Paediatrica Indonesiana

VOLUME 52 NUMBER 2 Marchº 2O12
Original Article
Paediatr Indones, Vol. 52, No. 2, March 2012 º 61
Efficacy comparison of cetirizine and loratadine for
allergic rhinitis in children
Juliana, Rita Evalina, Lily Irsa, M. Sjabaroeddin Loebis
Abstract
Background Allergic rhinitis represents a global health problem
affectin, 1O' to more than 1O' of the population worldwide.
Several studies in recent vears have described the efficacv of
second-,eneration antihistamines in voun,er children. lt is
not well established whether cetirizine is more effective than
loratadine in reducin, svmptoms of aller,ic rhinitis.
Objective 1he objective of this studv was to compare the efficacv
of loratadine with cetirizine for treatment of aller,ic rhinitis.
Methods We conducted a randomized, double-blind, controlled
trial of 1OO children, a,ed 13 to 16 vears, from Òctober to
November 2OO9 at two junior hi,h schools in Medan. Oroup
l received 1O m, of cetirizine and ,roup ll received 1O m, of
loratadine, each once dailv in the mornin, for 11 davs. Dru,
efficacv was assessed bv chan,es from baseline svmptom scores
and evaluation of therapeutic responses after 3 davs, 7 davs and
11 davs of treatment.
Results 1he efficacv of cetirizine compared to that of loratadine
was not statisticallv si,nificant in diminishin, nasal svmptoms
after 3 davs, 7 davs and 11 davs of treatment (P~O.1O, P~O.O7,
and P~O.O57, respectivelv). lvaluation of side effects, however,
revealed si,nificantlv fewer headaches in the cetirizine ,roup after
3 davs and 7 davs of treatment (P~O.O1 and P~O.O3, respectivelv)
than in the loratidine ,roup. ln addition, the loratadine ,roup
had si,nificantlv more instances of palpitations after 7 davs of
treatment (P~O.O1) compared to the cetirizine ,roup.
Conclusion 1here was no si,nificant difference in cetirizine and
loratadine treatment effectiveness on aller,ic rhinitis. However,
loratadine was found to cause more headaches and palpitations
than cetirizine. [Paediatr Indones. 2012;52:61-6].
Keywords: antihistamines, cetirizine, loratadine,
allergic rhinitis
1his studv was presented at the 1
th
lndonesian Pediatric Societv Annual
Scientific Meetin,, lebruarv 22 - 21, 2O1O, Medan.
lrom the Department of Child Health, Universitv of North Sumatra
Medical School, Adam Malik Hospital, Medan.
Reprint requests to: Juliana, MD, Department of Child Health, Medical
School, Universitv of North Sumatera/Adam Malik Hospital, Jl. Bun,a
lau No.17, Medan. Ph. ÷62-61-o361721/o365663, lax. ÷62-61-o361721.
Email: Juliana.md@live.com
A
ller,ic rhinitis (AR) is a ,lobal health
problem, affectin, 1O' to more than
1O' of the population worldwide.
1,2
Svmptomatic aller,ic rhinitis reduces
qualitv of life and mav contribute to impairment of
psvcholo,ical well-bein, and co,nitive function.
3
Antihistamines are the pharmacolo,ic corner -
stone of treatment for aller,ic rhinitis.
1
The
comparative effects of second ,eneration anti-
histamines, cetirizine and loratadine, amon, voun,er
patients have not been well documented. Cetirizine
and loratadine are anta,onists to the histamine H1
receptor and their metabolism mav lead to sedative
and cardiotoxic effects. 1hus, more research on these
dru,s is needed.
5,6
loratadine is 9o' metabolized in the liver and
excreted bv the kidnevs, while cetirizine metabolism
does not involve the liver, thou,h it is mostlv excreted
bv the kidnevs. However, Bucks et al found that
cetirizine is six times more potent than loratadine,
thus a hi,her dose of loratadine is often required to
Juliana et al: lfficacv comparison of cetirizine and loratadine for aller,ic rhinitis in children
62 º Paediatr Indones, Vol. 52, No. 2, March 2012
achieve a similar result.
