Download Suggestion from clinicians

Cetirizine
Removal from the List
Peer Feedback:
“Available OTC”
Note: other allergy medications are included on the list (budesonide, diphenhydramine).
Comment was vague, so review will focus on efficacy.
Literature Review Question:
What is the efficacy of cetirizine and other anti-allergy medications?
Literature Search:
eCPS - Respiratory Disorders: Allergic Rhinitis
References taken from eCPS page
Pubmed – ‘allergic rhinitis AND comparison AND efficacy AND antihistamine AND (Review OR
Meta-Analysis’
The diagnosis and management of rhinitis (2008)
Note: Letter at end of paragraph indicates strength of recommendation (see below for chart
explanation)
Pharmacologic therapy Oral antihistamines
61. Second-generation antihistamines are generally preferred over first-generation antihistamines
for the treatment of allergic rhinitis. First-generation antihistamines have significant potential to
cause sedation, performance impairment, and anticholinergic effects. Although occasionally
advantageous (eg, sleep induction when taken at bedtime or a reduction in rhinorrhea), these
properties are usually undesirable and are potentially dangerous. Second-generation
antihistamines have less or no tendency to cause these effects. B
62. Before prescribing or recommending a first-generation antihistamine, the physician should
ensure that the patient understands both the potential for adverse effects and the availability of
alternative antihistamines with a lower likelihood of adverse effects. D
63. There are important differences among the second-generation antihistamines in regard to
their sedative properties: fexofenadine, loratadine, and desloratadine do not cause sedation at
recommended doses; loratadine and desloratadine may cause sedation at doses exceeding the
recommended dose; cetirizine and intranasal azelastine may cause sedation at recommended
doses. A
64. Among the newer, nonsedating antihistamines, no single agent has been conclusively found
to achieve superior overall response rates. C
Second-generation oral antihistamines [Summary Statements 61-64]
Second-generation antihistamines are generally preferred over first-generation antihistamines for
treatment of allergic rhinitis because they have less tendency to cause sedation, performance
impairment, and/or anticholinergic adverse effects.307-311 First-generation antihistamines may
produce performance impairment in school176,312,313 and driving314-318 that can exist without
subjective awareness of sedation;310 and the use of first-generation antihistamines has been
associated with increased automobile and occupational accidents.314-319 Individual variation
exists with respect to development of sedative effects with first-generation
antihistamines.307,309,313 Concomitant use of other central nervous system (CNS)–active
substances, such as alcohol and sedatives, may further enhance performance impairment from
these antihistamines.307,309 In part because of prolonged plasma half-life and metabolites
(Table VII), these undesirable and potentially dangerous side effects cannot be eliminated by
administration of first-generation antihistamines only at bedtime.320-325 Anticholinergic effects
include dryness of mouth and eyes, constipation, inhibition of micturition, and an increased risk
for provocation of narrow-angle glaucoma. Increased sensitivity and a greater incidence of preexisting comorbid conditions, such as prostatic hypertrophy, elevated IOP, and cognitive
impairment, place older adults in a high-risk category for the side effects of first-generation
antihistamines. The anticholinergic effects of the first-generation antihistamines may explain the
reported better control of rhinorrhea compared with the second-generation antihistamines. The
overall efficacy of first-generation antihistamines compared with second generation for the
management of allergic rhinitis symptoms has not been adequately studied. Second-generation
antihistamines differ in their onset of action, sedation properties, skin test suppression, and
dosing guidelines (Table VIII). No single agent has been conclusively shown to have superior
efficacy.326,327 Exceeding the recommended dosage may result in increased sedation with
many of these products309,323,328-330 that do not produce sedation at recommended doses.
Although antihistamines can be used on an intermittent basis, such as for episodic allergic
rhinitis, it has been shown that continuous treatment for seasonal or perennial allergic rhinitis is
more effective,331 primarily because of unavoidable, ongoing allergen exposure.
Intranasal corticosteroids
74. Intranasal corticosteroids are the most effective medication class for controlling symptoms of
allergic rhinitis. A
75. In most studies, intranasal corticosteroids have been shown to be more effective than the
combined use of an antihistamine and leukotriene (LT) antagonist in the treatment of seasonal
allergic rhinitis. A
76. Intranasal corticosteroids may provide significant relief of symptoms of seasonal allergic
rhinitis when used not only on a regular basis but also on an as-needed basis. B However, asneeded use may not be as effective as continuous use of intranasal corticosteroids. D
77. When comparing the available intranasal corticosteroids, the overall clinical response does
not appear to vary significantly between products irrespective of the differences in topical
