ARIA Pharm Guide

8/8/2019 ARIA Pharm Guide

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Visit the ARIA Web site at www.whiar.org

Distribution of this Pharmacists Guide has been made possibleby educational grants from:

ARIA has received educational grants from:

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M AN AGEM EN T OF

ALLERGIC RHIN ITISSYM PTOM S IN

THE PHARM ACY

ARIA IN THE PHARM ACY

M AN AGEM EN T OF

ALLERGIC RHIN ITISSYM PTOM S IN

THE PHARM ACY

BASED O N THE

ALLERGIC RHIN ITIS AN D ITS IM PACT ON ASTHM A W ORKSHO P REPORT

In collabora tion w ith the World Hea lth Orga nisation

ARIA_Pharm_Guide_8.5x11 1/6/06 11:59 AM Page c3


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1

M EM BERS OF THE W ORKSHOPS

Paris, October 23, 2002 San Antonio, N ovember 17, 2002

Jean Bousquet, Chai rPaul van Cauwenberge, Co-Chair

MM AA NN AA GG EEMM EENN TT OO FF AA LLLLEERRGG II CC RRHH II NN II TTII SS

SSYY MM PPTTOO MM SS II NN TTHH EE PPHH AA RRMM AA CCYY

ARIA IN THE PHARM ACYALLERGIC RHINITIS AND ITS IMPACT ON ASTHMA

Christine BondSergio BoniniHlne BousquetG. Walter Canonica

Peter Howarth

Nikolai KhaltaevMarek L. KowalskiJean-Marc LederRichard F. Lockey

Eli O. Meltzer

Robert NaclerioKristof N ekamMaria Pia OrruDavid Price

F. Estelle R. Simons

Mary TeresiErkka ValovirtaA. Maurizio VignolaDennis Williams

Alan Wright

Members of the workshops

Christine Bond, MR Pharm S, PhD, Professor of Primary Care (Pharmacy), Depar tment of General Practice and Primary Care, University of Aberdeen,Aberdeen, UK

Sergio Bonini, MD, Professor of Medicine, Second University of Naples; Scientific Director, San Raffaele H and Institute of Neurobiology and MolecularMedicine, Italian National Research Council, Rome, Italy

Hlne Bousquet, Pharmacist, Analyses Bio-Medicales LR, Montpell ier, FranceJean Bousquet, MD, Pharm D, Professor of Pneumology, University of Montpellier, France; Director of the Allergy Programme, Institut Pasteur, Paris, France

and ARIA ChairmanG. Walter Canonica, MD, Professor of Pneumology, Allergy and Respiratory Diseases, DIMI - Dept. of Internal Medicine, University of Genoa, Genoa, Italy

Peter How arth, B.Sc.(Hons), D.M ., F.R.C.P., University of Southampton, Southampton, UKNikolai Khaltaev, MD, Team Leader, Management of Non-communicable Diseases/ Chronic Respira tory Diseases and Ar thritis Unit, World Health Organi zation,

20 Avenue Appia, 1211 GENEVA 27, SwitzerlandMa rek L. Kowa lski, MD, PhD, Dept. of Clinical Immunology and Allergy, Faculty of Medicine, Medical University of Lodz, Lodz, Poland

Jean-Marc Leder, Doctor of Pharmacy, Grande Pharmacie du 20, Paris, FranceRichard F. Lockey, MD, Director of the Division of Allergy and Immunology; Professor of Medicine, Pediatrics and Public Health and the Joy McCann

Culverhouse Chair in Allergy and Immunology, University of South Florida College of Medicine and James A. Haley Veterans Hospital,Tampa, Florida, USA

Eli O. Meltzer, MD, Clini cal Professor of Pediatri cs, University of California, San Diego, Co -Director Allergy and Asthma Medical Group and Research Center,San Diego, California, USA

Robert Na clerio, MD, Professor and Chief, Otolaryngology, Head and Neck Surgery, University of Chicago, Chicago, Illinois, USAKristof Nek am, MD, PhD, Professor, Dept. of Allergology and Clinical Immunology, Hospital of the Hospitaller Brothers of St John, Budapest, Hungary

Maria Pia Orru, Pharm D, Cagliari , ItalyDavid Price, General Practice Airways Group, Professor of Primary Care Respiratory Medicine, University of Aberdeen, Aberdeen, UK

F. Estelle R. Simons, MD, Professor, Department of Pediatrics & Child Health, Department of Immunology, University of Manitoba, Winnipeg, Manitoba, CanadaMa ry Teresi, Pharm D, Director Pediatric Allergy/ Pulmonary Clini cal Trial s, University of Iowa, Iowa Ci ty, Iowa, USA

Erkka Valovirta, MD, PhD, EFA, Brussels, Belgium and Turku Allergy Center, Turku, FinlandPaul van Cauwenberge, MD, PhD, Professor and Chairman, Department of Otorhinolaryngology, Ghent University, Belgium and ARIA Co-Chairman

A. M aurizio Vignola, MD, Italian National Research Council and University of Palermo, Palermo, ItalyDennis Williams, Pharm D Associate Professor, Division of Pharmacotherapy, School of Pharmacy, University of Nor th Carolina, Chapel Hil l, N orth Carol ina, USA

Alan Wright, Healthcare Consultant, Beaconsfield, UK

Address for correspondence: Jean Bousquet, MD

Endorsing organisationsAPhA: American Pharmacists AssociationARIA: Allergi c Rhinitis and its Impact on AsthmaCESPHARM

EAACI: European Academy of Allergology and Clinical ImmunologyEFA: European Federation of Allergy and A irways Diseases Patients AssociationsIPCRG: International Primary Care Respiratory Group

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2

TABLE OF CON TEN TS

IN TRODUCTION ............................................................................................ 3

RECOGN ISIN G ALLERGIC RHIN ITIS IN THE PHARM ACY ............................ 5

Recognising allergic rhinitis ............. ..... ..... ......... ..... ......... ..... ..... ......... ..... .. 5

Differentiating allergy from other causes including infection ............ ......... ....... 6

Assessing the severity of allergic rhinitis ........................................................ 6

Management by pharmacists or referral to physician ................. ..... ..... ......... .. 6

Asthma co-morbidity ............. .............. ............... .............. .............. .............. 7Conjunctivitis .............. .............. .............. .............. .............. ............... ......... 7

M AN AGEM EN T OF ALLERGIC RHIN ITIS........................................................ 8

Environmental control ............. ............... .............. .............. .............. ............ 8

Options for pharmacological treatment of allergic rhinitis ......... ..... ......... ..... .... 8

Allergen-specific immunotherapy (vaccination) ..... ..... ..... ......... ..... ..... ......... ...13

Alternative therapies ............. .............. .............. .............. .............. .............15

A pharmacy protocol for treating allergic rhinitis ............. ..... ..... ......... ..... .....15

M AN AGEM EN T OF OCULAR SYM PTOM S ..................................................16

THE M AN AGEM EN T OF ALLERGIC RHIN ITIS AN D ASTHM A ......................17

CON CLUSION ..............................................................................................19

REFERENCES ................................................................................................ 20



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Allergic rhinitis is a symptomatic disorder of the noseinduced by an immunoglobulin (IgE)-mediated inflam-mation of the nasal membranes in response to allergenexposure(1). Predominant symptoms are rhinorrhea,nasal obstruction, nasal itching and sneezing, whichimprove spontaneously or with treatment(1-3).

The high prevalence of allergic rhinitis and its effecton quality of life have led to it being classified as amajor chronic respiratory disease(1, 4). It is reported toaffect 10% to 40% of the global population and itsprevalence is increasing both in children and adults.

Allergic rhinitis can significantly reduce qualityof life(5), impairing sleep and adversely affectingleisure, social life, school performance(6) and workproductivity(7). The direct and indirect financial costs ofallergic rhinitis are substantial. Indirect costs includesick leave, school and work absenteeism and loss ofproductivity(8, 9).

