Slides for ZOSTAVAX

Chia sẻ: Than Kha Tu | Ngày: | Loại File: PDF | Số trang:23

0
40
lượt xem
5
download

Slides for ZOSTAVAX

Mô tả tài liệu
  Download Vui lòng tải xuống để xem tài liệu đầy đủ

Description: • Lyophilized preparation of the Oka/Merck strain of live, attenuated VZV. • Each 0.65-mL dose contains a minimum of 19,400 plaqueforming units (PFU).

Chủ đề:
Lưu

Nội dung Text: Slides for ZOSTAVAX

  1. ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] Approved by the Food and Drug Administration on May 25, 2006 1 1
  2. Description • Lyophilized preparation of the Oka/Merck strain of live, attenuated VZV. • Each 0.65-mL dose contains a minimum of 19,400 plaque- forming units (PFU). • Each dose also contains sucrose, hydrolyzed porcine gelatin, sodium chloride, monosodium L-glutamate, sodium phosphate dibasic, potassium phosphate monobasic, and potassium chloride; residual components of MRC-5 cells, including DNA and protein, and trace quantities of neomycin and bovine calf serum. • Contains no preservatives. 2 Description • ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is a lyophilized preparation of the Oka/Merck strain of live, attenuated VZV. • Each 0.65-mL dose of the vaccine contains a minimum of 19,400 plaque-forming units (PFU) of attenuated virus. • Each dose also contains sucrose, hydrolyzed porcine gelatin, sodium chloride, monosodium L-glutamate, sodium phosphate dibasic, potassium phosphate monobasic, and potassium chloride; residual components of MRC-5 cells, including DNA and protein, and trace quantities of neomycin and bovine calf serum. • The product does not contain preservatives. 2
  3. Indications and Usage • ZOSTAVAX is indicated for the prevention of herpes zoster (shingles) in individuals 60 years of age and older. • ZOSTAVAX is not indicated for the treatment of zoster or postherpetic neuralgia. 3 Indications and Usage • ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is indicated for the prevention of herpes zoster (or shingles) in individuals 60 years of age and older. • ZOSTAVAX is not indicated for the treatment of zoster or postherpetic neuralgia. 3
  4. Contraindications • ZOSTAVAX should not be administered to individuals: – With a history of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine (see WARNINGS). – With a history of primary or acquired immunodeficiency states including leukemia; lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system; or AIDS or other clinical manifestations of infection with human immunodeficiency viruses (see WARNINGS). – On immunosuppressive therapy, including high-dose corticosteroids. – With active untreated tuberculosis. – Who are or may be pregnant (see PRECAUTIONS, Pregnancy). 4 Contraindications ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is contraindicated in individuals who: • Have a history of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine (see WARNINGS). • Have a history of primary or acquired immunodeficiency states including leukemia; lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system; or AIDS or other clinical manifestations of infection with human immunodeficiency viruses (see WARNINGS). • Are on immunosuppressive therapy, including high-dose corticosteroids. • Have active untreated tuberculosis. • Are or may be pregnant. (Please refer to PRECAUTIONS, Pregnancy in the Prescribing Information.) 4
  5. Clinical Pharmacology: The Shingles Prevention Study Design Subjects Enrolled N=38,546 Adverse Event (AE) Substudy n=6,616 Immunogenicity Substudy n=1,395 Age 60 to 69 years Age ≥70 years n=20,747 n=17,799 Zoster vaccine Placebo Zoster vaccine Placebo n=10,378 n=10,369 n=8,892 n=8,907 Oxman MN, Levin MJ, Johnson GR, et al. N Engl J Med. 2005;352:2271–2284. 5 Clinical Pharmacology: The Shingles Prevention Study Design • The Shingles Prevention Study was a placebo-controlled, randomized, double-blind study.1 • The study enrolled a total of 38,546 subjects who were 60 years of age or older.1 • Randomization was stratified by age1: – 60 to 69 years of age – ≥70 years of age • Subjects were randomized to receive either a single dose of zoster vaccine (n=19,270) or placebo (n=19,276).1 • The median follow-up of the study was 3.1 years (range 31 days to 4.9 years). • The study excluded people who were immunocompromised or using corticosteroids on a regular basis, anyone with a previous history of HZ, and those with