ORIGINAL RESEARCH ARTICLE
`
`Drug Invest. 8 (4): 225-233, 1994
`0114-2402/94/0004-0225/$04.50/0
`
`© Adls International Limited. All rights reserved
`
`Evaluation of Fluticasone Propionate
`Aqueous Nasal Spray Taken Alone
`and in Combination with Cetirizine
`in the Prophylactic Treatment of
`Seasonal Allergic Rhinitis
`
`C. Benincasa1 and R.S. Lloyd2
`
`Allen and Hanburys Ltd, Uxbridge, Middlesex, England
`2 Weeping Cross Surgery, Stafford, England
`
`Summary
`
`This was a multicentre, double-blind study in 454 patients to compare the
`effectiveness and tolerability of fluticasone propionate nasal spray (FPANS)
`200µg used once daily for 8 weeks on its own or in combination with oral cetiriz(cid:173)
`ine 10mg once daily in the treatment of seasonal allergic rhinitis. The results
`showed no significant difference between treatments in any of the symptoms or
`in the proportion of symptom-free days. Watery eyes were recorded as being the
`most troublesome symptom in the previous hayfever season, whilst during the
`study patients were, on average, free of eye symptoms for 56% of the time.
`Additionally, no difference was detected between the two groups with regard to
`the use of rescue medication. More than 75% of patients concluded at the end of
`the study that their symptoms had been adequately controlled and, similarly,
`investigators rated both treatments as being successful for the majority of patients.
`Overall, this study suggests that there is no significant difference in efficacy
`between FPANS 200µg, taken once daily in the morning, and FPANS 200µg once
`daily in combination with oral cetirizine 10mg, in the prophylactic treatment of
`seasonal allergic rhinitis.
`
`Seasonal allergic rhinitis (SAR), defined as a
`noninfectious inflammatory reaction of the nasal
`mucosa to allergens such as pollen from grasses
`and trees, clinically presents with symptoms rang(cid:173)
`ing from uncomfortable nasal congestion, chronic
`or recurrent sneezing ancl rhinorrhoea, to headache
`
`and cough. Additionally, some patients complain
`of nasal itching, eye irritation, and wheeziness
`(seasonal allergic asthma).U,21 The pathogenesis
`of seasonal allergic rhinitis is believed to involve
`immediate type 1 allergic reactions with diagnosis
`confirmed by the 'skin prick test' if necessary.
`
`