Asthma and rhinitis are common co-morbiditiessuggesting the concept of one airway, one disease(1).In addition, allergic rhinitis is associated withconjunctivitis and sinusitis.

Recently, advances in our understanding of themechanisms underlying inflammation of the upper andlower airways have led to improved therapeuticstrategies for managing allergic rhinitis. Practiceguidelines incorporating these advances have beendeveloped(1). In addition, a new classification ofallergic rhinitis aids the establishment of an appropriateinitial treatment strategy based on the duration andintensity of the patient's symptoms and lifestylelimitations(1, 10).

Many patients who suffer from allergic rhinitis do notrecognise the process as such and do not consult a

physician(10, 11)

. Others commonly seek self-treatmentfor relief of symptoms using proven or unproventherapies.

Worldwide, pharmacists receive sophisticatedclinical training. Given the well-known and well-publicised recognition of iatrogenic disease,pharmacists' skills represent an enormous potentialresource to maximise the benefits and minimise theadverse events associated with pharmacotherapy (12).Pharmaceutical care includes the prevention, treatmentor cure of a disease(13). Interest and expectation thatpharmacists provide broader pharmaceutical careservices has therefore increased (14). Pharmaceuticalcare for the patient is likely to be optimal when there iscollaboration between pharmacists, patients and other

health care professionals, specifically physicians.

In many countries, advice in pharmacies may notnecessarily be from a qualified pharmacist, but from amember of staff under the supervision of a pharmacist.

As trusted health care professionals in the community,pharmacists are well placed to identify the symptomsof allergic rhinitis and to recommend appropriatetreatment. In some countries, there has recently beenan increase in effective and safe medicines availablewithout prescription for the treatment of allergicrhinitis. This guide provides a practical, step-by-step

approach to aid pharmacists in advising patients: in recognising allergic rhinitis and assessing i ts

severity, in understanding the effect of treatment on rhinitis

and co-morbidities, in determining whether management in the

pharmacy is appropriate, in initiating an appropriate treatment and

monitoring plan, and in proposing appropriate preventive measures.

This should:

increase collaboration between pharmacists,physicians and other health careprofessionals,

3

IN TRODUCTION



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reduce the burden incurred by allergic rhinitis andits co-morbidi ties,

aid in the identification of undiagnosed oruncontrolled asthma, and improve cost-effectiveness in the

management of allergic rhinitis.

This document is a guide. It is not intended to be amandatory standard of care document for individualcountries. It is provided as a basis for pharmacists andtheir staff, as well as for organisations involved in thetreatment of respiratory allergic diseases in variouscountries to develop relevant local standards of carefor their patients. When implementing recommenda-tions, the local plan should consider the infrastructureof pharmacy practice, workforce and regulations in theindividual country.

In the present document, the physical examination andtesting of patients for allergic rhinitis will not bedetailed as relevant information has been published in

the ARIA workshop report(1). Likewise, allergenavoidance, allergen specific immunotherapy and

patient education are not emphasised to the extentthey are utilised on the overall management. Thepharmacist's role in providing education and inrecommending strategies for avoiding exposure toallergens and irritants is recognised. However, thisdocument focuses on appropriate initial pharmacotherapyrecommendations from the pharmacist. For greaterdetail about these other areas, the reader is referred tothe ARIA workshop report(1).

Medications available without a prescription (over thecounter: OTC) from a physician vary in countriesthroughout the world. Pharmacists can advise andtreat patients, depending on the symptoms presentedby the patient and the medications which are avail-able. When there is any doubt about what should orshould not be recommended, or if a question existsabout an alternative diagnosis, the patient should bereferred to a physician for further evaluation.

4



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Recognising allergic rhinitis

Some patients who consult the pharmacist will havehad allergic rhinitis previously diagnosed by a physi-cian, others will have made an appropriate self-diag-nosis, some will not have any diagnosis of rhinitis ormay even have an incorrect diagnosis (e.g. a viralinfection, a cold). The pharmacist should alwaystherefore ask patients to give an account of his or hersymptoms to assist in recognising the disease andassessing the severity. The most commonly reported

symptoms are sneezing, an itchy, congested nose(nasal blockage) and a runny nose (nasal discharge orrhinorrhea) (Table 1)(11, 15). The eyes, paranasal sinusesand eustachian tube may be affected, resulting initchy, watery or red eyes, temporary ear fullness, apopping, itchy throat and pressure over the cheeksand forehead. Other symptoms may include malaise,headache, weakness, inability to concentrate and fatigue.

If the patient does not give sufficient information aboutsymptoms to arrive at a diagnosis, more informationcan be elicited by structured questioning (Table 2). It isoften relatively easy to differentiate sneezers andrunners who may have allergic rhinitis from isolatedblockers who are almost never allergic.

Differentiating allergy from other causesincluding infection:

Allergic rhinitis presents with symptoms similar to thoseof a number of other conditions and may be confused

with a viral infection such as the common cold andwith chronic sinusitis. (Figure 1) presents an algorithmfor differentiating allergic rhinitis from another cause

or infectious diseases. The presence of nasal itching,rhinorrhea, sneezing and eye symptoms are usuallyconsistent with allergic rhinitis.

Assessing the severity of allergic rhinitis:

A recent classification of allergic rhinitis (intermittent orpersistent) has replaced the previous classification of

5

RECOGNISING ALLERGIC RHINITIS

IN THE PHARMACY

Table 1. Clini cal classification of rhi nitis (2, 10).

Sneezers and runners Blockers

Sneezing Especially paroxysmal in bouts Little or none

Rhinorrhea Always present: watery, anterior Variable, can be thick mucous,

and sometimes posterior and generally more posteriorNasal itching Yes, often No

Nasal blockage Variable Often severe

Diurnal rhythm Worse on awakening, improves during the day Constant day and night, may beand usually worsens again in the evening worse at night and is often severe

Conjunctivitis Often present None

Tab le 2. Questions to elicit information.

What is your main symptom? (Check for rhinorrhea, sneezing, itchynose, nasal congestion and/ or obstruction, watery or itchy eyes.)

Has a physician ever diagnosed that you have hay fever, al lergicrhinitis or asthma?

How long have you had these symptoms?

Do you have the symptoms all the time or do they come and go?

Are you aware of anything that seems to bring the symptoms on,such as being outdoors, around animals, or related to somethingyou handle at work or at home?

Is your nasal discharge clear and watery? (Purulent discharge sug-

gests infection.) Are you experiencing any wheezing or shortness of breath? (Yes

may indicate asthma.)

Do you have an earache or pain in your face? (Yes mayindicate otitis media or sinusitis.)

Do you have eye symptoms?

Do you have a family member with allergy problems?

What medications have you already tr ied for these symptoms?

Do you have any other medical conditions or are you on any othermedication?



8/26

seasonal and perennial forms(1). This classification ismore appropriate as it is based on the patient'ssymptoms and needs, and forms a practical basis forassessing and managing allergic rhinitis (Figure 2).

Management by pharmacists orreferral to a physician:

Once allergic rhinitis has been identified, its severitycan be assessed by asking the patient to what extentsymptoms affect daily life. Where symptoms are inter-mittent (i.e. occurring fewer than 4 days per week orfor less than 4 weeks) or mild (i.e. causing minimalinterference with daily living), pharmacist managementmay be appropriate depending on medication availability.

Referral to a physician should be considered in caseswhere: persistent, moderate to severe symptoms of rhini tis

are present (although initial treatment might be pro-vided by a pharmacist while waiting to see a physician),

symptoms are suggestive of undiagnosed asthma oruncontrolled asthma in patients with a diagnosis ofasthma (e.g. wheezing or shortness of breath),

symptoms of infection (mucopurulent discharge, sorethroat, myalgia, asthenia, fever) are reported,

subjects whose symptoms do not respond to ini tialpharmacy management within 2 to 4 weeks,

bothersome side effects are experienced.

Referral to a physician is also advisable duringpregnancy, because some medications should beadministered with caution.