conditions that might interfere with study evaluations, including people with cognitive impairment, severe hearing loss, those who were non-ambulatory and those whose survival was not considered to be at least 5 years. • The clinical trial included 2 substudies1: – The Adverse Event (AE) Monitoring Substudy, which comprised 6,616 subjects. – An immunogenicity substudy, which comprised 1,395 subjects. • Zoster cases were confirmed by polymerase chain reaction (93%), viral culture (1%), or in the absence of viral detection, by the Clinical Evaluation Committee (6%). • Individuals in both vaccination groups who developed zoster were given famciclovir and, as necessary, pain medications.1 Reference: 1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271–2284. 5
  6. Patient Demographics in the Shingles Prevention Study Vaccine Group Placebo Group Characteristic N=19,270 N=19,276 Age n (%) 60 to 69 years 10,378 (53.9) 10,369 (53.8) ≥70 years 8,892 (46.1) 8,907 (46.2) Gender n (%) Male 11,403 (59.2) 11,357 (58.9) Female 7,867 (40.8) 7,919 (41.1) Race n (%) White 18,393 (95.4) 18,381 (95.4) Black 395 (2.0) 420 (2.2) Hispanic 265 (1.4) 248 (1.3) Other or unknown 217 (1.1) 227 (1.2) Oxman MN, Levin MJ, Johnson GR, et al. N Engl J Med. 2005;352:2271–2284. 6 Patient Demographics in the Shingles Prevention Study • Baseline patient characteristics were similar in both vaccination groups in the Shingles Prevention Study.1 – The age distribution of enrolled patients was 59 to 99 years in both groups. – The gender distribution was 59% male and 41% female.1 – The racial distribution of white (95%), black (2%), Hispanic (1%), and other (1%) was also similar in both groups.1 Reference: 1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271–2284. 6
  7. Prevention of Herpes Zoster –51% Placebo 700 (95% CI: 44%, 58%) ZOSTAVAX 600 642 Number of zoster cases 500 –64% 400 (95% CI: 56%, 71%) –41% 300 315 334 (95% CI: 28%, 52%) 261 200 156 –18% 100 122 (95% CI: –29%, 48%) 47 37 0 11.1 5.4 10.8 3.9 11.4 6.7 12.2 9.9 Incidence rate of zoster per 1,000 person-years Overall 60–69 70–79 ≥80 Age (years) 7 Prevention of Herpes Zoster • ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] significantly reduced the risk of developing zoster compared with placebo*: 315/19,254 cases (5.4 cases per 1,000 person-years) vs 642/19,247 cases [11.1 cases per 1,000 person-years]). The protective efficacy was 51% (95% CI: 44%, 58%).1 – Vaccine efficacy for the prevention of zoster was highest for those subjects 60 to 69 years of age and declined with increasing age. – ZOSTAVAX reduced the incidence of zoster by 64% in individuals 60 to 69 years of age (ZOSTAVAX, n=10,370; placebo, n=10,356); by 41% in individuals 70 to 79 years of age (ZOSTAVAX, n=7,621; placebo, n=7,559); and by 18% in individuals 80 years of age or older (ZOSTAVAX, n=1,263; placebo, n=1,332). • As with any vaccine, vaccination with ZOSTAVAX may not result in protection of all vaccine recipients. • The duration of protection after vaccination with ZOSTAVAX is unknown. In the Shingles Prevention Study, protection from zoster was demonstrated through 4 years of follow-up. The need for revaccination has not been defined. *Primary analysis was performed on the modified intent-to-treat (MITT) population that included all randomized patients who were followed for at least 30 days postvaccination and did not develop an evaluable case of zoster within the first 30 days postvaccination. Reference: 1. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271–2284. 7
  8. Postherpetic Neuralgia* in the Shingles Prevention Study 50 Placebo ZOSTAVAX With Postherpetic Neuralgia 40 % of HZ Cases 30 –26% (95% CI: –69%, 68%) –39%** –55% 25.5 20 (95% CI: 7%, 59%) (95% CI: 18%, 76%) 17.2 18.9 –5% 10 12.5 (95% CI: –107%, 56%) 8.6 6.9 6.6 7.7 0 Number of PHN Cases 80 27 23 8 45 12 12 7 Number of HZ Cases 642 315 334 122 261 156 47 37 Overall 60–69 70–79 ≥80 Age (years) *Zoster-associated pain rated as ≥3 on a 10-pt scale and occurring or persisting at least 90 days after rash onset. **Age-adjusted estimate based on the age strata (60–69 and ≥70 years of age) at randomization. 