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Official reprint from UpToDate®

www.uptodate.com © 2022 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Pharmacotherapy of allergic rhinitis

Authors: Richard D deShazo, MD, Stephen F Kemp, MD
Section Editor: Jonathan Corren, MD
Deputy Editor: Anna M Feldweg, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: May 2022. | This topic last updated: Jun 21, 2021.

INTRODUCTION

Allergic rhinitis is characterized by sneezing, rhinorrhea and nasal obstruction, as well as

pruritus of the nose and palate. It is also frequently associated with postnasal drip, cough,
irritability, and fatigue. Some patients have concomitant allergic conjunctivitis and/or asthma.
Symptoms can be present year-round, seasonally, or episodically upon exposure to specific
allergens.

The pharmacologic management of allergic rhinitis is presented in this topic review. The clinical
manifestations, diagnosis, differential diagnosis, and pathogenesis of allergic rhinitis are
discussed separately. (See "Allergic rhinitis: Clinical manifestations, epidemiology, and
diagnosis" and "Pathogenesis of allergic rhinitis (rhinosinusitis)".)

OVERVIEW OF TREATMENT

The management of allergic rhinitis involves the following components:

● Pharmacotherapy, which is the focus of this review. Most patients with allergic rhinitis
require pharmacotherapy for satisfactory symptom control. As more medications become
available without a prescription, patients can extensively self-treat, although the side
effects of some over-the-counter allergy medications, particularly the excessive sedation
and anticholinergic effects caused by older antihistamines, can be significant. In general,
patients who self-treat tend to under-utilize glucocorticoid nasal sprays and over-utilize
older, sedating antihistamines. The challenge for clinicians is to educate patients about

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the relative efficacy of different therapies and assure that patients with significant
symptoms are adequately treated with medications that do not cause undue side effects.

The management of allergic rhinitis in a specific patient is influenced by the frequency and
severity of symptoms, the age of the patient, and the presence of concurrent conditions
[1-9]. In this review, an approach to specific patient groups is presented initially, followed
by a detailed discussion of available medications. (See 'Approach to specific patient
groups' below and 'Commonly-used therapies' below.)

● Allergen avoidance, which is reviewed separately. (See "Allergen avoidance in the

treatment of asthma and allergic rhinitis".)

● Allergen immunotherapy (when appropriate), which is reviewed separately.

Immunotherapy may be given as subcutaneous injections or (for a limited number of
allergens) as sublingual tablets. Of note, subcutaneous immunotherapy helps prevent the
development of asthma in children with allergic rhinitis and thus should be given special
consideration in the pediatric population. (See "Subcutaneous immunotherapy (SCIT) for
allergic disease: Indications and efficacy" and "Sublingual immunotherapy for allergic
rhinitis and conjunctivitis: SLIT-tablets".)

Consensus guidelines have been published for the management of allergic rhinitis [1-12]. The
recommendations in this topic review are consistent with these guidelines. (See 'Society
guideline links' below.)

APPROACH TO SPECIFIC PATIENT GROUPS

Young children (<2 years of age) — The development of allergic rhinitis requires repeated
exposure to inhaled allergens and is therefore less prevalent in children under two years of age.
If a child under two years appears to have persistent nasal symptoms, other disorders should
be considered, such as “daycare syndrome” (ie, repeated viral infections of the upper respiratory
tract), adenoidal hypertrophy, or chronic rhinosinusitis. (See "Chronic rhinosinusitis: Clinical
manifestations, pathophysiology, and diagnosis" and "The pediatric physical examination:
HEENT", section on 'Adenoidal hypertrophy'.)

If a child under two years of age is determined to have allergic rhinitis after an evaluation for
other causes, treatment options include the following:

● Minimally-sedating antihistamines (cetirizine, loratadine, and fexofenadine) are

available in liquid formulations. Cetirizine and fexofenadine are approved for children ≥6

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months of age. (See 'Minimally-sedating agents' below.)

Sedating antihistamines (eg, diphenhydramine, chlorpheniramine, others) should be

avoided in young children because these agents can cause paradoxical agitation and may
be dangerous in infants [13]. (See 'Sedating antihistamines' below.)

● Cromolyn (sodium cromoglycate) nasal spray is available without a prescription and has
essentially no adverse effects because it is not absorbed systemically. It is a good choice
for parents who are very concerned about the potential side effects of other medications
and are willing to administer something regularly. The authors use cromolyn extensively
in infants and small children and find it very useful when applied consistently. However,
cromolyn is less effective than glucocorticoid nasal sprays and more difficult to administer
than oral antihistamines. (See 'Cromolyn sodium' below.)

Severe symptoms — Changing to a glucocorticoid nasal spray is the next step for children with
severe symptoms not responsive to the above measures ( table 1). Mometasone furoate,
fluticasone furoate, and triamcinolone acetonide are approved by the US Food and Drug
Administration (FDA) for use in children ≥2 years [14,15]. All choices are safe in young children
with little differences between them, except some have more scent and volume than others (eg,
fluticasone) and therefore may be less accepted by young children. The dose for each of these
agents in young children is 1 spray per nostril once daily. If necessary, 2 sprays per nostril can
be tried for a limited period (we limit to two weeks and reassess symptoms) in view of the age-
limited dose approval and the concern for potential systemic side effects (eg, adrenal
suppression) in children at the higher dose.

Older children and adults — For children ≥2 years of age, the approach to pharmacotherapy is
essentially the same as that in adults and depends upon the severity and persistence of
symptoms.

Mild or episodic symptoms — Patients with mild or episodic symptoms that are related to
predictable allergen exposures (visiting a relative's house with a pet) can be managed with one
of the following options:

● A second-generation oral antihistamine: This can be administered regularly or as

needed (ideally two to five hours before an exposure for cetirizine and fexofenadine, while
loratadine peaks eight hours after administration). Cetirizine (approved for children ≥6
months), loratadine, and fexofenadine (both approved for children ≥2 years) are similarly
efficacious and are available in syrups. (See 'Minimally-sedating agents' below.)

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● An antihistamine nasal spray (eg, azelastine or olopatadine): The FDA has approved the
use of intranasal azelastine in children >6 years of age and the use of intranasal
olopatadine in children >12 years of age (its safety and efficacy have not been evaluated in
younger children). (See 'Antihistamine nasal sprays' below.)

● A glucocorticoid nasal spray (more effective than antihistamines) administered regularly

or as needed ( table 1). For predictable exposures, we suggest initiating therapy two
days before, continuing through, and for two days after the end of exposure [16,17].
Mometasone furoate, fluticasone furoate, and triamcinolone acetonide are approved by
the FDA for use in children ≥2 years of age [14,15].

● Cromolyn nasal spray administered regularly or as needed (ideally 30 minutes before an

exposure). Taken in this manner, cromolyn is helpful for brief exposures (minutes to
hours). For prolonged exposures, administration should ideally begin four to seven days in
advance. Some parents and clinicians prefer to try cromolyn first in children because of its
excellent safety profile. (See 'Cromolyn sodium' below.)

It should be explained to patients that each of these therapies is more effective when taken
regularly, although as-needed use may be sufficient for very mild symptoms.

Persistent or moderate-to-severe symptoms

Glucocorticoid nasal sprays are the most effective pharmacologic therapy for allergic rhinitis
and are recommended by guidelines as the best single therapy for patients with persistent or
moderate-to-severe symptoms, including seasonal symptoms [10,12]. All of the available
preparations are similarly effective, although the newer agents (sometimes called second-
generation) are more convenient and probably safer for long-term use than the older agents
because of lower bioavailability ( table 1). Glucocorticoid nasal sprays with low bioavailability
and once-daily dosing (all except flunisolide, which is not commonly used) may have a
theoretical advantage in children, although this has not been proven. Mometasone and
fluticasone furoate are approved by the FDA for use in children ≥2 years of age [14]. Fluticasone
propionate is approved for children ≥4 years of age. (See 'Glucocorticoid nasal sprays' below.)

For patients with moderate-to-severe symptoms and/or in those who fail to respond adequately
to initial therapy with glucocorticoid nasal sprays, a second agent can be added. Options
include an antihistamine nasal spray, oral antihistamines, and antihistamine/decongestant
combination products. There are few clinical trials directly comparing different combinations of
these therapies, and the choice of additional agents should be based upon the patient's
residual symptoms, preferences, and coexistent conditions:

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● Addition of an antihistamine spray – Antihistamine nasal sprays include azelastine and

olopatadine (see 'Antihistamine nasal sprays' below). Sprays containing both a
glucocorticoid and an antihistamine (eg, azelastine hydrochloride/fluticasone propionate)
are convenient and may provide additional benefit over either therapy alone, especially for
breakthrough symptoms [18,19]. (See 'Combination corticosteroid/antihistamine sprays'
below.)