Management by a physician is also appropriate forchildren under 12, because of difficulties in establish-ing the diagnosis and selecting theproper medications to avoid side effects, and thefrequent off-label use of medicines in this age group.

(Table 3) lists these and other circumstances in whichreferral to a physician is desirable.

Asthma co-morbidity

Allergic rhinitis and asthma often co-exist. Allergicrhinitis is regarded as a risk factor for thedevelopment of asthma(1). In patients with asthma,

6

Symptoms suggestive ofallergic rhinit is

Symptoms usually NOT associated withallergic rhinit is

unilateral symptoms nasal obstruction without other symptoms mucopurulent rhinorrhea posterior rhinorrhea (post nasal drip)

with thick mucusand/ or no anterior rhinorrhea

pain recurrent epistaxis anosmia

2 or more of the following symptoms for > 1 hr on mostdays

watery anterior rhinorrhea sneezing, especially paroxysmal nasal obstruction nasal pruritis conjunctivitis

Classify and assess severity Refer the patient rapidly to a physician

Intermittent

4 days per week or 4 weeks

Persistent

> 4 days per week and > 4 weeks

Mild

normal sleep no impairment of daily

activities, sport, leisure

normal work and school no troublesome symptoms

Moderate-severeone or more items

abnormal sleep

impairment of daily

activities, sport, leisure impairment of work and

school activities

troublesome symptoms

Figure 2. Classification of allergic rhinitisaccording to ARIA (1).

Figure 1. Differentiating allergi c rhinit is from other causes.



9/26

7

rhinitis may be associated with a poor control of thedisease. Patients with persistent rhinitis should be

questioned for symptoms of asthma. Patients withasthma should be questioned for symptoms of rhinitis.Patients with undiagnosed asthma or those withuncontrolled asthma should be advised to consult a

physician for proper evaluation. This is particularlyimportant in children (see also The management ofallergic rhinitis and asthma, page 17).

Conjunctivitis:

Eye symptoms are common in patients suffering fromallergic rhinitis but do not exist in all patients withrhinitis. In some cases, eye symptoms may predomi-nate over rhinitis(16), hence the term rhinoconjunctivitiscannot replace the term rhinitis. The presence of con-junctivitis should always be considered. On the otherhand, conjunctivitis is not always induced by allergic

triggers (Figure 3).

Photophobia (light sensitivity) is an important symptomto be noted and, if present, needs a physician evalua-tion. Eye itching is common in allergic conjunctivitis.In contrast, eye burning is rarely a sign of allergicconjunctivitis.

Tab le 3 . Circumstances when refer ral to a physician is

advisable before treatment for all ergic rhinit is.

Children under 12

Pregnant or breast-feeding women

Symptoms not usually associated with allergic rhinitis

Unilateral obstruction

Anosmia (loss of smell)

Nasal obstruction without rhinorrhea (discharge)

Thick green or yellow mucous secretion

Posterior rhinorrhea

Recurrent epistaxis (nose bleed)

Severe persistent allergic rhinitis

Symptoms of undiagnosed asthma Symptoms of uncontrolled asthma

Earache (may indicate otitis)

Symptoms unresponsive to treatment

Unacceptable side effects of treatment

Figu re 3: Differentiating al lergic conjunctivit is from other causes and selection of treatment by pharmacists.

Symptoms suggestive ofallergic conjunctivitis

If after 7-15 daysNo Improvement

Refer the patientto a doctor

Do the symptoms concernthe patient or the pharmacist?

1 or more of the following symptomsfor > 1 hr on most days: symptoms associated with rhinitis bilateral eye symptoms eye itching watery eyes red eyes NO photophobia

Symptom s NOT suggestiveof allergic conjunctivitis

1 or more of the following symptoms: symptoms NOT associated with rhinitis unilateral conjunctivitis NO eye itching BUT eye burning dry eyes photophobia

oral H1-blocker*/ $

or ocular H1-blocker*/

or ocular chromone*/

*: depending on drug availability not in prefered order$: non-sedating H1-blockers are prefered: formulations without preservatives are better tolerated

no

yes



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The management of allergic rhinitis should encompasspatient education, allergen and pollutant (e.g.tobacco) avoidance when possible, pharmacotherapyand validated allergen specific immunotherapy (1, 17).

Environmental control:

There is some controversy about allergen avoidance. Inasthma, a recent meta-analysis showed that somemeasures were effective in reducing symptoms(18). Ifavoidance measures are to be considered in allergic

rhinitis, allergen sensitivity should be documented.However, a meta-analysis in rhinitis did not show thatmite avoidance was clinically effective, possiblybecause of methodological problems(19). More studiesare needed to evaluate avoidance measures for otherinhalant allergens.

Reduction of active and passive smoking should beadvised and assistance provided (pharmacotherapyand support) when appropriate.

Options for pharmacological treatment ofallergic rhinitis:

Pharmacological treatment should take into accountthe efficacy, safety and cost-effectiveness of medica-tions, the patient's preference and the objective oftreatment(20), severity of the disease, as well as thepresence of co-morbidities (Table 4). Medicationsused for rhinitis are most commonly administeredintranasally or orally. The efficacy of medications maydiffer between patients.

Many medications used in the treatment of allergicrhinitis are available without a medical prescription,although there is a large disparity between countries.There are proposals for harmonisation across theEuropean Union (EU). In many countries, new genera-tion H1-antihistamines, intranasal glucocorticosteroidsand chromones are available without a prescription.In other countries, only sedating antihistamines anddecongestants are available without a prescription.Non-sedating H1-oral antihistamines arerecommended because of their considerably lower

incidence of side effects compared to sedating antihist-amines(21, 22). Patients may not always perceivesedation and mental impairment. Common treatmentscurrently available for allergic rhinitis (includingprescription-only medicines) are listed in (Table 5)(10)

and pharmacists are able to advise patients on bothprescribed and OTC medications.

The pharmacological treatment of allergic rhinitisproposed by ARIA is an evidence-based(23) andstepwise approach depending on the classificationof the symptoms. (Figure 4) provides the overallapproach to treatment.

Oral and local H1-antihistamines

Both oral and topical (intranasal and ocular)antihistamine preparations are available without pre-scription for the treatment of allergic rhinitis in manybut not all countries. H1-blockers or H1-antihistaminesare medications blocking histamine at the H1-receptorlevel (neutral antagonists or inverse agonists)(24). Some

8

MANAGEMENT OF

ALLERGIC RHINITIS

Tab le 4: Responses to commonly asked questions:

Medications are for the relief of symptoms and have no long-lasting effect when stopped. Therefore, in

persistent disease, maintenance treatment is required. Tachyphylaxis does not usually occur with prolonged treatment except for intranasal decongestants.

Continuous treatment with other medications is effective.

Most medications recommended in this guideline do not have significant long-term side effects and can be

administered for prolonged periods.



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also possess additional anti-allergic properties. Duringthe last 20 years, pharmacological research hasproduced compounds with minimal sedative effect andimpairment: the so-called second-generation H1-antihistamines, as opposed to the first-generationH1-antihistamines

(25) (Table 5).

Oral antihistamines are effective against symptomsmediated by histamine, including rhinorrhea,sneezing, nasal itching and eye symptoms(1, 26), butare less effective on nasal congestion(27, 28). Theyimprove the quality of life of the patient. They are usedregularly for the treatment of intermittent and persistent

9

moderate mildsevere

Not in preferred order oral H1-blocker intranasal H1-blocker and/or decongestant intranasal steriod

(chromone)

if failure: step-upif improved; continue

for 1 month

Intermittent symptoms Persistent symptoms

mild

Not in preferred order oral H1-blocker intranasal H1-blocker and/or decongestant

moderatesevere

intranasal steroid

step downand continuetreatment for 1 month

increase rhinorrheaintranasal ster iod add ipratropium

dose itch/sneeze blockageadd H1-blocker add decongestant

or oral steroid (short term)

surgical referral

If conjunctivitis add: oral H1-blocker or intraocular H1-blocker or intraocular chromone (or saline)

consider specific immunotherapy

review the patientafter 2-4 weeks

improved failure

failure

review diagnosisreview compliancequery infectionsor other causes

in persistent rhinitisreview the patientafter 2-4 weeks

Figure 4. Stepwise approach for the treatment of allergic rhinitis according to ARIA (10).