`

`226
`
`Benincasa & Lloyd
`
`The prevalence of the condition in the UK pop(cid:173)
`ulation ranges from 10 to 15%, with the incidence
`apparently increasing, possibly due to pollution.l31
`The hayfever season in the UK starts in about
`March (tree pollination), continues through June
`and July (grass pollination), and ends in August
`after weed pollination, although some sensitivity
`to mould spores can occur in August or September. l31
`There are several approaches to the treatment of
`seasonal allergic rhinitis, including avoidance of
`the appropriate allergy, topical nasal sprays or eye
`drops, and systemic therapies.l41 For the past 20
`years, topical corticosteroids have been used suc(cid:173)
`cessfully in the treatment of allergic rhinitis. These
`drugs have vasoconstrictor and anti-inflammatory
`properties that alleviate the symptoms of rhinitis.
`Fluticasone propionate nasal spray (FPANS) is a
`recent addition to the currently available topical
`corticosteroids, which, at a once-daily dose of
`200µg, has been shown to be highly effective in the
`treatment of allergic rhinitisl51 and equivalent in
`efficacy to that of other comparator topical corti(cid:173)
`costeroids (intranasal beclomethasone dipropion(cid:173)
`ate 168µg twice dailyl6,71 and flunisolide lO0µg
`twice dailyl81). Furthermore, FPANS possesses 2
`distinct advantages over other topically active cor(cid:173)
`ticosteroids: (a) being effective as a once-daily
`dosage, the drug may act as an aid to patient com(cid:173)
`pliance,l91 and (b) it has extremely low oral bio(cid:173)
`availabilityl101 and therefore a low potential to pro(cid:173)
`duce unwanted systemic side effects. This lack of
`systemic activity has been demonstrated in healthy
`volunteers taking either high oral doses of
`fluticasone propionatellO,ll] or high intranasal
`dosesllOJ over a period of several days.
`Systemic antihistamines have also been used as
`a treatment for SAR, with the original histamine
`Hi-receptor antagonists now being replaced by
`second generation nonsedative drugs in this
`class.l41 Cetirizine dihydrochloride is an antihista(cid:173)
`mine in this group that has been shown to be effec(cid:173)
`tive in controlling the symptoms of hayfever at a
`once-daily dosage of 10mg.l121 Furthermore, it has
`been shown to produce a significant improvement
`in eye irritation and'watering.l 121 While intranasal
`
`corticosteroid therapy is highly effective in reduc(cid:173)
`ing the nasal symptoms associated with seasonal
`allergic rhinitis, it may be less effective in control(cid:173)
`ling eye symptoms.l131 In a recent study in which
`loratidine and beclomethasone dipropionate were
`used in combination, there was some evidence that
`overall control of symptoms improved.l141
`This study aimed to evaluate the efficacy and
`safety ofFPANS 200µg once daily, taken alone and
`in combination with one tablet of cetirizine dihy(cid:173)
`drochloride 10mg, in the treatment of seasonal al(cid:173)
`lergic rhinitis.
`
`Patients and Methods
`
`Patients
`
`Patients eligible to take part in this study were
`males or females aged over 12 years who had re(cid:173)
`quired treatment for the symptoms ofhayfever dur(cid:173)
`ing the month of June in the 2 previous years.
`Patients must have had at least two of the following
`symptoms, one of which should have been a nasal
`symptom: sneezing, nasal itching, runny nose,
`nasal congestion, eye watering/irritation and head(cid:173)
`ache. Patients were to remain in their usual envi(cid:173)
`ronment throughout the study.
`Patients not eligible were those who had re(cid:173)
`ceived a prescription medicine for the treatment of
`an upper or lower respiratory tract infection within
`the previous 2 weeks, or had received treatment for
`allergic rhinitis within the last week. Any patients
`who had received intranasal corticosteroids or oral
`corticosteroids within the previous 4 weeks were
`also excluded, as were those who had received
`ketotifen or sodium cromoglycate in the same time
`period. Patients taking astemizole within the pre(cid:173)
`vious 6 weeks, depot corticosteroids within 8
`weeks, or receiving desensitisation injections to
`grass pollen in the previous 6 months were also
`excluded.
`Additional exclusion criteria included: nasal
`surgery in the previous 2 months, nasal infections
`or significant nasal pathology (polyps, septal devi(cid:173)
`ation, hypertrophy of turbinates), chronic infective
`rhinosinusitis, serious concomitant disease, treat-
`
`© Adls International Limited. All rlghts reserved.
`
`Drug Invest. 8 (4) 1994
`
`