6
Òther second ,eneration
antihistamines, such as terfenadine and astemizole,
also had similar effects compared to cetirizine, but
these dru,s are metabolized rapidlv in the liver
and have cardiotoxic effects.
6,7
1he purpose of
this studv was to compare the efficacv of cetirizine
and loratadine for treatment of aller,ic rhinitis in
children.
Methods
We conducted a randomized, double-blind, controlled
trial from Òctober to November 2OO9 at two junior
hi,h schools in Medan. Data were collected bv
questionnaire. Patients were enrolled in the studv if
thev had svmptoms of aller,ic rhinitis (runnv nose,
sneezin,, nasal stuffiness, eve itchiness, eve redness,
sleep disturbance, impaired co,nitive functionin,,
or school absence) and were atopic. We included
children a,ed 13 to 16 vears, who were dia,nosed
with aller,ic rhinitis that was confirmed bv nasal
examination. 1o evaluate severitv of the disease,
we used a rhinitis aller,ic scorin, svstem: O~ no
evident svmptoms, 1~ mild svmptoms not interferin,
with dailv activities and/or sleep, 2~ moderate
svmptoms somewhat interferin, with dailv activities
and/or sleep, and 3~ severe svmptoms with major
Figure 1. Study profle
475 students
150 with allergic rhinitis
Evaluation on days 3, 7 and 14 of treatment
Loratadine
n = 50
1 student absent for
evaluation (7
th
day)
- <13 yrs old (40)
- Refused to join (5)
- Taking antihistamines (5)
49 students completed
treatment
Cetirizine
n = 50
1 student absent for
evaluation (3
rd
day)
49 students completed
treatment
Enrolled students
n= 100
Juliana et al: lfficacv comparison of cetirizine and loratadine for aller,ic rhinitis in children
Paediatr Indones, Vol. 52, No. 2, March 2012 º 63
interference in dailv activities and/or sleep.
11
We
excluded subjects with a historv of documented
asthma, sinusitis, common cold, otitis media,
nasal anatomic abnormalites, known idiosvncratic
reactions to cetirizine or loratadine, corticosteroid
use within two weeks of the first test dose, oral or
topical decon,estant and antihistamine use within
21 hours of the first test dose, and those who refused
to consume the dru,.
Patients were divided into two ,roups bv
simple randomization usin, random tables. Oroup l
received 1O m, cetirizine and ,roup ll received 1O m,
loratadine, with each medication taken once a dav
orallv for 11 davs. We evaluated the patients at visit
1 for screenin,, after 3 davs (visit 2), after 7 davs (visit
3) and after 11 davs (visit 1) of treatment. Subjects
were not allowed to consume other antihistamines or
corticosteroids durin, treatment period.
1reatment efficacv was assessed bv chan,es
from baseline svmptom scores and side effects were
assessed after therapeutic response at 3 davs, 7
davs, and 11 davs of treatment. Svmptoms were
observed and phvsical examination was performed
at each visit. 1his studv was approved bv the lthics
Committee of the Medical School Universitv of
North Sumatera.
Chi-square test was performed to analvze
treatment efficacv and side effects. Differences were
considered si,nificant if P< O.O5. We used SPSS
version 15 for data processin,. Òur studv was an
intention to treat analvsis.
Results
We screened 175 students, of which 15O suffered from
aller,ic rhinitis. liftv of these students were excluded
for the followin, reasons: 1O students were a,ed
below 13 vears, 5 students refused to participate, and
5 students were alreadv takin, antihistamines. 1he
remainin, 1OO students were randomized into two
,roups of 5O, each of whom received treatment with
1O m, loratadine or 1O m, cetirizine (Figure 1).
