Important Considerations in Selecting an Antihistamine

1
Important Considerations in Selecting an
Antihistamine
2
Case 1

• 34-year-old teacher
• Chief complaints runny nose/itchy nose/ itchy
  eyes/sneezing
• What further history is needed?
• What time of year do the symptoms occur?
• Early and late spring
• Late summer and early fall, especially sneezing
  and eye symptoms
• Some symptoms are always present, especially
  rhinorrhea

3
Case 1

• Do the symptoms occur both indoors and outdoors?
• Outdoor symptoms are worse on beautiful sunny
  days in the spring and late summer
• Indoor symptoms are worse when around someone
  vacuuming the carpet or making a bed
• Any use of cigarettes?
• Any pets at home?
• Any cockroach exposure?
• No

4
Case 1

• What time of day are symptoms worse?
• At night and in the morning
• Nose and eyes itch all night
• Sometimes awakens from sleep due to symptoms
• Feels tired upon awakening in the morning,
  especially during the spring and late summer
• Sometimes feels like not going to work due to
  symptoms in the morning

5
Case 1

• Any symptoms during your childhood or teenage
  years?
• Symptoms worse for the past 5 years, but
  remembers hay fever as a teenager for several
  years
• Any family history of hay fever, asthma, eczema
  in parents or siblings?
• Both parents have similar nasal and ocular
  symptoms a sister has asthma

6
Case 1

• What treatments have you tried?
• Over-the-counter diphenhydramine- and
  chlorpheniramine-containing products. They have
  caused drowsiness and dry mouth. The drowsiness
  has a negative impact on his daily activities.
• What is the preliminary diagnosis? Why?

7
Case 1

• Diagnosis
• Perennial allergic rhinitis with seasonal
  exacerbations
• Seasonal allergic rhinoconjunctivitis
• Basis for diagnosis
• Seasonal and perennial symptoms
• Nasal plus eye involvement with itching suggests
  allergy
• Family history and onset before age 20 suggests
  allergy

8
Case 1

• What else should you ask in the history?
• History of asthma coughing, wheezing, shortness
  of breath, nocturnal awakening by cough,
  exercise-induced dyspnea?
• Rationale allergic rhinitis is often associated
  with asthma, with 3858 of allergic rhinitis
  patients having either clinical asthma symptoms
  or evidence of lower airway hyper-reactivity.1,2
  

1. Mullarkey M. J Allergy Clin Immunol,
198065122-126. 2. Smith JM. In Middleton E, et
al, eds. Allergy Principles and Practice. 3rd
ed. St. Louis, Mo CV Mosby Company
19882892-929.
9
Case 1

• Physical exam
• Blood pressure, pulse, temperature normal
• Ocular exam injected sclerae and cobblestoning
  of conjunctiva
• Nasal exam pale, bluish mucosa with watery
  serous discharge and edematous turbinates no
  colored discharge
• Ears normal tympanic membranes
• Oral exam no increased tonsils or adenoids
• Neck no adenopathy
• Lungs clear
• Skin without rashes or dermatitis

10
Case 1

• Any diagnostic testing? If so, what?

• Either skin test or allergen-specific IgE blood
  test for relevant inhalant allergens
• Consider spirometry (WHO Guidelines ARIA all
  patients with allergic rhinitis assessed for
  asthma)

• Results
• Positive for IgE directed against tree, grass,
  and weed pollens, and against dust mite
• No evidence of cat, dog, or mold-related IgE
  reactivity

11
Case 1

• What do you advise the patient?

• Environmental precautions
• Perennial allergens dust mites
• Plastic mattress and pillow encasement
• Eliminate carpeting and draperies and stuffed
  furniture
• Wash bedding at high temperature (gt130? F)
• Frequent cleaning of floors and furniture
  surfaces
• Use a dehumidifier
• Vacuum with a hepa-filterequipped vacuum

12
Case 1

• Seasonal allergens Pollens
• Keep windows closed at night during pollen season
• Use a room hepa-filter air cleaner or window air
  conditioner
• Avoid early morning outdoor exercise (when pollen
  count is highest)

13
Case 1

• What might influence the initial therapeutic
  options?
• Patient is a teacher wants to avoid drowsiness
  has not tolerated sedating antihistamines
• Patient has both seasonal and perennial symptoms
• Patient has both nasal and ocular symptoms
• Patient feels worse upon awakening in the morning
• What are the therapeutic options and issues?
• First-line treatment consider use of oral
  nonsedating antihistamines for both nasal and
  ocular symptoms
• Intranasal corticosteroids would relieve nasal
  symptoms but not be very effective for the
  non-nasal symptoms