Allergen avoidance

Diagnosis of allergic rhinitis(history skin prick tests or serum specific IgE)

TREAT IN STEPWISE APPROACH(adolescents and adults)



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allergic rhinitis, and can also be used to preventsymptoms associated with occasional allergen exposure.

First-generation oral H1-antihistamines are associated

with sedation and central nervous system impairment

(21)

.These include performance of cognitive and skilledtasks such as learning and driving. These impairmentscan be potentiated by alcohol, other sedative medica-tions and compound the sleep disturbance of thedisease. Side effects may not always be perceived bythe patients. If administered, patients should beadvised of the potential side effects of first-generationoral H1-antihistamines. First-generation oralantihistamines may also have anticholinergic sideeffects, including dry mouth, dry eyes, difficulty inurinating and worsening of glaucoma(1, 29). Second-generation H1-antihistamines are in general less likelyto cause sedation and impairment. They do not have

anticholinergic effects. Second-generation H1-oral anti-histamines are recommended because they are equallyeffective and have fewer side effects resulting in abetter risk-benefit ratio.

Some but not all oral H1-antihistamines undergohepatic metabolism via the cytochrome P450system and may be prone to drug interactions. Certainmedications, herbal products, foods and dietarysupplements can affect the bioavailability of somesecond-generation antihistamines.

Major concerns exist about the arrhythmogenic actionof terfenadine, astemisole and high doses of diphenhy-

dramine which have exceptionally been associatedwith fatalities. This is not a class effect (27). The use ofterfenadine and astemisole is therefore not advised.

H1-antihistamines are also approved for youngchildren(30).

In general, first-generation antihistamines have a shortduration of action and require dosing several timesdaily (31). Most of the second-generation oral H1-anti-histamines have a rapid onset of action (20 minutes to2 hours) and a long duration of effect (up to 24 hours)allowing once-daily dosing(27). Acrivastine has a

shorter duration of action and should be administeredtwice daily(27).

H1-antihistamines given topically (intranasally orocularly) are as effective as oral antihistamines atthe site of their administration in reducing itching,

sneezing, runny nose and eye symptoms(1, 26, 27, 32). Theycan be effective within 20 minutes of administration(33).Topical H1 antihistamines require twice-a-day dosing.In general, topical antihistamines are well-tolerated.

However, intranasal glucocorticosteroids aresignificantly more effective than oral or topicalantihistamines for the treatment of allergic rhinitis(34)

and nasal congestion.

Intranasal glucocorticosteroids

Intranasal glucocorticosteroids are currently themost effective class of medications available for thetreatment of allergic and non-allergic rhinitis(35).Intranasal glucocorticosteroids are available withoutmedical prescription in some countries. The effective-ness of intranasal glucocorticosteroids is based ontheir local activity; the administration of an equivalent

amount of medication orally produces no benefit. Therationale for using intranasal glucocorticosteroids inthe treatment of allergic rhinitis is that high medicationconcentrations can be achieved at receptor sites in thenasal mucosa, with minimal risk of systemic adverseeffects(1).

Glucocorticosteroids can suppress many stages of theallergic inflammatory process(36) by interacting withtranscription factors(37). Due to their mechanism ofaction, efficacy appears after 7-8 hours of dosing, butmaximum efficacy may require up to 2 weeks. Thesemedications are effective at improving all symptoms ofallergic rhinitis.

Intranasal glucocorticosteroids have also been shownto improve quality of life, increase a user's sense ofwell-being, improve performance at work and schooland reduce sleep problems associated with nasalcongestion(38, 39). They may also have a prophylacticeffect when administered before the onset of the pollenseason(40).

If nasal congestion is present, or symptoms arefrequent, an intranasal glucocorticosteroid is themost appropriate fi rst-line treatment(41). Intranasalglucocorticosteroids are the most appropriate first-

line treatment for allergic rhinitis if there is nasalcongestion and if symptoms occur frequently or arepersistent (1). Intranasal glucocorticosteroids have beenshown to be more effective against nasal symptomsthan oral or topical antihistamines(35) or topical sodiumcromoglycate(42).

10



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11

Tab le 5 . Medications available for the treatm ent of allergic rhinit is(including prescription-only medicines) (10).

Oral H1 antihistamines

Local H1 antihistamines(intranasal, ocular)

Intranasalglucocorticosteroids

Local chromones(intranasal, ocular)

Oral decongestants

2nd generation

AcrivastineAzelastineCetirizineDesloratadineEbastineFexofenadineLevocetirizineLoratadineMizolastine

1st generation

ChlorpheniramineClemastineDiphenhydramineHydroxyzineKetotifenMequitazine

OxatomideOthers

Cardiotoxic

AstemizoleTerfenadine

AzelastineLevocabastineOlopatadine

BeclomethasoneBudesonideCiclesonideFluticasoneFlunisolideMometasone

Triamcinolone

Sodium cromoglycateNedocromil

EphedrinePhenylephrinePhenylpropanolaminePseudoephedrineOthers

blockage of H1 receptor some anti-allergic

activity new generation

medications can be usedonce daily

no development oftachyphylaxis

blockage of H1 receptor some anti-allergic activity

for azelastine

reduce nasalhyperreactivity

potently reduce nasalinflammation

poorly known

sympathomimeticmedications

relieve symptoms ofnasal congestion

2nd generation

no sedation for mostmedications

no anti-cholinergic effect no cardiotoxicity acrivastine has sedative

effects oral azelastine may

induce sedation and hasa bitter taste

1st generation

sedation is common andmay not be perceived

potentiation of impair-ment induced by alcohol

anti-cholinergic effectmay occur

minor local side effects azelastine: bitter taste

and sedation in someindividuals

minor local side effects wide margin for systemic

side effects growth concerns raised

by BDP in young children in young children,

consider the combinationof intranasal and inhaledmedications

minor local side effects

hypertension palpitations restlessness agitation tremor insomnia headache

dry mucous membranes urinary retention exacerbation of

glaucoma orthyrotoxicosis

2nd generation oral H1-antihistamines arepreferred for theirfavourable efficacy/safety ratio andpharmacokinetics

2nd generationmedications can be usedonce daily

rapidly effective (lessthan 1 hour) on nasaland ocular symptoms

poorly effective on nasalcongestion

cardiotoxic medicationsshould be avoided

rapidly effective (< 30mins) on nasal or ocularsymptoms

the most effectivepharmacologicaltreatment of allergicrhinitis

effective on nasalcongestion

effect on smell effect observed after 7-8hrs but maximal effect upto 2 weeks

intraocular chromonesare effective

intranasal chromones lesseffective than othertherapies; their effect isshort-lasting

overall excellent safety

use oral decongestantswith caution in patientswith other disease

oral H1 antihistamine/decongestant combina-tion products may bemore effective than either

product alone but sideeffects are combined

Classification Gener ic names Mechanism of action Side effects Comments

Table continues on next page



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12

In past studies, regular treatment with glucocorticos-teroids was found to be more effective than as-neededtreatment(43), and regular treatment was thought to benecessary. However, recent studies show that glucocor-ticosteroids administered as needed (prn) have a similaror better efficacy than oral-H1 antihistamines on nasal

symptoms(44), but as needed (prn) use is less effectivethan continuous treatment.

