Barriers to treatment of Allergic Rhinitis

The problem
The vast majority of treated patients remain symptomatic1

Barriers to treatment of Allergic Rhinitis

References:

  1. Bousquet et al. Impact of Allergic Rhinitis Symptoms on Quality of Life in Primary Care. Int Arch Allergy Immunol. 2013;160(4):393–400.

Introducing a new class of treatment

Dymista® is a new class of treatment for AR, incorporates azelastine hydrochloride (AZE; 137 μg per spray) and fluticasone propionate (FP, 50 μg per spray), two potent drugs from different medication classes with complementary effects in a novel patented formulation Dymista® is indicated for the relief of symptoms of moderate to severe seasonal AR (SAR) and perennial AR (PAR).

Dymista nasal spray

References:
  1. Summary of Product Characteristics for KSA, Revision Date. July-2020.

Indications

Dymista® is indicated in patients 12 years and older (depending on the country) to relieve the symptoms of moderate to severe seasonal and perennial allergic rhinitis if the use of either intranasal antihistamine or corticosteroid alone is not considered sufficient.1 Seasonal and perennial allergic rhinitis are allergic reactions to substances such as pollen, house mites, moulds, dust or pets.2,3

References:
  1. Summary of Product Characteristics for KSA, Revision Date. July-2020.
  2. Ciprandi G, et al. Seasonal and perennial allergic rhinitis: is this classification adherent to real life? Allergy. 2005 Jul;60(7):882-70
  3. Crown WH, et al. Seasonal versus perennial allergic rhinitis: drug and medical resource use patterns. Value Health. 2003 Jul-Aug;6(4):448-56.

Mode of Action

Dymista® – Mode of Action

The inflammatory response is split into an early and late phase, and induces all the symptoms associated with allergic rhinitis (Figure).1–3

 Mode of Action

Adapted from Bjermer et al., 2019.

Pharmacotherapies (allergic rhinitis treatment) interact with the allergic rhinitis pathophysiological pathway at different points, reflecting their different modes of action and how effective they are at providing symptomatic relief.

Comprising both an intranasal corticosteroid (i.e. fluticasone propionate) and an intranasal anti-histamine (i.e. azelastine) in a patented formulation,6 Dymista not only benefits from the anti-inflammatory effect of fluticasone, but also from the anti-inflammatory, anti-histaminic, mast-cell stabilizing and anti-leukotriene activity of azelastine delivered in a single spray., thus providing better relief from allergic rhinitis symptoms compared to other treatments.1,7–10

 

References:

  1. Bjermer L, Westman M, Holmström M, Wickman MC. The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option. Allergy Asthma Clin Immunol Off J Can Soc Allergy Clin Immunol. 2019;15:24. doi:10.1186/s13223-018-0314-1
  2. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63 Suppl 86:8-160. doi:10.1111/j.1398-9995.2007.01620.x
  3. Global Atlas of Allergic Rhinitis & Chronic Rhinosinusitis. Eur Acad Allergy Clin Immunol. http://webcast.eaaci.cyim.com/mediatheque/media.aspx?mediaId=60232&channel=8518
  4. Stull DE, Roberts L, Frank L, Heithoff K. Relationship of nasal congestion with sleep, mood, and productivity. Curr Med Res Opin. 2007;23(4):811-819. doi:10.1185/030079907x178793
  5. Bousquet PJ, Demoly P, Devillier P, Mesbah K, Bousquet J. Impact of allergic rhinitis symptoms on quality of life in primary care. Int Arch Allergy Immunol. 2013;160(4):393-400. doi:10.1159/000342991
  6. Summary of Product Characteristics for KSA, Revision Date. July-2020.
  7. Mösges R. All of ARIA in one puff? Int Arch Allergy Immunol. 2014;163(3):163-164. doi:10.1159/000357188
  8. Horak F, Zieglmayer UP. Azelastine nasal spray for the treatment of allergic and nonallergic rhinitis. Expert Rev Clin Immunol. 2009;5(6):659-669. doi:10.1586/eci.09.38
  9. Roca-Ferrer J, Pujols L, Pérez-González M, et al. Superior effect of MP-AzeFlu than azelastine or fluticasone propionate alone on reducing inflammatory markers. Allergy Asthma Clin Immunol Off J Can Soc Allergy Clin Immunol. 2018;14:86. doi:10.1186/s13223-018-0311-4
  10. Meltzer E, Ratner P, Bachert C, et al. Clinically relevant effect of a new intranasal therapy (MP29-02) in allergic rhinitis assessed by responder analysis. Int Arch Allergy Immunol. 2013;161(4):369-377. doi:10.1159/000351404

