AFLURIA QUADRIVALENT SIDE EFFECTS
- Generic Name: afluria quadrivalent 2016
- Brand Name: Afluria Quadrivalent 2016
- Drug Class: Vaccines, Inactivated, Viral
SIDE EFFECTS
In adults 18 through 64 years of age, the most commonly reported injection-site adverse reaction observed in clinical studies with AFLURIA QUADRIVALENT administered by needle and syringe was pain (≥40%). The most common systemic adverse events observed were myalgia and headache (≥20%).
In adults 65 years of age and older, the most commonly reported injection-site adverse reaction observed in clinical studies with AFLURIA QUADRIVALENT administered by needle and syringe was pain (≥20%). The most common systemic adverse event observed was myalgia (≥10%).
The safety experience with AFLURIA (trivalent formulation) is relevant to AFLURIA QUADRIVALENT because both vaccines are manufactured using the same process and have overlapping compositions.
In adults 18 through 64 years of age, the most commonly reported injection-site adverse reactions observed in a clinical study with AFLURIA (trivalent formulation) using the PharmaJet Stratis Needle-Free Injection System were tenderness (≥80%), swelling, pain, redness (≥60%), itching (≥20%) and bruising (≥10%). The most common systemic adverse events were myalgia, malaise (≥30%) and headache (≥20%).
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a vaccine cannot be directly compared to rates in the clinical studies of another vaccine and may not reflect the rates observed in clinical practice.
Clinical safety data for AFLURIA QUADRIVALENT have been collected in one clinical trial, Study 1, a randomized, double-blind, active-controlled trial conducted in the US in 3449 subjects ages 18 years and older. Subjects in the safety population received one dose of either AFLURIA QUADRIVALENT (N=1721) or one of two formulations of comparator trivalent influenza vaccine (AFLURIA, TIV-1 N=864 or TIV-2 N=864) each containing an influenza type B virus that corresponded to one of the two B viruses in AFLURIA QUADRIVALENT (a type B virus of the Yamagata lineage or a type B virus of the Victoria lineage), respectively. The mean age of the population was 58 years, 57% were female, and racial groups consisted of 82% White, 16% Black, and 2% other; 5% of subjects were Hispanic/Latino. The age sub-groups were 18 through 64 years and 65 years and older with mean ages of 43 years and 73 years, respectively. In this study, AFLURIA QUADRIVALENT and comparator trivalent influenza vaccines were administered by needle and syringe.
Local (injection-site) adverse reactions and systemic adverse events were solicited for 7 days post-vaccination (Table 1). Injection site cellulitis, cellulitis-like reactions (defined as concurrent Grade 3 pain, redness, and swelling/lump), and Grade 3 swelling/lump were monitored for 28 days post-vaccination. Unsolicited adverse events were collected for 28 days post-vaccination. Serious adverse events (SAEs), including deaths, were collected for 180 days post-vaccination.