`

`Fluticasone Propionate Alone and with Cetirizine
`
`227
`
`Table I. Patient characteristics (total study population)
`
`Total no. of patients
`Males
`Females
`Mean age (years) [range]
`
`Duration of seasonal allergic rhinitis
`<10y
`>10y
`
`Severity of seasonal allergic rhinitis
`Mild
`Moderate
`Severe
`
`Hayfever symptoms of previous year
`Headache
`Sneezing
`Watering eyes
`
`Most troublesome symptom last year
`Watering eyes
`
`No. of patients (%)
`FPANSalone
`227
`95(42)
`132 (58)
`31 [12-80]
`
`FPANS plus cetirizine.
`227
`99(44)
`128 (56)
`30 [12-66)
`
`104 (46)
`123(54)
`
`21 (9)
`160 (70)
`46(20)
`
`81 (36)
`216(95)
`207(91)
`
`108(48)
`
`109 (48)
`118(52)
`
`12 (5)
`162 (71)
`53(23)
`
`98 (43)
`216 (95)
`201 (89)
`
`126 (56)
`
`Most widely used medications
`169 (74)
`176 (78)
`Antihistamines (49% of all medications)
`Corticosteroids (29% of all medications)
`108 (48)
`97(43)
`Abbreviations: FPANS = fluticasone propionate aqueous nasal spray 200µg once daily in the morning; FPANS plus cetirizine = fluticasone
`propionate aqueous nasal spray 200µg once daily in the morning plus one tablet of cetirizine 10mg.
`
`ment with concomitant medication likely to inter(cid:173)
`fere with the efficacy of the study medication, re(cid:173)
`current conjunctivitis, the wearing of soft contact
`lenses, and pregnancy or lactation. Women of
`childbearing potential were only included if the
`investigator considered that they were taking ade(cid:173)
`quate contraceptive precautions.
`Finally, patients with asthma were eligible for
`entry into the study provided that they were un(cid:173)
`likely to require a change in medication over the
`8-week study period.
`All patients were required to give their written
`informed consent before participating in the study,
`with those under the age of 16 years providing the
`consent of a parent or legal guardian. The study
`was approved by one local Ethics Committee on
`behalf of all panicipating centres.
`
`Design
`
`This was a double-blind, multicentre, parallel
`group study carried out amongst general practice
`patients in the UK. Eligible patients were ran(cid:173)
`domly assigned to one of two treatment groups;
`either FPANS 200µg once daily (2 actuations per
`nostril) in the morning plus 1 placebo tablet, or
`FPANS 200µg once daily in the morning plus one
`cetirizine l 0mg tablet. Medication was taken for 8
`weeks starting on 14 May, 1990, to ensure that
`treatment was commenced before the beginning of
`the expected hayfever season in the UK Patients
`were also provided with eye drops containing a
`mixture of antazoline and xylometazoline (Otriv(cid:173)
`ine-Antistin®, Ciba Vision) to be used if eye symp(cid:173)
`toms became troublesome.
`
`© Adls International Limited. All rights reserved.
`
`Drug Invest. 8 (4) 1994
`
`

`

`228
`
`Benincasa & Lloyd
`
`Table II. Mean symptom scores• for the total population
`
`Total no. of patient■
`NINI symptoms
`Mean
`SD
`
`Range
`(Missing)
`Eye symptoms
`Mean
`
`SD
`Range
`(Missing)
`Headacha
`Mean
`SD
`
`Range
`
`FPANSalone
`227
`
`FPANS plus cetirizine
`227
`
`95% Confidence interval
`
`1.5
`1.4
`
`0.0107.1
`
`(30)
`
`1.3
`
`1.3
`
`O.Oto6.2
`
`(30)
`
`0.4
`0.9
`
`O.Oto 6.0
`
`1.5
`
`1.6
`O.Oto 8.4
`(29)
`
`1.1
`
`1.3
`
`O.Oto7.3
`(30)
`
`0.4
`0.7
`
`O.Oto4.0
`
`--0.3 to 0.3
`
`--0.1 to 0.4
`
`--0.1 to 0.2
`
`(31)
`(30)
`(Missing)
`a Symptoms were rated on a 10-point scale: O = absent to 9 = very severe.
`Abbreviations: FPANS = fluticasone propionate aqueous nasal spray 200µg once daily in the morning; FPANS plus cetirizine = fluticasone
`propionate aqueous nasal spray 200µg once daily in the morning plus one tablet of cetirizine 10mg.
`
`Table Ill. Proportion of symptom-free days• for the total population
`
`FPANSalone
`227
`
`FPANS plus cetirizine
`227
`
`95% Confidence interval
`
`O.Oto 1.0
`
`Range
`(31)
`(Missing)
`(30)
`a A score of O represents no days symptom-free, a score of 1 indicates that all days were symptom-free.
`Abbreviationsr FPANS = fluticasone propionate aqueous nasal spray 200µg once daily in the morning; FPANS plus cetirizine = fluticasone
`propionate aqueous nasal spray 200µg once daily in the morning plus one tablet of cetirizine 10mg.
`
`© Adls International Limited. All rights reserved.
`
`Drug Invest. 8 (4) 1994
`
`Total no. of patient■
`Naul symptoms
`Mean
`SD
`Range
`
`(Missing)
`Eye symptoms
`Mean
`
`SD
`Range
`
`(Missing)
`Hud11Ch1
`Mean
`SD
`
`0.45
`
`0.38
`0.0101.0
`(30)
`
`0.56
`
`0:36
`
`O.Oto 1.0
`(30)
`
`0.86
`0.22
`
`0.46
`0.4
`O.Oto 1.0
`
`(29)
`
`0.57
`
`0.36
`
`0.0101.0
`
`(30)
`
`0.85
`
`--0.08 to 0.07
`
`--0.09 to 0.05
`
`--0.03 to 0.06
`
`0.25
`0.0101.0
`
`