Efficacy 

The value of Dymista®1,2

Multiple components in Dymista®
Multiple components contribute to the overall product effectiveness of Dymista®: The two active ingredients and the formulation.

Dymista controls symptoms

Superior Efficacy

Dymista® has been shown to be more effective as fluticasone propionate or azelastine alone at treating the entire rhinitis symptom spectrum. In a randomised, double-blind, placebo-controlled, 2-week trial involving 779 patients with moderate-to-severe seasonal allergic rhinitis, Dymista® administered as one spray to each nostril twice-daily provided greater nasal and ocular symptom improvement than azelastine (INAH) or fluticasone propionate (INS) administered alone (one spray to each nostril twice-daily).3

Greater improvement in Nasal symptoms

Greater improvement in ocular symptoms

Day one symptoms free

Real life symptom control

Dymista®’s clinical efficacy has been confirmed in real life.4

Patients scores are lower by day one

Five-minute onset of action

Dymista® provides a 5-minute onset of action,10 giving your patients rapid symptom relief. In a randomised, placebo-controlled, double-blind, double-dummy, 3-period crossover trial of 82 patients with a history of allergic rhinitis and a positive skin prick test to ragweed pollen, subjects had allergic rhinitis symptoms induced by ragweed pollen in an allergen environmental exposure chamber. Patients received single-dose Dymista®, or the two medications oral loratadine and intranasal fluticasone propionate (FP + loratadine), or placebo, and were monitored for 4 hours.2

Change from baseline after 5 minutes

  • Dymista® reduced TNSS at 5 minutes and throughout the 4-hour assessment period (p<0.05 vs. placebo).2 Loratadine plus FP was not significantly different from placebo until 150 minutes (p<0.05).2
  • Dymista® was superior over the entire assessment period compared with placebo (p<0.001).2

References:

  1. Klimek L, et al. Effectiveness of MP29-02 for the treatment of allergic rhinitis in real-life: Results from a noninteNentional study. Allergy Asthma Proc. 2015;36:40–47.
  2. Bousquet J, et al. Onset of Action of the fixed combination intranasal azelastine-fluticasone propionate in an allergen exposure chamber. JACI in Practice. 2018; Volume 6, Issue 5:1726-1732.
  3. Meltzer EO, et al. MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate) in the treatment of seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial of efficacy and safety. Allergy Asthma Proc. 2012 Jul-Aug;33(4):324-32.
  4. Price D, Shah S, Bhatia S, et al. A new therapy (MP29-02) is effective for the long-term treatment of chronic rhinitis. J Investig Allergol Clin Immunol. 2013;23(7):495-503.

Safety & Tolerability

Dymista® is suitable for long term use1-3

For patients to get the full therapeutic benefit, regular usage of Dymista® nasal spray is essential, and Dymista® is suitable for long-term use.
Treatment should be continued for as long as the patient is exposed to the allergen(s).3
A 52-week open-label study showed Dymista® has a large therapeutic spectrum, covering not only seasonal allergic rhinitis but also perennial allergic rhinitis with consistent superiority over an intranasal corticosteroid.

References:

  1. Meltzer E, Ratner P, Bachert C, et al. Clinically relevant effect of a new intranasal therapy (MP29-02) in allergic rhinitis assessed by responder analysis. Int Arch Allergy Immunol. 2013;161(4):369-377. doi:10.1159/000351404.
  2. .Price D, Shah S, Bhatia S, et al. A new therapy (MP29-02) is effective for the long-term treatment of chronic rhinitis. J Investig Allergol Clin Immunol. 2013;23(7):495-503.
  3. .Summary of Product Characteristics for KSA, Revision Date. July-2020.

