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Flumist (Influenza Virus Vaccine Live Intranasal) - Side Effects and Adverse Reactions



See CLINICAL STUDIES for a description of the number of participants in clinical trials.


Across all clinical trials, serious adverse events (SAEs) were monitored after vaccination for 42 days in children and for 28 days in adults. SAEs occurred at a similar rate (<1%) in FluMist and placebo recipients for both healthy children and healthy adults.

Overall, across the placebo-controlled trials in adults and children, the incidence of selected adverse reactions that may be complications of wild-type influenza (such as pneumonia, bronchitis, bronchiolitis, or central nervous system events) was similar in FluMist and placebo groups.


In all placebo-controlled studies, allantoic fluid from uninfected eggs was used as the placebo. In randomized, placebo-controlled trials, 4719 healthy children 5-17 years of age and 2864 healthy adults 18-49 years of age received FluMist and 2327 healthy children and 1454 healthy adults received the placebo. In placebo-controlled clinical trials conducted in healthy populations, solicited adverse events and daily temperatures were collected on diary cards. These solicited events included runny nose/nasal congestion, sore throat, cough, irritability, headache, chills, vomiting, muscle aches, and decreased activity and a feeling of tiredness/weakness.


Table 3 shows an analysis of solicited events for the Pediatric Efficacy Study in the subset of healthy children 60-71 months of age. The largest absolute differences between FluMist and placebo after Dose One were observed in the incidences of headache and runny nose/nasal congestion. No differences were observed for fever (>100°F oral). Following Dose Two, the largest absolute differences between FluMist and placebo were runny nose/nasal congestion and cough. There was no significant increase in influenza-like illness (ILI) as defined by the CDC in the FluMist group compared to the placebo group. CDC has defined CDC-ILI as having fever (temperature >/=100[ordm ]F oral) plus either cough or sore throat on the same day or on consecutive days.

Table 3
Summary of Solicited Events Observed within 10 Days after Each Dose for Vaccine
and Placebo Recipients; Healthy Children 60-71 Months of Age
Event Post-Dose One Post-Dose Two
FluMist Placebo FluMist Placebo
214 a 95 a 161 a 75 a
% % % %
Any event 65.4 61.4 66.5 53.3
Cough 26.8 32.7 38.5 30.7
Runny Nose/Nasal Congestion 48.1 44.2 46.0 32.0
Sore Throat 12.6 19.8   9.3 16.0
Irritability 19.5 16.8   9.9   9.3
Headache 17.8 11.6   6.8 16.0
Chills   6.1   5.3   2.5   4.0
Vomiting   4.7   3.2   5.6 12.0
Muscle Aches   6.1   4.2   5.0   4.0
Decreased Activity 14.0 12.6 10.6 13.3
Fever b
   Temp 1   9.5   9.9   4.3   4.0
   Temp 2   2.2   2.0   0.6   1.3
   Temp 3   0.0   0.0   0.0   0.0
Note: There were no statistically significant differences in any of these events (p-value >0.05); Fisher's exact method.
a Number of evaluable subjects (those who returned diary cards) for each event.
b Fever
Temp 1: Oral >100°F, rectal or aural >100.6°F, or axillary >99.6°F.
Temp 2: Oral >102°F, rectal or aural >102.6°F, or axillary >101.6°F.
Temp 3: Oral >104°F, rectal or aural >104.6°F, or axillary >103.6°F.

For the cohort of 128 children who received FluMist across three consecutive years, rates of solicited adverse events were not significantly increased when compared to placebo recipients [15].


A large randomized, double-blind, placebo-controlled trial in healthy children 1 through 17 years of age was conducted at 31 clinics in the Northern California Kaiser-Permanente Health Maintenance Organization (HMO) to assess the rate of medically attended events (MAEs) within 42 days of vaccination. Participants were randomized 2:1 (vaccine:placebo). A total of 6657 evaluable children 5-17 years of age were enrolled, including 3244 boys and 3413 girls. Of these 6657 children, 2606 were 5-8 years of age and 4051 were 9-17 years of age. Dose Two for children less than nine years of age was to be administered 28 to 42 days after Dose One.

Data regarding MAEs were obtained from the Kaiser-Permanente computerized health care utilization databases for hospitalizations, emergency department visits and clinical visits. MAEs were analyzed individually and within four pre-specified grouped diagnoses: acute respiratory tract events, systemic bacterial infections, acute gastrointestinal tract events, and rare events potentially related to influenza. For these four pre-specified grouped diagnoses, no significant increase in risk for FluMist recipients was seen in the combined analyses across all utilization settings, doses, and age groups. Selected respiratory tract illnesses of special interest (pneumonia, bronchitis, bronchiolitis, and croup) were included in acute respiratory tract events and were not associated with increased risk for FluMist recipients in any protocol-specified analysis. No systemic bacterial infection occurred. In FluMist recipients, an increased risk was not observed for rare events that have been reported with naturally occurring influenza virus infection, including seizures, febrile seizures, and epilepsy. No cases of encephalitis, acute idiopathic polyneuritis (Guillain-Barré syndrome), Reye syndrome, or myocarditis (influenza-associated rare disorders) were reported in this study.

