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Afluria (Influenza Virus Vaccine) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Overall Adverse Reactions

Serious allergic reactions, including anaphylactic shock, have been observed during postmarketing surveillance in individuals receiving AFLURIA. Administration of CSL's 2010 Southern Hemisphere influenza vaccine [formulated to contain A/California/7/2009 (H1N1), A/Wisconsin/15/2009 (H3N2) and B/Brisbane/60/2008 (B Strain)] has been associated with increased postmarketing reports of fever and febrile seizures in children predominantly below the age of 5 years as compared to previous years (see Warnings and Precautions [5.1] ).

In adults, the most common local (injection-site) adverse reactions observed in clinical studies with AFLURIA were tenderness, pain, redness (erythema), and swelling. The most common systemic adverse reactions observed were headache, malaise, and muscle aches (myalgia).

In children, the most common local (injection-site) adverse reactions observed in a clinical study with AFLURIA were pain, redness and swelling. The most common systemic adverse reactions observed were irritability, rhinitis, fever, cough, loss of appetite, vomiting/diarrhea, headache, muscle aches and sore throat.

Safety Experience from Clinical Studies

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 data for AFLURIA have been obtained in four clinical studies, three in adult populations (Studies 1 to 3) and one in a pediatric population (Study 4) (see Clinical Studies [14] ). Clinical safety data are provided for two of the adult studies (Studies 1 and 2) and one pediatric study (Study 4). Rates of solicited fever in children from a second pediatric study (Study 5) are also provided.

A US study (Study 1) included 1,357 subjects for safety analysis, ages 18 to less than 65 years, randomized to receive AFLURIA (1,089 subjects) or placebo (268 subjects) (see Clinical Studies [14] for study demographics). There were no deaths or serious adverse events reported in this study.

A UK study (Study 2) included 275 subjects, ages 65 years and older, randomized to receive preservative-free AFLURIA (206 subjects) or a European-licensed trivalent inactivated influenza vaccine as an active control (69 subjects) (see Clinical Studies [14] ). There were no deaths or serious adverse events reported in this study.

An open-label, uncontrolled study in children, conducted in Australia (Study 4), included 298 subjects, ages 6 months to less than 9 years. All subjects received preservative-free AFLURIA administered as two doses, one month apart (see Clinical Studies [14] ). Subjects were subdivided into two age groups: children ages 6 months to less than 3 years (151 subjects) received two 0.25 mL doses of AFLURIA and children ages 3 years to less than 9 years (147 subjects) received two 0.5 mL doses of AFLURIA. There were no deaths or vaccine-related serious adverse events reported in this study.

The safety assessment was identical for the two adult studies. Local (injection-site) and systemic adverse events were solicited by completion of a symptom diary card for 5 days post-vaccination (Table 1). Unsolicited adverse events were collected for 21 days post-vaccination (Table 2). These unsolicited adverse events were reported either spontaneously or when subjects were questioned about any changes in their health post-vaccination. All adverse events are presented regardless of any treatment causality assigned by study investigators.

In the open-label pediatric study (Study 4), solicited adverse events were recorded for up to 7 days (Table 3) and unsolicited adverse events were recorded for 30 days post-vaccination (Table 4). Data are presented following each dose for each age group. All adverse events are presented regardless of any treatment causality assigned by study investigators.

Rates of solicited fever in the seven days following vaccination with the 2009-2010 formulation of AFLURIA or another U.S. licensed influenza vaccine (manufactured by Sanofi Pasteur, Inc.) in children 6 months to less than 18 years of age (Study 5) are shown in Table 5.

