AFLURIA QUADRIVALENT 2020 SIDE EFFECTS

  • Generic Name: 2020 influenza vaccine suspension for intramuscular injection
  • Brand Name: Afluria Quadrivalent 2020
Last updated on MDtodate: 10/04/2022

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%).

In children 5 through 8 years, the most commonly reported injection-site adverse reactions when AFLURIA QUADRIVALENT was administered by needle and syringe were pain (≥ 50%) and redness and swelling (≥ 10%). The most common systemic adverse event was headache (≥ 10%).

In children 9 through 17 years, the most commonly reported injection-site adverse reactions when AFLURIA QUADRIVALENT was administered by needle and syringe were pain (≥ 50%) and redness and swelling (≥ 10%). The most common systemic adverse events were headache, myalgia, and malaise and fatigue (≥ 10%).

In children 6 months through 35 months of age, the most frequently reported injection site reactions in the clinical study with AFLURIA QUADRIVALENT administered by needle and syringe were pain and redness (≥ 20%). The most common systemic adverse events were irritability (≥ 30%), diarrhea and loss of appetite (≥ 20%).

In children 36 through 59 months of age, the most commonly reported injection site reactions were pain (≥ 30%) and redness (≥ 20%). The most commonly reported systemic adverse events were malaise and fatigue, and diarrhea (≥ 10%).

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.

Adults

Clinical safety data for AFLURIA QUADRIVALENT in adults have been collected in one clinical trial, Study 1, a randomized, double-blind, active-controlled trial conducted in the U.S. 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
Any Gr 3 Any Gr 3 Any Gr 3 Any Gr 3 Any Gr 3 Any Gr 3
Local Adverse Reactionsd
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 Eventse
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 (Oral), Grade 3 = ≥ 102.2°F (Oral); Grade 3 for all other adverse events is that which prevents daily activity.

 

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 135 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

Percentageb of Subjects Reporting Event
Subjects 18 through 64 years
AFLURIA (trivalent formulation)
PharmaJet Stratis Needle-Free Injection System
N=540-616 c
Needle and Syringe
N=599-606 c
Any Grade 3 Any Grade 3
Local Adverse Reactionsd
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 (Oral), Grade 3 = ≥ 102.2°F (Oral); 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.

 

In adults 18 through 64 years who received AFLURIA (trivalent formulation) administered by 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%).

Children 5 Years Through 17 Years Of Age

Clinical safety data for AFLURIA QUADRIVALENT in older children and adolescents have been collected in one clinical trial, Study 3, a randomized, observer-blinded, comparator-controlled trial conducted in the U.S. in 2278 subjects aged 5 through 17 years. Subjects were stratified into one of two age cohorts of 5 through 8 years or 9 through 17 years (51.2% and 48.8% of the study population, respectively). The mean age of the population was 9.5 years, 52.1% were male, and racial groups consisted of 73.3% White, 20.7% Black, 0.8% Asian, 0.3% American Indian/Native American, and 0.7% Native Hawaiian/Pacific Islander; 23.8% of subjects were Hispanic/Latino. The mean ages of subjects 5 through 8 years and 9 through 17 years were 6.7 years and 12.5 years, respectively. Subjects in the safety population (N=2252) received either AFLURIA QUADRIVALENT (N=1692) or a U.S.-licensed comparator quadrivalent influenza vaccine (N=560). Study subjects were scheduled to receive either a single vaccination or two vaccinations 28 days apart based on their previous vaccination history. In this study, AFLURIA QUADRIVALENT and comparator vaccine were administered by needle and syringe.

Local (injection site) adverse reactions and systemic adverse events were solicited for 7 days post-vaccination. Cellulitis-like reactions (defined as concurrent Grade 3 pain, redness, and swelling/lump) at the injection site were monitored for 28 days post-vaccination. Subjects were instructed to report and return to clinic within 24 hours in the event of a cellulitis-like reaction. Unsolicited adverse events were collected for 28 days post-vaccination. All solicited local adverse reactions and systemic adverse events following any vaccination (first or second dose) are presented in Table 3.