In this study, in individuals 5-17 years of age, four individual MAEs were significantly increased and 11 were significantly decreased. Of the four individual MAEs associated with increased risk, a biological association with FluMist is plausible for one: abdominal pain. Of the 11 individual MAEs associated with decreased risk, a biologically plausible association with FluMist exists for seven: asthma, bronchitis, conjunctivitis, cough, viral syndrome, otitis media, and wheezing/shortness of breath. However, in the same study, a statistically significant increase in asthma or reactive airways disease was observed for children 12-59 months of age following Dose One (Relative Risk 3.53, 90% CI: 1.1,15.7). As a result of this finding, FluMist is not indicated for children <60 months of age.


In the placebo-controlled Adult Effectiveness Study, the rates of solicited adverse events in the subset of healthy adults 18-49 years of age are shown in Table 4. Statistically significant differences were observed for any event, cough, runny nose, sore throat, chills, and tiredness/weakness. Fever >100°F was similar in FluMist and placebo recipients after a single dose. There was no significant increase in influenza-like illness (ILI) as defined by the CDC in the FluMist group compared to the placebo group.

Table 4
Summary of Solicited Events Observed within 7 Days
after Each Dose for Vaccine and Placebo Recipients; Healthy Adults 18-49 Years of Age
FluMist Placebo
Event N=2548 a N=1290 a
% %
Any event 71.9 * 62.6
Cough 13.9 * 10.8
Runny Nose 44.5 * 27.1
Sore Throat 27.8 * 17.1
Headache 40.4 38.4
Chills 8.6 *   6.0
Muscle Aches 16.7 14.6
Tiredness/Weakness 25.7 * 21.6
   Oral Temp >100°F 1.5   1.3
   Oral Temp >101°F 0.5   0.7
   Oral Temp >102°F 0.1   0.2
   Oral Temp >103°F 0.0   0.0
*Denotes statistically significant p-value </=0.05; no adjustments for multiple comparisons; Fisher's exact method.
a Number of evaluable subjects (those who returned diary cards). [97.9% of FluMist recipients and 97.9% of placebo recipients.]


In addition to the solicited events, parents of subjects in the Pediatric Efficacy Trial also reported other adverse events that occurred during the course of the trial. Among healthy children age 60-71 months, the events that occurred in at least 1% of FluMist recipients and at a higher rate compared to placebo were: abdominal pain (3.7% FluMist vs 0% placebo), otitis media (1.4% FluMist vs 0% placebo), accidental injury (2.3% FluMist vs 2.1% placebo), diarrhea (3.7% FluMist vs 1.1% placebo), following Dose One and otitis media (3.1% FluMist vs 1.3% placebo) following Dose Two. None of these differences were statistically significant.

In addition to the solicited events, adults who participated in the Adult Effectiveness Study also reported other adverse events that occurred during the course of the clinical trial. For adults 18-49 years of age in the Adult Effectiveness Study, nasal congestion (9.2% FluMist vs 2.2% placebo), rhinitis (6.3% FluMist vs 3.1% placebo), and sinusitis (4.1% FluMist vs 2.2% placebo) were reported significantly more often by FluMist recipients compared to placebo recipients.

Adverse events reported post-licensure have included nausea, rash, hypersensitivity reactions (including anaphylaxis, facial edema, and urticaria). These events occurred at similar rates in FluMist versus placebo recipients in pre-licensure studies.

Annually, 20-40 cases of Guillain-Barré syndrome (GBS) that occur within 42 days of administration of inactivated influenza vaccine are reported to VAERS. In 2003-2004, one case of GBS with temporal association with FluMist was reported. Evidence of a causal relationship between influenza vaccines, including FluMist, has not been established.

Guillain-Barré Syndrome and Influenza Vaccines

The 1976 swine influenza vaccine was associated with an increased frequency of Guillain-Barré syndrome (GBS). Among persons who received the swine influenza vaccine in 1976, the rate of GBS that exceeded the background rate was <10 cases/1 million persons vaccinated with the risk for influenza vaccine-associated GBS higher among persons aged >25 years than persons <25 years. Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is unclear. Obtaining strong epidemiologic evidence for a possible limited increase in risk is difficult for such a rare condition as GBS, which has an annual incidence of 10-20 cases/1 million adults. Thus, investigations to date indicate no substantial increase GBS associated with influenza vaccines (other than the swine influenza vaccine in 1976), and that, if influenza vaccine does pose a risk, it is probably slightly more than one additional case/1 million persons vaccinated. Cases of GBS after influenza infection have been reported, but no epidemiologic studies have documented such an association [1].

The incidence of GBS among the general population is low, but persons with a history of GBS have a substantially greater likelihood of subsequently experiencing GBS than persons without such a history. Thus, the likelihood of coincidentally experiencing GBS after influenza vaccination is expected to be greater among persons with a history of GBS than among persons with no history of this syndrome [1].


Reporting by vaccine recipients or the parents/guardians of vaccinees and health care providers of all adverse events occurring after vaccine administration is encouraged. The U.S. Department of Health and Human Services (DHHS) has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine. The VAERS toll-free number is 1-800-822-7967. Reporting forms may also be obtained at the FDA Web site at: http://www.vaers.org.

Drug label data at the top of this Page last updated: 2006-11-23

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