Prevalin Product Information – HCPs

1. ORIGIN AND BRIEF DESCRIPTION

Brief description:

Prevalin™ Allergy is clinically proven to reduce allergic rhinitis symptoms, as it blocks allergens that cause the allergic reaction. Prevalin™ Allergy is a nasal spray that works directly where the allergic reaction starts on the respiratory mucosa of the nose. Prevalin™ Allergy’s proven technology uses a combination of oils and emulsifiers, which form an allergen impermeable micro-gel barrier. ¹

2. PRODUCT DESCRIPTION

2.1 SKU’s

Prevalin Allergy – 20 ml
Prevalin Allergy Kids – 20 ml (exact same formulation as adult, but difference in delivered dose per spray (squirt): 0.070 ml per squirt for children, versus 0.140 ml per squirt for adults).

2.2 Formula/ product components

Prevalin™ Allergy consists of Bentonite veegum, xanthan gum, glycerol monostearate, potassium phosphate, dipotassium phosphate, glycerin, sesame oil, water, mixed tocopherols, spearmint oil, preservatives (phenoxyethanol, caprylyl glycol, potassium sorbate). ¹

2.3 Insight on the condition/ disease

2.3.1 Allergic rhinitis

According to the WHO, allergic rhinitis is a global health problem. It effects at least 10 – 25% of the world population, with increasing prevalence.It affects up to 40% of children and 25% of adults in the US. ^2,3

Allergic rhinitis is an IgE-mediated hypersensitivity reaction. It is characterized by rhinorrhea, nasal pruritus (i.e. nasal itching), nasal congestion and sneezing. Important non-nasal symptoms commonly associated with allergic rhinitis include itching eye, tearing eye, itching ears and/or palate, and eye redness. The occurrence of these symptoms is temporally connected to the exposure to allergens. The symptoms are seasonally provoked by pollen (seasonal allergic rhinitis, SAR, hay fever) or throughout the year, due to chronic exposure to dust mites, mold allergens or animal dandruff (perennial allergic rhinitis, PAR). ²

Adapted from ref. 4
Fig. 1 Early and late phases showing the pathophysiological processes and drivers of allergic rhinitis and the potential sites for pharmacological intervention. ECP eosinophil cationic protein, ICAM-1 intercellular adhesion molecule-1, IgE immunoglobulin E, IL interleukin

Importantly, allergen avoidance should be indicated when possible and should be an integral part of the management strategy. However, using topical microemulsion made of glycerol esters for topical application in the nose has been developed, with the aim of conferring a protective effect in patients with allergic rhinitis. Its mechanism of action consists of creating a lipid coating that spreads over the surface of the nasal mucosa. Acting this way, the protective effect is achieved by creating a lipid barrier that prevents allergens being deposited onto the nasal mucosa and reaching the specific IgE of the mucosal immune system cells and engulfing allergens already present in the nasal mucosa. As such, the allergic reaction will be blocked by the application of the microemulsion at the very beginning of the allergic cascade, in contrast to commonly used symptomatic medications such as antihistamines or corticosteroids, which act at the end of this cascade. ⁵

2.3.2 Symptoms of allergic rhinitis & impact on quality of life.

The allergic response occurs in two phases, which are considered the “early” and “late” phase responses. Despite the high prevalence of Allergic Rhinitis, it is often undiagnosed. It is characterized by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhea. Many causative agents have been

linked to AR including pollens, molds, dust mites, and animal dander. ⁶

Allergic rhinitis has a significant impact on patients, as it interferes with their quality of life as well as their productivity in school and job. ^7,8

2.4 Indications

Prevalin™ Allergy’s is an ideal solution for hay fever and allergic rhinitis. It is clinically proven to reduce allergic rhinitis symptoms, as it blocks allergens that cause the allergic reaction. It works directly where the allergic reaction starts, on the respiratory mucosa of the nose and forms an allergen-impermeable micro-gel barrier. PREVALIN™ ALLERGY’s patented Nasya™ technology uses a combination of oils and emulsifiers, which give unique transformation properties from gel to liquid for easy dispersion. Upon settling on the nasal mucosa, PREVALIN™ ALLERGY reverts to its original gel-like consistency to

form an allergen-impermeable micro-gel barrier. ¹

2.5 Method of use and posology

Use Prevalin™ Allergy as soon as you feel the first symptoms, before the allergic reaction has fully developed.¹