● Addition of a minimally-sedating oral antihistamine – The combination of

glucocorticoid nasal sprays and oral antihistamines has not shown clear advantage over
glucocorticoid sprays alone in most studies [1,20]. (See 'Dosing of commonly used agents'
below.)

● Addition of a minimally-sedating oral antihistamine/decongestant combination –

These provide better symptom-relief than antihistamines alone, although the adverse
effects of the decongestant component limit their use in some patients ( table 2).
Adverse effects of oral decongestants are discussed below. (See 'Oral
antihistamine/decongestant combinations' below.)

With comorbid conditions

Allergic conjunctivitis — In patients with both allergic rhinitis and allergic conjunctivitis,
we prefer a combination of a glucocorticoid nasal spray and ophthalmic antihistamine drops,
such as epinastine, azelastine, emedastine, or olopatadine, rather than glucocorticoid sprays
plus oral antihistamines ( table 3). A small number of randomized trials have shown the
addition of antihistamine eye drops to be more effective and cause less ocular drying than the
addition of oral antihistamines [21,22]. However, oral antihistamines can be more practical in
children, who often object to administration of eye drops.

Some glucocorticoid nasal sprays (eg, mometasone furoate and fluticasone furoate) have been
shown to have a small but statistically significant effect on allergic eye symptoms [23-26].
However, many patients require an additional agent for adequate relief.

Cromolyn sodium is available in ophthalmic preparations and may also be useful as

prophylactic therapy before predictable allergen exposures (ie, visiting a home with cats).

Further information about the management of allergic conjunctivitis is found separately. (See
"Allergic conjunctivitis: Management", section on 'Antihistamines with mast cell-stabilizing
properties'.)

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Moderate-to-severe asthma — Up to 40 percent of patients with allergic rhinitis are

believed to have concomitant asthma. Although there are no biologic therapies approved
specifically for allergic rhinitis, these agents are available for moderate-to-severe asthma that is
not controlled with high doses of inhaled glucocorticoids and also improve the symptoms of
allergic rhinitis [27].

● Omalizumab, an anti-IgE monoclonal antibody that is approved for asthma and chronic
urticaria, was shown in a systematic review and meta-analysis of 11 studies of 2870
patients to reduce daily nasal symptoms, rescue medication use, and improve quality of
life in patients with uncontrolled allergic rhinitis [28].

● Dupilumab, an anti-interleukin (IL)-4 receptor alpha monoclonal antibody that is approved

for asthma and chronic rhinosinusitis with nasal polyposis, also improves symptoms of
allergic rhinitis. A post hoc analysis of dupilumab trial data involving patients with
perennial allergic rhinitis and concomitant uncontrolled persistent asthma demonstrated
significant improvement in rhinitis-associated symptoms of congestion, rhinorrhea,
sneezing, and postnasal drainage [29].

Use of biologics for asthma is reviewed separately. (See "Treatment of severe asthma in
adolescents and adults", section on 'Selecting among biologic agents'.)

Pregnant women — The treatment of allergic rhinitis in pregnant women is reviewed in detail
separately. (See "Recognition and management of allergic disease during pregnancy", section
on 'Allergic rhinitis/conjunctivitis'.)

Breastfeeding women — LactMed is an online database of information on medications and

lactation hosted by the US National Library of Medicine [30]. The safety of various medications
during lactation is summarized in the table ( table 4). General guidelines have been proposed
[31]:

● All patients should practice allergen avoidance. (See "Allergen avoidance in the treatment
of asthma and allergic rhinitis".)

● Nasal saline sprays or irrigation can always be tried for any nonspecific relief it can
provide. (See 'Nasal saline' below.)

● Intermittent congestion (symptoms less than four days per week) may be treated
judiciously with a topical decongestant spray. (See 'Therapies requiring caution' below.)

● Mild persistent symptoms (symptoms more than four days/week and more than four
weeks/year) may be treated with intranasal budesonide or cromolyn and supplemented by
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cetirizine or loratadine.

● Moderate-to-severe persistent symptoms may be treated with maintenance intranasal

budesonide and/or immunotherapy injections and supplemented as needed with
cetirizine or loratadine.

Older adults — Glucocorticoid nasal sprays are the first-line agents for older adults with
allergic rhinitis ( table 1). Minimally-sedating antihistamines can be used safely in some older
adult patients, although a few may experience adverse effects, and slowed metabolism may
warrant lower starting doses [32]. Antihistamine nasal sprays are also a good option. We avoid
first-generation, sedating antihistamines in older adults [33]. (See 'Adverse effects and safety'
below.)

COMMONLY-USED THERAPIES

Nasal saline — Nasal saline sprays or irrigation with larger volumes of saline can wash
allergens from the nasal passages. Saline can be used alone for mild symptoms or just before
other topical medications, so that the mucosa is freshly cleansed when the medications are
applied. Nasal irrigation with saline can be performed as needed only, daily at baseline, or twice
daily for increased symptoms. Many brands of saline nasal sprays are available over-the-
counter. Large volume irrigations (>200 mL per side) should only be suggested to patients old
enough to perform the irrigation themselves.

For large volume irrigation, a variety of over-the-counter devices, including squeeze bottles,
neti pots, and bulb syringes are effective, provided the system delivers an adequate volume of
solution into the nose.

Nasal irrigation carries little risk if properly performed. Instructions for patients are provided (
table 5). Patients can make their own irrigation solutions or buy commercially prepared
solutions or kits. The saline solution may be warmed or used at room temperature. Patients
should use distilled, sterilized, or previously boiled water because a small number of cases of
primary amebic meningoencephalitis (PAM) have been contracted from using tap water that
was contaminated with the amoeba Naegleria fowleri to perform sinus irrigation [34,35].
Although rare, PAM is usually fatal. N. fowleri is found worldwide and is usually contracted from
swimming in freshwater lakes and rivers, geothermal heated bodies of water, or inadequately
chlorinated pools [36]. Irrigation devices can also become contaminated with the bacteria
present in the patient's nasal cavities, although it is not clear that this causes any clinically

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significant problems. Still, irrigation devices should be cleaned as directed and replaced
regularly [37].

Saline irrigation is associated with improvement in a variety of rhinitis conditions. Direct

evidence for benefit in allergic rhinitis specifically includes the following:

● One randomized study of the impact of nasal irrigation in children with acute sinusitis
found that among those with concomitant allergic rhinitis, nasal irrigation significantly
improved rhinorrhea, nasal congestion, throat itching, sleep quality symptoms, and nasal
air flow [38]. A second study in children found that the effects of nasal irrigation were
additive with those of intranasal glucocorticoids [39]. Nasal irrigation is particularly helpful
when there are crusted nasal secretions due to chronic, thick drainage.

● Another randomized study of pregnant women found nasal saline irrigation to be

beneficial for treatment of allergic rhinitis [40].

Overview of medications — The most effective single therapy for patients with persistent and
significant nasal symptoms is a glucocorticoid nasal spray. Other therapies include oral
antihistamines, antihistamine nasal sprays, mast cell stabilizers (the cromoglycates), leukotriene
modifiers, and ipratropium. The features and efficacy of the various agents are reviewed in this
section.

In contrast, nasal decongestant sprays (eg, phenylephrine, oxymetazoline, others) and systemic
glucocorticoids should not be used for routine treatment of allergic rhinitis. (See 'Therapies
requiring caution' below.)

Glucocorticoid nasal sprays — Glucocorticoid nasal sprays are the most effective single
maintenance therapy for allergic rhinitis and cause few side effects at the recommended doses
[10,12]. These agents are particularly effective in the treatment of nasal congestion, which often
does not respond to oral antihistamines. Specific agents include beclomethasone, flunisolide,
budesonide, fluticasone propionate, mometasone furoate, fluticasone furoate, and ciclesonide,
and doses are shown in the table ( table 1). A limited number of comparative studies among
different glucocorticoid nasal sprays have not demonstrated significant differences in efficacy,
nor is there any evidence that doses greater than the recommended maximum for each
preparation provide additional benefit [41,42]. Several glucocorticoid nasal sprays are available
without a prescription.