14
Case 1

• Among the prescription antihistamines, consider
  the following
• Cetirizine may cause drowsiness, although it is
  approved for both SAR and PAR
• Fexofenadine is nonsedating, but is not indicated
  for PAR
• Desloratadine is the only Rx nonsedating
  antihistamine approved for both SAR and PAR
• Desloratadine has demonstrated efficacy at the
  end of the dosing interval (through to the next
  morning after morning dosing) for relief of both
  nasal and non-nasal symptoms in SAR and PAR

15
Definition and Prevalence of Allergic Rhinitis

• Group of nasal disorders characterized by 1 or
  more symptoms1
• Sneezing Nasal itching
• Rhinorrhea Nasal congestion
• Allergic rhinitis
• Most common type of chronic rhinitis
  (inflammation of the nasal mucous membranes)
• Affects up to 40 million Americans2
• Remains constant in young adults but gradually
  declines in later years3

1. Dykewicz MS. J Allergy Clin Immunol.
2003111S520-S529. 2. Dykewicz MS, et al. Ann
Allergy Asthma Immunol. 199881(5, pt
2)478-518. 3. Fireman P. Allergic rhinitis. In
Atlas of Allergies. Philadelphia, Pa JB
Lippincott Co 19919.2-9.18.
16
Definition and Prevalence of Allergic Rhinitis

• 40 of cases of allergic rhinitis are PAR1
• 40 of cases of allergic rhinitis are a combined
  SAR and PAR1
• 20 of cases of allergic rhinitis are SAR1
• No seasonal variation in PAR symptoms, but
  seasonal allergens can cause exacerbations
• 38 to 58 of allergic rhinitis patients also
  have asthma2,3

1. Skoner D. J Allergy Clin Immunol.
2001108S2-S8. 2. Mullarkey M. J Allergy Clin
Immunol, 198065122-126. 3. Smith JM. In
Middleton E, et al, eds. Allergy Principles and
Practice. 3rd ed. St. Louis, Mo CV Mosby
Company 19882892-929.
17
Clinical Features That Distinguish Seasonal and
Perennial Allergic Rhinitis (SAR and PAR)

• SAR
• Symptoms occur or increase at certain seasons and
  correlate with presence of seasonal allergens
• Watery rhinorrhea Pruritus of eyes, nose,
• Nasal congestion ears, throat
• Repetitive sneezing Watery eyes
• Patients may not present with all symptoms

The Allergy Report, 2000, Vol. 2
18
Clinical Features That Distinguish Seasonal and
Perennial Allergic Rhinitis (SAR and PAR)

• PAR
• Symptoms are intermittent or continuous
  throughout year
• Prominent and severe nasal blockage/congestion
• Postnasal discharge
• Clear rhinorrhea, sneezing less prominent than in
  SAR
• Pruritus of eyes and throat less frequent than in
  SAR
• Perennial symptoms may also be accompanied by
  seasonal exacerbations

The Allergy Report, 2000, Vol. 2 Skoner D. J
Allergy Clin Immunol. 2001108S2-S8.
19
Natural History of Allergic Rhinitis
20
Continuing Evolution of AntihistaminesDistinct
Chemical Entities

• Metabolites have different characteristics than
  their mother compound
• Hydroxyzine Cetirizine
• Active metabolite of hydroxyzine
• Sedation potential reduced, but not eliminated
• Terfenadine Fexofenadine
• Active metabolite of terfenadine
• No statistically significant prolongation of QT
  interval
• Loratadine Desloratadine
• Active metabolite of loratadine
• Half-life 27-hours