`

`Fluticasone Propionate Alone and with Cetirizine
`
`229
`
`Table IV. Proportion of days for which rescue medication8 was not taken (total study population)
`
`Total no. of patients
`Mean
`
`FPANSalone
`227
`0.81
`
`FPANS plus cetirizine
`
`99% Confidence interval
`
`227
`0.82
`
`-0.05 to 0.10
`
`SD
`Range
`
`0.29
`0.00 to 1.0
`(48)
`(Missing)
`(54)
`a A score of 0 indicates rescue medication was required, a score of 1 indicates medication was not required every day.
`
`0.26
`0.00 to 1.0
`
`Abbreviations: FPANS = fluticasone propionate aqueous nasal spray 200µg once daily in the morning; FPANS plus cetirizine = fluticasone
`propionate aqueous nasal spray 200µg once daily in the morning plus one tablet of cetirizine 10mg.
`
`Methods
`
`At the initial clinic visit, investigators recorded
`demographic details for each patient together with
`a brief clinical history and an assessment of the
`severity of symptoms during the hayfever season
`of the previous year and the medication taken.
`Patients were reassessed at clinic visits follow(cid:173)
`ing 3 and 8 weeks' treatment.
`Patients were issued with a daily diary card on
`which to record scores for their nasal and eye
`symptoms, and headache. These symptoms were
`scored on a 10-point categorical rating scale,
`where 0 = no symptoms, 1-3 = mild symptoms, 4-6
`= moderate symptoms, and 7-9 = severe symp(cid:173)
`toms. Additionally, patients were asked to record
`their use of study medication, eye drops, and any
`other concurrent medication.
`At the end of the study, patients were asked
`whether or not they felt that study medication had
`adequately controlled nasal and eye symptoms and
`
`Table V. Percentage of patients reporting adequate control of
`symptoms
`
`Nasal symptoms
`Eye symptoms
`
`FPANSalone
`(n = 227)
`88%
`75%
`
`FPANS plus cetirizine
`(n =227)
`89%
`82%
`
`Headache
`
`86%
`83%
`Abbreviations: FPANS = fluticasone propionate aqueous nasal
`spray 200µg once daily in the moming; FPANS plus cetirizine =
`fluticasone propionale aqueous nasal spray 200µg once daily in the
`moming plus one tablet of cetirizi.ne 10mg.
`
`headache. The investigator was also asked to as(cid:173)
`sess the measure of success of the study treatment
`in controlling the symptoms of seasonal allergic
`rhinitis.
`
`Analysis
`
`Symptom~ (nasal symptoms, eye symptoms and
`headache) collected in the daily diary cards for
`weeks 3 to 8 inclusive (the period during which
`pollen count was the highest) were used in the as(cid:173)
`sessment of symptom scores and symptom-free
`days. Treatment groups were compared for all
`measures of efficacy using a normal test; confi(cid:173)
`dence intervals, 95% (symptoms) or 99% (use of
`rescue medication and overall assessments), were
`calculated using the appropriate standard error.
`For the analysis of the proportion of symptom(cid:173)
`free days and daily symptom scores, p values ~0.05
`were considered to indicate a statistically signifi(cid:173)
`cant result. For the analysis of the proportion of
`days free of relief medication and patient's and
`physician's assessment scores, p values ~0.01
`were considered to indicate a statistically signifi(cid:173)
`cant result.
`Results were analysed before and after exclud(cid:173)
`ing patients who violated the study protocol, and
`as the outcome of these analyses were similar, data
`collected for the total (intention-to-treat) popula(cid:173)
`tion are presented in this paper.
`
`e Adls International Limited. All rights reserved.
`
`Drug Invest. 8 (4) 1994
`
`