8 Postherpetic Neuralgia in the Shingles Prevention Study • Postherpetic neuralgia was defined as zoster-associated pain (rated as ≥3 on a 10- point scale by the patient) occurring or persisting at least 90 days following the onset of rash in evaluable cases of zoster. • Overall, the benefit of ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] in the prevention of postherpetic neuralgia can be primarily attributed to the effect of the vaccine on the prevention of zoster. Vaccination with ZOSTAVAX reduced the incidence of postherpetic neuralgia in individuals 70 years of age and older who developed zoster postvaccination. • Following completion of the Shingles Prevention Study, a separate analysis was conducted to evaluate the reduction in PHN in the group of individuals who have been vaccinated with ZOSTAVAX, but who had developed zoster. In the analysis, the overall efficacy of ZOSTAVAX for reduction of postherpetic neuralgia in patients who developed zoster following vaccination was 39% (95% CI: 7%, 59%). This is an age-adjusted estimate calculated based on the age strata of 60 to 69 and 70 years of age and older at randomization. • The vaccine efficacy against postherpetic neuralgia in patients who developed zoster following vaccination was 5% (95% CI: –107%, 56%) in patients 60 to 69 years of age; 55% (95% CI: 18%, 76%) in patients 70 to 79 years of age: and 26% (95% CI: –69%, 68%) in patients 80 years of age and older. 8
  9. Specific Complications* of Zoster Among HZ Cases in the Shingles Prevention Study ZOSTAVAX Placebo Complication (N = 19,270) (N = 19,276) % Among % Among ( n = 321) (n = 659) Zoster Cases Zoster Cases Allodynia 135 42.1 310 47.0 Bacterial Superinfection 3 0.9 7 1.1 Dissemination 5 1.6 11 1.7 Impaired Vision 2 0.6 9 1.4 Ophthalmic Zoster 35 10.9 69 10.5 Peripheral Nerve Palsies (motor) 5 1.6 12 1.8 Ptosis 2 0.6 9 1.4 Scarring 24 7.5 57 8.6 Sensory Loss 7 2.2 12 1.8 N=number of subjects randomized n=number of zoster cases, including those cases occurring within 30 days postvaccination, with these data available *Complications reported at a frequency of ≥1% in at least one vaccination group among patients with zoster. 9 Specific Complications of Zoster Among HZ Cases in the Shingles Prevention Study • The table shows the number of patients with specific complications of zoster among zoster cases that were reported in the Shingles Prevention Study at a frequency of ≥1% in at least one vaccination group among subjects with zoster. – The number of zoster cases included the cases that developed within 30 days after vaccination. • Prespecified zoster-related complications were reported less frequently in subjects who received ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] compared to subjects who received placebo. • Among HZ cases, zoster-related complications were reported at similar rates in both vaccination groups. • Visceral complications reported by fewer than 1% of subjects with zoster included 3 cases of pneumonitis and 1 case of hepatitis in the placebo group, and 1 case of meningoencephalitis in the vaccine group. 9
  10. Immunogenicity Substudy In the Shingles Prevention Study, ZOSTAVAX elicited higher VZV-specific antibody responses at 6 weeks after vaccination compared with placebo 2.00 in VZV antibody* Fold increase 1.75 1.7 (95% CI: 1.6, 1.8) 1.50 1.25 1.0 1.00 ZOSTAVAX Placebo n= 691 n= 704 *As measured by gpELISA=glycoprotein enzyme-linked immunosorbent assay. 10 Immunogenicity Substudy • Immune responses to vaccination were evaluated in a subset of 1,395 subjects enrolled in the Shingles Prevention Study. • The vaccine elicited higher VZV-specific antibody responses at 6 weeks after vaccination compared with placebo. – There was a 1.7-fold increase in VZV antibody geometric mean titers (GMT) as measured by gpELISA* (95% CI: 1.6, 1.8). – The specific antibody level that correlates with protection from zoster has not been established. *gpELISA = glycoprotein enzyme-linked immunosorbent assay. 10
  11. Warnings • Vaccination with a live attenuated vaccine, such as ZOSTAVAX, may result in a more extensive vaccine-associated rash or disseminated disease in individuals who are immunosuppressed. Safety and efficacy of ZOSTAVAX have not been evaluated in individuals on immunosuppressive therapy, nor in individuals receiving daily topical or inhaled corticosteroids or low-dose oral corticosteroids. • Neomycin allergy commonly manifests as a contact dermatitis, which is not a contraindication to receiving this vaccine. Persons with a history of anaphylactic reaction to topically or systemically administered neomycin should not receive ZOSTAVAX (see