Zyrtec package insert, Pfizer Inc. Oppenheimer
JJ, et al. Expert Opin Invest Drugs.
200211807-817. Norman P, et al. Drugs Today
(Barc). 200137215-227.
21
Continuing Evolution of Antihistamines
Hydroxyzine
Yes (cetirizine)
Active metabolites?
3 h (up to 20 h)
Elimination t½
Severe sedation (used as a sedative), fatigue,
dry mouth
Adverse effects
CNS depressants, anticholinergics
Interactions
Atarax (hydroxyzine) prescribing information,
Pfizer Inc.
22
Continuing Evolution of Antihistamines
Cetirizine
Negligible
Active metabolites?
8.3 h
Elimination t½
Mild-to-moderate sedation, fatigue, dry mouth
Adverse effects
Not clinically relevant
Interactions
Zyrtec (cetirizine) prescribing information
Pfizer Inc.
23
Continuing Evolution of Antihistamines
Terfenadine
Yes (fexofenadine)
Active metabolites?
16-23 h
Elimination t½
QT interval prolongation
Adverse effects
Erythromycin, Ketoconazole ? AUC
Interactions
24
Continuing Evolution of Antihistamines
Fexofenadine
No
Active metabolites?
14.4 h
Elimination t½
Similar to placebo
Adverse effects
Interactions
Erythromycin 109 AUC Ketoconazole 164 AUC
Not clinically relevant
Should not be taken closely in time with
aluminum- and magnesium-containing antacids (-41
AUC)
Allegra package insert, Aventis Inc.
25
Continuing Evolution of Antihistamines
Loratadine
Desloratadine
Active metabolites?
8.4 h
Elimination t½
Similar to placebo
Adverse effects
Interactions
Erythromycin 40 AUC Ketoconazole 307 AUC
Cimetidine 109 AUC Not clinically relevant
Data on file Schering Corporation.
26
Continuing Evolution of Antihistamines
Desloratadine
3-hydroxydesloratadine
Active metabolites?
27 h
Elimination t½
Similar to placebo
Adverse effects
Interactions
Erythromycin 14 AUC Ketoconazole 39 AUC
Cimetidine 19 AUC Not clinically relevant
CLARINEX package insert Schering Corporation.
27
Continuing Evolution of Antihistamines
Conclusions

• Active metabolite antihistamines are distinct
  chemical entities
• Drug interaction and pharmacokinetic parameters
  can change compared with parent antihistamines

CLARINEX package insert, Schering Corporation.
28
Continuing Evolution of Antihistamines
Conclusions (cont)

• CLARINEX (desloratadine) has
• No clinically relevant interaction with food or
  other drugs
• A side effect profile similar to placebo
• A long duration of action that allows for
  once-daily dosing
• A long 27-hour half-life

29
Allergy Symptom Severity by Time of Day
Time of Day at which Symptoms Are Most Severe

Binder E, et al. Allergy. 198237389-396.
30
Allergy Symptoms Are at Their Worstin the Morning

• Most AR patients report symptom severity is worse
  in the morning1
• Pollen concentrations are usually highest between
  5 AM and 10 AM2
• In patients with AR, sneezing, congestion,
  itching most frequently commence before
  breakfast1
• Also, like many illnesses, AR is influenced by
  circadian rhythms1

1. Smolensky MH, et al. J Allergy Clin Immunol.
1995951084-1096. 2. American Academy of
Allergy, Asthma, Immunology Available at
www.epa.gov/iaq/pubs/moldresources.html.
31
Circadian Variation in Rhinitis Symptoms

• AR symptoms vary during the day,
• but are most severe during the morning hours

10
12
12
Arbitrary Units
12
8
10
10
6
5
Time (Clock Hours)
Time (Clock Hours)
Time (Clock Hours)
Time (Clock Hours)
Peak-to-trough differences were statistically
significant (Plt0.008).
Reinberg A, et al. J Allergy Clin Immunol.
19888151-62.
32
CLARINEX (desloratadine) in SAR in the Spring
and Fall Allergy SeasonsDesign

• Assessing CLARINEX efficacy and safety in
  patients with moderate to severe SAR during
  spring and fall seasons
• Two separate studies
• Spring (n 346)
• Fall (n 328)
• Patients 12 years of age or older
• Minimum 2-year history of SAR
• Clinically symptomatic SAR (moderate to severe)
  at screening baseline
• Treatments CLARINEX 5 mg QD or placebo QD x
  14 d