Subjects' characteristics are shown in Table
1. 1he mean a,e in the cetirizine ,roup was 13.1O
vears while in that of the loratadine ,roup was 13.3o
vears. 1here were 31 females in the cetirizine ,roup
(6o') and 29 in the loratadine ,roup (5o'). At the
first visit, 21 students in the cetirizine ,roup had a
moderate aller,ic rhinitis score while 29 students
had a severe score. ln the loratadine ,roup, 16 had
moderate and 31 had severe scores. 1he majoritv of
subjects (63') had severe aller,ic rhinitis scores at
baseline.
Table 2 shows scores of aller,ic rhinitis at
davs 3, 7, and 11 of treatment. Òn davs 3 and 7,
there were decreased svmptoms of rhinitis in both
,roups, but there was no statisticallv si,nificant
difference between the two ,roups (P~O.1O for dav
Table 2. Scores of allergic rhinitis at days 3, 7, and 14 of
treatment.
Evaluated scores
rhinitis
Cetirizine
n(%)
Loratadine
n(%)
P
Day-3
Mild
Moderate
Severe
Day-7
No symptoms
Mild
Moderate
Severe
Day-14
No symptoms
Mild
Moderate
Severe
3 (6)
30 (60)
17 (34)
18 (36)
4 (8)
26 (52)
2 (4)
43 (86)
6 (12)
0 (0)
1 (2)
1 (2)
27 (54)
22 (44)
10 (20)
9 (18)
24 (48)
7 (14)
37 (74)
5 (10)
7 (14)
1 (2)
0.400
0.070
0.057
Table 1. Baseline characteristics
Characteristics
Cetirizine,
n (%)
Loratadine,
n (%)
Sex
Male
Female
Age
13 years old
14 years old
15 years old
Mean age, years
Symptoms
Runny nose
Sneezing
Stuffness
Eye itchiness
Eye redness
Sleep disturbance
Ìmpaired school performance
School absence
Allergic rhinitis score
Moderate
Severe
16 (32)
34 (68)
30 (60)
15 (30)
5 (10)
13.40
45 (90)
49 (98)
44 (88)
17 (34)
18 (36)
31 (62)
27 (54)
5 (10)
21 (42)
29 (58)
21 (42)
29 (58)
32 (64)
10 (20)
8 (16)
13.38
42 (84)
49 (98)
48 (96)
18 (36)
16 (32)
31 (62)
39 (78)
10 (20)
16 (32)
34 (68)
Juliana et al: lfficacv comparison of cetirizine and loratadine for aller,ic rhinitis in children
64 º Paediatr Indones, Vol. 52, No. 2, March 2012
3 and P~O.O7 for dav 7). Òn dav 11, the majoritv of
subjects in both ,roups were free from svmptoms, but
difference in the two ,roups was also not statisticallv
si,nificant (P~O.O57).
Table 3 reports the observation of svmptoms
after 3, 7, and 11 davs of treatment. 1here was
improvement in svmptoms in each ,roup, but there
were no statisticallv si,nificant differences between
the two ,roups.
Table 4 shows the incidence of side effects after
3, 7, and 11 davs of treatment. 1here were si,nificant
differences between the two ,roups after 3 davs and 7
davs of treatment. Headaches were more frequentlv
present in the loratadine ,roup compared to the
cetirizine ,roup (dav 3, P~O.O1 and dav 7, P~O.O3).
ln addition, at 7 davs, we observed more palpitations
in the loratadine ,roup than in the cetirizine ,roup
(P~O.O1).
Discussion
An estimated 2O to 1O million Americans are affected
bv aller,ic rhinitis. 1he actual prevalence of the
condition is difficult to discern as manv sufferers self-
medicate without seekin, medical care.
o
Accordin,
to the lnternational Studv on Asthma and Aller,v
in Childhood (lSAAC), the prevalence of aller,ic
rhinitis is 1.1 - 39.7' at the a,e of 13 to 11 vears.
1,2
ln a,reement, we found 32' (15O/175) of students
screened to have this condition. Òur subjects' mean
a,e was 13.1 vears.