In clinical studies, intranasal glucocorticosteroids arewell tolerated, and adverse effects are few in number,mild in severity and have the same incidence asplacebo(45). The current intranasal preparations arewell tolerated. Crusting, dryness and minor epistaxismay occur in about 5% of patients which areoccasionally persistent and may be a reason forstopping treatment. The occurrence of epistaxis undertreatment needs physician evaluation. Evidence showsthat long-term use of intranasal glucocorticosteroids

is free of the concerns associated with long-term use oforal glucocorticosteroids. Even with long-term use,modern formulations of intranasal glucocorticosteroidshave no effect on the hypothalamic-pituitary-adrenalaxis and do not induce nasal mucosal atrophy(46-48). Inchildren, the rate of growth was slightly reduced in

those regularly treated with beclomethasone over oneyear by intranasal route(49). The clinical significance ofthis reduced rate of growth is unknown. This effect doesnot appear to be a class effect since recent studies haveshown normal growth rates in children treated withnewer intranasal glucocorticosteroids(50). However, it is

reasonable to monitor the growth of children receivinglong-term treatments with intranasal glucocorticosteroids.

The pharmacist should advise patients on the propermethod of administering intranasal glucocortico-steroids, including the importance of directing the spraylaterally and not medially (towards the nasal septum).

Systemic glucocorticosteroids

Oral glucocorticosteroids are rarely needed to controlsevere symptoms of allergic rhinitis. Although thesemedications are effective, they cause unacceptable

systemic side effects if used for a prolonged period oftime.

The Intramuscular injection of glucocorticosteroids isnot usually recommended due to the possible occur-rence of systemic side effects.

Tab le 5. Medications available for the treatment of al lergic rhinit is(including prescription-only medicines) (10).

Intranasal decongestants

Intranasal anticholinergics

Antileukotrienes

Oral/ IMglucocorticosteroids

EpinephrineNaphazolineOxymethazolinePhenylephrineTetrahydrozolineXylomethazolineOthers

Ipratropium

MontelukastPranlukastZafirlukast

BetamethasoneDeflazacortDexamethasoneHydrocortisoneMethylprednisolonePrednisolonePrednisoneTriamcinolone

sympathomimetic med-ication

relieve symptoms ofnasal congestion

anticholinergics blockalmost exclusively anteri-or watery rhinorrhea

block CystLT receptor

potentially reduce nasalinflammation

reduce nasalhyperreactivity

same side effects as oraldecongestants but lessintense

rhinitis medicamentosa (arebound phenomenaoccurring with prolongeduse > 10 days)

minor local side effects almost no systemic anti-

cholinergic activity

well tolerated

systemic side effects com-mon, in particular withIM medications

depot injections maycause local tissue atrophy

act more rapidly andmore effectively than oraldecongestants

limit duration of treat-ment to < 10 days toavoid rhinitis medica-mentosa

effective in allergic andnon-allergic patients withrhinorrhea

more data needed toposition thesemedications

when possible, intranasalglucocorticosteroidsshould replace oral or IMmedications

however, a short courseof oral glucocortico-steroids may be neededwith severe symptoms

Classi fication Gener ic names Mechanism of action Side effects Comments



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13

The Intranasal injection of glucocorticosteroids is notusually recommended due to the possible occurrenceof blindness.

Chromones

Intranasal and ocular formulations of chromones, suchas sodium cromoglycate, are available without medicalprescription in many countries.

Sodium cromoglycate or nedocromil have an excellentsafety profile. They reduce the symptoms of allergicrhinitis, but limited efficacy and the need for frequentdosing (as frequent as 4 times daily) are disadvan-tages. Chromones are generally less effective thanother medications used for the treatment of allergicrhinitis(1).

Ocular sodium cromoglycate or nedocromil areeffective and have a place in the treatment of allergicconjunctivitis(32). Single-dose formulations withoutpreservatives are often better tolerated by the patient.

N-acetyl-aspartyl glutamic acid (NAAGA), a C3convertase inhibitor, is used topically as an intranasalor ocular formulation(51). In rhinitis, it was found tohave a slightly greater efficacy than cromoglycate, butit was less well tolerated.

Decongestants

Oral, intranasal and ocular decongestants are oftenavailable without prescription.

Both oral and intranasal decongestants may be usedin the treatment of nasal congestion associated withallergic rhinitis. Nasal decongestant sprays havea greater effect on nasal obstruction than oraldecongestants(1). However, the use of nasaldecongestant sprays is limited by rebound congestion,the potential for irreversible tissue hypertrophy(52) anda decreasing duration of effect after 10 days of use(53).Rhinitis medicamentosa is a condition of nasalhyperreactivity, mucosal swelling and tolerance that isinduced or aggravated by the overuse of topical

decongestants with or without a preservative. Packageinserts for these medications therefore place strictlimits on their recommended duration of use. Oculardecongestants can be used in the treatment ofconjunctivitis, but they are also capable of causingrebound eye congestion.

Attention should be paid to a range of possiblecontraindications and warnings associated with oraldecongestants, including those regarding their use inthe elderly, in patients suffering from hypertension,

hyperthyroidism, prostate hypertrophy, glaucoma andpsychiatric disorders, as well as in patients takingbeta-blockers and monoamine oxidase inhibitors(1).Due to its side effects, phenylpropanolamine has beenwithdrawn in the US and some other countries.

Short courses (less than 10 days) of topical decongestantsmay be useful in reducing severe nasal blockage whenstarting the administration of other medications(1).

Oral or ocular combination products containingantihistamines and decongestants are available andare effective for symptomatic relief of nasal and ocularsymptoms.

Anticholinergics

Anticholinergic agents can help reduce anterior wateryrhinorrhea, but they have no effect on nasal blockageor on other symptoms of allergic rhinitis.

Antileukotrienes

Antileukotrienes are a new class of medicationfor the treatment of allergic rhinitis. They modulateinflammation. They have an efficacy comparable tothat of oral antihistamines(54).

Allergen-specific immunotherapy (vaccination):

Allergen-specific vaccination is the practice ofadministering gradually increasing quantities of anallergen extract to an allergic subject to ameliorate thesymptoms associated with the subsequent exposure tothe causative allergen. The efficacy of immunotherapyusing inhalant allergens to treat allergic rhinitisand asthma is evidence-based when optimally adminis-tered(1, 17, 55). Standardised therapeutic vaccines whichare available for the most common allergens are favoured.

In some countries, immunotherapy is dispensed bypharmacists, but it is not recommended to beadministered by pharmacists.

Subcutaneous immunotherapy raises contrastingefficacy and safety issues. Thus, the use of optimaldoses of vaccines labelled either in biological units or



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in mass of major allergens has been proposed.Maintenance doses of 5 to 20 g of the major allergenare optimal doses for most allergen vaccines.

Subcutaneous immunotherapy should be performed bytrained personnel supervised by a physician, andpatients should be monitored for 30 minutes afterinjection. Medications and equipment for treatment ofrare but potentially life-threatening acute allergicreactions triggered by subcutaneous immunotherapyshould be available.

Subcutaneous specific immunotherapy (not available inall countries) is indicated in patients:

with moderate-severe or persistent allergic rhinitiswho are inadequately controlled by conventionalpharmacotherapy,

who do not wish to be on pharmacotherapy,

in whom pharmacotherapy produces undesirableside effects,

who do not want to receive long-termpharmacological treatment.

High-dose nasal and sublingual-swallow specificimmunotherapy may be used:

with doses at least 20 to 100 times greater thanthose used for subcutaneous immunotherapy,

in patients who had side effects or refusedsubcutaneous immunotherapy,

the indications follow those of subcutaneousinjections.

Allergen-specific immunotherapy interferes with thebasic mechanisms of the allergy and alters the naturalcourse of allergic diseases, resulting in immediatesymptomatic relief and offering the patient a long-lasting and preventive effect. These are observedusing both subcutaneous(56) and sublingual routes(57).Subcutaneous immunotherapy was shown to reduce theonset of new sensitisations(58), as well as the develop-ment of asthma in patients with allergic rhinitis(59).