Meltzer EO, et al. Clin Drug Invest.
20012125-32.
33
Morning Efficacy of CLARINEX (desloratadine) in
SAR Spring Allergy Season Improvement in
Symptoms vs Placebo After First Dose
93 Mean Change From Baseline (CLARINEX vs
Placebo) in AM Instantaneous Total Symptom
Scores (TSS)
At baseline, a total nasal symptom score (sum of
4 individual symptoms) of at least 6 and a total
non-nasal symptom score (sum of 4 individual
symptoms) of at least 5 (each symptom scored 0 to
3 where 0no symptoms and 3severe symptoms) was
required for trial eligibility. TSS ranges from
0no symptoms to 24maximum symptoms. Baseline
AM instantaneous symptom score was 14.2 for
desloratadine 5 mg patients and 13.7 for placebo
patients The AM instantaneous symptom score
measured how subjects felt at the moment of
assessment (upon awakening 24 hours after the
last dose)
-3
Plt0.01
DL Placebo
Mean Change From Baseline in AM Instantaneous
TSS
(n172) -2.9
-2
(n174) -1.5
-1
0.0
Meltzer EO, et al. Clin Drug Invest.
20012125-32. Data on file, Schering Corporation.
34
CLARINEX (desloratadine) in SAR in the
SpringEfficacy
Primary endpoint
Meltzer EO, et al. Clin Drug Invest.
20012125-32.
35
CLARINEX (desloratadine) in SAR in the
SpringEfficacy
AM Instantaneous TSS (2-Week Average)
Meltzer EO, et al. Clin Drug Invest. 2001
21(1)25-32. Data on File, Schering Corporation.
36
CLARINEX (desloratadine) in SAR in the Spring
Efficacy Symptom Relief vs Placebo
Primary Efficacy Variable AM/PM Reflective TSS
Meltzer EO, et al. Clin Drug Invest.
20012125-32.
37
Efficacy and Safety of CLARINEX (desloratadine)
in Patients With SAR
Data on File, Schering Corporation. Meltzer EO,
et al. Clin Drug Invest. 20012125-32.
38
CLARINEX (desloratadine) in SAR in the Fall
Allergy Season Efficacy

• Results similar to those in spring allergy season
  study
• CLARINEX significantly more effective than
  placebo in reducing AM/PM reflective 12-hour TSS
  (P0.02)
• CLARINEX significantly more effective than
  placebo in reducing total nasal symptom scores
  (Plt0.05)
• CLARINEX significantly more effective than
  placebo in reducing total non-nasal symptom
  scores (P 0.04)

Meltzer EO, et al. Clin Drug Invest.
20012125-32.
39
CLARINEX (desloratadine) in SAR in the Spring
and Fall Allergy SeasonsAdverse Events
Comparable to Placebo
Patients
Fall
Spring
CLARINEX 5 mg 16 3 3 0 3
CLARINEX 5 mg 24 7 5 6 2
Placebo 14 2 2 2 2
Placebo 27 3 1 7 2
Adverse Event Headache Pharyngitis Dry
mouth Dysmenorrhea Somnolence
Occurring in ?5 of patients in any individual
study group, without regard to relationship to
treatment.
Meltzer EO, et al. Clin Drug Invest.
20012125-32.
40
CLARINEX (desloratadine) in SAR Summary

• CLARINEX 5 mg QD significantly improved spring
  and fall allergy symptoms vs placebo
• After the first dose, efficacy was demonstrated
  at the end of the dosing interval (24 hours),
  allowing patients to wake up with symptoms under
  control
• CLARINEX adverse events were similar to placebo
• CLARINEX 5 mg QD is indicated for the relief of
  the nasal and non-nasal symptoms of SAR in
  patients 12 years of age and older

41
CLARINEX (desloratadine) in PARDesign

• 4-week randomized, double-blind,
  placebo-controlled trial to assess desloratadine
  efficacy and safety in relieving the symptoms of
  PAR
• 676 patients with PAR
• 11 to 79 years of age with 2-year history of
  moderate to severe PAR, with positive skin tests
• Clinically symptomatic at screening
• Assessments
• Primary efficacy variable mean change from
  baseline in average AM/PM instantaneous total
  symptom score (TSS) over 4 weeks of treatment
• AM/PM reflective TSS and nasal and non-nasal TSS

Simons FE. J Allergy Clin Immunol.
2003111617-622.
42
CLARINEX (desloratadine) in PARNasal Symptom
Scores
AM/PM Instantaneous Total Nasal Symptom Scores
(Excluding Congestion)
Plt0.001 Plt0.017
Simons FE. J Allergy Clin Immunol.
2003111617-622. Data on file Schering
Corporation.
43
CLARINEX (desloratadine) in PARNon-Nasal
Symptom Scores
AM/PM Reflective Total Non-Nasal Symptom Scores
Plt0.037
Data on file Schering Corporation.
44
CLARINEX (desloratadine) in PAR Adverse Events
Similar to Placebo
Occurring in ?2 of patients in any individual
study group, without regard to relationship to
treatment.
Simons FE. J Allergy Clin Immunol.
2003111617-622.
45
CLARINEX (desloratadine) in PAR Summary