Step 1: Before using PREVALIN™ ALLERGY, shake the bottle vigorously in upright position at least 4 times
Step 2: Turn the bottle upside down and shake again at least 4 times
Step 3: Remove the cap from the bottle
Step 4: Prime the pump before initial use. To prime, press the white applicator down for 5-10 seconds and then release. Repeat until a full spray is obtained.
Step 5: Tilt head slightly forward. Hold the bottle upright, insert the tip fully into nostril and spray once. Spray once more if necessary. Do this for both nostrils.
Step 6: Tilt head backwards briefly after application and breathe normally through your nose

2.6 Mode of action

Prevalin™ works on 3 levels:

Defusing pollen: Prevalin™ “defuses” the pollen already inside the nose. ¹
Barrier against pollen: Its fine mist forms a microgel barrier to prevent further pollen from infecting the muco¹ Through the formation of a gel barrier, the allergens no longer come in contact with the nasal mucosa and the mast cells, which, when triggered, contribute to allergy symptoms. ⁸
Clearance of pollen: Prevalin™ stimulates clearance of the allergens in the nose.¹The sesame oil creates an increase of the ciliary beat frequency. ⁹

A more extensive background on these 3 modes of action can be found below:

2.6.1 Defusing of pollen – through lipid encapsulation

The components in the pollen that trigger an allergic reaction are called ‘allergens’ (indicated as

pink balls in the figure). ¹⁰

Adapted from ref. 10

Pollen allergens are integral pollen constituents. They are primarily localized within the pollen grain in specific patterns of distribution and have to be released during a process of activation in order to become bioavailable.¹⁰

How does allergen release from pollen work?

Pollen induce allergic reactions through the release of allergens. ⁹ Most often it is a small, highly water soluble protein or glycoprotein (with a molecular weight of > 10 kDa). They are primarily localized within the pollen grain in specific patterns of distribution and have to be released during a process of activation in order to become bioavailable. The allergens then bind to receptors on the immune cells to exert their effect. ⁹

a. Step 1: The allergen becomes bioavailable

In a dry atmosphere, pollen are very stable and can contain their allergens for centuries. Under humid conditions, allergens are released from pollen grains. This liberation of allergens is pH- and temperature-dependent, with maximal values at at 37 °C and pH 9. Allergen liberation from pollen grains can occur in two different compartments: first, on the mucosal surface of the upper respiratory tract after exposure to pollen; and second, outside the individual organism in the ambient air itself. The allergens in grass pollen that are able to provoke IgE-mediated allergic responses are extremely water soluble. ¹⁰

a. Step 2: The allergen binds to the immune

In the sensitized host, mast cells residing in the nasal mucosa have IgE antibodies, specific to the offending antigens, bound to the cell surface by high-affinity receptors (FceR1). Upon subsequent antigen challenge, allergen binds to adjacent IgE antibodies on mast cells, causing cross-linking of the molecules and signaling the subsequent degranulation of the mast cell, with the release of inflammatory mediators, such as histamine. ⁷

How do lipids prevent allergen release from pollen?

The protective effect is achieved by creating a lipid barrier that prevents allergens being deposited onto the nasal mucosa and reaching the specific IgE of the mucosal immune system cells and engulfing allergens already present in the nasal mucosa. As such, the allergic reaction will be blocked by the application of the microemulsion at the very beginning of the allergic cascade, in contrast to commonly used symptomatic medications such as antihistamines or corticosteroids, which act at the end of this cascade. ⁵

2.6.2 Pollen clearance

The effectiveness of mucociliary clearance is influenced by CBF, the composition of mucus and anatomic structures. A disturbed mucociliary clearance leads to recurrent episodes of acute and potentially chronic rhinosinusitis, bronchitis, and otitis media. Therefore, it is important not to disturb this defense mechanism. ⁹

The incubation with sesame oil was found to increase the CBF only after 10 minutes of exposure. ⁹

2.7 Acts 5 times faster

Comparison with other hay fever tablets:

The most effective and safest way to decrease the allergic symptoms is to eliminate exposure to the allergens. Avoidance or elimination of allergens present in the breathing air is, in most cases, not possible. ⁸

To this end, clinical studies investigating the onset, and the duration, of efficacy have been reviewed and the findings detailed in the table below. (Reference 13)