CONTRAINDICATIONS). • ZOSTAVAX is not a substitute for VARIVAX* [Varicella Virus Vaccine Live (Oka/Merck)] and should not be used in children. *Registered trademark of Merck & Co., Inc. 11 Warnings • Vaccination with a live attenuated vaccine, such as ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)], may result in a more extensive vaccine-associated rash or disseminated disease in individuals who are immunosuppressed. • Safety and efficacy of ZOSTAVAX have not been evaluated in individuals on immunosuppressive therapy, nor in individuals receiving daily topical or inhaled corticosteroids or low-dose oral corticosteroids. • Neomycin allergy commonly manifests as a contact dermatitis, which is not a contraindication to receiving this vaccine. Persons with a history of anaphylactic reaction to topically or systemically administered neomycin should not receive ZOSTAVAX (see CONTRAINDICATIONS). • ZOSTAVAX is not a substitute for VARIVAX* [Varicella Virus Vaccine Live (Oka/Merck)] and should not be used in children. *Registered trademark of Merck & Co., Inc. 11
  12. Selected Precautions • General – 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 acute illness (eg, fever >38.5°C [>101.3°F]) – The duration of protection is unknown. In the Shingles Prevention Study, protection from zoster was demonstrated through 4 years of follow-up. The need for revaccination has not been defined. – As with any vaccine, vaccination with ZOSTAVAX may not result in protection of all vaccine recipients. – The use of ZOSTAVAX in individuals with a previous history of zoster has not been studied. 12 Selected Precautions • 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 acute illness (eg, fever >38.5°C [>101.3°F]). • The duration of protection after vaccination with ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] is unknown. In the Shingles Prevention Study, protection from zoster was demonstrated through 4 years of follow-up. The need for revaccination has not been defined. • As with any vaccine, vaccination with ZOSTAVAX may not result in protection of all vaccine recipients. • The use of ZOSTAVAX in individuals with a previous history of zoster has not been studied. 12
  13. Selected Precautions (cont) • Transmission – Transmission of the vaccine virus has not been reported in clinical trials. – Postmarketing 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 without a VZV-like rash has been reported but has not been confirmed. – 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. – Vaccinees should be informed of the theoretical risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox. 13 Selected Precautions (cont) • Transmission of the vaccine virus has not been reported in clinical trials. • Postmarketing 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 without a VZV-like rash has been reported but has not been confirmed. • 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. • Vaccinees should be informed of the theoretical risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox. 13
  14. Selected Precautions (cont) • Drug Interactions – Concurrent administration of ZOSTAVAX and antiviral medications known to be effective against VZV has not been evaluated. – Concurrent administration of ZOSTAVAX and other vaccines has not been evaluated. • Pregnancy (Category C) – ZOSTAVAX should not be administered to pregnant females; furthermore, pregnancy should be avoided for 3 months following vaccination. • Nursing Mothers – Caution should be exercised if ZOSTAVAX is administered to a nursing woman. • Pediatric Use – ZOSTAVAX should not be used in children. 14 Selected Precautions (cont) • Concurrent administration of ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] and antiviral medications known to be effective against VZV has not been evaluated. Concurrent administration of ZOSTAVAX and other vaccines has not been evaluated. • ZOSTAVAX should not be administered to pregnant females; furthermore, pregnancy should be avoided for 3 months following vaccination. • Some viruses are excreted in human milk; however, it is not known whether VZV is secreted in human milk. Therefore, caution should be exercised if ZOSTAVAX is administered to a nursing woman. • ZOSTAVAX should not be used in children. 14