potency, lipid solubility, and binding affinity. C
78. Intranasal corticosteroids may be useful in the treatment of some forms of non-allergic rhinitis.
A
79. Intranasal corticosteroids when given in recommended doses are not generally associated
with clinically significant systemic side effects. A
80. Although local side effects are typically minimal with the use of intranasal corticosteroids,
nasal irritation and bleeding may occur. Nasal septal perforation is rarely reported. B
Intranasal corticosteroids [Summary Statements 74-80]
Intranasal corticosteroids are the most effective medications for treating allergic rhinitis. In most
studies, intranasal corticosteroids are more effective than the combined use of an antihistamine
and a LT antagonist.375-379 The clinical response does not appear to vary significantly between
intranasal corticosteroids that are currently available (Table VIII).53,380-382 The onset of
therapeutic effect of intranasal corticosteroid occurs between 3 and 12 hours.383-385 The asneeded dosing (which equated to 55% to 62% of days) of an intranasal corticosteroid (fluticasone
propionate) has been shown to be effective in the treatment of seasonal allergic
rhinitis380,386,387 but may not be as efficacious as continuous use. In 1 study, PRN use of an
intranasal corticosteroid (fluticasone propionate) was superior to PRN use of an oral
antihistamine (loratadine) for seasonal allergic rhinitis.380 Intranasal corticosteroids are also
effective in the treatment of nonallergic rhinitis, especially NARES388-390 and vasomotor
rhinitis.389,391,392 Intranasal corticosteroids may also benefit ocular allergy symptoms
associated with allergic rhinitis (see Summary Statement 19). Intranasal corticosteroids when
given in recommended doses are not generally associated with clinically significant systemic side
effects. Studies in both children and adults have failed to demonstrate any consistent, clinically
relevant effect from intranasal corticosteroids on the hypothalamic-pituitary-adrenal (HPA)
axis,393-401 ocular pressure or cataract formation,393,402-404 or bone density.405-407 In
children, growth effect may be a better indicator of systemic effect than HPA axis suppression.
The transient effect on growth suppression that has been demonstrated in children after
administration of intranasal corticosteroids is dependent on the specific intranasal corticosteroid,
and the dose administered, technique used for measuring growth, time of administration, and
concomitant use of oral or inhaled corticosteroid. Studies with intranasal fluticasone propionate,
mometasone furoate, and budesonide have shown no effect on growth at recommended doses
compared with placebo408-410 and reference values (at as much as 2 times the recommended
doses).400 Growth suppression from intranasal corticosteroids has been reported only with longterm use of beclomethasone dipropionate that exceeded recommended doses409 or
administration to toddlers.411 Local side effects of intranasal corticosteroids such as nasal
irritation, bleeding, and nasal septal perforation412,413 are rare and can be avoided with proper
administration technique. The patient should be periodically examined to assure that these side
effects are not present. Preparations containing propylene glycol and benzalkonium chloride may
result in local irritation or ciliary dysfunction, respectively414,415 (Table VIII).
Classification of recommendations and evidence
Category of evidence
Strength of Recommendation
Ia. Evidence from meta-analysis of randomized controlled
trials
A Directly based on category I evidence
Ib. Evidence from at least 1 randomized controlled trial
B Directly based on category II evidence or extrapolated
recommendation from category I evidence
IIa. Evidence from at least 1 controlled study without
randomization
C Directly based on category III evidence or extrapolated
recommendation from category I or II evidence
IIb. Evidence from at least 1 other type of quasiexperimental study
D Directly based on category IV evidence or extrapolated
recommendation from category I, II, or III evidence
III. Evidence from nonexperimental descriptive studies,
such as comparative studies
IV. Evidence from expert committee reports or opinions or
clinical experience of respected authorities, or both
Wallace, Dana V., et al. "The diagnosis and management of rhinitis: an updated practice
parameter." Journal of allergy and clinical immunology 122.2 (2008): S1-S84.
Inhaled Corticosteroids in Allergic Rhinitis (2007)
Note: allergic rhinitis (AR); budesonide aqueous nasal spray (BANS), fluticasone propionate
nasal spray (FPNS), mometasone furoate nasal spray (MFNS), and triamcinolone aqueous nasal
spray (TANS); intranasal corticosteroid (INS)
Proper management of AR, as with any chronic disease, is determined in part by patients’
acceptance and adherence to their treatment regimen, which is affected by factors such as
efficacy, safety, dosing regimens, patient preference, and cost of treatment. Analysis of oncedaily administration of BANS, FPNS, MFNS, and TANS show their clinical efficacy in AR
treatment.