Dosing & Administration

Dosage
Always use Dymista Nasal Spray exactly as your doctor has told you. Check with your doctor or pharmacist , if you are not sure. It is essential to use Dymista Nasal Spray regularly to gain the full therapeutic benefit. Contact with the eyes should be avoided.

Adults and adolescents (12 years and above)
  • The recommended dose is one spray into each nostril in the morning and evening.

  • Use in Children under 12 years
  • This medicine is not recommended for children under 12 years

  • Use in renal and hepatic impairment
  • There are no data in patients with renal and hepatic impairment.
  • Dymista ® should only be administered via the nasal route.
    INSTRUCTION FOR USE
    Preparing the spray
    1. Shake the bottle gently for 5 seconds by titling upwards and downwards and then remove the protective cap (see figure 1).
    2. The first time the nasal spray is used, you must prime the pump by squirting it into the air.
      How to use Video
      Remove the cap
      Administer in nasal cavity
    3. Prime the pump by putting two fingers on either side of the spray pump and place your thumb on the bottom of the bottle.
    4. Press down and release the pump 6 times until a fine mist appears (see figure 2).
    5. Now your pump is primed and ready to use.
    6. If the nasal spray has not been used for more than 7 days, you will need to re-prime the pump once by pressing down and releasing the pump.
    Using the spray
    1. Shake the bottle gently for 5 seconds by tilting it upwards and downwards and then remove the protective cap (see figure 1).
    2. Blow your nose to clear your nostrils.
    3. Keep your head tilted downwards towards your toes. Do not tilt head backwards.
    4. Hold the bottle upright and carefully insert the spray tip into one nostril.  
    5. After each use wipe the spray tip with a clean tissue or cloth and then replace the protective cap

    References:

    1. Summary of Product Characteristics for KSA, Revision Date. July-2020.

    Highlights of Prescribing Information

    Contraindications
    If you are allergic to azelastine hydrochloride or fluticasone propionate or any of the other ingredients of this medicine.
    Warnings and Precautions
    Talk to your doctor or pharmacist before using Dymista Nasal Spray if:

    • You had an recent operation on your nose.
    • You have an infection in your nose. Infections of the nasal airways should be treated with antibacterial or antifungal medication. If you are given medication for an infection in your nose you can continue to use Dymista Nasal Spray to treat your allergies.
    • You have tuberculosis or an untreated infection.
    • You have a change in vision or a history of increased ocular pressure, glaucoma and/or cataracts, if this applies to you, you will be closely monitored whilst using Dymista Nasal Spray.
    • You suffered from impaired adrenal function. Care must be taken when transferring from systemic steroid treatment to Dymista Nasal Spray.
    • Your suffer from a severe liver disease. You risk of suffering from systemic side-effects is increased.

    In these cases your doctor will decide whether you can use Dymista Nasal Spray.
    It is important that you take your dose as stated in section 3 below or as advised by your doctor. Treatment with higher than recommended doses of nasal corticosteroids may result in adrenal suppression, a condition that may produce weight loss, fatigue, muscle weakness, low blood sugar, salt cravings, joint pains, depression and darkening of the skin. If this happens your doctor may recommend another medicine during periods of stress or elective surgery.
    To avoid adrenal suppression your doctor will advise you to take the lowest dose at which effective control of your symptoms of rhinitis is maintained.
    Taking nasal glucocorticoids (such as Dymista) may when taken for a long time cause children and adolscents to grow more slowly. The doctor will check your child's height regularly, and make sure he or she is taking the lowest possible effective dose.
    Contact your doctor if your experience blurred vision or other visual disturbances.
    If you are unsure whether the above applies to you, talk to your doctor or pharmacist before using Dymista Nasal Spray.
    Children
    This medicine is not recommended for children under just 12 years.
    Other medicines and Dymista Nasal Spray
    Tell your doctor or pharmacist, if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
    Some medicines may increase the effects of Dymista Nasal Spray and your doctor may wish to monitor you carefully if you are taking these medicines (Including some medicines for HIV: ritonavir, Cobicistat and medicines for the treatment of fungal infections:Ketaconazole).
    Pregnancy and breast-feeding
    If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using Dymista Nasal Spray.