  15. Adverse Reactions • ZOSTAVAX was evaluated for safety in approximately 21,000 adults. • Shingles Prevention Study – Routine safety monitoring • ZOSTAVAX: n=15,925; placebo: n=16,005 • Patients were actively followed for safety outcomes through Day 42 postvaccination. • Subjects were followed passively for safety after Day 42 postvaccination to the end of the study. – AE Monitoring Substudy • ZOSTAVAX: n=3,345; placebo: n=3,271 • Vaccination report cards used to record AEs for 42 days postvaccination • Monthly surveillance for hospitalization 2 to 5 years postvaccination 15 Adverse Reactions • Overall, ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] has been evaluated in approximately 21,000 adults. • In the Shingles Prevention Study, patients were given either a single dose of the zoster vaccine (n=19,270) or placebo (n=19,276). • 15,925 subjects who received ZOSTAVAX and 16,005 subjects who received placebo, were actively followed for safety outcomes through Day 42 postvaccination. Patients were followed passively for safety after Day 42 postvaccination to the end of the study. • Patients enrolled in the AE Monitoring substudy (3,345 who received ZOSTAVAX and 3,271 who received placebo) used vaccination report cards to record AEs during the 42-day postvaccination period. Monthly surveillance for hospitalization was conducted through the end of the study, 2 to 5 years postvaccination. – 97% of patients in both vaccination groups completed the vaccination report cards. 15
  16. Number of Subjects With ≥1 Serious Adverse Experience (0-42 Days Postvaccination) in the Shingles Prevention Study Relative ZOSTAVAX Placebo Risk n/N n/N (RR) Cohort % % (95% CI) Overall Study Cohort 255/18,671 254/18,717 1.01 (all ages) 1.4% 1.4% (0.85, 1.20) 60-69 years old 113/10,100 101/10,095 1.12 1.1% 1.0% (0.86, 1.46) 70-79 years old 115/7,351 132/7,333 0.87 1.6% 1.8% (0.68, 1.11) ≥80 years old 27/1,220 21/1,289 1.36 2.2% 1.6% (0.78, 2.37) AE Monitoring Substudy Cohort 64/3,326 41/3,249 1.53 (all ages) 1.9 1.3 (1.04, 2.25) 60-69 years old 22/1,726 18/1,709 1.21 1.3% 1.1% (0.66, 2.23) 70-79 years old 31/1,383 19/1,367 1.61 2.2% 1.4% (0.92, 2.82) ≥80 years old 11/217 4/173 2.19 5.1% 2.3% (0.75, 6.45) N = number of subjects in cohort with safety follow-up n = number of subjects reporting an SAE 0–42 days postvaccination 16 Number of Subjects With ≥1 Serious Adverse Experience (0-42 Days Postvaccination) in the Shingles Prevention Study • In the overall study population, SAEs occurred at a similar rate of 1.4% in patients who received either ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] or placebo (relative risk [RR]: 1.01). – Investigator-determined, vaccine-related SAEs were reported for 2 subjects vaccinated with ZOSTAVAX (asthma exacerbation and polymyalgia rheumatica) and 3 patients who received placebo (Goodpasture’s syndrome, anaphylactic reaction, and polymyalgia rheumatica). • In the AE Monitoring Substudy, the rate of SAEs was increased in the group that received ZOSTAVAX compared to the placebo group (1.9% vs 1.3%, respectively; RR: 1.53). • The overall incidence of death occurring from Day 0 to Day 42 postvaccination was similar in both groups: 14 deaths occurred in subjects who received ZOSTAVAX and 16 deaths occurred in the placebo group. The most common cause of death in both groups was cardiovascular disease (10 in the group who received ZOSTAVAX and 8 in the group who received placebo). The overall incidence of death occurring at any time during the study was similar between vaccination groups (4.1%). 16
  17. Selected Serious Adverse Experiences (SAE) Reported More Frequently After ZOSTAVAX than After Placebo Days 0-42 Postvaccination in the Shingles Prevention Study AE Monitoring Substudy Entire Study Cohort ZOSTAVAX Placebo ZOSTAVAX Placebo N = 3,326 N = 3,249 N = 18,671 N = 18,717 n (%) n (%) n (%) n (%) Overall Cardiovascular events by body system 20 (0.6) 12 (0.4) 81 (0.4) 72 (0.4) Coronary Artery Disease-related conditions1 10 (0.3) 5 (0.2) 45 (0.2) 35 (0.2) N=number of subjects with safety follow-up n=number of subjects reporting SAE within the category 1CAD-related conditions: angina pectoris, coronary artery disease, coronary occlusion, cardiovascular disorder, myocardial ischemia, & myocardial infarction 17 Selected Serious Adverse Experiences (SAE) Reported More Frequently After ZOSTAVAX than After Placebo Days 0-42 Postvaccination in the Shingles Prevention Study • This table displays selected cardiovascular SAEs occurring in the SPS within 42 days postvaccination. • For the entire Shingles Prevention Study population, the rates of overall cardiovascular events (0.4%), including coronary artery disease-related conditions (0.2%), were similar in subjects vaccinated with ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] or placebo. • In the AE Monitoring Substudy of the Shingles Prevention Study, between Days 0 to 42 postvaccination, the rate of overall cardiovascular events was higher after ZOSTAVAX (0.6%) than after placebo (0.4%), including the rate of coronary artery disease-related conditions postvaccination (ZOSTAVAX 0.3%, placebo 0.2%). 17