• CLARINEX is the only prescription nonsedating
  antihistamine approved for moderate to severe PAR
• CLARINEX 5 mg QD provides effective relief of
  nasal and non-nasal symptoms of moderate to
  severe PAR
• CLARINEX efficacy was demonstrated
  instantaneously at the 24th hour as well as
  throughout the dosing interval (24 hours)

Data on file Schering Corporation. Simons FE. J
Allergy Clin Immunol. 2003111617-622.
46
CLARINEX (desloratadine) Summary of Adverse
Events Similar to Placebo
of Patients
DL 5 mg (n1655)
Placebo (n1652)
Adverse event
Pharyngitis 4.1 2.0
Dry mouth 3.0 1.9
Myalgia 2.1 1.8
Fatigue 2.1 1.2
Somnolence 2.1 1.8
Dysmenorrhea 2.1 1.6
Occurring in ?2 of patients in any individual
study group, without regard to relationship to
treatment.
CLARINEX package insert. Kenilworth, NJ
Schering Corp.
47
CLARINEX (desloratadine) in CIU Study 1 Design

• 6-week randomized, double-blind,
  placebo-controlled trial
• 190 patients 12 to 79 years of age
• gt6 weeks history of moderate to severe CIU and
  experiencing an active flare
• CIU wheals present ?3 days/week and at screening
• Disease of at least moderate severity at
  screening
• At least moderate pruritus at screening and
  baseline
• CLARINEX 5 mg or placebo QD x 6 weeks

Ring J, et al. Int J Dermatol. 20014072-76. Ring
J, et al. Allergy. 20015628-32. Data on file
Schering Corporation.
48
CLARINEX (desloratadine) in CIU Study 1 Design
(cont)

• Primary efficacy variable mean AM/PM reflective
  patient diary score for pruritus over the first
  week of treatment
• Additional assessments
• Improvement in symptoms (scored twice daily)
• Severity of symptoms now (AM instantaneous)
• Severity of symptoms in past 12 hours (AM/PM
  reflective)
• Number of hives, size of largest hive, total
  symptom score
• Interference with sleep and daily activities

Ring J, et al. Int J Dermatol. 20014072-76. Ring
J, et al. Allergy. 20015628-32. Data on file
Schering Corporation.
49
CLARINEX (desloratadine) in CIU Study
1Improvement in AM/PM Reflective Pruritus Score
Day 2
Week 1
Week 6
CLARINEX
0
Placebo
-10
Plt0.001
-20
-30
Primary endpoint
Reduction From Baseline
-40

-50

-60
-70

-80
Ring J, et al. Int J Dermatol. 20014072-76.
Ring J, et al. Allergy. 20015628-32. Data on
file, Schering Corporation.
50
CLARINEX (desloratadine) in CIU Study 1Number
and Size of Hives
Ring J, et al. Allergy. 20015628-32.
51
CLARINEX (desloratadine) in CIU Study
1Symptom-Related Interference With Sleep
Ring J, et al. Int J Dermatol. 20014072-76.
52
CLARINEX (desloratadine) in CIU Study
1Symptom-Related Interference With Daily
Activities
After 1 dose
Week 1
Week 2
Week 3
Week 4
Week 5
Week 6
0
20

P0.020 ?Plt0.001
40
Reduction From Baseline
60
?
?
?
80
?
?
?
100
Ring J, et al. Int J Dermatol. 20014072-76.
53
CLARINEX (desloratadine) in CIUSummary

• CLARINEX 5 mg QD was significantly more
  effective than placebo in improving
• Pruritus
• Number of hives
• Size of largest hive
• Total symptom scores
• Interference with sleep and daily activities
• No significant adverse events reported

Ring J, et al. Int J Dermatol. 20014072-76. Ring
J, et al. Allergy. 20015628-32.
54
CLARINEX (desloratadine) in CIU Summary of
Adverse Events in Adult and Adolescent Patients



Reported by 2 of patients in either group.
CLARINEX package insert, Schering Corporation.
55
Efficacy of Prescription Antihistamines
Desloratadine is the only nonsedating
prescription antihistamine approved for the
treatment of PAR
Not contained in Allegra labeling.
CLARINEX package insert, Schering Corporation.
Zyrtec package insert, Pfizer Inc. Allegra
package insert, Aventis Pharmaceuticals, Inc.
56
Sedation Profiles for Prescription Antihistamines
CLARINEX package insert, Schering
Corporation. Allegra package insert, Aventis
Pharmaceuticals, Inc. Zyrtec package insert,
Pfizer Inc.
57
Food Effects on Antihistamines

