Afluria

SIDE EFFECTS

In children 5 through 17 years of age, the most common injection site reactions observed in clinical studies with AFLURIA administered by needle and syringe were pain (≥ 60%), redness (≥ 20%) and swelling (≥ 10%). The most common systemic adverse events were headache, myalgia (≥ 20%), irritability, malaise and fever (≥ 10%).

The safety experience with AFLURIA QUADRIVALENT (influenza vaccine), a four strain version of AFLURIA is relevant because both vaccines are manufactured using the same process and have overlapping compositions (see DESCRIPTION).

In children 6 months through 35 months of age, the most frequently reported injection site reactions in a 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 frequently reported injection site reactions in a clinical study with AFLURIA QUADRIVALENT administered by needle and syringe were pain (≥ 30%) and redness (≥ 20%). The most commonly reported systemic adverse events were malaise and fatigue, and diarrhea (≥ 10%).

In adults 18 through 64 years of age, the most common injection-site adverse reactions observed in clinical studies with AFLURIA administered by needle and syringe were tenderness (≥ 60%), pain (≥ 40%), swelling (≥ 20%), redness and itching (≥10%). The most common systemic adverse events observed were muscle aches (≥ 30%), headache and malaise (≥20%).

In adults 65 years of age and older, the most common injection-site adverse reactions observed in clinical studies with AFLURIA administered by needle and syringe were tenderness (≥ 30%) and pain (≥ 10%). No systemic adverse reactions occurred in ≥ 10% of subjects in this age group.

In adults 18 through 64 years of age, using the PharmaJet Stratis Needle-Free Injection System, the most common injection-site adverse reactions observed in a clinical study with AFLURIA up to 7 days post-vaccination were tenderness (≥ 80%), swelling, pain, redness (≥ 60%), itching (≥ 20%) and bruising ≥ 10%). The most common systemic adverse events within this period 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.

Children - AFLURIA

In clinical studies, AFLURIA has been administered to, and safety information collected for, 3,009 children ages 6 months through 17 years. The exposure in children includes 1,601 aged 6 months to less than 5 years, 756 children ages 5 years to less than 9 years and 652 children ages 9 years through 17 years. Clinical safety data for AFLURIA in children are presented from three clinical studies (Studies 1, 2 and 3). Data from a comparator-controlled trial (Study 1) are presented, followed by pooled data from two open label studies (Studies 2 and 3). Subjects 6 months through 8 years of age received one or two vaccinations, administered by needle and syringe, as determined by previous vaccination history (for further details on clinical study design, dosing and demographics see Clinical Studies).

Study 1 included 1,468 subjects for safety analysis, ages 6 months through 17 years, randomized to receive AFLURIA (735 subjects) or another U.S.-licensed trivalent inactivated influenza vaccine (manufactured by Sanofi Pasteur, Inc.) (733 subjects).

Study 2 included 1,976 subjects for safety analysis, ages 6 months through 17 years. All subjects received AFLURIA.

Study 3 included 298 subjects for safety analysis, ages 6 months through 8 years. All subjects received AFLURIA.

The safety assessment was similar for the three pediatric studies. Local (injection site) adverse reactions and systemic adverse events were solicited for 7 days post-vaccination (Tables 2 and 3). Unsolicited adverse events were collected for 30 days post-vaccination. All adverse events are presented regardless of any treatment causality assigned by study investigators.

Among the pediatric studies, there were no vaccine-related deaths or vaccine-related serious adverse events reported in children 5 years of age and older.

In the comparator-controlled trial (Study 1), the rate of fever after the first dose of AFLURIA in subjects aged 5 through 8 years was 16% as compared to 8% in subjects who received the comparator. The rate of fever in subjects aged 9 through 17 years following a single dose of AFLURIA was 6% as compared to 4% in subjects who received the comparator. In all three pediatric studies, the rates of fever in subjects aged 5 through 8 years who received AFLURIA were lower after dose 2 than dose 1.

Data in Tables 2 and 3 are presented for children 5 years and older.

Table 2: Proportion of Subjects 5 through 17 Years of Age with Solicited Local Adverse Reactions or Systemic Adverse Events within 7 Days after Administration of First or Second Dose of AFLURIA, Irrespective of Causality (Study 1)

Table 3: Proportion of Subjects 5 through 17 Years of Age with Solicited Local Adverse Reactions or Systemic Adverse Events Within 7 Days after Administration of AFLURIA, Irrespective of Causality (Studies 2 and 3)

In Study 1, unsolicited adverse events that occurred in ≥ 5% of subjects 5 through 8 years following the first or second dose of AFLURIA included cough (15%) and pyrexia (9%). Unsolicited adverse events that occurred in ≥ 5% of subjects 9 through 17 years following a single dose of AFLURIA included cough (7%), oropharyngeal pain (7%), headache (7%) and nasal congestion (6%).

