Afluria

Name: 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%).

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 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%).

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.

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

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 ages 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 US-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 vaccinerelated serious adverse events reported in children 5 years of age and older.

In this section, safety data from the pediatric studies are limited to children 5 years of age and older. AFLURIA is not approved for use in children less than 5 years of age. See Warnings and Precautions [5.1] and Use in Specific Populations [8.4] for risks of AFLURIA in children less than 5 years of age. 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)

  Percentagea of Subjects in each Age Group Reporting Event
Subjects 5 through 8 years Subjects 9 through 17 years
AFLURIA
N=161b
Comparator
N=165b
AFLURIA
N=254b
Comparator
N=250b
After the First Dose
Local Adverse Reactions
Pain 63 60 66 60
Redness 23 27 17 17
Induration 17 17 15 16
Systemic Adverse Events
Myalgia 34 30 40 37
Malaise 24 13 22 20
Headache 21 19 27 26
Any Fever 16 8 6 4
Fever ≥102.2°F 5 1 3 1
Nausea/ Vomiting 12 8 9 10
Diarrhea 7 7 8 10
  AFLURIA
N=39b
Comparator
N=53b
   
After the Second Dose
Local Adverse Reactions
Pain 36 38 - -
Redness 10 19 - -
Induration 8 17 - -
Systemic Adverse Events
Diarrhea 13 6 - -
Headache 13 13 - -
Myalgia 13 17 - -
Malaise 5 8 - -
Nausea/ Vomiting 3 8 - -
Any Fever 0 2 - -
Fever ≥102.2°F 0 0 - -
a Proportion of subjects reporting each solicited 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).
b N = number of subjects in the Safety Population for each treatment group.

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)

  Percentagea of Subjects in each Age Group Reporting Event
Studies 2 and 3
Subjects 5 through 8 years
Study 2
Subjects 9 through 17 years
Dose 1
N=82-595b
Dose 2
N=82-426b
Dose 1
N=397b
Local Adverse Reactions
Pain 61 56 68
Erythema 24 23 17
Swelling 17 17 13
Systemic Adverse Events
Irritabilityd 18 16 -
Headache 16 10 27
Malaise or feeling generally unwellc 16 8 17
Any Fever 13 6 5
Fever ≥ 102.2°F 3 2 1
General Muscle Ache (Myalgia) 12 8 20
Nausea/Vomitingc 7 3 5
Vomiting/Diarrhead 5 6 -
Loss of appetited 5 4 -
Diarrheac 4 2 5
a Proportion of subjects reporting each solicited 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).
b N = number of subjects in the Safety Population for each treatment group. Denominators for Dose 1 were: N=82 for Vomiting/Diarrhea, Irritability, Loss of appetite, N=513 for Malaise, Diarrhea, Nausea/ Vomiting and N=593-595 for all other parameters. Denominators for Dose 2 were: N=82 for Vomiting/ Diarrhea, Irritability, Loss of appetite, N=344 for Malaise, Diarrhea and Nausea/Vomiting and N=421-426 for all other parameters.
c These preferred terms were used to describe Solicited Adverse Events in Study 2.
d These preferred terms were used to describe Solicited Adverse Events in Study 3.

In Study 1, unsolicited adverse events that occurred in ≥ 5% of subjects who received AFLURIA in ages 5 years through 8 years following the first or second dose included cough (15%) and pyrexia (9%). Unsolicited adverse events that occurred in ≥ 5% of subjects who received AFLURIA in ages 9 years through 17 years following the first dose 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 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 who received AFLURIA in ages 9 years through 17 years following the first dose included upper respiratory tract infection (9%) and headache (8%).

Adults

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 4 through 6) conducted in the US and one clinical study (Study 7) conducted in the UK. Study 4 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 5 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 6 included 1,266 subjects for safety analysis, ages 65 years and older, randomized to receive AFLURIA (630 subjects) or another US-licensed trivalent inactivated influenza vaccine (manufactured by Sanofi Pasteur Inc.) as an active comparator (636 subjects) (see Clinical Studies). Study 7 included 275 subjects for safety analysis, ages 65 year and older, randomized to receive AFLURIA (206 subjects) 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 (injectionsite) adverse reactions and systemic adverse events were solicited for 5 days post-vaccination (Table 4, studies 4 through 6). 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 4: 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 4, 5 and 6)

  Percentage a of Subjects in each Age Group Reporting Event
Study 4
Subjects 18 through 64 years
Study 5
Subjects 18 through 64 years
Study 6
Subjects ≥ 65 years
AFLURIA
N=1087- 1088 b
Placebo
N=266 b
AFLURIA
N=10,015 b
Placebo
N=5005 b
AFLURIA
N=630 b
Comparator
N=636 b
Local Adverse Reactions
Tenderness
(Pain on touching)
60 18 69 17 36 31
Pain
(without touching)
40 9 48 11 15 14
Redness 16 8 4 <1 3 1
Swelling 9 1 4 <1 7 8
Bruising 5 1 1 1 <1 1
Systemic Adverse Events
Headache 26 26 25 23 9 11
Malaise 19 19 29 26 7 6
Muscle aches 13 9 21 12 9 8
Nausea 6 9 7 6 2 1
Chills/ Shivering 3 2 5 4 2 2
Fever 1 1 3 2 <1 1
a Proportion of subjects reporting each solicited 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).
b N = number of subjects in the Safety Population for each treatment group.