`

`230
`
`Benincasa & Lloyd
`
`Adverse Events
`
`Reports of adverse events were summarised as
`either serious (including anything requiring with(cid:173)
`drawal from the study) or minor, and tabulated.
`For the purpose of this study, a minor adverse
`event included events/symptoms requiring
`treatment, and therefore included reports of
`events/symptoms that were attributable to either
`seasonal allergic rhinitis or the use of other antihis(cid:173)
`tamines. Serious adverse events were defined as
`life-threatening events, death, events requiring or
`prolonging hospitalisation, events that were dis(cid:173)
`abling or incapacitating, congenital anomaly, can(cid:173)
`cer or drug overdose, or clinical or laboratory
`events leading to drug withdrawal.
`
`Results
`
`Study Population
`
`A total of 455 patients drawn from 64 general
`practices in the UK entered the study. One patient
`withdrew before the study medication was given
`and was not assigned to any treatment group. 227
`patients were allocated to each of the 2 treatment
`
`Table VI. Serious adverse event reports (total study population)
`FPANS
`FPANS plus
`cetirizine
`alone
`(n = 227)
`(n = 227)
`Total number of reports
`12(5%)
`10(4%)
`Drowsiness/tiredness/lethargy 2
`3
`Dizziness/nausea
`1
`0
`1
`Headache
`Exacerbation of rhinitis
`2
`Chest infection
`0
`Nasal condition
`0
`Epistaxis
`Shortness of breath
`Eye disorders
`Allergic rash
`Pain in joints
`Pregnancy
`0
`Ear disorders
`Abbreviations: FPANS = fluticasone propionate aqueous nasal
`spray 200µg once daily in the morning; FPANS plus cetirizine =
`fluticasone propionate aqueous nasal spray 200µg once daily in
`the morning plus one tablet of cetirizine 10mg.
`
`1
`0
`0
`0
`
`2
`0
`0
`
`Table VII. Most commonly reported minor adverse events
`Adverse event
`FPANS alone
`FPANS plus
`[no. of reports
`cetirizine
`(% of total)]
`[no. of reports
`(%of total)]
`64(22)
`14 (5)
`12(4)
`11 (4)
`
`82 (28)
`6 (2)
`10(3)
`10 (3)
`
`Headache
`Tiredness
`Tension headache
`Drowsiness/lethargy/
`sleepiness
`Acute nasopharyngitis
`Sore throat
`Epistaxis
`Eye disorders
`Exacerbation of rhinitis
`Upper respiratory tract
`infection
`Abbreviations: FPANS = fluticasone propionate aqueous nasal
`spray 200µg once daily in the morning; FPANS plus cetirizine =
`fluticasone propionate aqueous nasal spray 200µg once daily in the
`morning plus one tablet of cetirizine 10mg.
`
`12(4)
`6(1)
`8(3)
`13(4)
`10(3)
`8 (3)
`
`12(4)
`12 (4)
`12(4)
`9(3)
`7(2)
`9 (3)
`
`their demographic details are
`groups, and
`summarised in table I.
`The treatment groups were well balanced with
`respect to age, gender, and severity and duration of
`seasonal ailergic rhinitis, with the majority of pa(cid:173)
`tients in each group having a history of moderate
`or severe seasonal allergic rhinitis for more than 10
`years.
`During the hayfever season of the previous year,
`most patients in both groups had experienced nasal
`and eye symptoms, watering eyes being the most
`troublesome symptom. Previous use of medication
`for rhinitis was similar in the 2 groups (table I).
`
`Symptoms
`
`There were no significant differences between
`treatments at the 5% level in any of the symptoms
`or in the proportion of symptom-free days (tables
`II and III). All mean symptom scores were low,
`indicating that both treatments were successful in
`controlling the symptoms of seasonal allergic rhi(cid:173)
`nitis. An analysis of the proportion of symptom(cid:173)
`free days in the 6-week analysis period showed
`that, on average, patients were free of nasal symp(cid:173)
`toms for 45% of the time, eye symptoms for 56%
`of the time, and headache for 85% of the time.
`
`© Adls lnternotlonal Limited. All rights reserved.
`
`Drug Invest. 8 (4) 1994
`
`