Although there are a limited number of comparative studies, results suggest that there is little
overall difference between INSs in terms of their efficacy. All once-daily INSs (BANS, MFNS,
FPNS, and TANS) appear to be well tolerated, with comparable adverse event profiles. Healthy
volunteers treated with FPNS did show significantly lower overnight urinary cortisol levels
compared with placebo treatment,48 but no significant effects on HPA axis function, markers of
bone formation, and white blood cell count were seen with BANS, MFNS, or TANS.49
In the studies reviewed, the four leading INSs (BANS, FPNS, MFNS, and TANS) administered
once daily are effective and well tolerated for the treatment of SAR and PAR in adult patients. All
four INSs showed similar efficacy. There was little indication of any difference between INSs in
systemic effects; however, BANS is the only INS currently rated pregnancy category B and may
be preferred for use during pregnancy. The inert ingredients in BANS and TANS are very similar
and are likely responsible for the greater patient preference compared with that observed for
FPNS and MFNS. Although BANS and TANS may be preferred by a greater percentage of
patients based on their attributes, it should be noted that some patients do express a preference
for the sensory attributes of FPNS and MFNS. When selecting an appropriate INS for patients,
factors preferred by each patient should be considered to help promote patient acceptance of
treatment and better adherence to therapy
Herman, Howard. "Once-daily administration of intranasal corticosteroids for allergic rhinitis: a
comparative review of efficacy, safety, patient preference, and cost." American journal of
rhinology 21.1 (2007): 70-79.
eCPS (2014)
Antihistamines help relieve most symptoms of acute allergic rhinitis such as sneezing, rhinorrhea,
nasal itch and conjunctivitis, but are not usually recommended for the treatment of nasal
congestion. Desloratadine has demonstrated modest improvement in the symptom of nasal
congestion, and is indicated for relief of this symptom.4 There is some evidence to suggest similar
results for fexofenadine;5 however, fexofenadine is not indicated for the relief of congestion.
Antihistamines are most effective if used prophylactically; however, onset of action is fast enough
such that they are also effective when used on an as-needed basis. Once-daily dosing of the
newer antihistamines is usually sufficient.
Although sedation and anticholinergic side effects are common with the older antihistamines (also
known as first-generation or sedating antihistamines), these side effects are usually not seen with
newer agents (second-generation or nonsedating antihistamines). Patients who are unaware of
sedation may be impaired with respect to attention, memory, vigilance and speed. These effects
persist into the next day. Caution is advised in the elderly as they may be more susceptible to the
anticholinergic effects of the first-generation antihistamines. Patients whose occupations require
vigilance or concentration should receive only nonsedating antihistamines, as they do not affect
performance and have no anticholinergic effects.2,6,7,8,9 Of the newer antihistamines, cetirizine is
more likely to cause some sedation, especially at higher doses. Patients with hepatic impairment
may be at increased risk of adverse effects, and dosage modification may be required (seeTable
2). The currently available second-generation antihistamines have not caused QT c interval
prolongation.2
Although older studies of long-term dosing with first-generation antihistamines have
demonstrated loss of effectiveness, they are flawed by lack of evidence of adherence to therapy.
No loss of effectiveness has been shown up to 1 year. 10
Intranasal corticosteroids are the mainstay of therapy for moderate to severe rhinitis
symptoms. Indeed, intranasal corticosteroids as monotherapy have been shown to be more
effective than combined use of an antihistamine and leukotriene antagonist.11 They can be given
on an as-needed basis in seasonal allergic rhinitis; however, continuous use more effectively
provides symptom relief. In addition, they are effective in managing ocular symptoms associated
with allergic rhinitis. Newer preparations have a lower spray volume, which may be preferred by
some. Budesonide is available as a dry powder nasal inhaler and offers an alternative for those
who dislike aqueous sprays. A 2- to 4-week trial may be needed to see maximal effect although
benefit is seen in the first day of therapy compared to placebo in controlled trials.
Class
Antihistamines,
Ethanolamines,
first-generation
Drug
Dosage
Adverse Effects
Drug
Interactions
Comments
Costa
diphenhydramine
Benadryl
Preparations,
genericsb
Adults and children≥12
y: 25–50 mg TID–QID;
maximum4
doses/day or300 mg/day
Children 6–<12 y:12.5–
25 mg Q4–6H;
maximum 150 mg/day
Children 2–5 y:6.25
mg Q4–6H;
maximum37.5 mg/day
CNS: sedation,
fatigue, dizziness,
impairment of
cognition and
performance (the
patient may be
unaware of
impairment).2
Anticholinergic:
dryness of the mouth
and eyes,
constipation,
inhibition of
micturition, potential
precipitation of
narrow-angle
glaucoma, thickening
Increased CNS

depression:
alcohol,
sedatives,
tranquilizers,
barbiturates.