Efficacy and onset of action — Glucocorticoid nasal sprays are more effective than oral
antihistamines for relief of nasal congestion and blockage, nasal discharge, sneezing, nasal itch,

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postnasal drip, and total nasal symptoms, as demonstrated in randomized trials and a meta-
analysis [1,16,43,44].

Glucocorticoid nasal sprays have also been shown to be more effective than antihistamines
nasal sprays in most studies, as reviewed below. (See 'Antihistamine nasal sprays' below.)

Most glucocorticoid nasal sprays have an onset of action of a few hours [45-47]. However,
maximal effect may require several days or weeks in patients with longstanding untreated
symptoms.

Optimal use — Our approach is to start therapy with the maximal dose for age. Once
symptoms are adequately controlled, the dose can be "stepped-down" at one-week intervals to
the lowest effective dose. Patients with severe symptoms will require daily use on a chronic
basis. Some patients can reduce the frequency of use gradually and maintain symptom control
with every other day or as-needed use. Newer preparations act within 3 to 12 hours, and as-
needed use may be sufficient, particularly in patients with mild or episodic symptoms [16]. (See
'Mild or episodic symptoms' above.)

Clinicians should become comfortable with several preparations, since each has its advantages
and disadvantages relating to added fragrances, taste, and/or irritation.

To optimize the effects of this therapy and compliance with treatment, we suggest the
following:

● Preparations with once-daily dosing are convenient and can help optimize compliance. All
formulations have a once-daily recommended dosing, except for one, flunisolide (which is
twice daily).

● Proper positioning of the head can prevent the spray from draining down the throat.
With the aqueous (nonaerosol) glucocorticoid nasal sprays, the patients should be
instructed to keep their head pointed slightly downward during spraying and avoid tilting
the head back. In addition, they should avoid pointing the spray at the septum, which can
become irritated. A patient education topic on rhinitis, which reviews techniques for use of
nasal sprays, is provided separately. (See "Patient education: Allergic rhinitis (Beyond the
Basics)".)

● If mucous crusting is present, patients can rinse the nose with a saline nasal spray or
irrigation before the nasal glucocorticoid is administered. Treatment failures can occur
if mucus or other debris prevent the medication from coating the nasal mucosa. (See
'Nasal saline' above.)

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● For patients who are so obstructed that the spray will not penetrate significantly into the
nostril, we suggest use of a decongestant spray 10 minutes before the nasal
glucocorticoid, but this should only be done for five days to avoid the complications of
decongestant sprays. After that, the glucocorticoid spray should be continued alone. If the
nasal decongestant spray is not effective in relieving the obstruction, a very short course
of oral glucocorticoids may be. (See 'Combined with decongestant sprays' below and
'Refractory symptoms' below.)

"Dry" aerosol formulations — In the United States, two products are available that use a "dry"
aerosol delivery system, beclomethasone dipropionate hydrofluoroalkane (HFA) (Qnasl [brand
name]) and ciclesonide HFA (Zetonna [brand name]). These may be more agreeable to patients
who dislike the wet run-off or taste side effects that are experienced with some of the aqueous
sprays ( table 1).

With the aerosol products, patients should be instructed to tilt the head back slightly, dispense
the spray, hold the breath for a few seconds, and then exhale through the mouth. The product
insert also advises to avoid blowing the nose for 15 minutes after use. The nosepiece should be
wiped with a clean, dry tissue weekly, although not cleaned with water.

Safety and adverse effects — Concerns with long-term use of many glucocorticoid
preparations include adrenal suppression, slowed growth in children, decrease in bone mineral
density, glaucoma, and cataract formation. With nasal sprays, the risk of these long-term
complications appears to be small because of the relatively low doses involved, as discussed
below. A practice guideline on rhinitis concluded that studies in both children and adults have
failed to demonstrate that these adverse effects are consistent or clinically relevant to the use
of glucocorticoid nasal sprays [1]. However, epistaxis and nasal septal perforation are potential
adverse effects that are unique to nasal sprays. Because adverse effects are possible,
glucocorticoid nasal sprays of any type should be tapered to the lowest effective dose in all
patients once symptoms are controlled. (See 'Optimal use' above.)

Glucocorticoid nasal sprays may be divided into first- and second-generation preparations.
Second-generation agents are preferred because they are equally efficacious but theoretically
carry a lower risk of systemic effects because of markedly lower total bioavailability (oral and
nasal) compared with first-generation agents [48-51]:

● First generation – Beclomethasone, flunisolide, triamcinolone, and budesonide (10 to 50

percent bioavailability)

● Second generation – Fluticasone propionate (<2 percent), mometasone furoate (<0.1

percent), ciclesonide (<0.1 percent), and fluticasone furoate (<1 percent)
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Potential systemic effects with long-term use — The potential for systemic absorption of
glucocorticoid nasal sprays, with effects on the hypothalamic-pituitary axis (HPA) and growth in
children, has been evaluated in many studies. Most have shown no or limited HPA suppression
at recommended doses, especially with second-generation agents [52-58]. However, studies
have suggested a small effect on growth with both first-generation and second-generation
agents [59-62]. As an example, reduction in growth velocity of -0.27 cm/year (95% CI -0.48 to
-0.06 cm/year) was demonstrated in one large study of 474 prepubescent children, ages 5 to 8.5
years at screening, randomized to fluticasone furoate or placebo for 52 weeks for the treatment
of perennial allergic rhinitis [62]. However, the dose of active agent was 110 mcg daily, which is
the maximum recommended dose for this age group, and the protocol used in this study did
not allow for dose reduction once symptoms were controlled, which is the desired approach to
therapy. There was no detectable change in 24-hour urinary cortisol excretion to suggest
adrenal suppression. Agents that are dosed once daily are preferred in growing children, since
these are believed to (although not documented to) be less likely to impact the HPA and growth
[48]. (See 'Optimal use' above.)

Drug interactions between intranasal fluticasone and strong inhibitors of CYP3A4 enzymes (eg,
ritonavir, itraconazole, nefazodone) can effectively raise the dose of glucocorticoid and result in
clinically-significant adrenal suppression [63]. Although it is unclear how frequently this adverse
outcome occurs, we suggest that patients receiving treatment with ritonavir, azole antifungals,
or other strong inhibitors of CYP3A4 be treated with a glucocorticoid nasal spray other than
fluticasone at the lowest effective dose or that the treating clinician at least be vigilant for signs
and symptoms of Cushing syndrome. Budesonide, beclomethasone, triamcinolone, and
flunisolide appear to be safer options.

Growth in children should be monitored when any glucocorticoid-containing medication is

prescribed, especially if additional glucocorticoid-based medications are given, such as inhaled
agents for asthma or topical corticosteroids for atopic dermatitis [64]. Longer-term studies of
the effects on growth caused by inhaled glucocorticoids administered for asthma treatment
(which deliver higher doses per actuation) are reassuring, although caution is still warranted.
(See "Major side effects of inhaled glucocorticoids", section on 'Growth deceleration'.)

A small number of studies have examined the effects of glucocorticoid nasal sprays on other
adverse effects, such as bone mineral density, intraocular pressure, or cataract formation [65-
67]. A meta-analysis of 10 randomized control trials comprised of 2226 adult and adolescent
patients with allergic rhinitis revealed no significant risk of elevated intraocular pressure or
development of posterior subcapsular cataracts after treatment for one year with
glucocorticoid nasal sprays [68]. Some studies have demonstrated detrimental effects, although

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it is unclear whether these are large enough to result in clinically important outcomes over
time.

Local irritation — Local irritation of the nasal mucosa including drying and burning and
discomfort from the run-off into the throat of the liquid medication is reported by 2 to 10
percent of patients using sprays [69]. Formulations containing alcohol or propylene glycol are
more irritating than aqueous preparations ( table 1). Sometimes patients can minimize these
complications by using proper administration technique and by gradually reducing the dose
once symptoms are controlled to the lowest effective dose for that individual. It is helpful to
demonstrate proper use of all inhaled medications at the time of initial prescription and again
at follow-up visits. Aqueous pump and dry aerosol sprays have different instructions for use
(see 'Optimal use' above). A patient education topic on rhinitis, which reviews techniques for
optimal use of nasal sprays, is provided separately. (See "Patient education: Allergic rhinitis
(Beyond the Basics)".)