`

`Fluticasone Propionate Alone and with Cetirizine
`
`231
`
`Use of Rescue Medication
`
`The proportion of days for which rescue medi(cid:173)
`cation (i.e. antazoline-xylometazoline eye drops)
`was not required was calculated over the 6-week
`analysis period. There was no evidence of any dif(cid:173)
`ference between treatments, with all patients re(cid:173)
`quiring extra eye medication on approximately
`20% of the days (table IV).
`
`Overall Assessments
`
`At the end of the study, patients were asked
`whether the study treatment had adequately con(cid:173)
`trolled their nasal, eye and headache symptoms,
`and their responses are summarised in table V. A
`high proportion of patients in both treatment
`groups (> 7 5 % ) found that all symptoms were ade(cid:173)
`quately controlled.
`The investigator was asked to determine the
`success or failure of treatment on the basis that any
`patient who withdrew from the study because of
`inadequate symptom control constituted a treat(cid:173)
`ment failure. 12 patients (7 in the FPANS group
`and 5 in the FPANS plus cetirizine group) with(cid:173)
`drew on these grounds. Overall, both treatments
`were rated as successful for the majority of patients
`(FPANS 83%, FPANS plus cetirizine 86% ).
`
`Withdrawals
`
`67 patients (15%) were withdrawn from the
`study; 37 from the FPANS group and 30 from the
`FPANS plus cetirizine group. Some of these
`patients gave more than one reason for withdrawal,
`and these may be grouped as follows: adverse
`events ( 19 per group), failure to attend or noncom(cid:173)
`pliance (27 in the FPANS group and 11 in the
`FPANS plus cetirizine group), 'other' reasons (3 in
`the FPANS group and 6 in the FPANS plus cetiriz(cid:173)
`ine group).
`
`Adverse Events
`
`Safety data were collected from the whole of the
`8-week treatment period.
`A total of 21 patients (5%) reported 22 serious
`adverse events (12 in the FPANS group and 10 in
`
`the FPANS plus cetirizine group). These events
`were evenly distributed between the 2 groups (ta(cid:173)
`ble VI) and, of these, 1 event (drowsiness) in the
`FPANS group and 4 events (itching/soreness of
`eyes, epistaxis, exacerbation of rhinitis) in the
`FPANS plus cetirizine group were judged to be
`almost certainly related to study medication. A
`further 6 events in the FPANS group and 2 in
`the FPANS plus cetirizine group were regarded
`as either possibly or probably related to study
`medication.
`A total of 295 minor adverse events were re(cid:173)
`ported by 124 patients in the FPANS group (55%),
`while 286 events were reported by 133 patients in
`the FPANS plus cetirizine group (59%). The ma(cid:173)
`jority of these events were generally associated
`with the symptoms of seasonal allergic rhinitis. 14
`(5%) of these reports in the FPANS group and 17
`( 6%) in the FPANS plus cetirizine group were con(cid:173)
`sidered to be almost certainly related to study treat(cid:173)
`ment. Additionally, a further 40 (14%) in the
`FPANS group and 54 (19%) in the FPANS plus
`cetirizine group were considered either probably
`or possibly related to treatment.
`The most frequently reported adverse event was
`heada~he, with slightly more headaches being re(cid:173)
`ported by patients in the FPANS group (82 reports)
`than in the FPANS plus cetirizine group (64 re(cid:173)
`ports; table VII). A comparison of these data with
`the efficacy data shows that this symptom proved
`troublesome for a few patients only. There were
`more reports of tiredness in the FPANS plus
`cetirizine group (14 reports) than in the FPANS
`alone group (6 reports).
`
`Discussion
`
`The results of this study show that there is no
`significant difference in efficacy between FPANS
`200µg taken once daily in the morning and FPANS
`200µg plus cetirizine 10mg taken once daily in the
`morning in controlling the symptoms of seasonal
`allergic rhinitis. Both treatments were effective in
`preventing symptoms for more than half the time
`studied and the low overall mean symptom scores
`showed that the symptoms recorded were gener-
`
`© Adls International Limited. All rlgh!s reserved.
`
`Drug Invest. 8 (4) 1994
`
`