Oral antihistamines provide symptom relief in 1 to 2 hours. INAH (Intranasal antihistamines) offer a quicker onset of action within 15 minutes along with greater overall efficacy.¹⁴

INCS (Intranasal corticosteroids) take at least 2 weeks of regular use to achieve maximal benefit, while oral antihistamines are maximally effective within 1 to 8 days.¹⁴

Drug		Time to action (hours)
First generation¹¹	Chlorpheniramine	3
	Diphenhydramine	2
	Doxepin	NA
	Hydroxyzine	2
Second generation¹¹	Acrivastine	1
	Cetirizine	1
	Loratadine	2
	Fexofenadine	2
	Levocetirizine	1
	Desloratadine	2
Corticosteroids¹²	Mometasone	2.5
Corticosteroids¹²	Budesonide	8

Adapted from del Cuvillo et al 2006, Schranet al 1996, Simons & Simons 1999

*Based on erythema and wheal testing

& Mark S. Dykewicz et al 2020

The data above supports the claim that Prevalin™ “acts 5x faster than hay fever tablets”. The data

demonstrates an onset of action for Prevalin™ of 3 minutes in comparison to the INAH ranging from 15 to 30 minutes, and an average of 150 minutes for oral antihistamines ^1,1²

Therefore, Prevalin™ has been shown to act 5x faster than the alternative therapies.

3. PRODUCT SAFETY

GOOD SAFETY PROFILE

PREVALIN™ ALLERGY is a drug free solution. Suitable for use by athletes, pregnant & breastfeeding women.

PREVALIN™ ALLERGY’s ingredients are inert and non-toxic. Its patented formula contains no alcohol. PREVALIN™ ALLERGY does not cause drowsiness and is suitable for adults and children of 12 years and above. PREVALIN™ ALLERGY is not known to interact with other

medicines or with other forms of allergy treatment. The application of PREVALIN™ ALLERGY should not affect the efficacy of anti-histamines tablets. ¹

4. References

Prevalin™ Information leaflet, revision date: March 2019
Luond-Valeskeviciute, , Haenggi, B. & Gruenwald, J., 2010. Efficacy of three thicotropic nasal spray preparations on seasonal allergicrhinitis assessed by allergenchallenge in an environmental exposure unit. WebmedCentral ALLERGY.
Brown, J.M., Wilson, T.M. & Metcalfe, D.D., 2008. The mast cell and allergic diseases: role in pathogenesis and implications for therapy. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology, 38, pp.4–18.
Bjermer, L., Westman, M., Holmström, M. et al. The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option. Allergy Asthma Clin Immunol 15, 24 (2019). https://doi.org/10.1186/s13223-018-0314-1
Ojeda, P. et al., 2013. A topical microemulsion for the prevention of allergic rhinitis symptoms: results of a randomized, controlled, double-blind, parallel group, multi center, multinational clinical trial (Nares study). Allergy, asthma, and clinical immunology: official journal of the Canadian Society of Allergy and Clinical Immunology, 9, p.32. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23981504.
Skoner, , 2001. Allergic rhinitis: definition, epidemiology, pathophysiology, detection and daignosis. J Allergy Clin Immunol, 108, pp.S2–8.
Naclerio, , 1997. Pathophysiology of perennial allergic rhinitis. Allergy, 52, pp.7–13.
Stoelzel, K. et al., 2014. Safety and efficacy of Nasya/Prevalin in reducing symptoms of allergic rhinitis. The Clinical Respiratory Journal, 8, pp.382–390. Available at: http://doi.wiley.com/10.1111/crj.12080.
Neher, et al., 2008. Influence of essential and fatty oils on ciliary beat frequency of human nasal epithelial cells. American journal of rhinology, 22(2), pp.130–134.
Behrendt, & Becker, W.M., 2001. Localization, release and bioavailability of pollen allergens: The influence of environmental factors. CurrentOpinion in Immunology, 13, pp.709–715.
Del Cuvillo A, Mullol J, Bartra J, Dvila I, Juregui I, Montoro J, Sastre J, Valeron AL. Comparative pharmacology of the H1antihistamines. J Invest Alergol Clin Immunol 2006;16(S1):3-12.
Dykewicz, S., Wallace, D. V., Amrol, D. J., et al. (2020). Rhinitis 2020: A practice parameter update. J Allergy Clin Immunol, 146(4), 721-767