Epistaxis — There are two types of nosebleed problems with the use of glucocorticoid nasal
sprays, which are scant blood found in the nasal mucus (common) and frank epistaxis
(uncommon):

● Mucosal irritation may lead to traces of blood in the mucus, which is often remedied by
simply stopping treatment on the side of the nose where bloody mucus has been noted
for a few days and then restarting therapy. Proper administration technique should be
reviewed.

● Significant epistaxis is reported with both glucocorticoid nasal sprays and placebo in
clinical trials and may therefore partly result from mechanical trauma of repeated
spraying, although when placebo rates were subtracted, nosebleed was still noted in 2 to
12 percent of patients using different glucocorticoid preparations. This can be particularly
bothersome for older patients, who may do better with azelastine spray if the problem
persists. Frank epistaxis is often hard to prevent, and once it occurs, it may require future
avoidance of glucocorticoid nasal sprays.

● Recurrent or chronic epistaxis, even mild in degree, requires evaluation for chronic nasal
inflammation, which can occur in a number of conditions. These include vasomotor
rhinitis, chronic nasal staphylococcal infection, and unusual disorders, such as Behçet
syndrome, granulomatosis with polyangiitis (GPA), or chronic invasive fungal
rhinosinusitis. In our experience, episodic epistaxis also occurs in any dry nose syndrome,
such as rhinitis associated with continuous positive airway pressure (CPAP) therapy, sicca
syndrome associated with Sjögren syndrome, or atrophic rhinosinusitis. The drying effects

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of cigarette smoking, caffeinated beverages, and medications with anticholinergic

properties can also predispose to bleeding. Recurrent or chronic epistaxis should prompt
rhinoscopy to determine the origin of the bleeding, even in patients thought to have
epistaxis induced by installation of various medications, since malignancy of the nasal
mucosa is also in the differential diagnosis.

Rare septal perforation — Nasal sprays should always be directed away from the septum.
There are rare reports of nasal septal perforation with glucocorticoid nasal sprays [70,71].
However, long-term studies of large numbers of patients have not found evidence of damage to
the nasal mucosa, despite years of use in the majority of patients [1,71].

Mechanisms of action — Glucocorticoids inhibit allergic inflammation in the nose at many

levels [72,73]. These agents downregulate inflammatory responses by binding to intracellular
glucocorticoid receptors in the cytoplasm of inflammatory cells. The receptors undergo
conformational changes upon activation, entering the cell nucleus where they bind with
glucocorticoid response elements located on anti-inflammatory genes. These activated genes
transcribe messenger RNA for anti-inflammatory proteins. At the same time, activated
glucocorticoid receptors suppress the transcription of most cytokine and chemokine genes,
whose products promote inflammation. (See "Glucocorticoid effects on the immune system".)

Combined with decongestant sprays — The use of decongestant sprays alone for more than
a few days should be avoided due to the risk of rhinitis medicamentosa. However, there may be
a role for once-daily treatment with the combination of a glucocorticoid nasal spray plus a
decongestant spray in adult patients who do not respond optimally to glucocorticoid alone.
Combined therapy was evaluated in a randomized trial of 60 adult subjects with perennial
allergic rhinitis [74]. Participants were randomly assigned to receive once-nightly treatment
with fluticasone furoate, oxymetazoline hydrochloride, the combination of both, or placebo for
four weeks of treatment. Both symptom scores and objective nasal volume (determined with
acoustic rhinometry) improved with combination therapy, relative to placebo or oxymetazoline
alone. Nasal symptoms were less in the combination group compared with the fluticasone
monotherapy group, although nasal volumes were not statistically different. There was no
evidence of rhinitis medicamentosa in the combination group. Further study is needed,
although we have noted preliminary success in several adult patients in our clinical practice. We
attempt to discontinue the vasoconstrictor spray once symptoms are controlled. (See 'Therapies
requiring caution' below.)

Oral antihistamines

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Minimally-sedating agents — Antihistamines typically reduce itching, sneezing, and

rhinorrhea but are less effective for nasal congestion compared with glucocorticoid sprays. H1
antihistamines are divided into first- and second-generation agents. The second-generation
antihistamines are minimally sedating and are preferred over first-generation agents because
they have similar efficacy and fewer central nervous system effects. Second-generation agents
include cetirizine and loratadine. These lipophobic agents were developed primarily to avoid
the unwanted anticholinergic and central nervous system effects of the first-generation drugs
[75-77]. Metabolites of second-generation agents, such as fexofenadine (metabolite of
terfenadine), desloratadine (metabolite of loratadine), and levocetirizine (purified isomer of
cetirizine) were designed to have fewer central nervous system effects than their parent
compounds, although confirmatory evidence is lacking [75,78-80].

Onset of action of the oral second-generation agents is within one hour for most, and peak
serum levels are attained in two to three hours [81,82]. They are dosed once or twice daily and
appear to be similarly efficacious to each other [1,83-86]. There is no convincing evidence that
doses of second-generation antihistamines greater than those maximally recommended
provide additional benefit for allergic rhinitis, and higher than recommended doses are
associated with sedation in some cases [87]. However, many clinicians find that using minimally-
sedating antihistamines twice daily when symptoms are severe is helpful with little sedation.

Dosing of commonly used agents

● Cetirizine – The standard dose of 10 mg once daily is appropriate for adults and children
ages ≥6 years.

The usual dose for children ages 2 to 5 years is 5 mg once daily. Smaller children ages 6
months to 2 years may be given 2.5 mg once daily. The maintenance dose for patients
with significant renal and/or hepatic insufficiency should be reduced by one-half.

● Levocetirizine – Levocetirizine is an active enantiomer of cetirizine and produces effects

equivalent to cetirizine at about one-half of the dose. For adults and children ≥12 years,
the standard dose is 5 mg once daily. For children ages 6 to 11 years, the standard dose is
2.5 mg once daily in the evening. Levocetirizine is unlikely to be effective as an alternative
for patients who do not respond adequately to cetirizine. Significant dose alteration is
necessary in renal insufficiency. The small percentage of patients who experience sedation
can take cetirizine in the evening.

● Loratadine – Loratadine is a long-acting selective H1 antihistamine chemically distinct

from cetirizine and has a standard dose of 10 mg once daily for ages ≥6 years.

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For children ages 2 to 5 years, the usual dose is 5 mg once daily. For patients with
significant renal and/or hepatic insufficiency, the usual dose is administered every other
day.

● Desloratadine – Desloratadine is the major active metabolite of loratadine and produces

effects equivalent to loratadine at about one-half of the dose. For adults and children ≥12
years, the standard dose is 5 mg once daily.

For children ages 6 to 11 years, the dose is 2.5 mg once daily, and for those ages 1 to 5
years, the dose is 1.25 mg once daily. A lower dose of 1 mg once daily is approved in the
United States for small children ages 6 months to 1 year. For patients with significant renal
and/or hepatic insufficiency, the usual dose is administered every other day.

● Fexofenadine – The suggested dose of fexofenadine is 180 mg daily for ages ≥12 years or
30 mg twice daily for children ages 2 to 11 years. A lower dose of 15 mg twice daily is
approved in the United States for small children ages 6 months to 2 years. For patients
with significant renal insufficiency, the adult dose should be reduced to 60 mg once daily.
It is best taken without food and specifically not with fruit juices.

Mechanism of action — H1 antihistamines are not actually receptor antagonists, but rather
inverse agonists. They bind the H1 receptor and downregulate its constitutive activity, shifting
the equilibrium from the active form of the H1 receptor to the inactive form [88]. Some
antihistamines also reduce eosinophil survival [89].

In experimental models, second- and third-generation antihistamines also have a variety of

anti-inflammatory properties, including decreased mast cell mediator release and
downregulation of adhesion molecule expression [90]. Inhibition of interleukin 4 (IL-4) and
interleukin 13 (IL-13) production may explain reports of their dose-dependent beneficial effect
in asthma [91,92].

Role in therapy — Second-generation antihistamines are a popular option for many patients,
especially those with mild or intermittent symptoms. Patients who experience adverse effects
with the second-generation antihistamines (which is rare) or who prefer a local therapy are also
better treated with glucocorticoid nasal sprays. We prefer glucocorticoid nasal sprays for
patients with chronic or more significant symptoms because of their superior efficacy.