1he dia,nosis of aller,ic rhinitis is usuallv made
on the basis of the patient's historv and the results of
phvsical examination. ln addition to classic svmptoms
of nasal con,estion, itchv nose, sneezin,, rhinorrhea,
and itchv, waterv eves, other important considerations
include a familv historv of aller,ic rhinitis, a historv of
Table 3. Clinical symptoms evaluation on days 3, 7 and 14 after cetirizine or loratadine treatment
Symptoms
Day 3
P
Day 7
P
Day 14
P cetirizine
n (%)
loratadine
n (%)
cetirizine
n (%)
loratadine
n (%)
cetirizine
n (%)
loratadine
n (%)
Runny nose
Sneezing
Stiffness
Eye itchiness
Eye redness
Sleep disturbance
Ìmpaired school performance
School absence
40 (80)
40 (80)
33 (66)
9 (18)
7 (14)
6 (12)
6 (12)
1 (2)
36 (72)
44 (88)
34 (68)
13 (26)
6 (12)
11 (22)
11 (22)
2 (4)
0.34
0.20
0.83
0.33
0.76
0.18
0.18
0.55
24 (48)
27 (54)
19 (38)
4 (8)
5 (10)
2 (4)
4 (8)
1 (2)
27 (54)
34 (68)
27 (54)
9 (18)
6 (12)
5 (10)
9 (18)
1 (2)
0.15
0.15
0.10
0.13
0.74
0.24
0.13
1.00
2 (4)
2 (4)
3 (6)
2 (4)
1 (2)
0 (0)
0 (0)
1(2)
2 4)
7(14)
6(12)
4 (8)
2 (4)
2 (4)
3 (6)
1 (2)
1.00
0.08
0.29
0.40
0.92
0.15
0.07
1.00
Table 4. Side effects on day 3, 7 and 14 of cetirizine or loratadine treatment
Side effects
Day 3
P
Day 7
P
Day 14
P cetirizine
n (%)
loratadine
n (%)
cetirizine
n (%)
loratadine
n (%)
cetirizine
n (%)
loratadine
n (%)
Sedation
Dizziness
Confusion
Bitter taste
Nausea
Vomiting
Dry mouth
Headaches
Breathing diffculty
Urinary incontinence
Tiredness
Palpitations
Blurred vision
22 (44 )
12 (24)
5 (10)
19 (38)
11 (22)
2 (4)
23 (46)
4 (8)
2 (4)
1 (2)
13 (26)
5 (10)
1 (2)
19 (38)
12 (24)
6 (12)
21 (42)
10 (20)
2 (4)
25 (50)
13 (26)
6 (12)
4 (8)
18 (36)
2 (4)
2 (4)
0.48
0.62
0.74
0.68
0.86
1.00
0.68
0.01
0.14
0.16
0.27
0.23
0.55
24 (48)
16 (32)
7 (14)
15 (30)
11 (22)
5 (10)
21 (42)
8 (16)
4 (8)
2 (4)
14 (28)
0 (0)
4 (8)
17 (34)
10 (20)
4 (8)
21 (42)
8 (16)
1 (2)
17 (34)
17 (34)
5 (10)
5 (10)
18 (36)
4 (8)
2 (4)
0.15
0.17
0.33
0.21
0.44
0.09
0.41
0.03
0.72
0.24
0.39
0.04
0.40
22 (44)
9 (18)
4 (8)
13 (26)
5 (10)
1 (2)
16 (32)
6 (12)
2 (4)
1 (2)
12 (24)
0 (0)
3 (6)
18 (36)
9 (18)
7 (14)
17 (34)
4 (8)
1 (2)
12 (24)
10 (20)
3 (6)
0 (0)
11 (22)
2 (4)
1 (2)
0.41
1.00
0.33
0.38
0.72
1.00
0.37
0.27
0.64
0.31
0.81
0.15
0.30
Juliana et al: lfficacv comparison of cetirizine and loratadine for aller,ic rhinitis in children
Paediatr Indones, Vol. 52, No. 2, March 2012 º 65
other atopic diseases, previous treatment experiences
and suspected tri,,ers.
o
lor the purposes of our
studv, the dia,nosis of aller,ic rhinitis was made from
assessin, classic svmptoms, obtainin, a familv historv
of aller,ic rhinitis, a historv of other atopic diseases
and phvsical examination.