    Dymista Nasal Spray contains benzalkonium chloride

    It may cause irritation of the nasal mucosa and bronchospasm. Tell your doctor or pharmacist if you feel discomfort when using the spray. The preservative contained in Dymista (benzalkonium chloride) can cause swelling of the nasal mucosa, especially with prolonged use. If there is reason to suspect such a reaction (persistent blocked nose), a medicinal product that does not contain any preservative should be used in the nose if possible. If such preservative- free medicinal products for intranasal use are not available, a different pharmaceutical form should be considered.

    Driving and using Machines
    Dymista Nasal Spray has minor influence on the ability to drive and use machines.
    Very rarely, you may experience fatigue or dizziness due to the disease itself or when using Dymista Nasal Spray. In these cases, do not drive or operate machinery, please be aware that drinking alcohol may enhance these effects.

    Drug Interactions
    Fluticasone propionate
    Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after intranasal dosing, due to extensive first-pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the gut and liver. Hence, clinically significant drug interactions mediated by fluticasone propionate are unlikely. A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations. During Post marketing use, there have been reports of clinically significant drug interactions in patients receiving intranasal or inhaled fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects. Co-treatment with other CYP 3A4 inhibitors, including cobicistat-containing products, is also expected to increase the risk of systemic side effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects. Studies have shown that other inhibitors of cytochrome P450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. Nevertheless, care is advised when co-administering potent cytochrome P450 3A4 inhibitors (e.g. ketoconazole), as there is potential for increased systemic exposure to fluticasone propionate.
    Azelastine hydrochloride
    No specific interaction studies with azelastine hydrochloride nasal spray have been performed. Interaction studies at high oral doses have been performed. However, they bear no relevance to azelastine hydrochloride nasal spray, as the recommended nasal doses result in much lower systemic exposure. Nevertheless, care should be taken when administering azelastine hydrochloride in patients taking concurrent sedative or central nervous medications because the sedative effect may be strengthened. Alcohol may also enhance this effect

    References:

    1. Summary of Product Characteristics for KSA, Revision Date. July 2020.

    Clinical Information

    Dymista® – Clinical Information

    Poorly controlled allergic rhinitis negatively affects asthma control to the same degree as smoking.1

    Asthma and rhinitis are linked on several levels (Figure),2,3 a phenomenon termed ’one airway one disease.4 At the epidemiology level, up to 60% of patients with allergic rhinitis have clinical asthma;5 the prevalence of asthma is more than 6 times higher in subjects with rhinitis than in those without.6 Both diseases also share a common anatomy, triggers and the same inflammatory process (pathology of allergic rhinitis).2,7 Furthermore, control of one affects control of the other.1 For example, the presence of severe rhinitis is associated with asthma exacerbations in co-morbid patients,8 and those with both asthma and rhinitis also use more asthma medication,9 have more physician visits and more hospitalizations for asthma.10 Finally, although rare, the risk of developing asthma is approximately 3-times greater for allergic rhinitis patients.11 Given this relationship between allergic rhinitis and asthma, it is likely that reducing inflammation in the nose will improve outcomes in the lungs for those patients with both diseases.

    Relation between Rhinitis and allergy

    The allergic rhinitis treatment efficacy hierarchy hypothesis The allergic rhinitis treatment hierarchy hypothesis postulates that an allergic rhinitis treatment which provides more effective control of allergic rhinitis symptoms should, in turn, have a greater positive impact on co-morbid asthma control (Figure). Intranasal corticosteroids are more effective than oral antihistamines for the treatment of allergic rhinitis12 Dymista® is more effective than intranasal corticosteroids for the treatment of allergic rhinitis16

    Asthma control Vs rhinitis control
    Achieving effective and rapid asthma control by virtue of effectively treating uncontrolled co-morbid allergic rhinitis may delay or defer the need to step-up asthma therapy

    Dymista®: Helping to improve asthma outcomes for allergic rhinitis patients with co-morbid asthma

    Given the relationship between allergic rhinitis and asthma, it is likely that reducing inflammation in the nose will improve outcomes in the lungs for those patients with both diseases. It is, therefore, crucial to achieve rhinitis control in patients with co-morbid asthma.