Efficacy — The following general statements can be made concerning the efficacy of second-
and third-generation antihistamines:

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● Antihistamines are less effective than glucocorticoid nasal sprays, especially for the relief
of nasal congestion, as previously presented [16,44]. (See 'Efficacy and onset of action'
above.)

● Second-generation antihistamines are equally or more efficacious than cromolyn in

relieving symptoms. (See 'Cromolyn sodium' below.)

There is no evidence that pharmacologic tolerance develops to antihistamines [93]. In addition,

the specific allergic sensitivities a patient has does not impact the antihistamine that is
prescribed, although agents are sometimes marketed as effective for perennial or seasonal or
indoor or outdoor allergies. This marketing simply reflects the clinical trials that were
performed.

Adverse effects — The second-generation antihistamines are less sedating than the first-
generation agents, although cetirizine is sedating for approximately 10 percent of patients
[94,95]. Loratadine is nonsedating for most adults at the customary dose of 10 mg once daily,
although sedation can occur at higher doses [95]. Fexofenadine is nonsedating at
recommended doses and even at higher than recommended doses [94,96,97].

● Second-generation antihistamines have varying degrees of anticholinergic effects. Drying

of the eyes, in particular, is noticeable to some patients [98].

● Some oral antihistamines may be associated with weight gain, although it is unclear if this
is due to stimulation of appetite or reduced activity secondary to sedation and fatigue.
Like other central nervous system effects, weight gain is more prominent with the older,
first-generation agents, although it can occur in some patients with the second-generation
agents [99]. Weight gain would be predicted to be minimal with fexofenadine [100],
although we are aware of no studies directly assessing the second-generation agents for
this particular untoward effect. Our experience suggests that increased hunger and
weight gain with nonsedating antihistamines is minimal to none in most patients.

● St. John's wort may decrease loratadine and fexofenadine levels, making these
antihistamines less effective [101-104]. However, the magnitude and significance of the
interaction is uncertain.

Sedating antihistamines — First-generation antihistamines are all sedating and include

diphenhydramine, chlorpheniramine, hydroxyzine, brompheniramine, and others. These agents
have a limited role in the treatment of most patients because of their numerous adverse
effects. We strongly prefer second- and third-generation antihistamines when oral preparations
are desired. Most of these agents are available over-the-counter, both as single agents and in
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combination with other drugs. They are similarly efficacious, compared with each other, with
only minor differences [1].

Adverse effects and safety — First-generation antihistamines cause significant sedation

because they are lipophilic and easily cross the blood-brain barrier [105]. Central nervous
system symptoms are reported by 20 percent or more of patients, and adverse effects on
intellectual and motor function are well-documented, even in the absence of subjective
awareness of sedation [75,106,107]. Adverse effects are summarized in the table ( table 2).

● Impairments affect driving performance and have been implicated in fatal motor vehicle
accidents [75,108-111]. First-generation antihistamines are prohibited in many states for
some transportation workers (eg, pilots, bus drivers), and individuals taking these agents
are considered to be under the influence of drugs [112]. Despite this, a report from the
Federal Aviation Administration noted increasing pilot use of these drugs over the past 15
years and reported detection of these agents in 4 and 11 percent of fatalities/accidents in
1990 and 2004, respectively [113]. Other measures of cognitive effects include
performance defects on tests of divided attention, working memory, vigilance, and speed
[1,114,115].

● First-generation antihistamines are problematic in children. In school-aged children, both

untreated allergic rhinitis and the use of sedating antihistamines are associated with
impaired school performance [108,115]. In very young children, first-generation
antihistamines can cause paradoxical agitation, and over-the-counter cold remedies
containing them have been linked to a small number of deaths in children <2 years of age
[13]. (See "The common cold in children: Management and prevention", section on 'Over-
the-counter medications'.)

● First-generation antihistamines may also be problematic in older adults who are more
susceptible to their anticholinergic effects, including dry mouth and eyes, urinary
hesitancy, and confusion ( table 2) [116].

Antihistamine nasal sprays — Azelastine and olopatadine are available as nasal sprays and
are similarly effective [117-119].

Azelastine is available in two strengths, 0.1% or 0.15%. The 0.15% became available over-the-
counter in the United States in 2021.

● Only the lower strength should be used in children 6 months to 6 years of age. The dose is
1 spray per nostril twice daily.

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● Children 6 to 12 years can use either strength at a dose of 1 spray per nostril twice daily.

● In older children and adults, the dosing of both strengths is the same: 1 or 2 sprays per
nostril once or twice daily. We favor titrating to the lowest effective dose.

Olopatadine (available without a prescription) is available in one strength.

● The dose for children 6 to 11 years is 1 spray per nostril twice daily.

● The dose for children ≥12 years and adults is 2 sprays per nostril twice daily.

These agents appear to have some anti-inflammatory effect and can improve nasal congestion
[120-122]. Antihistamine nasal sprays have a rapid onset of action (less than 15 minutes) and
can be administered "on demand" [2]. The onset of action is somewhat faster than that of
glucocorticoid nasal sprays [46]. However, azelastine has a bitter taste that can be bothersome
to some patients (which has been corrected in newer preparations) and was mildly sedating in
some clinical trials, although not in others [123].

Guidelines generally suggest glucocorticoid nasal sprays in preference to antihistamine sprays

based upon the fact that the majority of comparison studies favor glucocorticoids [5,124]. In
noninferiority trials, both olopatadine and azelastine compared favorably with fluticasone
propionate [19,125,126].

Combination corticosteroid/antihistamine sprays — The combination of a topical

antihistamine and a topical corticosteroid may be helpful for patients who do not obtain
sufficient relief with one agent [127]. In a randomized trial, 3398 patients with moderate-to-
severe allergic rhinitis were treated for two weeks with either the combination of azelastine and
fluticasone, fluticasone alone, azelastine alone, or placebo, with complete or near-complete
resolution of total symptoms in 12, 9, 7, and 4 percent of patients, respectively [18]. A
combination spray containing azelastine hydrochloride 137 mcg and fluticasone propionate 50
mcg (Dymista [brand name]) is available in the United States and is approved for children older
than 12 years and adults. The dose is 1 spray per nostril, twice daily.

Oral antihistamine/decongestant combinations — Nonsedating antihistamines combined

with the decongestant pseudoephedrine provide better symptom relief than either agent alone
[128]. Available second-generation combination agents include loratadine-pseudoephedrine,
cetirizine-pseudoephedrine, and fexofenadine-pseudoephedrine. There are numerous first-
generation antihistamine/decongestant combination products that have been available without
a prescription for years, although we generally avoid these because of the adverse effects of
oral decongestants (see next section).

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Adverse effects of decongestants — Decongestants have a variety of adverse effects,

including hypertension, insomnia, irritability, and headache ( table 2). In the United States,
increasing abuse of pseudoephedrine (both as a stimulant in athletics and in the illegal
production of methamphetamines) has led to the substitution of phenylephrine for
pseudoephedrine in many over-the-counter first-generation combination preparations.
However, phenylephrine is less effective for the treatment of rhinitis symptoms and may not be
superior to placebo at the 10 mg dose that is commonly available over-the-counter [129,130].

Decongestants are relatively contraindicated in patients with hypertension, contraindicated in

those receiving monoamine oxidase inhibitor therapy, and should be used with caution in
patients with closed angle glaucoma, cardiovascular or cerebrovascular disease,
hyperthyroidism, or bladder neck obstruction.

LESS-USED THERAPIES

Less-used therapies include cromolyn sodium nasal spray, ipratropium bromide nasal spray,
and therapies requiring caution (montelukast, nasal decongestant sprays, and systemic
glucocorticoids).

Cromolyn sodium — Cromolyn sodium is a mast cell stabilizer. The dose is 1 to 2 sprays, three
to four times daily. It inhibits mast cell release of histamine and other inflammatory mediators
by inhibiting the intermediate conductance chloride channel pathways of mast cells,
eosinophils, epithelial and endothelial cells, fibroblasts, and sensory neurons [131].

Cromolyn sodium is more effective than placebo in the treatment of seasonal allergic rhinitis. It
also has no serious side effects and is available over-the-counter as a nasal spray. However,
most studies show it to be less effective than glucocorticoid nasal sprays or second-generation
antihistamines [132].