Table 1: Proportion of Subjects Per Age Cohort with Any Solicited Local Adverse Reactions or Systemic Adverse Events within 7 Days after Administration of AFLURIA QUADRIVALENT or Trivalent Influenza Vaccine (Study 1)a
| Percentage (%) b of Subjects in each Age Cohort Reporting an Event | ||||||||||||
| Subjects 18 through 64 years | Subjects ≥ 65 years | |||||||||||
| AFLURIA Quadrivalent N= 854 c |
TIV-1 N= 428 c |
TIV-2 N= 430 c |
AFLURIA Quadrivalent N= 867 c |
TIV-1 N= 436 c |
TIV-2 N= 434 c |
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| Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | Any | Gr 3 | |
| Local dverse Reactions d | ||||||||||||
| Pain | 47.9 | 0.7 | 43.7 | 1.4 | 50.7 | 1.2 | 24.6 | 0.1 | 22.7 | 0 | 21.0 | 0.2 |
| Swelling/Lump | 3.7 | 0.1 | 2.3 | 0 | 3.5 | 0.2 | 3.2 | 0.5 | 1.8 | 0 | 1.6 | 0 |
| Redness | 2.9 | 0 | 2.8 | 0 | 2.8 | 0 | 4.2 | 0.3 | 2.1 | 0 | 2.5 | 0.2 |
| Systemic Adverse Events e | ||||||||||||
| Myalgia (muscle ache) | 25.5 | 1.9 | 23.4 | 1.4 | 24.2 | 1.2 | 12.7 | 0.3 | 14.0 | 0.7 | 12.2 | 0.5 |
| Headache | 21.7 | 1.7 | 15.2 | 0.9 | 19.1 | 1.2 | 8.4 | 0 | 7.1 | 0.2 | 7.8 | 0.7 |
| Malaise | 8.9 | 0.7 | 9.1 | 0 | 9.3 | 0.7 | 4.4 | 0.5 | 5.0 | 0.2 | 5.1 | 0.2 |
| Nausea | 6.9 | 0.6 | 7.7 | 0.5 | 6.3 | 1.2 | 1.6 | 0 | 1.8 | 0 | 2.1 | 0.2 |
| Chills | 4.8 | 0.6 | 4.4 | 0.2 | 4.7 | 0.5 | 2.0 | 0 | 2.1 | 0.5 | 1.4 | 0.2 |
| Vomiting | 1.5 | 0.4 | 0.9 | 0 | 2.3 | 0.7 | 0.5 | 0.1 | 0 | 0 | 0.7 | 0.2 |
| Fever | 1.1 | 0.4 | 0.9 | 0 | 0.5 | 0 | 0.2 | 0 | 0.9 | 0 | 0.5 | 0.2 |
| Abbreviations: Gr 3, Grade 3. a NCT02214225 b Proportion of subjects reporting each solicited local adverse reaction or systemic adverse event by study vaccine group based on the number of subjects contributing any follow up safety information for at least one data value of an individual sign/symptom. c N = number of subjects in the Safety Population for each study vaccine group. d Local adverse reactions: Grade 3 pain is that which prevents daily activity; Swelling/Lump and redness: any = ≥ 20mm diameter, Grade 3 = ≥ 100mm diameter. e Systemic adverse events: Fever: any = ≥ 100.4°F, Grade 3 = ≥ 102.2°F; Grade 3 for all other adverse events is that which prevents daily activity. |
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In the 28 days following vaccination, no subject experienced cellulitis or a cellulitis-like reaction. All Grade 3 swelling/lump reactions began within 7 days of vaccination and are included in Table 1.
In the 28 days following vaccination, 20.5%, 20.1%, and 20.7% of adults 18 through 64 years and 20.3%, 24.1%, and 20.0% of adults ≥65 years who received AFLURIA QUADRIVALENT, TIV-1, and TIV-2, respectively, reported unsolicited adverse events. Rates of individual events were similar between treatment groups, and most events were mild to moderate in severity.
In the 180 days following vaccination, 2.3%, 1.6%, and 1.5% of all subjects who received AFLURIA QUADRIVALENT, TIV-1, and TIV-2, respectively, experienced SAEs, including six deaths, five in the AFLURIA QUADRIVALENT group and one in the TIV-2 group. The majority of SAEs occurred after Study Day 28 and in subjects ≥65 years of age who had co-morbid illnesses. No SAEs or deaths appeared related to the study vaccines.
Safety information has also been collected in a clinical study of AFLURIA (trivalent formulation) administered using the PharmaJet Stratis Needle-Free Injection System (Study 2). Study 2 included 1,247 subjects for safety analysis, ages 18 through 64 years, randomized to receive AFLURIA by either the PharmaJet Stratis Needle-Free Injection System (624 subjects) or needle and syringe (623 subjects). No deaths or vaccine-related serious adverse events were reported in Study 2. Local (injection-site) adverse reactions and systemic adverse events were solicited for 7 days post-vaccination (Table 2).