We did not perform dia,nostic tests to establish
the aller,ic rhinitis dia,nosis because manv subjects
refused to ,ive blood samples nor consent to patient
skin prick tests. Published ,uidelines from the American
Academv of Asthma, Aller,v and lmmunolo,v, as well
as other expert panels, recommended confirmatorv
testin, when aller,ic rhinitis is clinicallv suspected.
1here is no evidence to support the superioritv of
this recommendation over direct empiric trial of
medications, and most primarv care phvsicians choose
to treat empiricallv based upon the historv and phvsical
examination.
Dia,nostic tests include skin prick testin,,
intradermal testin,, and in vitro blood tests.
Nasal challen,e testin,, nasal smears, sinus
transillumination, and nasopharvn,oscopv are
non-specific tests. Non-specific tests are not
recommended for routine evaluation, but mav be
useful in selected cases when aller,en specific tests
have failed to clarifv the causes of rhinitis.
o
Second-,eneration antihistamines are selective
for peripheral H1 receptors. 1hese a,ents are associated
with less sedative anticholiner,ic effects than non-
selective first-,eneration antihistamines.
6
1he efficacv
and safetv of some second-,eneration antihistamines
in children have been assessed in a number of well-
desi,ned clinical trials.
9,1O
ln contrast with our findin,s,
a studv in Mexico reported that 1O m, of cetirizine can
reduce the major svmptoms of aller,ic rhinitis (runnv
nose, sneezin,, itchv nose, and waterv eves) better
than loratadine and placebo.
1
Òur studv showed no
si,nificant difference in the effectiveness of loratadine
and cetirizine in treatin, aller,ic rhinitis.
1he majoritv of our participants suffered from
severe aller,ic rhinitis based on the scorin, svstem
we used. We classified the aller,ic rhinitis svmptoms
into cate,ories of mild, moderate and severe. Mild was
defined as no interference with dailv activities and/or
sleep. Moderate was defined as some interference with
dailv activities and/or sleep. And severe was defined
as si,nificant/major interference with dailv activities
and/or sleep.
11
We found no si,nificant difference in sedative
effect between the cetirizine ,roup and the loratadine
,roup after 3, 7, and 11 davs of treatment (P~O.1o,
P~O.15, P~O.11, respectivelv). ln contrast, studies in
Mexico and the USA reported a si,nificantlv hi,her
sedative side effects in the cetirizine ,roup than in
the loratadine ,roup (P<O.OO1).
1,12
Another review
showed the side effects (such as headaches) of both
cetirizine and loratadine were about 1 to 12'.
9
But
a clinical studv on loratadine reported no sedative or
anticholiner,ic effect, which was clinicallv si,nificant
when this dru, was compared to placebo.
13
A studv of 39o patients was conducted to
determine the effects of cetirizine on health-related
qualitv of life in patients with seasonal aller,ic
rhinitis. Cetirizine was shown to be efficacious for
total svmptom severitv, as well as for qualitv of life
measures includin, activities of dailv livin,, practical
problems, svmptom distress, sleep disturbance, and
emotional difficulties.
11
Similar to our studv, the
svmptoms of sleep disturbance and impaired school
performance decreased followin, the end of treatment
with cetirizine, but no statistical difference was shown
compared to loratadine ,roup.
Second-,eneration antihisitmines such as
cetirizine, loratadine, fexofenadine and ebastine
are thou,ht to have cardiotoxic effects such as
hvpertension, hvpotension, palpitation, supraventri-
cular tachvarrhvthmia, svncope and tachvcardia,
thou,h plasma concentrations are hi,her compared
to astemizol and terfenadin.
15
Òur studv found
statisticallv si,nificant differences in the presence
of palpitations between the two ,roups on dav 7 of
treatment.
We conclude there was no si,nificant difference
between cetirizine and loratadine in treatment
effectiveness of aller,ic rhinitis. However, loratadine
was more frequentlv associated with side effects of
headaches and palpitations.
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