Immunotherapy is now recognised as complementary

to the pharmacological treatment for respiratoryallergy. It is suggested that immunotherapy shouldbe initiated early in the course of the disease, whenirreversible damage is not yet established and whenit is still possible to modify the progression of thedisease. However, it is usual to start this treatment afterthe age of 5.

14

Symptoms of allergic rhinitis

Mild persistentModerate-severe intermittent

Mild intermittent

Refer to physician

Moderate-severepersistent

Oral H1-blocker*/ $or nasal H1-blocker*and/ or decongestant*or nasal steroid*/ or nasal chromone*

Oral H1-blocker*/ $

or nasal H1-blocker*

or decongestant*

or nasal chromone*

or nasal saline

If after 7-15 daysNo improvement

*: depending on drug availability and not inpreferred order

$: non-sedating H1-blockers should be preferred: if nasal obstruction predominates, intranasal

steroids are the first-line treatment

Figure 5. Selection of allergic rhinitis treatment by pharmacists.



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Alternative therapies:

The use of complementary and alternative therapies(e.g. homeopathy, herbal medicines, acupuncture) for

the treatment of rhinitis is increasing. In the ARIAdocument(1), a review of the literature found thatthere was insufficient evidence to support the efficacyof alternative therapy. Since then, there have been afew further publications, but the design of the trials ortheir outcome measures did not make it possible toreach a definitive conclusion and recommend theiruse in the management of allergic rhinitis(60-65). Arecent Cochrane Collaboration study has beencarried out in asthma and concluded that thereis not enough evidence to reliably assess thepossible role of homeopathy in asthma(66). Thereis an urgent need for well-designed, large,randomised, controlled and properly powered

clinical trials to evaluate the efficacy and safety ofalternative therapies in the management of allergicdiseases.

Herbal medicine can induce pharmacologicalinteractions with medications used in the treatmentof allergic rhinitis or other illnesses(67). Health careprofessionals should ask their patients about the

use of herbal products and consider the possibility ofherb-drug interactions(67).

A pharmacy protocol for treating allergic rhinitis:

With recent changes in the regulatory status of somemedications for allergic rhinitis symptoms, pharmacistsmay recommend more therapies which are availablewithout prescription. The use of these medications islikely to result in cost savings for both the patient andthe health care professional (68). The involvement of thepharmacist in the overall management of the patient isalso likely to reduce risks of overdosing and druginteractions(69, 70).

Based on the above considerations, a recommendedpharmacy protocol for managing allergic rhinitis isshown in (Figure 5).

Allergic rhinitis, like other chronic diseases, requiresmonitoring for:

improvement of symptoms and quality of li fe, assessment of the safety of OTC and prescribed

medications, need for referral to a physician, need to discontinue or reinstate medications.

15



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Asthma may be severe and even life threatening.When pharmacists identify patients with undiagnosedor untreated asthma, or with asthma which is notoptimally controlled, they should encourage theseindividuals to obtain appropriate medical care.

There are many similarities between the nasal andbronchial mucosa, the major difference being the richvascular supply to the nose that accounts for nasalobstruction being a symptom of allergic rhinitis. In thebronchi, smooth muscle accounts for the bronchospasmseen in asthma. The upper and lower airways maywell be affected by a common inflammatory process(71)

with interconnected mechanisms, suggesting theconcept of one airway, one disease(72).

Epidemiological studies consistently show that allergicrhinitis and asthma often co-exist: at least 75% ofpatients with asthma complain about rhinitis symptoms,and 20-30% of those with allergic rhinitis also haveasthma(73). Allergic rhinitis is also a risk factor for asth-ma(74). Therefore, patients with persistent symptoms ofallergic rhinitis should be referred to their physician tobe evaluated for asthma. In the ARIA document(1), it isrecommended that evaluation should include a medical

history, chest examination and assessment of airflowobstruction before and after taking a bronchodilator.The diagnosis of asthma should follow the guidance inthe recent update of the GINA guidelines(75).

If a patient has persistent allergic rhinitis, he/ sheshould be questioned about his or her symptoms ofasthma (Figure 6 and Table 6). If there is any suspi-

16

With the exception of nasal decongestants and anti-cholinergics, all the major treatments discussed aboveare effective against the ocular symptoms of allergicrhinitis (Figure 3). Sodium cromoglycate, nedocromilsodium, NAAGA and H1-antihistamines (azelastine,levocabastine, ketotifen, olopatadine) are also avail-able as eye drops. Intranasal glucocorticosteroids haveshown some effect in eye symptoms associated with

allergic rhinitis(35). Intraocular glucocorticosteroids areeffective but, because of known side effects, shouldonly be prescribed and monitored by eye care profes-sionals. The use of antihistamine or chromone eyedrops is justified if ocular symptoms are the predomi-nant and/ or persistent feature of the patient's allergicrhinitis, persisting despite use of oral H1-antihistaminesand/ or intranasal glucocorticosteroids.

MANAGEMENT OF

OCULAR SYMPTOMS

THE MANAGEMENT OF ALLERGICRHINITIS AN D ASTHMA

Table 6:Questions that should be asked if apatient is suspected of having asthma (76).

Do you find yourself short of breath?

Do you make whistling noises (wheeze) whenyou breathe?

Does your chest feel tight?

Do you have a cough regularly?

Are these symptoms particularly noticeablefirst thing in the morning, during the night orwith exercise?



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17

The patient does not know

if he (she) is asthma tic

If YES to any of these questionsyour patient may be asthmatic

If YES to any of these questionsyour patient has uncontrolled asthma

4 simple questions:

Have you had an attack or recurrent attacks of wheezing?

Do you have a troublesome cough, especially at night?

Do you cough or wheeze after exercise?

Does your chest feel tight?

1 or more of the following:* Have you had difficulty sleeping because of your asthma

symptoms (including cough)?

Have you had your usual asthma symptoms during the day?

Has your asthma interfered with usual activities (e.g. house-work, work or school)?

Do you need your reliever inhaler (blue) more than once a day?

Patient with a diagnosis of asthma

Refer the patient to a physician

Figure 6. Assessing asthma in a p atient with persistent allerg ic rhinit is

*from the National Asthma Campaign, conquering asthma

Tab le 7: Questions to ask patients diagnosed with asthma toreveal the level of a sthma control (77).

In the last month:

Have you had di fficulty sleeping because of your asthma symptoms (including cough)?

Have you had your usual asthma symptoms during the day (cough, wheeze, chest tightness or

breathlessness)?

Has your asthma interfered with your usual activities (e.g., housework, work, school)?

Have you used your 2agonist more than once a day in the past week?

cion of undiagnosed asthma, the patient should bereferred to a physician.

If a patient has a diagnosis of asthma, he/ she shouldbe questioned to assess the level of asthmacontrol (Table 7).

If there is poor control (any positive answer to the(Table 7) questions), the patient should be advised toconsult a physician.

The treatment of asthma should follow the recentlypublished guidelines(75, 76).

It is important to manage co-morbidity of allergicrhinitis and asthma. Treatment of allergic rhinitis hasbeen associated with improved outcomes fromasthma(78).



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Allergic rhinitis is an increasing global health problem.The ARIA classification distinguishes between intermit-tent and persistent allergic rhinitis. Allergic rhinitis thatis intermittent or mild may be appropriate for manage-ment by the pharmacist. Referral to a physicianshould be considered in cases of symptoms that aremoderate to severe-persistent, suggestive of undiag-nosed or uncontrolled asthma, suggestive of infectionor non-allergic rhinitis, and for symptoms poorlyresponsive to treatment after 2 to 4 weeks.

The management of allergic rhinitis represents acollaboration between pharmacists, physicians, otherhealth care professionals and patients. The cost-effectiveness of these approaches should be tested inallergic rhinitis as it has been for asthma(79), reactiveairway diseases(80, 81) and other chronic diseases(68).

CONCLUSION

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1. Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy ClinImmunol2001;108(5 Suppl):S147-334.

2. International Consensus Report on Diagnosis and Management of Rhinitis. International Rhinitis ManagementWorking Group. Allergy1994;49(19 Suppl):1-34.