Table 2: Proportion of Subjects 18 through 64 Years of Age with Solicited Local Adverse Reactions or Systemic Adverse Events within 7 Days after Administration of AFLURIA (trivalent formulation) by PharmaJet Stratis Needle-Free Injection System or Needle and Syringe (Study 2)a
| Percentage b of Subjects Reporting Event | ||||
| Study 2 Subjects 18 through 64 years |
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| AFLURIA (trivalent formulation) | ||||
| PharmaJet Stratis Needle-Free Injection System N=540-616 c |
Needle and Syringe N=599-606 c |
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| Any | Grade 3 | Any | Grade 3 | |
| Local Adverse Reactions d | ||||
| Tenderness | 89.4 | 2.1 | 77.9 | 1.0 |
| Swelling | 64.8 | 1.7 | 19.7 | 0.2 |
| Pain | 64.4 | 0.8 | 49.3 | 0.7 |
| Redness | 60.1 | 1.3 | 19.2 | 0.3 |
| Itching f | 28.0 | 0.0 | 9.5 | 0.2 |
| Bruising | 17.6 | 0.2 | 5.3 | 0.0 |
| Systemic Adverse Events e | ||||
| Myalgia | 36.4 | 0.8 | 35.5 | 1.0 |
| Malaise | 31.2 | 0.7 | 28.4 | 0.5 |
| Headache | 24.7 | 1.3 | 22.1 | 1.3 |
| Chills | 7.0 | 0.2 | 7.2 | 0.2 |
| Nausea | 6.6 | 0.2 | 6.5 | 0.0 |
| Vomiting | 1.3 | 0.0 | 1.8 | 0.2 |
| Fever | 0.3 | 0.0 | 0.3 | 0.0 |
| a NCT01688921 b Proportion of subjects reporting each local adverse reaction or systemic adverse event by treatment group based on the number of subjects contributing at least one data value for an individual sign/symptom (individual event denominators). c N = number of subjects in the Safety Population for each treatment group. Denominators for the PharmaJet Stratis Needle-Free Injection System group were: N=540 for itching and N=605-616 for all other parameters. Denominators for the needle and syringe group were: N=527 for itching and N=599-606 for all other parameters. d Local adverse reactions: Grade 3 is pain, tenderness or itching that prevents daily activity; Swelling, redness or bruising: any = ≥ 25mm diameter, Grade 3 = > 100mm diameter. e Systemic adverse events: Fever: any = ≥ 100.4°F, Grade 3 = ≥ 102.2°F; Grade 3 for all other adverse events is that which prevents daily activity. f A total of 155 subjects (approximately randomly distributed between PharmaJet Stratis Needle-Free Injection System and needle and syringe groups) received Diary Cards without itching listed as a solicited symptom. |
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In adults 18 through 64 years who received AFLURIA (trivalent formulation) administered via PharmaJet Stratis Needle-Free Injection System, commonly reported unsolicited adverse events were headache (4.2%), injection site hematoma (1.8%), injection site erythema (1.1%), myalgia (1.0%) and nausea (1.0%).
Postmarketing Experience
Because postmarketing reporting of adverse events is voluntary and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. The adverse events described have been included in this section because they: 1) represent reactions that are known to occur following immunizations generally or influenza immunizations specifically; 2) are potentially serious; or 3) have been reported frequently. There are no postmarketing data available for AFLURIA QUADRIVALENT. The adverse events listed below reflect experience in both children and adults and include those identified during post-approval use of AFLURIA (trivalent formulation) outside the US since 1985.
The post-marketing experience with AFLURIA (trivalent formulation) included the following:
Blood And Lymphatic System Disorders
Thrombocytopenia
Immune System Disorders
Allergic or immediate hypersensitivity reactions including anaphylactic shock and serum sickness
Nervous System Disorders
Neuralgia, paresthesia, convulsions (including febrile seizures), encephalomyelitis, encephalopathy, neuritis or neuropathy, transverse myelitis, and GBS
Vascular Disorders
Vasculitis which may be associated with transient renal involvement
Skin And Subcutaneous Tissue Disorders
Pruritus, urticaria, and rash
General Disorders And Administration Site Conditions
Cellulitis and large injection site swelling
Influenza-like illness
SRC: NLM .