In Studies 2 and 3, unsolicited adverse events that occurred in ≥ 5% of subjects ages 5 years through 8 years after the first or second dose of AFLURIA included the following: upper respiratory tract infection (13%), cough (10%), rhinorrhea (7%), headache (5%), nasopharyngitis (5%) and pyrexia (5%). Unsolicited adverse events that occurred in ≥ 5% of subjects 9 through 17 years following a single dose of AFLURIA included upper respiratory tract infection (9%) and headache (8%).

Children 6 Months Through 59 Months Of Age - AFLURIA QUADRIVALENT

The safety experience with AFLURIA QUADRIVALENT (influenza vaccine), a four strain version of AFLURIA is relevant because both vaccines are manufactured using the same process and have overlapping compositions (see DESCRIPTION). The safety of AFLURIA in children 6 through 59 months is based on a clinical trial conducted with AFLURIA QUADRIVALENT, 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 (see Clinical Studies).

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

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 postvaccinations.

Adults - AFLURIA

In clinical studies comparing AFLURIA to placebo or a comparator trivalent inactivated influenza vaccine, a single dose of AFLURIA was administered to, and safety information collected for, 11,104 subjects ages 18 through 64 years and 836 subjects ages 65 years and older. Clinical safety data for AFLURIA in adults are presented from three clinical studies (Studies 5 through 7) conducted in the U.S. and one clinical study (Study 8) conducted in the UK.

Study 5 included 1,357 subjects for safety analysis, ages 18 through 64 years, randomized to receive AFLURIA (1,089 subjects) or placebo (268 subjects) (see Clinical Studies).

Study 6 included 15,020 subjects for safety analysis, ages 18 through 64 years, randomized to receive AFLURIA (10,015 subjects) or placebo (5,005 subjects) (see Clinical Studies).

Study 7 included 1,266 subjects for safety analysis, ages 65 years and older, randomized to receive AFLURIA (630 subjects) or another U.S.-licensed trivalent inactivated influenza vaccine (manufactured by Sanofi Pasteur Inc.) as an active comparator (636 subjects) (see Clinical Studies).

Study 8 included 275 subjects for safety analysis, ages 65 years and older, randomized to receive AFLURIA (206 subj ects) or a UK-licensed trivalent inactivated influenza vaccine (manufactured by GSK) as an active comparator (69 subjects).

The safety assessment was identical for the four adult studies. Local (injection-site) adverse reactions and systemic adverse events were solicited for 5 days post-vaccination (Table 5, studies 5 through 7). Unsolicited adverse events were collected for 21 days post-vaccination. All adverse events are presented regardless of any treatment causality assigned by study investigators.

Among adult studies, there were no vaccine-related deaths or vaccine-related serious adverse events reported.

Table 5: Proportion of Subjects 18 Years of Age and Older with Solicited Local Adverse Reactions or Systemic Adverse Events within 5 Days after Administration of AFLURIA or Placebo, Irrespective of Causality (Studies 5, 6 and 7)

In Study 5, headache was the only unsolicited adverse event that occurred in ≥ 5% of subjects who received AFLURIA or placebo (8% versus 6%, respectively).

In Study 6, unsolicited adverse events that occurred in ≥ 5% of subjects who received AFLURIA or placebo included headache (AFLURIA 12%, placebo 11%) and oropharyngeal pain (AFLURIA 5%, placebo 5%).

In Study 7, headache was the only unsolicited adverse event that occurred in ≥ 5% of subjects who received AFLURIA (5%).

Studies 1 to 8 were all conducted when AFLURIA and AFLURIA QUADRIVALENT were administered by needle and syringe.

Additionally, safety information has been collected in a clinical study of AFLURIA administered using the PharmaJet Stratis Needle-Free Injection System (Study 9). Study 9 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 7. Local (injection-site) adverse reactions and systemic adverse events were solicited for 7 days postvaccination (Table 6).

Table 6: 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 by PharmaJet Stratis Needle-Free Injection System or Needle and Syringe Irrespective of Causality (Study 9).

In Study 9, no unsolicited adverse events occurred in ≥5% of subjects who received AFLURIA administered by PharmaJet Stratis Needle-Free Injection System up to 28 days post-vaccination.

Postmarketing Experience

Because postmarketing reporting of adverse reactions 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 reactions 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. These adverse reactions reflect experience in both children and adults and include those identified during post-approval use of AFLURIA outside the U.S. since 1985.

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

Adverse Reactions Associated With Influenza Vaccination

Anaphylaxis has been reported after administration of AFLURIA. Egg protein can induce immediate hypersensitivity reactions among persons who have severe egg allergy. Allergic reactions include hives, angioedema, asthma, and systemic anaphylaxis (see CONTRAINDICATIONS)

Neurological disorders temporally associated with influenza vaccination, such as encephalopathy, optic neuritis/neuropathy, partial facial paralysis, and brachial plexus neuropathy, have been reported.

Microscopic polyangiitis (vasculitis) has been reported temporally associated with influenza vaccination.

Read the entire FDA prescribing information for Afluria (Influenza Virus Vaccine)