In Study 4, headache was the only unsolicited adverse event that occurred in ≥ 5% of subjects who received AFLURIA or placebo (8% versus 6%, respectively). In Study 5, 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 6, headache was the only unsolicited adverse event that occurred in ≥5% of subjects who received AFLURIA (5%).

Studies 1 to 7 were all conducted when AFLURIA was 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 8). Study 8 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 8. Local (injection-site) adverse reactions and systemic adverse events were solicited for 7 days post-vaccination (Table 5).

Table 5: 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 8).

  Percentage a of Subjects Reporting Event
Study 8
Subjects 18 through 64 years
AFLURIA
PharmaJet Stratis Needle- Free Injection System
N=540-616 b
Needle and Syringe
N=599-606 b
Local Adverse Reactions
Tenderness 89 78
Swelling 65 20
Pain 64 49
Redness 60 19
Itching c 28 10
Bruising 18 5
Systemic Adverse Events
Myalgia 36 36
Malaise 31 28
Headache 25 22
Chills 7 7
Nausea 7 7
Vomiting 1 2
Fever 0 0
a 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).
b 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.
c 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 Study 8, no unsolicited adverse events occurred in ≥5% of subjects who received AFLURIA administered via 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 US 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.

Afluria Usage

Use Afluria exactly as prescribed.

It is available in an injectable form to be given directly into a muscle (IM) by a healthcare professional, and should be administered every year.

How is this medicine (Afluria) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as a shot into a muscle.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

What are some other side effects of Afluria?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

For all patients taking Afluria:

  • Redness or swelling where the shot is given.
  • Pain where the shot was given.
  • Headache.
  • Muscle or joint pain.
  • Feeling tired or weak.

Young children:

  • Fever.
  • Upset stomach or throwing up.
  • Loose stools (diarrhea).
  • Not hungry.
  • Stomach pain.
  • Feeling sleepy.
  • Feeling fussy.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

How do I store and/or throw out Afluria?

  • If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Afluria has not been evaluated for carcinogenic or mutagenic potential or for impairment of fertility.

Before receiving Afluria

You may not be able to receive Afluria if you are allergic to eggs, or if you have;

  • a history of severe allergic reaction to a flu vaccine; or

  • a history of Guillain-Barre syndrome (within 6 weeks after receiving a flu vaccine).

  • if you are allergic to eggs.

To make sure you can safely receive Afluria, tell your doctor if you have any of these other conditions:

  • a bleeding or blood clotting disorder such as hemophilia or easy bruising;

  • a neurologic disorder or disease affecting the brain (or if this was a reaction to a previous vaccine);

  • a history of seizures;

  • a weak immune system caused by disease, bone marrow transplant, or by using certain medicines or receiving cancer treatments; or

  • if you are allergic to latex rubber.

You can still receive the Afluria vaccine if you have a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving Afluria.

The Centers for Disease Control and Prevention recommends that pregnant women get a flu shot during any trimester of pregnancy to protect themselves and their newborn babies from flu.

It is not known whether influenza virus vaccine passes into breast milk or if it could harm a nursing baby. Do not receive Afluria without telling your doctor if you are breast-feeding a baby. Afluria should not be given to a child younger than 6 months old.

What happens if I overdose?

An overdose of Afluria is unlikely to occur.

Afluria side effects

Afluria vaccine will not cause you to become ill with the flu virus that it contains. However, you may have flu-like symptoms at any time during flu season that may be caused by other strains of influenza virus.

You should not receive a booster vaccine if you had a life-threatening allergic reaction to Afluria after the first shot. Keep track of any and all side effects you have after receiving Afluria. If you ever need to receive Afluria in the future, you will need to tell your doctor if the previous shot caused any side effects. Get emergency medical help if you have any signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

  • a light-headed feeling, like you might pass out;

  • severe weakness or unusual feeling in your arms and legs (may occur 2 to 4 weeks after you receive the vaccine);

  • high fever;

  • seizure (convulsions); or

  • unusual bleeding.

Less serious Afluria side effects may include:

  • low fever, chills;

  • mild fussiness or crying;

  • redness, bruising, pain, swelling, or a lump where the vaccine was injected;

  • headache, tired feeling; or

  • joint or muscle pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report vaccine side effects to the US Department of Health and Human Services at 1-800-822-7967.

What other drugs will affect Afluria?

Before receiving Afluria, tell your doctor if you are using:

  • phenytoin;

  • theophylline; or

  • a blood thinner such as warfarin, Coumadin, Jantoven.

Also tell the doctor if you have recently received drugs or treatments that can weaken the immune system, including:

  • an oral, nasal, inhaled, or injectable steroid medicine;

  • medications to treat psoriasis, rheumatoid arthritis, or other autoimmune disorders, such as azathioprine (Imuran), etanercept (Enbrel), leflunomide (Arava), and others; or

  • medicines to treat or prevent organ transplant rejection, such as basiliximab (Simulect), cyclosporine (Sandimmune, Neoral, Gengraf), muromonab-CD3 (Orthoclone), mycophenolate mofetil (CellCept), sirolimus (Rapamune), or tacrolimus (Prograf).

If you are using any of these medications, you may not be able to receive the vaccine, or may need to wait until the other treatments are finished.

This list is not complete and other drugs may interact with Afluria . Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Influenza virus vaccine, inactivated Breastfeeding Warnings

Caution is recommended. Excreted into human milk: Unknown Excreted into animal milk: Data not available

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