• CLARINEX (desloratadine) and CLARINEX-D 24 HOUR
  (desloratadine 5 mg and pseudoephedrine sulfate,
  USP 240 mg) Extended Release Tablets
• Bioavailability unaffected by grapefruit juice
• No precautions regarding food
• According to the Allegra-D (fexofenadine and
  pseudoephedrine) prescribing information
• Based on the population pharmacokinetics analysis
  of the combined data from grapefruit and orange
  juice studies with the bioequivalence study data,
  the bioavailability of fexofenadine was reduced
  by 36
• clinical significance is unknown
• gt50 reduction in fexofenadine absorption when
  taken with a high-fat meal
• The rate or extent of pseudoephedrine absorption
  was not affected by food
• It is recommended that Allegra-D be administered
  on an empty stomach with water.

Allegra-D package insert, Aventis
Pharmaceuticals Inc. Banfield C, et al. Clin
Pharmacokinet. 200241311-318. CLARINEX package
insert, Schering Corporation. CLARINEX-D 24 HOUR
package insert, Schering Corporation.
58
DesloratadineNo Clinically Relevant
Interactions With Commonly Used Medications
After 23-day pretreatment period.
CLARINEX package insert, Schering Corporation.
59
Drug-Drug Interaction Potential

• Effects of Concomitant Medications on
  Fexofenadine AUC
• Two studies, each with 24 healthy volunteers,
  evaluated fexofenadine 120 mg BID (2 times
  recommended dose) coadministered with
• Erythromycin 500 mg q8h
• Resulted in fexofenadine AUC of 109
• Ketoconazole 400 mg QD
• Resulted in fexofenadine AUC of 164

There is no restriction in the Allegra package
insert on concomitant use of erythromycin or
ketoconazole.
Allegra, package insert, Aventis Pharmaceuticals
Corporation.
60
Drug-Drug Interaction Potential (cont)

• Effect of OTC Antacids
• A study evaluating fexofenadine 120 mg
  administered within 15 minutes of dosing with
  aluminum- and magnesium-containing antacid
  demonstrated a reduction of fexofenadine AUC of
  41
• 72 of allergic rhinitis sufferers surveyed have
  taken aluminum- and magnesium-containing antacids
• Allegra (fexofenadine) labeling precautions
• Allegra should not be taken closely in time with
  aluminum- and magnesium-containing antacids
• CLARINEX (desloratadine) has no precautions
  regarding antacids

Allegra package insert, Aventis Pharmaceuticals
Inc. CLARINEX package insert, Schering
Corporation. Usage of Antacid Medications Among
Allergy Sufferers. Survey. Conducted by Harris
Interactive Inc. NY, May 2004.
61
Pediatric CLARINEX (desloratadine) Syrup

• Only nonsedating antihistamine indicated for
  children as young as 6 months of age
• Indicated for the treatment of PAR
• in children ? 6 months of age
• Indicated for the treatment of SAR
• in children ? 2 years of age
• Indicated for the treatment of CIU
• in children ? 6 months of age
• Pleasant-tasting (bubble gum)

CLARINEX package insert, Schering Corporation.
62
Safety of CLARINEX (desloratadine)in Children
Aged 2 to 11 Years
In pediatric patients 6 months to 5 years of age,
the most frequently seen adverse events were
upper respiratory tract infection, diarrhea,
fever, urinary tract infection, and
varicella. Number of subjects reporting
treatment-emergent adverse events at least once
during the study. Without regard to relationship
to study drug.
Bloom M, et al. Current Med Res Opin. 2004 Vol 20
No.12 1959-1965
63
Comparison of Prescription Antihistamines
Non-sedating
CIU
PAR
SAR
?
CLARINEX (desloratadine)
?
?
?
gt 6 mos and older
gt 2 yrs old
gt 6 mos and older
?
Allegra 180 (fexofenadine)


?
gt 6 yrs old
Zyrtec (cetirizine)
?
?