`

`232
`
`Benincasa & Lloyd
`
`ally mild in severity. Overall assessments by the
`investigator indicated that treatment had been ef(cid:173)
`fective for more than 80% of patients in both
`groups, and the patients' own global assessment of
`treatment revealed that for more than 75% of
`patients in each treatment group, headache and na(cid:173)
`sal and eye symptoms had been adequately control(cid:173)
`led. This is in contrast to a study reported by
`Drouin et aI.,l14l in which there was an indication
`of an increased benefit in symptom control using a
`combination of intranasal corticosteroid and Hz(cid:173)
`antagonist. However, it is difficult to compare
`studies as both the drugs under investigation and
`methods employed were different to the study re(cid:173)
`ported here.
`A combined pollen count was not available for
`this study, primarily because of the wide variation
`in counts between rural and suburban centres.
`However, treatment for this study commenced in
`mid-May and continued through the months of
`June and July, a period that coincides with the
`hayfever season in the UK. Furthermore, the anal(cid:173)
`ysis of severity and incidence of symptoms were
`assessed during the period when, historically, pol(cid:173)
`len counts are at their highest (weeks 3 to 8).
`Patients were free of eye symptoms for approx(cid:173)
`imately 56% of the study period in both treatment
`groups. This was reflected in the low usage of res(cid:173)
`cue medication eye drops, which for both treat(cid:173)
`ments were only required for approximately 20%
`of the study period. Previous reports on the effects
`of FPANS on ocular symptoms have been contra(cid:173)
`dictory.l 15,16l Dolovich and colleaguesl15l found
`that eye symptoms were improved with fluticasone
`propionate compared with placebo, whereas
`Darnelll16l found that neither fluticasone propio(cid:173)
`nate nor terfenadine showed any improvement
`compared with placebo. FPANS is unlikely to have
`a direct effect on eye symptoms because its action
`is local, with negligible systemic activity.l 101 Im(cid:173)
`provements in ocular symptoms following treat(cid:173)
`ment with FPANS probably occur as the result of
`a retrograde passage of the corticosteroid via the
`nasolacrimal duct or psychological or reflex ef(cid:173)
`fects secondary to the relief of nasal symptoms. [SJ
`
`Nevertheless, the control of ocular symptoms that
`occurred in this study following treatment with
`FPANS alone or in combination with the antihista(cid:173)
`mine, cetirizine, occurred in a population who had
`found that eye symptoms were the most trouble(cid:173)
`some symptom they had experienced in the pre(cid:173)
`vious hayfever season.
`The number of patients who experienced seri(cid:173)
`ous adverse events (including those leading to
`withdrawal of study medication) in the FPANS and
`FPANS plus cetirizine groups was 5 and 4%, re(cid:173)
`spectively. Minor adverse events were generally
`associated with the symptoms of seasonal allergic
`rhinitis, headache being the most· commonly re(cid:173)
`ported minor adverse event. When these data were
`compared with the efficacy data showing the pa(cid:173)
`tients were free of headache for approximately
`85 % of the study period, it was revealed that in fact
`headache was a troublesome symptom for a few
`patients only.
`
`Conclusion
`In conclusion, this study suggests that there is
`no significant difference in efficacy between
`FPANS 200µg taken on its own once daily in the
`morning, and FPANS 200µg once daily in combi(cid:173)
`nation with oral cetirizine 10mg in the prophylactic
`treatment of seasonal allergic rhinitis.
`
`Acknowledgements
`This study was funded by Allen and Hanburys Ltd,
`Uxbridge, Middlesex, UK.
`
`References
`l. Davies R. Seasonal rhinitis in rhinitis mechanisms and manage(cid:173)
`ment. I Mackay, editor. Royal Society of Medicine 1989: 97-
`116
`2. Sibbald B. Epidemiology of seasonal and perennial rhinitis:
`clinical presentation and medical library. Thorax 1991; 46:
`895-901
`3. Allergy: conventional and alternative concepts. A report of the
`Royal College of Physicians Committee on Clinical Immu(cid:173)
`nology and Allergy. Clio Exp Allergy 1992; 22: Suppl. 3
`4. Horak F. Seasonal allergic rhinitis. Newer treatment ap(cid:173)
`proaches. Drugs 1993; 45 (4): 518-27
`5. Bryson HM, Faulds D. Intranasal fluticasone propionate. A re(cid:173)
`view of its pharmacodynamic and pharmacokinetic properties
`
`© Adis International Limited. All rights reserved.
`
`Drug Invest. 8 (4) 1994
`
`

