
Pre-filled 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 SC, preferably into the upper arm (deltoid region).
It is recommended that the vaccine be administered immediately after reconstitution, to minimize loss of potency.
Overdosage
There are no data with regard to overdosage.
Contraindications
Hypersensitivity to any components of Zostavax, including gelatin.
History of anaphylactic/anaphylactoid reaction to 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.
Primary and acquired immunodeficiency states due to conditions eg, acute and chronic leukemias; lymphoma; other conditions affecting the bone marrow or lymphatic system; immunosuppression due to human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS); cellular immune deficiencies.
Immunosuppressive therapy (including high-dose corticosteroids); however, 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 eg, for adrenal insufficiency.
Active untreated tuberculosis.
Use in pregnancy: Animal reproduction studies have not been conducted with Zostavax. It is also not known whether Zostavax can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. However, naturally occurring varicella-zoster virus (VZV) infection is known to sometimes cause fetal harm. Therefore, Zostavax should not be administered to pregnant females; furthermore, pregnancy should be avoided for 3 months following vaccination.
Special Precautions
The healthcare provider should question the patient about reactions to a previous dose of any varicella-zoster virus (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 Zostavax have not been established in adults who are known to be infected with HIV with or without evidence of immunosuppression (see Contraindications).
As with any vaccine, vaccination with Zostavax may not result in protection of all vaccine recipients.
Transmission: In clinical trials with 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 vaccines 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 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 the Ability to Drive or Operate Machinery: There are no data to suggest that Zostavax affects the ability to drive or operate machinery.
Use in 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 Zostavax is administered to a nursing woman.
Use in children: Zostavax is not recommended for use in this age group.
Use in the elderly: The mean age of subjects enrolled in the largest (N=38,546) clinical study of Zostavax was 69 years (59-99 years). Of the 19,270 subjects who received Zostavax, 10,378 were 60-69 years, 7629 were 70-79 years, and 1263 were ≥80 years. Zostavax was demonstrated to be generally safe and effective in this population.
Use In Pregnancy & Lactation
Use in pregnancy: Animal reproduction studies have not been conducted with Zostavax. It is also not known whether Zostavax can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. However, naturally occurring varicella-zoster virus (VZV) infection is known to sometimes cause fetal harm. Therefore, Zostavax should not be administered to pregnant females; furthermore, pregnancy should be avoided for 3 months following vaccination.
Use in 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 Zostavax is administered to a nursing woman.
Adverse Reactions
In clinical trials, Zostavax has been evaluated for general safety in >20,000 adults ≥50 years. Zostavax was generally well tolerated.
Zostavax Efficacy and Safety Trial (ZEST) in Subjects 50-59 Years: In the ZEST study, subjects received a single dose of either 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 Zostavax (anaphylactic reaction).
All subjects received a vaccination report card (VRC) to record adverse events occurring from days 1-42 post-vaccination 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 post-vaccination) 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 Zostavax versus subjects who received placebo (63.9% for Zostavax and 14.4% for placebo).
Within the 42-day post-vaccination reporting period in the ZEST, non-injection-site zosteriform rashes were reported by 34 subjects (19 for 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 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 post-vaccination reporting period in the ZEST, varicella-like rashes were reported by 124 subjects (69 for 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 Zostavax; however, the virus strain (wild type or Oka/Merck strain) could not be determined.
Shingles Prevention Study (SPS) in Subjects ≥60 Years: In the largest of these trials, shingles prevention study (SPS), 38,546 subjects received a single dose of either Zostavax (n=19,270) or placebo (n=19,276) and were monitored for safety throughout the study. During the study, a vaccine-related serious adverse experience was reported for 2 subject vaccinated with 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=3345 received Zostavax and n=3271 received placebo) were provided vaccination report cards to record adverse events occurring from days 0-42 post-vaccination 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. Severe adverse experiences were solicited (days 0-4 post-vaccination) and are designated with the asterisk (*) symbol.
Nervous System Disorders: 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 Zostavax versus subjects who received placebo (48% for 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 post-vaccination reporting period in the SPS, the number of reported zosteriform rashes among all subjects was small (17 for 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 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 post-vaccination 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 Zostavax, the reported rates of non-injection-site zosteriform and varicella-like rashes within 42 days post-vaccination 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 days 8 and 17) confirmed to be Oka/Merck strain.
In clinical trials evaluating Zostavax in subjects ≥50 years, 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 compared with subjects ≥60 years.
In a double-blind, placebo-controlled, randomized clinical trial, Zostavax was administered to 100 subjects ≥50 years with a history of HZ prior to vaccination to assess immunogenicity of 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.
In a double-blind, placebo-controlled, randomized clinical trial, Zostavax was administered to 206 subjects ≥60 years who were receiving chronic/maintenance systemic corticosteroid therapy at a daily dose equivalent of 5-20 mg of prednisone for at least 2 weeks prior to enrollment, and 6 weeks or more following vaccination to assess the immunogenicity and safety profile of Zostavax. In this clinical trial, the safety profile was generally similar to that seen in the adverse event monitoring substudy of the SPS. (See Contraindications).
To address concerns for individuals with an unknown history of vaccination with Zostavax, the safety and tolerability of a 2nd dose of Zostavax was evaluated. In a placebo-controlled, double-blind study, 98 adults ≥60 years received a 2nd dose of Zostavax 42 days following the initial dose; the vaccine was generally well tolerated. The frequency of vaccine-related adverse experiences after the 2nd dose of Zostavax was generally similar to that seen with the 1st dose.
Post-Marketing Experience: The following additional adverse reactions have been identified during post-marketing use of 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.
Skin and Subcutaneous Tissue Disorders: Rash.
Musculoskeletal and Connective Tissue Disorders: Arthralgia; myalgia.
General Disorders and Administration Site Conditions: Injection site rash and urticaria; pyrexia; transient injection site lymphadenopathy.
Immune System Disorders: Hypersensitivity reactions including anaphylactic reactions.
Drug Interactions
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 Zostavax and antiviral medications known to be effective against VZV has not been evaluated.
Zostavax and Pneumovax 23 should not be given concomitantly because concomitant use resulted in reduced immunogenicity of Zostavax (see Pharmacology: Pharmacodynamics under Actions).
Caution For Usage
Do not freeze the reconstituted vaccine. Discard if reconstituted vaccines is not used within 30 min.
A sterile syringe free of preservatives, antiseptics and detergents should be used for each injection and/or reconstitution of Zostavax because these substances may inactivate the vaccine virus.
A separate sterile needle and syringe should be used for administration of 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. (See Description.)
Storage
Shipment: During shipment, to ensure that there is no loss of potency, Zostavax must be maintained at a temperature of 8°C (46°F) or colder.
Vial: Store at an average temperature of 2-8°C (36-46°F) or colder until it is reconstituted for injection (see Dosage & Administration).
Protect from light before reconstitution.
Diluent: Store separately at room temperature (20-25°C, 68-77°F) or in the refrigerator at (2-8°C, 36-46°F).
ATC Classification
J07BK01 - varicella, live attenuated ; Belongs to the class of varicella viral vaccines.
Presentation/Packing
Vaccine (inj) (white to off-white, compact, crystalline pellet, lyophilized, single-dose vial) 0.65 mL x 1's, 10's.
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