?
gt 2 yrs old
gt 6 mos and older
gt 6 mos and older
CLARINEX package insert, Schering
Corporation. Allegra package insert, Aventis
Pharmaceuticals, Inc. Zyrtec package insert,
Pfizer Inc.
64
CLARINEX (desloratadine)Summary/Conclusions

• Nonsedating efficacy in the treatment of patients
  with moderate-to-severe
• Spring and fall SAR
• PAR
• CIU
• Morning relief in SAR and PAR
• Adverse events similar to placebo
• No precautions regarding antacids, high-fat diets
• No clinically relevant interactions with
  Erythromycin, Ketoconazole, Azithromycin,
  Fluoxetine, and Cimetidine
• No impairment while driving

65
CLARINEX (desloratadine)Summary/Conclusions

• CLARINEX family of products
• Tablets
• Pleasant-tasting syrup (bubble gum)
• RediTabs tablets
• 24-hour decongestant formulation
• Effective symptom relief
• Patients wake up with symptoms under control
• Nonsedating/nonimpairing while driving
• Can be taken without regard to food
• Well tolerated
• Long half-life (27 hours)

66
Case 2

• 21-year-old college student from New England
• Chief complaint sneezing spasms and nasal/ocular
  itching every year in the spring symptoms worsen
  by the summer to include nasal stuffiness
  accompanied by excess mucus in the nose and
  throat
• History of present illness
• Symptoms have occurred for the past 10
  yearstypically April-July
• Awakens feeling fatigued
• Tried Zyrtec (cetirizine) but found that she
  experienced sedation and it did not control nasal
  congestion
• Prefers a drug that she only has to take
  once per day

67
Case 2

• Further questions?
• Family history of allergies or asthma?
• Brother with hay fever no family history of
  asthma
• Environmental history pets, dust?
• No symptoms
• Environmental history tree pollen, grass pollen?
• Yes

68
Case 2

• Physical exam
• Nasal edematous, pale mucosa serous clear
  discharge
• Eyes no injection or redness of sclerae
  conjunctival exam normal
• Oral normal
• Ears normal
• Neck no lymphoadenopathy
• Skin normal
• Lungs clear

69
Case 2

• What diagnostic tests?
• Skin test or allergen-specific IgE blood test
• Results
• Positive for IgE reactivity to grass, mold,
  birch, oak, and ash
• Negative to weed, cat, dog, dust mite
• What diagnosis?
• Seasonal allergic rhinitis

70
Case 2

• Therapeutic considerations
• Both nasal and non-nasal symptoms
• College student who needs to avoid sedation
• Significant worsening of symptoms overnight with
  serious morning exacerbations
• Patient prefers the convenience of once-daily
  dosing

71
Case 2

• Treatment
• Spring CLARINEX (desloratadine)
• For the treatment of nasal and non-nasal symptoms
• Summer CLARINEX-D 24 HOUR (desloratadine 5 mg
  and pseudoephedrine sulfate, USP 240 mg) Extended
  Release Tablets
• For the treatment of both nasal and non-nasal
  symptoms, including congestion

72
CLARINEX-D 24 HOUR Extended Release Tablets
Part of An Expanding Family of Formulations

• Once-daily non-drowsy antihistamine with a
  decongestant (desloratadine 5 mg
  pseudoephedrine sulfate 240 mg)1 delivered via a
  proven Gel Control system over 24 hours
• Indicated for relief of nasal and non-nasal
  symptoms of SAR, including nasal congestion, in
  patients 12 yrs of age1

Desloratadine 5 mg and pseudoephedrine sulfate,
USP 240 mg SAR seasonal allergic rhinitis.
1. CLARINEX-D 24 HOUR package insert, Schering
Corporation.
73
CLARINEX-D 24 HOUR Extended Release Tablets
Unique Gel Control Delivery System Provides
24-Hour Relief

• Immediate release of 5 mg desloratadine when
  outer film coat dissolves
• When PSE tablet core encounters gastrointestinal
  fluid, gel layer is formed
• PSE diffuses out of the gel layer slowly as fluid
  permeates core tablet
• Core disintegrates through gel layer for gradual,
  controlled release of PSE.

