A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
FluMist Side Effects, and Drug Interactions - Influenza Virus Vaccine
FluMist Side Effects, and Drug Interactions - Influenza Virus Vaccine
SIDE EFFECTS
See CLINICAL STUDIES for a description
of the number of participants in clinical trials.
Serious Adverse Events
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 influenza (such as pneumonia, bronchitis, bronchiolitis, or central nervous
system events) was similar in FluMist and placebo groups.
Adverse Events in Placebo-Controlled Trials
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.
Solicited Adverse Events in Children
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.
|
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
|
| |
Post-Dose One
|
Post-Dose Two
|
|
FluMist
|
Placebo
|
FluMist
|
Placebo
|
|
214a
|
95a
|
161a
|
75a
|
|
Event
|
%
|
%
|
%
|
%
|
|
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
|
|
Feverb
|
|
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 [4].
Other Adverse Events in Children
In addition to the solicited events, parents also reported
other adverse events that occurred during the course of the clinical trials.
Among healthy children age 60-71 months in the Pediatric Efficacy
Study, 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.
Medically Attended Events in Children and Adolescents
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(s), 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.
Solicited Adverse Events in Adults
In the placebo-controlled Adult Effectiveness Study, the rate
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.
|
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
|
|
N=2548a
|
N=1290a
|
|
Event
|
(%)
|
(%)
|
|
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
|
|
Fever
|
|
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.]
Other Adverse Events in Adults
In addition to the solicited events, participants also reported
other adverse events that occurred during the course of the clinical trials.
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 EVENT REPORTING
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 INTERACTIONS
Children or adolescents who are receiving aspirin therapy or
aspirin-containing therapy should not receive FluMist (see CONTRAINDICATIONS).
FluMist should not be administered to persons on immunosuppressive therapy.
The concurrent use of FluMist with antiviral compounds that
are active against influenza A and/or B viruses has not been evaluated. However,
based upon the potential for interference between such compounds and FluMist,
it is advisable not to administer FluMist until 48 hours after the cessation
of antiviral therapy and that antiviral agents not be administered until two
weeks after administration of FluMist unless medically indicated.
There are no data regarding co-administration of FluMist with
other intranasal preparations, including steroids.
Concurrent Administration with Other Vaccines
The safety and immunogenicity of FluMist when administered
concurrently with other vaccines have not been determined. Therefore, FluMist
should not be administered concurrently with other vaccines. Studies of FluMist
in healthy individuals excluded subjects who received any live virus vaccine
within one month of enrollment and any inactivated or subunit vaccine within
two weeks of enrollment; therefore, health care providers should adhere to these
intervals when administering FluMist.
Laboratory Interactions
Data related to shedding of FluMist in children and adults
are limited. Nasopharyngeal secretions or swabs collected from vaccinees may
test positive for influenza virus for up to three weeks.
Carcinogenesis, Mutagenesis, Impairment of Fertility
FluMist has not been evaluated for its carcinogenic or mutagenic
potential or its potential to impair fertility.
Pregnancy (Category C)
Animal reproduction studies have not been conducted with FluMist.
It is also not known whether FluMist can cause fetal harm when administered
to a pregnant woman or affect reproduction capacity. Therefore, FluMist should
not be administered to pregnant women.
Nursing Mothers
It is not known whether FluMist is excreted in human milk.
Therefore, as some viruses are excreted in human milk and additionally, because
of the possibility of shedding of vaccine virus and the close proximity of a
nursing infant and mother, caution should be exercised if FluMist is administered
to nursing mothers.
Pediatric Use
The safety of FluMist in infants and children <60 months
of age has not been established (see CLINICAL
STUDIES, INDICATIONS AND USAGE,
and ADVERSE REACTIONS).
Geriatric Use
Clinical studies with FluMist did not include sufficient numbers
of adults age 65 years and older to determine if they respond differently from
younger individuals. The safe use of FluMist in persons 65 years and older has
not been established (see CLINICAL PHARMACOLOGY
and DOSAGE AND ADMINISTRATION).
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