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

ADVERSE REACTIONS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. As with any vaccine, there is the possibility that broad use of FLULAVAL could reveal adverse events not observed in clinical trials.

In clinical trials, the most common (≥10%) local and systemic adverse events were pain, redness, and/or swelling at the injection site, headache, fatigue, myalgia, low grade fever, and malaise.

Safety information for FLULAVAL was collected in 2 randomized, controlled clinical trials, one in the United States (IDB707-105) and the second in Canada (SPD707-104). The safety population from these trials includes 1,049 adults 18 years of age and older vaccinated with products representative of the licensed formulation of FLULAVAL. The US study included subjects 18 to 64 years of age who were randomized to receive FLULAVAL (N = 721) or a US-licensed trivalent, inactivated influenza virus vaccine (FLUZONE) (N = 279). The Canadian study compared 4 vaccine groups: FLULAVAL, a similar investigational formulation of FLULAVAL with reduced thimerosal, and 2 Canadian-licensed trivalent influenza vaccines.

Among recipients of FLULAVAL, 56.6% were women; 92.4% of subjects were white, 6.5% black, 2.7% Native American, and 1.0% Asian. In the US study, 74.8% of the recipients of FLULAVAL were Hispanic/Latino. The mean age of subjects in the US study was 38 years (range 18-64 years) and 19% of subjects were 50 to 64 years of age. In the Canadian study, the mean age was 63 years (range 50-92 years), and 46.6% were 65 years of age and older.

A series of symptoms and/or findings were specifically solicited by a diary/memory aid used by subjects for at least the day of vaccination and 3 days post-treatment (Table 1). Subjects were actively queried about changes in their health status through 42 days post-vaccination in the US trial, and six months post-vaccination in the Canadian study. In addition, spontaneous reports of adverse events were also collected (Table 2).

Table 1. Solicited Adverse Events in the First 4 Days After Administration of FLULAVAL or Comparator Influenza Vaccine

Results >1% reported to nearest whole percent; results >0 but ≤1 reported as 1%.
a US-licensed trivalent, inactivated influenza virus vaccine (FLUZONE).
b Includes subjects who received FLULAVAL and a similar investigational formulation of FLULAVAL with reduced thimerosal.
c Fever defined as ≥37.5°C in the US study, and ≥38.0°C in the Canadian study.
	US Trial Adults 18 to 64 years of age (80% <50 years of age)		Canadian Trial Adults 50 years of age and older
Adverse Events	FLULAVAL N = 721 %	Comparator Influenza Vaccinea N = 279 %	FLULAVALb N = 328 %
Local
Pain	24	31	21
Redness	11	10	14
Swelling	10	10	6
Systemic
Headache	18	17	10
Fatigue	17	15	10
Myalgia	13	16	11
Feverc	11	10	1
Malaise	10	10	4
Sore throat	9	9	5
Reddened eyes	6	5	3
Cough	6	7	3
Chills	5	2	3
Chest tightness	3	1	2
Facial swelling	1	1	1

Local adverse events occurred with similar frequency in the 2 trials. In the US study, the only significant difference between FLULAVAL and a US-licensed trivalent, inactivated influenza virus vaccine was an increased frequency of chills in subjects receiving FLULAVAL.

Table 2 summarizes the most common adverse events in the 2 clinical trials; adverse events were reported, either spontaneously or in response to queries about changes in health status. The most common events were headache and cough in both studies. These, as well as throat pain, were the only adverse events reported by >1% of subjects in the US trial. The Canadian trial featured a longer safety follow-up (6 months vs. 42 days) and enrolled a population exclusively 50 years of age and older. Therefore, spontaneous adverse event reports were more frequent in this trial. As indicated in Table 2, upper respiratory infection, arthralgia, myalgia, nasopharyngitis, back pain, injection site erythema, diarrhea, fatigue, nausea, and nasal congestion were each reported by ≥5% of the recipients of FLULAVAL in the Canadian study.

Table 2. Adverse Events Reported Spontaneously^a by ≥5% of Subjects in Either Clinical Trial of FLULAVAL

Results >1% reported to nearest whole percent; results >0 but ≤1 reported as 1%.
a Adverse events in this table were reported spontaneously or in response to queries about changes in health status.
b US-licensed trivalent, inactivated influenza virus vaccine (FLUZONE).
c Includes subjects who received FLULAVAL and a similar investigational formulation of FLULAVAL with reduced thimerosal.
	US Trial (safety follow-up 42 days) Adults 18 to 64 years of age (80% <50 years of age)		Canadian Trial (safety follow-up 6 months) Adults 50 years of age and older
Adverse Events	FLULAVAL N = 721 %	Comparator Influenza Vaccineb N = 279 %	FLULAVALc N = 328 %
Headache	7	7	19
Cough	2	2	15
Pharyngolaryngeal pain	2	3	12
Upper respiratory infection	1	1	9
Arthralgia	1	1	8
Myalgia	1	1	7
Nasopharyngitis	1	1	7
Back pain	1	1	6
Injection site erythema	1	1	5
Diarrhea	1	0	5
Fatigue	1	1	5
Nausea	1	1	5
Nasal congestion	1	1	5

Postmarketing Experience

The following additional adverse events have been identified during postapproval use of FLULAVAL. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their incidence rate or establish a causal relationship to the vaccine. Adverse events described here are included because: a) they represent reactions which are known to occur following immunizations generally or influenza immunizations specifically; b) they are potentially serious; or c) the frequency of reporting.

Blood and Lymphatic System Disorders: Lymphadenopathy.

Eye Disorders: Conjunctivitis, eye pain, photophobia.

Gastrointestinal Disorders: Dysphagia, vomiting.

General Disorders and Administration Site Conditions: Chest pain, injection site inflammation, rigors, asthenia, injection site rash, influenza-like symptoms, abnormal gait, injection site bruising, injection site sterile abscess.

Immune System Disorders: Allergic edema of the face, allergic edema of the mouth, anaphylaxis, allergic edema of the throat.

Infections and Infestations: Pharyngitis, rhinitis, laryngitis, cellulitis.

Musculoskeletal and Connective Tissue Disorders: Muscle weakness, back pain, arthritis.

Nervous System Disorders: Dizziness, paresthesia, hypoesthesia, hypokinesia, tremor, somnolence, syncope, Guillain-Barr© syndrome, convulsions/seizures, facial or cranial nerve paralysis, encephalopathy, limb paralysis.

Psychiatric Disorders: Insomnia.

Respiratory, Thoracic, and Mediastinal Disorders: Dyspnea, dysphonia, bronchospasm, throat tightness.

Skin and Subcutaneous Tissue Disorders: Urticaria, localized or generalized rash, pruritus, periorbital edema, sweating.

Vascular Disorders: Flushing, pallor.

Adverse Events Associated With Influenza Vaccines

Anaphylaxis has been reported after administration of FLULAVAL. Although FLULAVAL contains only a limited quantity of egg protein, this protein can induce immediate hypersensitivity reactions among persons who have severe egg allergy. Allergic reactions include hives, angioedema, allergic asthma, and systemic anaphylaxis [see Contraindications] .

The 1976 swine influenza vaccine was associated with an increased frequency of Guillain-Barr© syndrome (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 1 additional case/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 polyangitis (vasculitis) has been reported temporally associated with influenza vaccination.