Increased
anticholinergic
side effects:
TCAs,
scopolamine.
May increase
levels of
CYP2D6
substrates,
e.g.,

metoprolol,
Use with caution in the elderly as
they may be more susceptible to
side effects such as sedation and
syncope.
Avoid in patients with narrow-angle
glaucoma (increased IOP), urinary
obstruction (prostatic hypertrophy),
bladder neck obstruction (can cause
urinary retention), GIobstruction.
Observe infants and young children
for paradoxical excitation.
Discontinue 3 days before skin
testing procedure for allergy.
Administer with food to decrease GI
distress.
Thickening of bronchial secretions.
Available in chewable tablets, elixir
$
Class
Drug
Dosage
Drug
Interactions
Comments
of bronchial
secretions.
venlafaxine.
and liquid.
Increased CNS

depression:
alcohol,
sedatives,
tranquilizers,
barbiturates.
Increased
anticholinergic
side effects:
TCAs,
scopolamine.
Safe and well tolerated in children.
Discontinue 3 days before skin
testing procedure for allergy.
Metabolite of hydroxyzine.
Avoid in patients with a
hypersensitivity to hydroxyzine.
$
Use at regular intervals. Slow onset
(7–14 days for maximal effect).
Drug may fail to reach the site of
action if excessive nasal mucus
secretion or edema of the nasal
mucosa is present. May use a
vasoconstrictor (intranasal
decongestant) 2–3 days prior to the
suspension.
Aim spray up towards turbinates and
away from septum. Liquid forms may
be more effective than metereddose inhalers.
For the nasal suspension, initial
priming needed. Re-prime if not
used ≥4 days.
$$$$$
Adverse Effects
Antihistamines,
Piperidines,
secondgeneration
cetirizine
Reactine,
genericsb
Adults and children >12
y: 5–10 mg/day;maximum
20 mg/day
Children 6–12 y:5–10
mg/day
2–6 y: 2.5–5 mg/day
12–23 months: 2.5
mgonce daily;
maximum2.5 mg BID
Infants 6–11 months:0.25
mg/kg Q12H42
Moderate renal/hepatic
impairment: ≥12 y:5
mg/day
6–11 y: <2.5 mg/day
Somnolence (with
high dose), fatigue,
dry mouth, dizziness,
headache, diarrhea,
nausea, vomiting,
pharyngitis.
Corticosteroids
budesonide
Nasal suspension: Adults
and children≥6 y (64
µg/metered dose): initial
dose 2 sprays in each
nostril daily or 1 spray in
each nostril BID; may
decrease maintenance
dose to 1 spray in each
nostril daily
Nasal powder: Adults and
children≥6 y (100
µg/dose): initial dose: 2
applications in each
nostril in the morning or 1
application in each nostril
BID; maximum 400
µg/day
Burning or stinging,
nosebleeds.
Rhinocort
Aqua,Rhinocort
Turbuhaler,
generics
Legend: $ < $10
$$ 10–20


$$-$$$ 10–30
Costa
$$$ 20–30
Respiratory Disorders: Allergic Rhinitis; Paul Keith, MD, MSc, FRCPC; Date of Revision: June
2014
Medication
Uses
Contraindications (CI), drug
interactions (DI) or cautions
Adverse Effects
(common and severe)
cetirizine
antihistami
ne - allergic
rhinitis
CI: hypersensitivity, severe
renal impairment DI:
sedatives, alcohol
headaches, dry mouth,
sleepiness
Initial dose; typical
dose
10mg; 10mg
one time a day
Monitoring
budesoni
de
seasonal
allergic and
allergic/
non-allergic
perennial
and
vasomotor
rhinitis
CI: fungal or tuberculosis
infection DI: cimetidine,
ketoconazole, omperazole
itching throat, sore
throat, cough, fatigue,
nausea, dizziness, and
headache
100g/metered
dose nasal
spray; 2 sprays
per nostril one
time a day
diphenhy
dramine
antihistami
ne – allergic
reactions,
upper
respiratory
allergies
CI: neonates and
premature infants, breast
feeding
DI: MAOIs,
Sedatives
sedation, sleepiness,
dizziness, disturbed
coordination,
epigastric distress,
thickening of bronchial
secretions, drug rash,
hypotension, hemolytic
anemia, urinary
frequency
25mg; 25-50mg CBC with
every 6 hours
differntial,
or as needed
LFTs, RFT