3. van Cauwenberge P, Bachert C, Passalacqua G, Bousquet J, Canonica GW, Durham SR, et al. Consensusstatement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology.Allergy2000;55(2):116-34.

4. Strachan D, Sibbald B, Weiland S, Ait-Khaled N, Anabwani G, Anderson HR, et al. Worldwide variations inprevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma andAllergies in Childhood (ISAAC). Pediatr Allergy Immunol1997;8(4):161-76.

5. Tripathi A, Patterson R. Impact of allergic rhinitis treatment on quality of life. Pharmacoeconomics2001;19(9):891-9.

6. Simons FE. Learning impairment and allergic rhinitis. Allergy Asthma Proc1996;17(4):185-9.

7. Blanc PD, Trupin L, Eisner M, Earnest G, P PK, Israel L, et al. The work impact of asthma and rhinitis. Findingsfrom a population-based survey. J Clin Epidemiol2001;54(6):610-8.

8. Weiss KB, Sullivan SD. The health economics of asthma and rhinitis. I. Assessing the economic impact.J Allergy Clin Immunol2001;107(1):3-8.

9. Sullivan SD, Weiss KB. Health economics of asthma and rhinitis. II. Assessing the value of interventions.J Allergy Clin Immunol2001;107(2):203-10.

10. Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma (ARIA)- Executivesummary. Allergy2002;58:in press.

11. Dykewicz MS, Fineman S, Skoner DP, N icklas R, Lee R, Blessing-Moore J, et al. Diagnosis and management ofrhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma andImmunology. American Academy of Allergy, Asthma, and Immunology. Ann Allergy Asthma Immunol1998;81(5 Pt 2):478-518.

12. Pincus T, Sokka T, Stein CM. Pharmacist scope of practice. Ann Intern Med2002;136(1):79-85.13. Dessing RP. Ethics applied to pharmacy practice. Pharm World Sci2000;22(1):10-6.

14. Strom BL, Hennessy S. Pharmacist care and clinical outcomes for patients with reactive airways disease. Jama2002;288(13):1642-3.

15. Nathan A. How to treat hay fever and associated allergic conditions in the pharmacy. Pharm J2002;268:575-8.

16. Bonini S, Bonini S. Pathogenesis: allergic conjunctivitis. In: Denburg J, editor. Allergy and allergic diseases: themechanisms and therapeutic. Tollawa, USA: Human Press Inc;1998. p. 509-19.

17. Bousquet J, Lockey R, Malling H. WHO Position Paper. Allergen Immunotherapy: Therapeutic Vaccines forallergic diseases. Allergy1998;53, suppl 54.

18. Gotzsche PC, Johansen HK, Burr ML, Hammarquist C. House dust mite control measures for asthma. CochraneDatabase Syst Rev2001;3.

19. Sheikh A, Hurwitz B. House dust mite avoidance measures for perennial allergic rhinitis. Cochrane DatabaseSyst Rev2001(4):CD001563.

20. Marinker M. From compliance to accordance: achieving shared goals in medicine taking. Report of the RoyalPharmaceutical of Great Britain Working party. 1998.

21. Milgrom H, Bender B, Wamboldt F. Of injuries and antihistamines and dosing. Ann Allergy Asthma Immunol2002;89(3):221-3.

22. Weiler JM. The real-world risk of taking sedating antihistamines. Ann Allergy Asthma Immunol2002;89(3):224-5.

23. Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing guidelines. BMJ1999;318(7183):593-6.

20

REFERENCES



23/26

24. Leurs R, Church MK, Taglialatela M. H1-antihistamines: inverse agonism, anti-inflammatory actions andcardiac effects. Clin Exp Allergy2002;32(4):489-98.

25. Bousquet J, Van-Cauwenberge P, Bachert C, Canonica G, Demoly P, Durhma S, et al. Requirements formedications commonly used in the treatment of allergic rhinitis. Allergy2003:in press.

26. Howarth P. Antihistamines in rhinoconjunctivitis. Clin Allergy Immunol2002;17:179-220.27. Passalacqua G, Canonica GW, Bousquet J. Structure and classification of H1-antihistamines and overview oftheir activities. Clin Allergy Immunol2002;17:65-100.

28. Nielsen LP, Mygind N, Dahl R. Intranasal corticosteroids for allergic rhinitis: superior relief? Drugs2001;61(11):1563-79.

29. Passalacqua G, Bousquet J, Bachert C, Church MK, Bindsley-Jensen C, Nagy L, et al. The clinical safety ofH1-receptor antagonists. An EAACI position paper. Allergy1996;51(10):666-75.

30. Simons FE. H1-antihistamines in children. Clin Allergy Immunol2002;17:437-64.31. Simons FE, Simons KJ. The pharmacology and use of H1-receptor-antagonist drugs. N Engl J Med

1994;330(23):1663-70.32. Friedlaender M. Overview of ocular allergy treatment. Curr Allergy Asthma Rep2001;1(4):375-9.33. Noble S, McTavish D. Levocabastine. An update of its pharmacology, clinical efficacy and tolerabili ty in the

topical treatment of allergic rhinitis and conjunctivitis. Drugs1995;50(6):1032-49.34. Di Lorenzo G, Gervasi F, Drago A, Esposito Pellitteri M, Di Salvo A, Cosentino D, et al. Comparison of the

effects of fluticasone propionate, aqueous nasal spray and levocabastine on inflammatory cells in nasal lavageand clinical activity during the pollen season in seasonal rhinitics [In Process Citation]. Clin Exp Allergy1999;29(10):1367-77.

35. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergicrhinitis: systematic review of randomised controlled trials. BMJ1998;317(7173):1624-9.

36. Fokkens WJ, Godthelp T, Holm AF, Klein-Jan A. Local corticosteroid treatment: the effect on cells and cytokinesin nasal allergic inflammation. Am J Rhinol1998;12(1):21-6.

37. Adcock IM, Caramori G. Cross-talk between pro-inflammatory transcription factors and glucocorticoids.Immunol Cell Biol2001;79(4):376-84.

38. Ratner PH, Paull BR, Findlay SR, Hampel F, Jr., Martin B, Kral KM, et al. Fluticasone propionate given oncedaily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily. J AllergyClin Immunol1992;90(3 Pt 1):285-91.

39. Brogden RN, McTavish D. Budesonide. An updated review of its pharmacological properties, and therapeutic

efficacy in asthma and rhinitis [published errata appear in Drugs1992 Dec;44(6):1012 and 1993Jan;45(1):130]. Drugs1992;44(3):375-407.40. Graft D, Aaronson D, Chervinsky P, Kaiser H, Melamed J, Pedinoff A, et al. A placebo- and active-controlled

randomized trial of prophylactic treatment of seasonal allergic rhinitis with mometasone furoate aqueous nasalspray. J Allergy Clin Immunol1996;98(4):724-31.

41. Craig TJ, Teets S, Lehman EB, Chinchilli VM, Zwillich C. et al. Nasal congestion secondary to allergic rhinitisas a cause of sleep disturbance and daytime fatigue and the response to topical nasal corticosteroids.J Allergy Clin Immunol1998;101(5):633-7.

42. Bousquet J, Chanal I, Alquie MC, Charpin D, Didier A, Germouty J, et al. Prevention of pollen rhinitis symp-toms: comparison of fluticasone propionate aqueous nasal spray and disodium cromoglycate aqueous nasalspray. A multicenter, double-blind, double-dummy, parallel-group study. Allergy1993;48(5):327-33.

43. Juniper EF, Guyatt GH, O' Byrne PM, Viveiros M. Aqueous beclomethasone diproprionate nasal spray:regular versus as required use in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol1990;86(3 Pt 1):380-6.

44. Kaszuba SM, Baroody FM, deTineo M, Haney L, Blair C, Naclerio RM. Superiority of an intranasal corticos-teroid compared with an oral antihistamine in the as-needed treatment of seasonal allergic rhinitis. Arch InternMed2001;161(21):2581-7.