Cromolyn blocks symptoms associated with the immediate- and late-phase nasal allergen
challenge and is effective in doing so, even when used shortly before allergen inhalation. This
makes cromolyn particularly useful for individuals who experience episodic symptoms to
allergens, such as a cat, where it may be used 30 minutes prior to exposure. For seasonal
allergic rhinitis, it is most effective when initiated just prior to the pollen season, rather than
after symptoms have begun. Frequent dosing is required to attain a good effect in seasonal
allergic rhinitis. Dose frequency can be reduced after the first two to three weeks of treatment.

In summary, cromolyn sodium is very safe, but its utility is limited by the need for frequent
dosing and lower efficacy relative to other agents. It may be tried if other agents are not well-
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tolerated.

Ipratropium bromide — Ipratropium bromide, in the form of a 0.03% nasal spray can be useful
for decreasing rhinorrhea. The dose is 2 sprays per nostril two to three times daily. Ipratropium
bromide is a congener of atropine and may act by decreasing the release of substance P.
However, it is less effective than glucocorticoid nasal sprays for sneezing, pruritus, or nasal
obstruction [133]. Ipratropium bromide is also available in a stronger formulation (0.06%),
although this is specifically labeled for reduction of rhinorrhea associated with colds.

Ipratropium is not recommended as a first-line drug in allergic rhinitis. It is sometimes useful in

children or adults who have profuse rhinorrhea not otherwise controlled with topical nasal
corticosteroids, a complaint most commonly observed in adult patients with concomitant
allergic and nonallergic (or vasomotor) rhinitis. (See "Chronic nonallergic rhinitis", section on
'Prominent rhinorrhea without other symptoms'.)

Therapies requiring caution

Montelukast — Montelukast is a leukotriene receptor antagonist that is used in the

management of asthma and also has efficacy for allergic rhinitis, although the effects are
modest at best. In experimental allergic rhinitis, nasal congestion correlates best with
leukotriene C4 (LTC4) levels, whereas sneezing and nasal itching correlate with histamine levels.
For the symptoms of allergic rhinitis, montelukast is similarly effective to oral antihistamines
but less effective than glucocorticoid nasal sprays [44,134-137].

In the past, we found montelukast useful in the patient who could not tolerate or refused nasal
sprays [92,138-140]. However, concerns about the risk/benefit ratio of montelukast are
increasing. Neuropsychiatric changes have been reported in association with montelukast,
including dream abnormalities, insomnia, anxiety, depression, suicidal thinking, and in rare
cases, suicide. A boxed warning was added to the product insert in 2020 with a
recommendation from the US Food and Drug Administration (FDA) to avoid the use of
montelukast in patients with allergic rhinitis or mild asthma, in favor of other treatments. If this
medication is prescribed for allergic rhinitis, we inform all patients about this potential side
effect and advise them to stop the medication if they perceive adverse mood effects. (See
"Antileukotriene agents in the management of asthma", section on 'Adverse effects'.)

The dose of montelukast is 4 mg daily for children aged 6 months to <6 years, 5 mg daily for
children between 6 and <15 years of age, and 10 mg daily for patients 15 years of age and
older.

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Nasal decongestant sprays — Topical vasoconstrictor decongestants available include

phenylephrine, oxymetazoline, xylometazoline, and naphazoline. Oxymetazoline is particularly
popular due to its 12-hour duration of effect. Nasal decongestant sprays are highly effective for
nasal congestions, but they are not recommended as monotherapy in the chronic treatment
of allergic rhinitis because they can cause rhinitis medicamentosa. Rhinitis medicamentosa is a
disorder arising from the downregulation of alpha-adrenergic receptors, resulting in rebound
nasal congestion. It typically arises after three to seven days of use and can lead to a cycle of
nasal congestion both caused by and temporarily relieved by the medication, resulting in
escalating use and eventual dependency. (See "An overview of rhinitis", section on 'Nasal
decongestant sprays'.)

In contrast, the combination of a topical nasal decongestant and topical corticosteroid may
effectively treat symptoms without causing rhinitis medicamentosa. (See 'Combined with
decongestant sprays' above.)

Nasal decongestants are helpful when used just before air travel in patients who have
difficulties with middle ear and/or sinus equilibration with flying or in patients who have
problems with altitude changes. The long-acting agent, oxymetazoline, is administered twice
per day and is approved for limited use in children older than six years and adults.

Systemic glucocorticoids — Short courses (ie, a few days) of oral glucocorticoids usually
abolish symptoms of allergic rhinitis and may be indicated for severe allergic rhinitis symptoms
that are preventing the patient from sleeping or working [5]. This approach was more widely
used before nasal glucocorticoids and nonsedating antihistamines became available. However,
systemic glucocorticoids should not be given repeatedly or for prolonged periods of time for
the management of allergic rhinitis [141]. Similarly, we do not endorse injections of long-acting
glucocorticoids for this condition, because of unpredictable absorption and the inability to dose
adjust if side effects occur. (See "Major side effects of systemic glucocorticoids" and "Prevention
and treatment of glucocorticoid-induced osteoporosis".)

ALTERNATIVE AND COMPLEMENTARY THERAPIES

Several alternative and complementary therapies are available for the treatment of allergic
rhinitis and are reviewed separately. (See "Complementary and alternative therapies for allergic
rhinitis and conjunctivitis".)

Patients with allergic rhinitis who are taking herbal therapies for other reasons should be aware
of the following:

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● St. John's wort may decrease loratadine and fexofenadine levels, making these
antihistamines less effective. (See 'Adverse effects' above.)

● Patients with weed pollen allergies should be cautious about taking Echinacea purpurea,
which has extensive homology with ragweed pollen and has been implicated in
anaphylaxis in atopic patients [142].

REFRACTORY SYMPTOMS

Suspicion for chronic rhinosinusitis or rhinitis caused by other etiologies should be raised if a
patient with presumed allergic rhinitis fails to improve significantly as a result of one to two
months of consistently-used pharmacotherapy and appropriate allergen avoidance. Evaluation
for other conditions should be performed prior to pursuing allergen immunotherapy. (See
"Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis" and "Allergic
rhinitis: Clinical manifestations, epidemiology, and diagnosis", section on 'Differential
diagnosis'.)

REFERRAL

Referral to an allergist/immunologist should be considered for the following patients:

● Children with moderate-to-severe allergic rhinitis. Referral should be considered because

allergen immunotherapy has been shown to alter the progression of allergic disease and
subsequent development of asthma. (See "Subcutaneous immunotherapy (SCIT) for
allergic disease: Indications and efficacy", section on 'Preventive effects'.)

● Patients with prolonged or severe symptoms of rhinitis or significant residual symptoms

despite pharmacologic therapy and avoidance measures.

● Patients whose management might be enhanced by identification of allergic triggers.

● Patients with coexisting asthma or nasal polyposis (referral to a pulmonologist or

otolaryngologist, respectively, are other options for such patients).

● Patients with significant complications of allergic rhinitis, such as recurrent otitis media or
recurrent sinusitis.

● Patients with intolerable adverse effects from medications or side effects that interfere
with school/work productivity.

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● Patients who are interested in immunotherapy as a treatment option.

● Patients who have required systemic glucocorticoids to control symptoms.

Patients who are able to discontinue antihistamines without experiencing intolerable symptoms
should do so at least one week prior to their appointment, in case skin testing is indicated at
the initial visit. Intranasal glucocorticoids and asthma medications do not interfere with skin
testing and should not be discontinued. Patients with questions concerning which medications
to continue or withhold should be instructed to contact the specialist's office prior to their
appointment. (See "Overview of skin testing for allergic disease".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Rhinitis".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient education" and the keyword(s) of interest.)

● Basics topics (see "Patient education: Seasonal allergies in adults (The Basics)" and
"Patient education: Giving your child over-the-counter medicines (The Basics)" and
"Patient education: Seasonal allergies in children (The Basics)")

● Beyond the Basics topics (see "Patient education: Allergic rhinitis (Beyond the Basics)" and
"Patient education: Trigger avoidance in allergic rhinitis (Beyond the Basics)")

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SUMMARY AND RECOMMENDATIONS

● In most patients, allergic rhinitis is a persistent condition that requires ongoing therapy
over a period of years. Management combines allergen avoidance and pharmacologic
therapy, with allergen immunotherapy added for refractory or severe cases. Many
medications are available without a prescription, but some have significant adverse
effects. (See 'Overview of treatment' above.)