Desloratadine 5 mg and pseudoephedrine sulfate,
USP 240 mg PSE pseudoephedrine.
74
CLARINEX-D 24 HOUR Extended Release Tablets
Improves Symptoms in Patients with SAR
TSS (excluding nasal congestion) over a 2-week
treatment period
CLARINEX-D 24 HOUR (n333)
PSE 240 mg (n337)
DL 5 mg (n337)
Change from Baseline

Desloratadine 5 mg and pseudoephedrine sulfate,
USP 240 mg. Mean reduction in score averaged
over 2-week treatment period sem
0.22. P0.015 vs PSE P0.003 vs DL. SAR
seasonal allergic rhinitis TSS total symptom
score PSE pseudoephedrine DL desloratadine.
CLARINEX-D 24 HOUR package insert, Schering
Corporation.
75
CLARINEX-D 24 HOUR Extended Release Tablets
Improves Nasal Symptoms in Patients with SAR
Nasal Stuffiness/Congestion over a 2-week
treatment period
CLARINEX-D 24 HOUR (n333)
PSE 240 mg (n337)
DL 5 mg (n337)
Change from Baseline

Desloratadine 5 mg and pseudoephedrine sulfate,
USP 240 mg. Mean reduction in score averaged
over 2-week treatment period sem
0.034. P0.002 vs PSE Plt0.001 vs DL. SAR
seasonal allergic rhinitis PSE
pseudoephedrine DL desloratadine.
CLARINEX-D 24 HOUR package insert, Schering
Corporation.
76
CLARINEX-D 24 HOUR Extended Release Tablets
Benefits for Seasonal Allergy Sufferers
Desloratadine 5 mg and pseudoephedrine sulfate,
USP 240 mg Allegra-D is a registered
trademark of Sanofi-Aventis Pharmaceuticals Inc
Zyrtec-D is a registered trademark of Pfizer
Inc.
77
CLARINEX-D 24 HOUR Extended Release Tablets
Incidence of Adverse Events
Incidence of adverse events reported by 2 of
patients receiving CLARINEX-D 24 HOUR Extended
Release Tablets. Desloratadine 5 mg and
pseudoephedrine sulfate, USP 240 mg.
CLARINEX-D 24 HOUR package insert, Schering
Corporation.
78
Spontaneous Adverse Events Observed During
Clinical Practice

• The following spontaneous adverse events have
  been reported during the marketing of
  desloratadine as a single ingredient product
• Headache
• Somnolence
• Dizziness
• Tachycardia
• Palpitations
• Hypersensitivity reactions (rarely)
• Elevated liver enzymes
• Hepatitis (very rarely)

CLARINEX-D 24 HOUR package insert, Schering
Corporation.
79
CLARINEX-D 24 HOUR Extended Release Tablets
Contraindications

• CLARINEX-D 24 HOUR Extended Release Tablets is
  contraindicated in patients with
• Hypersensitivity to this medication or any of its
  ingredients, or to loratadine
• Narrow-angle glaucoma
• Urinary retention
• Severe hypertension
• Severe coronary artery disease
• Hypersensitivity to its components, to adrenergic
  agents, or to other drugs of similar chemical
  structures
• And in patients receiving MAO inhibitor treatment
  or within 14 days of stopping such treatment

Desloratadine 5 mg and pseudoephedrine sulfate,
USP 240 mg MAO monoamine oxidase.
CLARINEX-D 24 HOUR package insert, Schering
Corporation.
80
CLARINEX-D 24 HOUR Extended Release Tablets
Warnings

• CLARINEX-D 24 HOUR should be used with caution
  in patients with
• Hypertension
• Diabetes mellitus
• Ischemic heart disease
• Increased intraocular pressure
• Hyperthyroidism
• Renal impairment
• Prostatic hypertrophy
• CNS stimulation with convulsions or
  cardiovascular collapse with accompanying
  hypotension may be produced by sympathomimetic
  amines

Desloratadine 5 mg and pseudoephedrine sulfate,
USP 240 mg CNS central nervous system.
CLARINEX-D 24 HOUR package insert, Schering
Corporation.
81
CLARINEX-D 24 HOUR Extended Release Tablets
Summary

• CLARINEX-D 24 HOUR provides powerful morning
  relief with one dose even in patients with
  congestion
• CLARINEX-D 24 HOUR utilizes a proven Gel Control
  delivery system
• Gradual release of pseudoephedrine
• CLARINEX-D 24 HOUR is well tolerated and may be
  taken with or without food

Desloratadine 5 mg and pseudoephedrine sulfate,
USP 240 mg.
82
CLARINEX Family of Products

• The CLARINEX family of products offers a full
  spectrum of formulations for pediatric through
  adult patients to provide effective symptom
  relief
• CLARINEX Tablets
• CLARINEX RediTabs
• CLARINEX Syrup
• CLARINEX-D 24 HOUR Extended Release Tablets

DC0123 5/05
DesloratadineDesloratadine 5 mg and
pseudoephedrine sulfate, USP 240 mg.