XARIA PLUS

(Montelukast 10 mg, Fexofenadine 120 mg)

Non-sedating Combination for Allergic Rhinitis

Allergic Rhinits
Allergic rhinitis refers inflammation of

internal lining of nasal cavities

Often immune mediated due contact with an allergen

ARIA Report 2001

ALLERGIC RHINITIS

Not just symptoms of Sneezing..

Allergic Rhinitis
..Constellation of symptoms
Classical Symptoms
Repetitive sneezing Watery rhinorrhea Nasal itch

Others
Eye symptoms Ear symptoms Postnasal drainage

Nasal congestion
Symptoms last usually not more than an hour!

Allergic Rhinitis
simple yet .. complicated illness
An extremely common disease worldwide, affecting 10 to 25% of the population 1 in 6 people are said to be suffering from rhinitis The condition impacts heavily on health-related Quality of Life or Sleep
Work

QOL affected
Family Social

ARIA Report 2001; Sheikh WA in Allergy &Asthma :A Troipcal View, 2001

Allergic Rhinitis
..affects sleep quality
SOMNIAAR study
prospective, observational, multicentre survey 2275 patients with Allergic rhinitis were evaluated for effects on Sleep Results
53% had poor sleep quality 21% suffered from excessive diurnal somnolence
Colas C. Clin Exp Allergy 2012 Jan 18

Allergic Rhinitis
Pathophysiology & Symptoms
allergen IgE
preformed & newly formed mediators/cytokines

mast cell

IMMEDIATE RESPONSE
(5 -30 mins)

Histamine
(Sneezing)

Leukotrienes
(Aggravate inflammation / mucosal swelling including Congestion)

Allergic Rhinitis and its Impact on Asthma classification depending on Severity

*PER Persistent

Management often depends on identification of cause..

Allergic Rhinitis
Management

Avoid factors that cause symptoms

Evaluate for immunotherapy

(in known cases only)

Use appropriate treatments

Educate and follow-up

Pharmacotherapy
Antihistamines
First generation ( CPM)- Sedation, dryness of mouth, urinary retention Second generation- Less Sedative (do not cross BBB)

Nasal sprays Azelastine, Olopatadine bitterness, nose bleeding, sores in nose, birth defects (preclinical studies)

Decongestants
Local short-term use to prevent tolerance Oral tachycardia, High BP, prostate disease, glaucoma

Corticosteroids
For Severe allergic rhinitis

LeukoTriene Receptor Antagonist (LTRAs)

Monteleukast- decreases vascular permeability to reduce congestion or edema, reduces inflammatory progression, often used in pts with concomitant asthma

Pharmacotherapy
..choice of Antihistaminics
Fexofenadine Drug Metabolite of Terfenadine Desloratidine Active isomer of Loratidine Levocetirizine Active isomer of Cetirizine

Mechanism
Onset of action Half-life Somnolence Sedation Work performance

Selective H1 antagonist
0.5 hr 15 hrs 0 0 (Non-sedating by US FDA) No impairment of Work or Driving performance

Selective H1 antagonist
3 hr 27hr 0.7% 0.1% No impairment of Work or Driving performance

Selective H1 antagonist
1 hr 8 hr 2.1% 0.4% May hamper Work or Driving performance

Devillier P. Clin Pharmacokinet 2008; 47 (4): 217-230

Dhanya NB. IJDVL 2008; 74: 361-3

Pharmacotherapy
..choice of Anti-histaminics
Clinical efficacy often predicted by Wheal-flare suppression response

Comparative in-vitro study involving 30 volunteers given single dosages of Fexofenadine, Desloratidine & Levocetirizine
0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 -0.7 -0.8 -0.9 -1

Fexofenadine

Desloratidine

Levocetirizine

-0.3 mm

-0.3 mm

Wheal suppression (in mm) at 30 mins was faster for Fexofenadine

-0.9 mm
Dhanya NB. IJDVL 2008; 74: 361-3

Allergic Rhinitis and its Impact on Asthma guidelines on Combination therapy

Oral Antihistaminic

LTRA + Oral Antihistaminic

LTRA + Oral Antihistaminic

Intranasal Steroids

*PER Persistent

In asthmatics, Combination with LTRAs are preferred for concomitant Allergic Rhinitis

The prevalence of rhinitis among asthmatic patients is high, upto 80%.

Asian Pac J Allergy Immunol. 2009; 27(2-3): 167-171

Control of Leukotrienes prevents inflammatory changes in Asthmatics

XARIA PLUS
Rationale
Fexofenadine potent and highly selective antagonist of the peripheral histamine H1 receptors Duration of action is 24 hrs Reduces Histamine induced sneezing, nasal itching, rhinorrhea Only LTRA that is given once daily Reduces Leukotriene induced inflammation FOR additional nasal decongestant property Montelukast selective and orally active leukotriene receptor antagonist (LTRA) that inhibits the actions of leukotrienes

Complimentary action on Chemical mediators for Synergistic control of Allergic Rhinitis symptoms

XARIA PLUS
Rationale

XARIA PLUS
Adapted from ARIA 2007

Fexofenadine-Montelukast Combination
..relieves nasal obstruction, increases air flow
12 pts with Persistent Allergic Rhinitis Fexofenadine or Monteleukast or Fexofenadine + Monteleukast combination administered for 1 wk Significant improvement in Nasal obstruction for Combination arm (p<0.05)
20 % Relative improvement in Nasal air flow after 1 wk compared to placebo 16% 13%

15 % 10

11%

5 FEX + MONT Fexofenadine Montelukast

Lee DKC. Br J Clin Pharm 2004;57(6):714-9

Monteleukast+Fexofenadine FDC
Fixed dose combinations offers:
Simplification of treatment regimen Better patient adherence Reduces number of medications

Indications and Dosage

For relief and/or prevention of symptoms of Allergic Rhinitis in adults > 15 yrs of age One tablet to be taken once daily for symptomatic treatment

Allergens

Dust Smoke Pollution Grass Weeds Moulds Dander Feather Pollen grains

Allergen
Stage 1 Stage 2

Antibody

IgE

Degranulation

Histamine, LT Histamine Release

MAST CELLS

Acts Acts on on H1, H1 LT receptors (Nose / Eyes / Throat / Lung)

Allergic Rhinitis and its Impact on Asthma guidelines on Combination therapy

Glemont F

Glemont F

Intranasal CS + Glemont F

*PER Persistent

XARIA PLUS ..in allergic rhinitis with asthma

80% of Asthmatics have family history or concomitant history of Allergic Rhinitis Uncontrolled allergic rhinitis may lead to worsening of coexisting asthma

Treating allergic rhinitis helps in controlling asthma symptoms, and improving lung function tests
Combination with Monteleukast prevents Pro-inflammatory changes in Asthmatics Safely coprescribed with Anti-asthmatic medications

XARIA PLUS
(Montelukast+ Fexofenadine)

..for Fast action