● Glucocorticoid nasal sprays are the most effective single-agent maintenance therapy for
allergic rhinitis and cause few side effects at the recommended doses. They are
particularly effective in relieving nasal congestion. Specific agents include
beclomethasone, flunisolide, budesonide, fluticasone propionate, mometasone furoate,
fluticasone furoate, and ciclesonide ( table 1). Mometasone furoate, fluticasone furoate,
and triamcinolone acetonide are approved by the US Food and Drug Administration (FDA)
for use in children ≥2 years of age. (See 'Glucocorticoid nasal sprays' above.)

● First-generation sedating antihistamines are familiar to patients and available without a

prescription, but they have significant adverse effects, including sedation and impairment
of cognitive function, paradoxical agitation in young children, and anticholinergic side
effects in older adults. Second-generation agents, such as cetirizine, levocetirizine,
loratadine, desloratadine, and fexofenadine have few of these problems and are preferred
when antihistamine therapy is desired. (See 'Oral antihistamines' above.)

● An approach to treating specific patient groups is provided. (See 'Approach to specific

patient groups' above.)

● For older children and adults with mild or intermittent symptoms, we suggest a
glucocorticoid nasal spray, used regularly or only as needed (Grade 2A). We start at the
maximal recommended dose for age and then taper to the lowest effective dose once
symptoms are controlled. (See 'Glucocorticoid nasal sprays' above.)

● Some patients with mild symptoms may prefer other agents because of oral
administration or desire to avoid glucocorticoids. Thus, the following are appropriate
choices as well:

• An antihistamine nasal spray, such as azelastine or olopatadine, administered regularly

or as needed. (See 'Antihistamine nasal sprays' above.)

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• A second-generation oral antihistamine, administered regularly or as needed. (See

'Minimally-sedating agents' above.)

• Cromolyn nasal spray, administered regularly or as needed. This is often preferred by

parents of young children because of its excellent safety profile, although it is less
effective than other agents. (See 'Cromolyn sodium' above.)

● For patients with persistent or moderate-to-severe symptoms, we recommend

glucocorticoid nasal sprays as first-line therapy (Grade 1A). Several agents, such as
fluticasone propionate, mometasone furoate, and fluticasone furoate, have minimal
systemic bioavailability and are conveniently dosed once or twice daily ( table 1). We
start at the maximal recommended dose for age and then taper to the lowest effective
dose once symptoms are controlled. (See 'Persistent or moderate-to-severe symptoms'
above and 'Glucocorticoid nasal sprays' above.)

● If glucocorticoid nasal sprays alone are not sufficient to control symptoms, we suggest
adding an antihistamine nasal spray (such as azelastine or olopatadine) in preference to
other agents (Grade 2B). A combination nasal spray containing both azelastine and
fluticasone is available in the United States. Another option is the addition of an oral
antihistamine/decongestant combination, although we discourage regular use of these
medications. (See 'Combination corticosteroid/antihistamine sprays' above and 'Persistent
or moderate-to-severe symptoms' above.)

● For patients with both allergic rhinitis and allergic conjunctivitis whose symptoms are not
fully controlled with a glucocorticoid nasal spray, we suggest the addition of an
antihistamine eye drop ( table 3), rather than the addition of an oral antihistamine
(Grade 2B). However, patients with severe symptoms may require all three agents to
attain adequate relief. (See 'Allergic conjunctivitis' above.)

● Chronic rhinosinusitis or mixed rhinitis (ie, allergic and nonallergic) should be suspected if
a patient with presumed allergic rhinitis fails to improve significantly as a result of
pharmacologic therapy and appropriate allergen avoidance. (See 'Refractory symptoms'
above.)

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REFERENCES

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provided significantly greater improvement in daytime and nighttime nasal symptoms of
seasonal allergic rhinitis compared with montelukast. Ann Allergy Asthma Immunol 2003;
90:536.
135. Nathan RA. Do leukotriene receptor antagonists have a place in pharmacotherapy of
allergic rhinitis? Ann Allergy Asthma Immunol 2003; 90:466.
136. Wilson AM, O'Byrne PM, Parameswaran K. Leukotriene receptor antagonists for allergic
rhinitis: a systematic review and meta-analysis. Am J Med 2004; 116:338.

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137. Nayak A, Langdon RB. Montelukast in the treatment of allergic rhinitis: an evidence-based
review. Drugs 2007; 67:887.

138. Cingi C, Gunhan K, Gage-White L, Unlu H. Efficacy of leukotriene antagonists as

concomitant therapy in allergic rhinitis. Laryngoscope 2010; 120:1718.
139. Moinuddin R, deTineo M, Maleckar B, et al. Comparison of the combinations of
fexofenadine-pseudoephedrine and loratadine-montelukast in the treatment of seasonal
allergic rhinitis. Ann Allergy Asthma Immunol 2004; 92:73.

140. Lieberman PL, Settipane RA. Azelastine nasal spray: a review of pharmacology and clinical
efficacy in allergic and nonallergic rhinitis. Allergy Asthma Proc 2003; 24:95.
141. Aasbjerg K, Torp-Pedersen C, Vaag A, Backer V. Treating allergic rhinitis with depot-steroid
injections increase risk of osteoporosis and diabetes. Respir Med 2013; 107:1852.
142. Mullins RJ, Heddle R. Adverse reactions associated with echinacea: the Australian
experience. Ann Allergy Asthma Immunol 2002; 88:42.
Topic 7526 Version 54.0

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GRAPHICS

Glucocorticoid nasal sprays for treatment of rhinitis

Lower
age
Common Available Usual U
limit
brand Generic without a adult ped
Name when
name(s) and available prescription dose per dos
used in
strength (OTC) nostril no
children
(years)*

Second-generation (systemic bioavailability <1% or undetectable)

Ciclesonide Omnaris (50 No No Two 2 years 2 to

mcg/spray) sprays year
once daily or tw
spra
once

≥12
Two
once

Zetonna (37 No No One spray 12 years ≥12

mcg/spray) once daily One
once

Fluticasone Flonase No Yes Two 2 years One

furoate Sensimist (OTC) sprays spra
(27.5 mcg/spray) once daily once
in ch
2 to
year
with
spra
daily

Fluticasone ClariSpray, Yes Yes Two 4 years 4 to

propionate Flonase Allergy sprays year
Relief (OTC), once daily spra
GoodSense or one daily
Nasoflow (OTC), spray
≥12
Ticaspray (50 twice daily
Two
mcg/spray)
once
or o

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spra
daily

Mometasone Nasonex (50 Yes No Two 2 years 2 to

mcg/spray) sprays year
once daily spra
daily

≥12
Two
once

First-generation (systemic bioavailability 10 to 50%)

Beclomethasone Beconase AQ (42 No No One or 6 years One

mcg/spray) two sprays spra
twice daily twic
in ch
6 to
year
with
spra
daily

Pediatric: Qnasl No No Two 4 years 4 to

Children's (40 sprays year
mcg/spray) once daily spra
using 80 daily
Adolescent/adult:
mcg/spray 40
Qnasl (80
product mcg
mcg/spray)
prod

≥12
Two
once
usin
mcg
prod

Budesonide Rhinocort Allergy Yes Yes One to 6 years One

(OTC) (32 two sprays spra
mcg/spray) once daily once
in ch
6 to
year
with
spra
daily

Flunisolide Generic (formerly Yes No Two 6 years 6 to

Nasarel) (25 sprays two year
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mcg/spray) or three spra

times daily thre
(maximum time
two sprays or tw
four times spra
daily) twic

≥15
Two
two
thre
time

Triamcinolone GoodSense Nasal Yes Yes Two 2 years 2 to

Allergy (OTC), sprays year
Nasacort Allergy once daily spra
24 Hr (OTC), daily
Nasal Allergy 24
≥6 y
Hour (OTC),
One
generic (formerly
spra
Nasacort AQ) (55
once
mcg/spray)
in ch
6 to
year
with
spra
daily

Nasal sprays work best when they are administered properly and the medication remains in the
nose rather than draining down the back of the throat. Note that the recommended techniques for
the aqueous and aerosol sprays are different. If the nose is crusted or contains mucus, it should first
be cleaned with a saline nasal spray prior to use of intranasal sprays. Some people find that holding
the other nostril closed with a finger improves their ability to draw the spray into the upper nose.

Once symptoms are controlled, the daily dose can be reduced to the lowest dose that maintains
control.

Dosing and product descriptions are based upon products available in the United States and some
other countries. Product descriptions in other countries may differ in some detail. Consult the
Lexicomp drug monographs and local product information for additional detail.