Table 3: 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 Comparator (Study 3)a

Percentage (%) b of Subjects in each Age Cohort Reporting an Event
Subjects 5 through 8 years Subjects 9 through 17 years
AFLURIA Quadrivalent
N= 828-829c
Comparator
N= 273-274c
AFLURIA Quadrivalent
N= 790-792c
Comparator
N= 261c
Any Gr 3 Any Gr 3 Any Gr 3 Any Gr 3
Local Adverse Reactions d
Pain 51.3 0.8 49.6 0.7 51.5 0.3 45.2 0.4
Redness 19.4 3.5 18.6 1.8 14.8 1.9 16.1 1.9
Swelling/Lump 15.3 3.4 12.4 2.2 12.2 2.0 10.7 1.9
Systemic Adverse Events e
Headache 12.3 0.1 10.6 0.4 18.8 0.4 14.6 0.4
Myalgia 9.8 0.1 11.3 0.4 16.7 0.3 11.1 0.4
Malaise and Fatigue 8.8 0.4 5.8 0 10.0 0.4 7.7 0
Nausea 7.1 0.1 8.4 0 7.7 0 8.0 0
Diarrhea 5.2 0 3.6 0 5.4 0 4.2 0
Fever 4.5 1.2 3.6 0.7 2.1 0.5 0.8 0
Vomiting 2.4 0.2 4.4 0 1.8 0 2.3 0
Abbreviations: Gr 3, Grade 3 (severe); Comparator, Comparator quadrivalent influenza vaccine [Fluarix® Quadrivalent (GlaxoSmithKline Biologicals)]
aNCT02545543
b Percent (%) is derived from the number of subjects that reported the event divided by the number of subjects in the Solicited Safety Population with non-missing data for each age cohort, treatment group, and each solicited parameter.
cN = number of subjects in the Solicited Safety Population (subjects who were vaccinated and provided any solicited safety data) for each study vaccine group.
d Local adverse reactions: Grade 3 pain is that which prevents daily activity; swelling/lump and redness: any = > 0mm diameter, Grade 3 = > 30mm diameter.
e Systemic adverse events: Fever: any = ≥ 100.4°F (Oral), Grade 3 = ≥ 102.2°F (Oral); Grade 3 for all other adverse events is that which prevents daily activity or requires significant medical intervention.

 

In subjects 5 through 8 years of age, all solicited local adverse reactions and systemic adverse events were reported at lower frequencies after the second vaccination than after the first vaccination with AFLURIA QUADRIVALENT with the exception of vomiting (which occurred at the same rate of 2.2% after each vaccination).

One subject, 8 years of age, experienced a cellulitis-like reaction at the injection site after vaccination with AFLURIA QUADRIVALENT.

The most commonly reported unsolicited adverse events in the 28 days following the first or second dose of AFLURIA QUADRIVALENT in subjects 5 through 8 years of age were cough (2.4%), pyrexia (1.8%), rhinorrhea (1.2%), and headache (1.0%), and were similar to the comparator.

For subjects ages 9 through 17 years who received AFLURIA QUADRIVALENT, the most commonly reported unsolicited adverse events in the 28 days following vaccination were oropharyngeal pain (1.6%), cough (1.3%), and upper respiratory tract infection (1.0%), and were similar to the comparator.

No deaths were reported in Study 3. In the 180 days following vaccinations, AFLURIA QUADRIVALENT and comparator vaccine recipients experienced similar rates of serious adverse events (SAEs). None of the SAEs appeared related to the study vaccines except for one case of influenza B infection (considered a vaccine failure) in an AFLURIA QUADRIVALENT recipient.

Children 6 Months Through 59 Months Of Age

Clinical safety data for AFLURIA QUADRIVALENT in infants and young children have been collected in one clinical trial, Study 4, a randomized, observer-blind, comparator-controlled trial conducted in the U.S. in 2247 subjects aged 6 through 59 months. Subjects were stratified into one of two age cohorts of 6 through 35 months or 36 through 59 months (41.6% and 58.4% of the study population, respectively). The mean age of the population was 36.6 months, 51.6% were male, and racial groups consisted of 71.0% White, 21.5% Black, 1.1% Asian, 0.7% Native Hawaiian/Pacific Islander, and 0.3% American Indian/Native American; 26.4% of subjects were Hispanic/Latino. The mean ages of subjects 6 through 35 months and 36 through 59 months were 21.7 months and 47.1 months, respectively. Subjects in the safety population (N=2232) received either AFLURIA QUADRIVALENT (N=1673) or a U.S.-licensed comparator quadrivalent influenza vaccine (N=559). Study subjects were scheduled to receive either a single vaccination or two vaccinations 28 days apart based on their previous vaccination history. In this study, AFLURIA QUADRIVALENT and comparator vaccine were administered by needle and syringe.

Local (injection site) adverse reactions and systemic adverse events were solicited for 7 days post-vaccination. Cellulitis-like reactions (defined as concurrent Grade 3 pain, redness, and swelling/lump) at the injection site were monitored for 28 days post-vaccination. Subjects were instructed to report and return to clinic within 24 hours in the event of a cellulitis-like reaction. Unsolicited adverse events were collected for 28 days post-vaccination, and SAEs for 6 months following the last vaccination. All solicited local adverse reactions and systemic adverse events following any vaccination (first or second dose) are presented in Table 4.