Table 1: Proportion of Subjects With Solicited Local or Systemic Adverse EventsIn Study 1, 87% of solicited local and systemic adverse events were mild, 12% were moderate, and 1% were severe. In Study 2, 76.5% were mild, 20.5% were moderate, and 3% were severe. In both studies, most solicited local and systemic adverse events lasted no longer than 2 days. Within 5 Days After Administration of AFLURIA or Placebo, Irrespective of CausalityValues rounded to the nearest whole percent. (Studies 1 and 2, Adult Populations)
Study 1
Subjects ≥ 18 to < 65 years
Study 2
Subjects ≥ 65 years
Solicited Adverse Event AFLURIAIncludes subjects who received either the single-dose (preservative-free) or multi-dose formulation of AFLURIA.
n=1089
PlaceboThimerosal-containing placebo.
n=268
AFLURIA
n=206
Local
TendernessTenderness defined as pain on touching. 60% 18% 34%
PainPain defined as spontaneously painful without touch. 40% 9% 9%
Redness 16% 8% 23%
Swelling 9% 1% 11%
Bruising 5% 1% 4%
Systemic
Headache 26% 26% 15%
Malaise 20% 19% 10%
Muscle aches 13% 9% 14%
Nausea 6% 9% 3%
Chills/Shivering 3% 2% 7%
Fever ≥ 37.7C (99.9F) 1% 1% 1%
Vomiting 1% 1% 0%
Table 2: Adverse EventsIn Study 1, 63% of unsolicited adverse events were mild, 35% were moderate, and 2% were severe. In Study 2, 47% were mild, 51% were moderate, and 3% were severe. In both studies, most unsolicited adverse events lasted no longer than 5 days. Reported Spontaneously by ≥ 1% of Subjects Within 21 Days After Administration of AFLURIA or Placebo, Irrespective of CausalityValues rounded to the nearest whole percent. (Studies 1 and 2, Adult Populations)
Study 1
Subjects ≥ 18 to < 65 years
Study 2
Subjects ≥ 65 years
Adverse Event AFLURIAIncludes subjects who received either the single-dose (preservative-free) or multi-dose formulation of AFLURIA.
n=1089
PlaceboThimerosal-containing placebo.
n=268
AFLURIA
n=206
Headache 8% 6% 8%
Nasal Congestion 1% 1% 7%
Cough 1% 0.4% 5%
Rhinorrhea 1% 1% 5%
Pharyngolaryngeal Pain 3% 1% 5%
Reactogenicity Event 3% 3% 0%
Diarrhea 2% 3% 1%
Back Pain 2% 0.4% 2%
Upper Respiratory Tract Infection 2% 1% 0.5%
Viral Infection 0.4% 1% 0%
Lower Respiratory Tract Infection 0% 0% 1%
Myalgia 1% 1% 1%
Muscle Spasms 0.4% 1% 0%
Table 3: Proportion of Subjects With Solicited Local or Systemic Adverse EventsIn Study 4, 78% of all local and systemic solicited events experienced by children ages 6 months to less than 3 years were mild, 19% were moderate and 3% were severe; 76% of all events experienced by children ages 3 years to less than 9 years were mild, 20% moderate and 4% severe. Severe pain was reported by < 1% of children ages 6 months to less than 3 years and 3% in children ages 3 years to less than 9 years. Severe fever (> 103.1F axillary or > 104.0F oral) was reported by < 1% of subjects in children ages 6 months to less than 3 years and 1% of subjects in children ages 3 years to less than 9 years. Within 7 Days After Administration of AFLURIA, Irrespective of Causality Values rounded to the nearest whole percent. (Study 4, Pediatric Population)
Subjects ≥ 6 months to < 3 years
(n = 151)Dosage in children 6 months to less than 3 years of age was 0.25 mL.
Subjects ≥ 3 years to < 9 years
(n = 147)Dosage in children 3 years to less than 9 years of age was 0.5 mL.
Solicited Adverse Event Dose 1 Dose 2 Dose 1 Dose 2
Local
Pain 36% 37% 59% 62%
Erythema 36% 38% 37% 46%
Swelling 16% 21% 25% 27%
Systemic
Irritability 48% 41% 20% 17%
Rhinitis 37% 48% 21% 29%
FeverAxillary Temperature ≥ 37.5C (99.5 F) or Oral Temperature ≥ 38.0C (100.4 F). 23% 23% 16% 8%
Cough 21% 32% 19% 19%
Loss of appetite 19% 24% 8% 5%
Vomiting/Diarrhea 15% 14% 8% 7%
Headache 2% 1 3% 2 14% 11%
Myalgia 1% 3 3% 14% 8%
Sore throat 2% 5% 8% 11%
Wheezing/Shortness of breath 3% 9% 3% 2%
Ear ache 3% 3% 4% 1%

1 Data obtained from a total of 148 subjects.
2 Data obtained from a total of 150 subjects.
3 Data obtained from a total of 149 subjects.