`

`Fluticasone Propionate Alone and with Cetirizine
`
`233
`
`and therapeutic potential in allergic rhinitis. Drugs 1992;
`43(5): 760-75
`6. Laforce C, Dockhom R, Findlay S, et al. Fluticasone propionate
`treatment for seasonal allergic rhinitis is safe and effective in
`adults and adolescents. Abstract 60. J Allergy Clio Immunol
`1991; 87 (I: Pt 2): 153
`7. Ratner PH, Paull BR, Findlay SR, et al. Fluticasone propionate
`once daily is as effective as beclomethasone dipropionate
`twice daily in relieving symptoms of seasonal allergic rhini(cid:173)
`tis. Clio Exp Allergy 1990; 20 Suppl. 1: 98
`8. Johannessen TA. A comparison of fluticasone propionate,
`flunisolide and placebo in patients with seasonal allergic rhi(cid:173)
`nitis to birch pollen - a multi-centre trial. Clio Exp Allergy
`1990; 20 Suppl. I: 102
`9. Cramer JA, Mattson RH, Prevey ML, et al. How often is med(cid:173)
`ication taken as prescribed? A novel assessment technique.
`JAMA 1989; 261: 3273-7
`10. Harding SM. The human pharmacology of fluticasone propio(cid:173)
`nate. Respiratory Medicine 1990; 84 Suppl. A: 25-9
`11. Harding SM. Human pharmacology offluticasone. Abstract no.
`AS 04. 04. Allergologie 1989; 12: 77
`
`12. Davies BH, Mullins J, Couch HA. A comparison of cetirizine
`(Zirtek) and terfenadine (Triludan). Clio Trials J 1989; 26:
`100-7
`13. Beswick KBJ, Kenyan GS, Cherry JR. A comparative study of
`beclomethasone aqueous nasal spray with terfenadine tablets
`in seasonal allergic rhinitis. Curr Med Res Opin 1985; 9: 560-
`7
`14. Drouin MA. Is there a benefit to add loratidine to topical nasal
`steroids in patients with moderately severe seasonal allergic
`rhinoconjunctivitis? Allergy 1992: Suppl. 12 (47): 172
`15. Dolovich J, Anderson M, Chodirker W, et al. Fluticasone pro(cid:173)
`pionate: a large multi-centre trial. Respir Med 1990; 84 Suppl.
`A: 31-2
`16. Darnell R. Multi-centre study of fluticasone propionate aque(cid:173)
`ous nasal spray and terfenadine tablets in seasonal rhinitis.
`Clio Exp Allergy 1990; 20 Suppl. I: IOI
`
`Correspondence and reprints: Mr C. Benincasa, Allen &
`Hanburys Ltd, Stockley Park West, Uxbridge, Middlesex
`UBll lBT, England.
`
`© Adls International Limited. All rights reserved.
`
`Drug Invest. 8 (4) 1994
`
`