45. Meltzer EO, Orgel HA, Bronsky EA, Furukawa CT, Grossman J, LaForce CF, et al. A dose-ranging study offluticasone propionate aqueous nasal spray for seasonal allergic rhinitis assessed by symptoms,rhinomanometry, and nasal cytology. J Allergy Clin Immunol1990;86(2):221-30.

21



24/26

46. Minshall E, Ghaffar O, Cameron L, O'Brien F, Quinn H, Rowe-Jones J, et al. Assessment by nasal biopsy oflong-term use of mometasone furoate aqueous nasal spray (Nasonex) in the treatment of perennial rhinitis.Otolaryngol Head Neck Surg1998;118(5):648-54.

47. Holm AF, Fokkens WJ, Godthelp T, Mulder PG, Vroom TM, Rijntjes E. et al. A 1-year placebo-controlled study

of intranasal fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis: a safetyand biopsy study. Clin Otolaryngol1998;23(1):69-73.48. Laliberte F, Laliberte MF, Lecart S, Bousquet J, Klossec JM, Mounedji N. et al. Clinical and pathologic methods

to assess the long-term safety of nasal corticosteroids. French Triamcinolone Acetonide Study Group. Allergy2000;55(8):718-22.

49. Skoner D, Rachelefsky G, Meltzer E, Chervinsky P, Morris R, Seltzer J, et al. Detection of growth suppression inchildren during treatment with intranasal belcomethasone dipropionate. Pediatrics2000;105:e23.

50. Schenkel E, Skoner D, Bronsky E, Miller S, Pearlman D, Rooklin A, et al. Absence of growth retardation in chil-dren with perennial allergic rhinitis following 1-year treatment with mometasone furoate aqueous nasal spray.Pediatrics2000;101:e22.

51. Althaus MA, Pichler WJ. Nasal application of a gel formulation of N-acetyl-aspartyl glutamic acid (NAAGA)compared with placebo and disodium cromoglycate in the symptomatic treatment of pollinosis. Allergy1994;49(3):184-8.

52. Graf P. Rhinitis medicamentosa: aspects of pathophysiology and treatment. Allergy1997;52(40 Suppl):28-34.

53. Graf P, Enerdal J, Hallen H. Ten days' use of oxymetazoline nasal spray with or without benzalkonium chloridein patients with vasomotor rhinitis. Arch Otolaryngol Head Neck Surg1999;125(10):1128-32.

54. Meltzer E, Malmstrom K, Lu S, Brenner B, Wei L, Weinstein S, et al. Concomitant montelukast and loratadineas treatment for seasonal allergic rhinitis: placebo-controlled clinical trial. J Allergy Clin Immunol2000;105(5):917-22.

55. Abramson M, Puy R, Weiner J. Immunotherapy in asthma: an updated systematic review. Allergy1999;54(10):1022-41.

56. Durham SR, Walker SM, Varga EM, Jacobson MR, O 'Brien F, Noble W, et al. Long-term clinical efficacy ofgrass-pollen immunotherapy [see comments]. N Engl J Med1999;341(7):468-75.

57. Di-Rienzo v, Marcucci F, Puccinelli P, Parmiani S, Frati F, Sensi L, et al. Long-Lasting effect of sublingualimmunotherapy in children with asthma due to house dust mite: a 10-year prospective study. Clin Exp Allergy2003;33:in press.

58. Des-Roches A, Paradis L, Mnardo J-L, Bouges S, Daurs J-P, Bousquet J. et al. Immunotherapy with a stan-dardised Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sen-sitisations in children. J Allergy Clin Immunol1997;99:450-3.

59. Moller C, Dreborg S, Ferdousi HA, Halken S, Host A, Jacobsen L, et al. Pollen immunotherapy reduces thedevelopment of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol2002;109(2):251-6.

60. Taylor MA, Reilly D, Llewellyn-Jones RH, McSharry C, Aitchison TC. et al. Randomised controlled trial ofhomoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series. BMJ2000;321(7259):471-6.

61. Aabel S. No beneficial effect of isopathic prophylactic treatment for birch pollen allergy during a low-pollenseason: a double-blind, placebo-controlled clinical trial of homeopathic Betula 30c. Br Homeopath J2000;89(4):169-73.

62. Aabel S, Laerum E, Dolvik S, Djupesland P. Is homeopathic immunotherapy effective? A double-blind, place-bo-controlled trial with the isopathic remedy Betula 30c for patients with birch pollen allergy. Br Homeopath J2000;89(4):161-8.

63. Aabel S. Prophylactic and acute treatment with the homeopathic medicine, Betula 30c for birch pollen allergy:a double-blind, randomised, placebo-controlled study of consistency of VAS responses. Br Homeopath J2001;90(2):73-8.

64. Lewith GT, Watkins AD, Hyland ME, Shaw S, Broomfield JA, Dolan G, et al. Use of ultramolecular potencies ofallergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial.BMJ2002;324(7336):520.

22



25/26

65. Schapowal A. Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ2002;324(7330):144-6.

66. Linde K, Jobst KA. Homeopathy for chronic asthma. Cochrane Database Syst Rev2000;2.67. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs

2001;61(15):2163-75.68. Steinwachs DM. Pharmacy benefit plans and prescription drug spending. JAMA 2002;288(14):1773-4.69. Meltzer EO, Ehrlich PM. A step approach to the clinical management of allergic rhinitis: prescription and

over-the-counter therapeutic reference summary. Manag Care Interface1999;12(11):70-7.70. Bond C, Matheson C, Williams S, W illiams P, Donnan P. et al. Repeat prescribing: a role for community phar-

macists in controlling and monitoring repeat prescriptions. Br J Gen Pract2000;50(453):271-5.71. Chanez P, Vignola AM, Vic P, Guddo F, Bonsignore G, Godard P, et al. Comparison between nasal and

bronchial inflammation in asthmatic and control subjects. Am J Respir Crit Care Med1999;159(2):588-95.72. Simons FE. Allergic rhinobronchitis: the asthma-allergic rhinitis link. J Allergy Clin Immunol 1999;104(3 Pt

1):534-40.73. Leynaert B, Bousquet J, Neukirch C, Liard R, Neukirch F. et al. Perennial rhini tis: An independent risk factor for

asthma in nonatopic subjects: Results from the European Community Respiratory Health Survey. J Allergy ClinImmunol1999:301-4.

74. Wright AL, Holberg CJ, Martinez FD, Halonen M, Morgan W, Taussig LM. et al. Epidemiology of physician-

diagnosed allergic rhinitis in childhood. Pediatrics1994;94(6 Pt 1):895-901.75. Global strategy for asthma management and prevention. GINA. Update from NHLBI/ WHO Workshop Report

1995, Revised 2002. NIH PublicationN02-3659 2002.76. British Thoracic Society, Scottish Intercolleagiate Guidelines Network. 2002:in press.77. National Asthma Campaign. Conquering asthma. Action Plan. www.asthma.org.uk 1996.78. Adams RJ, Fuhlbrigge AL, Finkelstein JA, Weiss ST. Intranasal steroids and the risk of emergency department

visits for asthma. J Allergy Clin Immunol2002;109(4):636-42.79. Cordina M, McElnay JC, Hughes CM. Assessment of a community pharmacy-based program for patients with

asthma. Pharmacotherapy2001;21(10):1196-203.80. Weinberger M, Murray MD, Marrero DG, Brewer N, Lykens M, Harris LE, et al. Issues in conducting

randomised controlled trials of health services research interventions in nonacademic practice settings: the caseof retail pharmacies. Health Serv Res2002;37(4):1067-77.

81. Weinberger M, Murray MD, Marrero DG, Brewer N, Lykens M, Harris LE, et al. Effectiveness of pharmacist

care for patients with reactive airways disease: a randomised controlled trial. JAMA 2002;288(13):1594-602.

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