  18. Injection-Site and Systemic Adverse Experiences Reported by vaccine report card in ≥1% of adults who received ZOSTAVAX or placebo (0 to 42 days postvaccination) in the AE monitoring substudy of the Shingles Prevention Study ZOSTAVAX Placebo (n = 3,345) (n= 3,271) Adverse Experience % % Injection Site Erythema* 33.7 6.4 Pain/tenderness* 33.4 8.3 Swelling* 24.9 4.3 Hematoma 1.4 1.4 Pruritus 6.6 1.0 Warmth 1.5 0.3 Systemic Headache 1.4 0.8 *Designates a solicited adverse experience. Injection-site adverse experiences were solicited only from Days 0–4 postvaccination. 18 Injection-Site and Systemic Adverse Experiences • Vaccine-related injection-site reactions and systemic AEs reported at an incidence of 1% or greater in the AE Monitoring Substudy are shown in the table. • Most of these AEs were reported as mild in intensity. • The overall incidence of vaccine-related injection-site reactions was significantly greater in subjects who received ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] (48%) compared with those who received placebo (17%). • The numbers of patients with elevated temperature (≥38.3°C [≥101.0°F]) within 42 days postvaccination were similar in the ZOSTAVAX and the placebo groups (0.8% vs 0.9%, respectively). 18
  19. Adverse Events Occurring After Day 42 Postvaccination • AE Monitoring Substudy subjects in the Shingles Prevention Study were monitored for hospitalizations through monthly automated phone queries and the remainder of subjects were passively monitored for safety in this study from Day 43 postvaccination through study end. • Over the course of the study (4.9 years), 51 individuals (1.5%) receiving ZOSTAVAX were reported to have congestive heart failure (CHF) or pulmonary edema compared to 39 individuals (1.2%) receiving placebo in the AE Monitoring Substudy; 58 individuals (0.3%) receiving ZOSTAVAX were reported to have congestive heart failure (CHF) or pulmonary edema compared to 45 (0.2%) individuals receiving placebo in the overall study. 19 Adverse Events Occurring after Day 42 Postvaccination • This slide shows adverse events occurring after Day 42 postvaccination through the end of the study, a total of 4.9 years. 19
  20. Noninjection-Site Rash • Shingles Prevention Study (0–42 days postvaccination) – 53 noninjection-site zoster-like rashes reported • 17 for ZOSTAVAX vs 36 for placebo • Oka/Merck strain of VZV not detected in any of the 41 evaluable specimens – 59 varicella-like rashes reported • VZV not detected in any of the 10 evaluable specimens • Other clinical trials – Low reported rates of noninjection-site zoster-like and varicella-like rashes 20 Noninjection-Site Rash • Within the 42-day postvaccination reporting period in the Shingles Prevention Study, noninjection-site zoster-like rashes were reported in 17 subjects who received ZOSTAVAX® [Zoster Vaccine Live (Oka/Merck)] and in 36 subjects who received placebo. – Of the 53 rashes reported, 41 had specimens that were adequate for polymerase chain reaction (PCR) testing. – Wild-type VZV was detected in 25 specimens (5 for the zoster vaccine and 20 for placebo). – Oka/Merck strain of VZV was not detected in any of these specimens. • Of reported varicella-like rashes (n=59), VZV was not detected in any of the 10 specimens that were adequate for PCR testing. • In all other clinical trials with the zoster vaccine, the rates of reported noninjection- site zoster-like and varicella-like rashes within 42 days after vaccination were also low; of the 17 reported varicella-like and noninjection-site, zoster-like rashes in subjects receiving either the zoster vaccine or placebo, 10 were adequate for PCR testing. The Oka/Merck strain was identified by PCR from specimens of 2 subjects who reported varicella-like rashes (onset on Day 8 and 17). 20
Đồng bộ tài khoản