Table 4: Adverse EventsIn Study 4, for both doses and both groups combined, 47% of unsolicited adverse events were mild, 42% were moderate, and 12% were severe. Reported Spontaneously by ≥ 5% of Subjects Within 30 Days After Administration of AFLURIA, Irrespective of Causality (Study 4, Pediatric Population)
Subjects ≥ 6 months to < 3 years
(n = 151)Dosage in children 6 months to less than 3 years of age was 0.25 mL.
Subjects ≥ 3 to < 9 years
(n = 147)Dosage in children 3 years to less than 9 years of age was 0.5 mL.
Adverse Event Dose 1 Dose 2 Dose 1 Dose 2
Nasopharyngitis 5.3% 7.9% 5.4% 5.4%
Rhinitis 13.2% 9.9% 6.8% 10.9%
Upper Respiratory Tract Infection 9.9% 7.3% 6.1% 6.1%
Irritability 3.3% 5.3% 0.7% 0.7%
Headache 1.3% 0.7% 6.1% 4.1%
Cough 10.6% 13.2% 10.9% 13.6%
Rhinorrhea 7.3% 6.0% 6.8% 4.8%
Teething 14.6% 9.9% 0.0% 0.0%
Vomiting 5.3% 2.6% 2.0% 2.7%
Influenza-like Illness 13.9% 10.6% 6.8% 3.4%
Pyrexia 2.6% 9.3% 2.7% 4.1%
Table 5: Proportion of Subjects With Solicited FeverDefined as ≥99.5F axillary or ≥100.4F orally after first or second vaccination. Within 7 days of Vaccination with AFLURIA or U.S. Licensed Comparator Vaccine (Study 5, Pediatric Population)
Age Group
6 months to < 3 yearsDosage in subjects 6 months to less than 3 years was one or two 0.25 mL doses (depending on vaccination history) one month apart. Group sizes were n=229 for AFLURIA dose 1, n=228 for Comparator dose 1, n=96 for AFLURIA dose 2, and n=110 for Comparator dose 2. 3 to < 5 yearsDosage in subjects 3 years to less than 5 years was one or two 0.5 mL doses (depending on vaccination history) one month apart. Group sizes were n=91 for AFLURIA dose 1, n=90 for Comparator dose 1, n=29 for AFLURIA dose 2, and n=25 for Comparator dose 2. 5 to < 9 yearsDosage in subjects 5 years to less than 9 years was one or two 0.5 mL doses (depending on vaccination history) one month apart. Group sizes were n=161 for AFLURIA dose 1, n=165 for Comparator dose 1, n=39 for AFLURIA dose 2, and n=53 for Comparator dose 2. 9 to < 18 yearsDosage in subjects 9 years to less than 18 years was one 0.5 mL dose. Group sizes were n=254 for AFLURIA dose 1 and n=250 for Comparator dose 1.
Dose 1 Dose 2 Dose 1 Dose 2 Dose 1 Dose 2 Dose 1
AFLURIA 1 37% 15% 32% 14% 16% 0% 6%
Comparator 14% 14% 11% 16% 9% 2% 4%
1 2009-2010 formulation [A/Brisbane/59/2007, IVR-148 (H1N1), A/Uruguay/716/2007, NYMC X-175C (H3N2) (an A/Brisbane/10/2007-like strain), and B/Brisbane/60/2008].

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 US since 1985.

Blood and lymphatic system disorders

Transient thrombocytopenia

Immune system disorders

Allergic reactions including anaphylactic shock and serum sickness

Nervous system disorders

Neuralgia, paresthesia, and convulsions (including febrile seizures); encephalopathy, neuritis or neuropathy, transverse myelitis, and GBS

Vascular disorders

Vasculitis with transient renal involvement

Skin and subcutaneous tissue disorders

Pruritus, urticaria, and rash

Other 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 [4] ) .

The 1976 swine influenza vaccine was associated with an increased frequency of GBS. Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is unclear. If influenza vaccine does pose a risk, it is probably slightly more than one additional case per 1 million persons vaccinated.

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.

Drug label data at the top of this Page last updated: 2010-08-05

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