Table 4: 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 Comparator QIV (Study 4)a

Percentage (%)b of Subjects in each Age Cohort Reporting an Event
6 through 35 months 36 through 59 months
AFLURIA Quadrivalent
N= 668-669 c
Comparator
N= 226-227c
AFLURIA Quadrivalent
N= 947-949 c
Comparator
N= 317-318 c
Any Gr 3 Any Gr 3 Any Gr 3 Any Gr 3
Local Adverse Reactions d
Pain 20.8 0.1 25.6 0.4 35.5 0 31.4 0.6
Redness 20.8 0.6 17.6 1.8 22.4 2.3 20.8 5.3
Swelling/Lump 6.1 0.4 6.2 0.9 10.1 1.7 12.9 2.5
Systemic Adverse Events e
Irritability 32.9 0.7 28.2 0.4
Diarrhea 24.2 0.1 25.6 0.4 12.1 0.1 8.8 0.6
Loss of Appetite 20.0 0.3 19.4 0.4
Malaise and Fatigue 14.3 0.5 13.2 0.3
Myalgia 9.9 0.1 9.4 0
Nausea and/or vomiting 9.4 0.7 11.0 0 9.2 0.4 6.6 0.3
Headache 6.2 0.4 5.0 0
Fever f 7.2 2.5 11.9 2.6 4.8 1.2 6.0 0.9
Abbreviations: Gr 3, Grade 3 (severe); Comparator, Comparator quadrivalent influenza vaccine [Fluzone® Quadrivalent (Sanofi Pasteur)]
aNCT02914275
b Percent (%) is derived from the number of subjects that reported the event divided by the number of subjects in the Solicited Safety Population with non-missing data for each age cohort, treatment group, and each solicited parameter.
c N = number of subjects in the Solicited Safety Population (subjects who were vaccinated and provided any solicited safety data) for each study vaccine group.
d Local adverse reactions: Grade 3 pain is that which prevents daily activity (36 through 59 month subjects); or cried when limb was moved or spontaneously painful (6 through 35 month subjects); Swelling/Lump and redness: any = ≥ 0mm diameter, Grade 3 = ≥ 30mm diameter.
e Systemic adverse events: Fever: any = ≥ 99.5°F (Axillary), Grade 3 = ≥ 101.3°F (Axillary); Grade 3 for all other adverse events is that which prevents daily activity; Irritability, Loss of Appetite, Malaise and Fatigue, Myalgia and Headache are age specific systemic adverse events, where “-” denotes event was not applicable to that age cohort.
f Prophylactic antipyretics (acetaminophen or ibuprophen-containing medications) were not permitted. Antipyretics used to treat fever were permitted and rates of use were as follows: 6 through 35 months (Afluria QIV 5.9%, Comparator QIV 9.0%); 36 through 59 months (Afluria QIV 3.7%, Comparator QIV 2.5%).

 

In subjects 6 through 35 months of age, all solicited local adverse reactions and systemic adverse events were reported at lower frequencies after the second vaccination than after the first vaccination with AFLURIA QUADRIVALENT.

In subjects 36 through 59 months of age, all solicited local adverse reactions and systemic adverse events were reported at lower frequencies after the second vaccination than after the first vaccination with AFLURIA QUADRIVALENT.

The most commonly reported unsolicited adverse events in the 28 days following the first or second dose of AFLURIA QUADRIVALENT in subjects 6 through 35 months of age were rhinorrhea (11.2%), cough (10.4%), pyrexia (6.3%), upper respiratory tract infection (4.8%), diarrhea (3.7%), otitis media (2.4%), vomiting (2.4%), nasal congestion (2.4%), nasopharyngitis (1.9%), irritability (1.7%), ear infection (1.6%), croup infectious (1.4%), teething (1.3%), rash (1.2%), influenza like illness (1.0%) and fatigue (1.0%), and were similar to comparator.

The most commonly reported unsolicited adverse events in the 28 days following the first or second dose of AFLURIA QUADRIVALENT in subjects 36 through 59 months of age were cough (7.7%), rhinorrhea (4.9%), pyrexia (3.7%), upper respiratory tract infection (2.5%), vomiting (2.1%), nasal congestion (1.6%), nasopharyngitis (1.7%), ororpharyngeal pain (1.2%) diarrhea (1.1%) and fatigue (1.1%), and were similar to the comparator.

No deaths were reported in Study 4. In the 180 days following vaccinations, AFLURIA QUADRIVALENT and comparator vaccine recipients experienced similar rates of serious adverse events (SAEs), none of which were related to study vaccines. No vaccine-related febrile seizures occurred in Study 4. Unrelated SAEs of febrile seizures occurred in two AFLURIA QUADRIVALENT recipients (6 through 35 months age group) at 43 and 104 days post-vaccinations.

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 limited 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 U.S. 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 .