OTC: over-the-counter (available without a prescription in the United States and some other
countries).

* Lowest age use may differ from approved product labeling.

¶ Alcohol may contribute to dryness or irritation.

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Lexicomp Online. Copyright © 1978-2022 Lexicomp, Inc. All Rights Reserved.

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Some adverse effects of antihistamines and decongestants

Antihistamines

Anticholinergic effects

Dry mouth and eyes

Impotence

Urinary hesitancy

Glaucoma

Central nervous system effects

Sedation

Rarely stimulation (usually children)

Confusion (older patients)

Cognitive impairment

Miscellaneous effects

Weight gain

Hypersensitivity

Prolonged QT interval

Ventricular arrhythmias

Decongestants
Nervousness

Irritability

Insomnia

Headache

Urinary hesitancy

Tachycardia/palpitations

Hypertension

Nausea

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Ophthalmic medications for the treatment of allergic conjunctivitis

Pharmacologic class Usual adult dosing Pediatric dosing

Antihistamines with mast cell-stabilizing properties: Decreased itching should be evident

within 24 to 72 hours; may result in dry eye sensation or burning

Olopatadine 0.1% and 0.2% One drop per eye twice daily ≥2 years: One drop per eye
(OTC Pataday, generics), (0.1%); one drop per eye once twice daily (0.1%); one drop per
0.7% (OTC Pataday) daily (0.2% and 0.7%) eye once daily (0.2% and 0.7%)

Alcaftadine 0.25% (OTC One drop per eye once daily ≥2 years: One drop per eye
Lastacaft) once daily

Bepotastine 1.5% (Bepreve, One drop per eye twice daily ≥2 years: One drop per eye
generics) twice daily

Cetirizine 0.24% (Zerviate) One drop per eye twice daily ≥2 years: One drop per eye
twice daily

Epinastine 0.05% (generics) One drop per eye twice daily ≥2 years: One drop per eye
twice daily

Ketotifen 0.025% (multiple One drop per eye twice daily ≥3 years: One drop per eye
OTC products) twice daily

Azelastine 0.05% (generics) One drop per eye twice daily ≥3 years: One drop per eye
twice daily

Emedastine 0.05% (not One drop per eye up to four ≥3 years: One drop per eye up
available in US but may be times daily to four times daily
available in other countries)

Vasoconstrictor/antihistamine combination: Increased redness can occur temporarily

when medication is stopped

Naphazoline 0.25% and One to two drops per eye up to ≥6 years: One to two drops per
pheniramine 0.3% (OTC four times daily eye up to four times daily
Naphcon-A, generics)

Naphazoline 0.27% and

pheniramine 0.315% (OTC
Opcon-A, generics)

Mast cell stabilizers: Decreased itching may be evident within a few days or may take up
to four weeks

Cromolyn sodium 4% One to two drops per eye up to ≥4 years: One to two drops per
(generics) six times daily eye up to six times daily

Nedocromil 2% (Alocril) One to two drops per eye twice ≥3 years: One to two drops per
daily eye twice daily

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Lodoxamide 0.1% (Alomide) One to two drops per eye four >2 years: One to two drops per
times daily for up to three eye four times daily for up to
months three months

Pemirolast 0.1% (not One to two drops per eye up to ≥3 years: One to two drops per
available in US but may be four times daily for up to four eye up to four times daily for up
available in other countries) weeks to four weeks

United States (US) trade names are shown in parentheses following generic name.

OTC: over-the-counter (available without a prescription).

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Therapies for allergic rhinitis in lactating women

Amount passed to
Conclusions about maternal use during
Drug category infant in breast
breastfeeding
milk

Intranasal Minimal Compatible.

glucocorticoid sprays
(budesonide preferred)

Second-generation oral antihistamines

Cetirizine Minimal to small Large doses or prolonged use may cause

amounts sedation in nursing infant. May decrease milk
supply if combined with a sympathomimetic.

Loratadine Minimal to small Compatible but might reduce milk supply if

amounts combined with a sympathomimetic, such as
pseudoephedrine.

Antihistamine nasal Minimal Probably compatible. Use intranasal

sprays glucocorticoid preferentially.

Oral decongestants

Pseudoephedrine Passes into milk Use short-acting preparations only and take just
after breastfeeding to minimize amount entering
milk. Use intranasal glucocorticoid preferentially
for persistent congestion. Use topical
vasoconstrictor nasal spray for therapy of less
than four days.

Phenylephrine Little information Not recommended.

available

Cromolyn nasal spray Insignificant Compatible.

Leukotriene-receptor antagonists

Montelukast Unknown Use only if other compatible agents are not

sufficient and symptoms are significant. Avoid in
newborn or preterm infant.

Zafirlukast About 20% Use only if other compatible agents are not
sufficient and symptoms are significant. Avoid in
newborn or preterm infant.

Ipratropium nasal Unknown; maternal Probably compatible.

spray serum levels are
negligible and milk
levels will be very low,
if at all; any drug in

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milk would not be

absorbed by the infant

References:

1. Incaudo AF, Takach P. The diagnosis and treatment of allergic rhinitis during pregnancy and lactation. Immunol
Allergy Clin N Am 2006; 26:137.
2. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation, 10th ed, Lippincott Williams & Wilkins,
Philadelphia 2015.
3. LactMed: United States National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK501922/.

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How to perform nasal irrigation

Buffered normal saline nasal irrigation

The benefits

1. Saline (saltwater) washes the mucus and irritants from your nose.

2. The sinus passages are moisturized.

3. Studies have also shown that a nasal irrigation improves cell function (the cells that move the
mucus work better).

The recipe

Use a one-quart glass jar that is thoroughly cleansed.

You may use a large medical syringe (30 cc), water pick with an irrigation tip (preferred method),
squeeze bottle, or Neti pot. Do not use a baby bulb syringe. The syringe or pick should be sterilized
frequently or replaced every 2 to 3 weeks to avoid contamination and infection.

Fill with water that has been distilled, previously boiled, or otherwise sterilized. Plain tap water is
not recommended, because it is not necessarily sterile.

Add 1 to 1½ heaping teaspoons of pickling/canning salt. Do not use table salt, because it contains
a large number of additives.

Add 1 teaspoon of baking soda (pure bicarbonate).

Mix ingredients together and store at room temperature. Discard after 1 week.

You may also make up a solution from premixed packets that are commercially prepared
specifically for nasal irrigation.

The instructions

Irrigate your nose with saline 1 to 2 times per day.

If you have been told to use nasal medication, you should always use your saline solution
first. The nasal medication is much more effective when sprayed onto clean nasal
membranes, and the spray will reach deeper into the nose.

Pour the amount of fluid you plan to use into a clean bowl. Do not put your used syringe
back into the storage container, because it contaminates your solution.

You may warm the solution slightly in the microwave, but be sure that the solution is not
hot.

Bend over the sink (some people do this in the shower), and squirt the solution into each
side of your nose, aiming the stream toward the back of your head, not the top of your
head. The solution should flow into one nostril and out of the other, but it will not harm you
if you swallow a little.

Some people experience a little burning sensation the first few times that they use buffered

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saline solution, but this usually goes away after they adapt to it.

Adapted with permission from: Diseases of the Sinuses: Diagnosis and Management. Kennedy DW, Bolger WE, Zinreich SJ
(Eds), BC Decker, Hamilton, Ontario 2001. Copyright © Kennedy DW, Zinreich SJ.

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Contributor Disclosures
Richard D deShazo, MD No relevant financial relationship(s) with ineligible companies to
disclose. Stephen F Kemp, MD No relevant financial relationship(s) with ineligible companies to
disclose. Jonathan Corren, MD Grant/Research/Clinical Trial Support: AstraZeneca [Severe
asthma];Genentech [anti-ST2 in asthma];Novartis [Asthma];Regeneron [Allergic rhinitis, atopic dermatitis,
eosinophilic esophagitis];Stallergenes [Allergic rhinitis]. Consultant/Advisory Boards: Genentech
[Asthma];Novartis [Asthma];Regeneron [Asthma, nasal polyps];Sanofi [Asthma, nasal polyps];TEVA
[Asthma]. Speaker's Bureau: AstraZeneca [Asthma];Genentech [Asthma];Sanofi [Asthma, nasal polyps]. All
of the relevant financial relationships listed have been mitigated. Anna M Feldweg, MD No relevant
financial relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

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