    Dymista® improves asthma control: results from a non-interventional study

    Patients with allergic rhinitis and asthma treated with Dymista® experienced: 

    • A rapid, statistically significant and sustained improvement in allergic rhinitis control, and a concomitant 46.2% improvement in asthma control, reaching the ARIA control zone in less than 3 days (Figure).28
    • A reduction in their asthma rescue medication use
    • 69% of these co-morbid patients treated with Dymista® were able to reduce or considerably reduce their asthma rescue medication use, a marker of improved asthma control (Figure).28
    Asthma VAS score 

    Implications:
    Achieving effective and rapid asthma control by virtue of effectively treating uncontrolled co-morbid allergic rhinitis with Dymista® may delay or defer the need to step-up asthma therapy and is likely a more cost-effective approach. Don’t forget to assess your asthma patients for allergic rhinitis, since one reason for uncontrolled asthma is the presence of uncontrolled allergic rhinitis.1

    Pie chart

    Adapted from Klimek, et al. 2019.

    Did you know that poor rhinitis control impacts asthma control to the same degree as smoking!1

    Dymista® may be considered the allergic rhinitis medication of choice for asthma co-morbid patients since it is the most effective and rapidly acting allergic rhinitis medication currently available.25,26

    Evidence to support Dymista®’s position as the treatment of choice for allergic rhinitis and asthma co-morbid patients comes from real-life observational, pre-post cohort and socioeconomic studies.27–30

    Dymista® for allergic rhinitis helps to improve asthma control by almost 50% in allergic rhinitis and asthma co-morbid patients.28

    References:

    1. Clatworthy J, Price D, Ryan D, Haughney J, Horne R. The value of self-report assessment of adherence, rhinitis and smoking in relation to asthma control. Prim Care Respir J J Gen Pract Airw Group. 2009;18(4):300-305. doi:10.4104/pcrj.2009.00037
    2. Bousquet J, Vignola AM, Demoly P. Links between rhinitis and asthma. Allergy. 2003;58(8):691-706.
    3. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63 Suppl 86:8-160. doi:10.1111/j.1398-9995.2007.01620.x
    4. Grossman J. One airway, one disease. Chest. 1997;111(2 Suppl):11S-16S. doi:10.1378/chest.111.2_supplement.11s
    5. Yawn BP, Yunginger JW, Wollan PC, Reed CE, Silverstein MD, Harris AG. Allergic rhinitis in Rochester, Minnesota residents with asthma: frequency and impact on health care charges. J Allergy Clin Immunol. 1999;103(1 Pt 1):54-59.
    6. Leynaert B, Neukirch C, Kony S, et al. Association between asthma and rhinitis according to atopic sensitization in a population-based study. J Allergy Clin Immunol. 2004;113(1):86-93. doi:10.1016/j.jaci.2003.10.010
    7. Scadding G, Walker S. Poor asthma control?--then look up the nose. The importance of co-morbid rhinitis in patients with asthma. Prim Care Respir J J Gen Pract Airw Group. 2012;21(2):222-228. doi:10.4104/pcrj.2012.00035
    8. Ohta K, Tanaka H, Tohda Y, et al. Asthma exacerbations in patients with asthma and rhinitis: Factors associated with asthma exacerbation and its effect on QOL in patients with asthma and rhinitis. Allergol Int Off J Jpn Soc Allergol. Published online June 6, 2019. doi:10.1016/j.alit.2019.04.008
    9. Magnan A, Meunier JP, Saugnac C, Gasteau J, Neukirch F. Frequency and impact of allergic rhinitis in asthma patients in everyday general medical practice: a French observational cross-sectional study. Allergy. 2008;63(3):292-298. doi:10.1111/j.1398-9995.2007.01584.x
    10. Thomas M, Kocevar VS, Zhang Q, Yin DD, Price D. Asthma-related health care resource use among asthmatic children with and without concomitant allergic rhinitis. Pediatrics. 2005;115(1):129-134. doi:10.1542/peds.2004-0067
    11. Shaaban R, Zureik M, Soussan D, et al. Rhinitis and onset of asthma: a longitudinal population-based study. Lancet Lond Engl. 2008;372(9643):1049-1057. doi:10.1016/S0140-6736(08)61446-4
    12. Foresi A. A comparison of the clinical efficacy and safety of intranasal fluticasone propionate and antihistamines in the treatment of rhinitis. Allergy. 2000;55 Suppl 62:12-14.
    13. Price D, Kemp L, Sims E, et al. Observational study comparing intranasal mometasone furoate with oral antihistamines for rhinitis and asthma. Prim Care Respir J J Gen Pract Airw Group. 2010;19(3):266-273. doi:10.4104/pcrj.2010.00040
    14. Lohia S, Schlosser RJ, Soler ZM. Impact of intranasal corticosteroids on asthma outcomes in allergic rhinitis: a meta-analysis. Allergy. 2013;68(5):569-579. doi:10.1111/all.12124
    15. Price D, Scadding G, Ryan D, et al. The hidden burden of adult allergic rhinitis: UK healthcare resource utilisation survey. Clin Transl Allergy. 2015;5:39. doi:10.1186/s13601-015-0083-6
    16. Meltzer E, Ratner P, Bachert C, et al. Clinically relevant effect of a new intranasal therapy (MP29-02) in allergic rhinitis assessed by responder analysis. Int Arch Allergy Immunol. 2013;161(4):369-377. doi:10.1159/000351404
    17. Price D, Shah S, Bhatia S, et al. A new therapy (MP29-02) is effective for the long-term treatment of chronic rhinitis. J Investig Allergol Clin Immunol. 2013;23(7):495-503.
    18. Berger W, Bousquet J, Fox AT, et al. MP-AzeFlu is more effective than fluticasone propionate for the treatment of allergic rhinitis in children. Allergy. 2016;71(8):1219-1222. doi:10.1111/all.12903
    19. Bousquet J, Meltzer EO, Couroux P, et al. Onset of Action of the Fixed Combination Intranasal Azelastine-Fluticasone Propionate in an Allergen Exposure Chamber. J Allergy Clin Immunol Pract. 2018;6(5):1726-1732.e6. doi:10.1016/j.jaip.2018.01.031
    20. Klimek L, Petr, C, Galffy, G, et al. Asthma-related outcomes in a real world study of MP-AzeFlu to treat allergic rhinitis. In: ; 2019:TP0795.
    21. Klimek L, Petr, C, Galffy, G, et al. Effectiveness of MP-AzeFlu in patients with different allergic rhinitis phenotypes: a German, multicentre, prospective study. In: ; 2019:TP1545.
    22. De Jong H, Voorham J, Scadding G, et al. Evaluating the Real-life Effect of MP-AzeFlu On Asthma Outcomes In Patients With Allergic Rhinitis and Asthma In UK Primary Care. J Allergy Clin Immunol Pr. 2020;Submitted.
    23. Harrow B, Sedaghat AR, Caldwell-Tarr A, Dufour R. A Comparison of Health Care Resource Utilization and Costs for Patients with Allergic Rhinitis on Single-Product or Free-Combination Therapy of Intranasal Steroids and Intranasal Antihistamines. J Manag Care Spec Pharm. 2016;22(12):1426-1436. doi:10.18553/jmcp.2016.22.12.1426
    24. Grossman J. One airway, one disease. Chest. 1997;111(2 Suppl):11S-16S. doi:10.1378/chest.111.2_supplement.11s
    25. Meltzer E, Ratner P, Bachert C, et al. Clinically relevant effect of a new intranasal therapy (MP29-02) in allergic rhinitis assessed by responder analysis. Int Arch Allergy Immunol. 2013;161(4):369-377. doi:10.1159/000351404
    26. Bousquet J, Schünemann HJ, Togias A, et al. Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence. J Allergy Clin Immunol. 2020;145(1):70-80.e3. doi:10.1016/j.jaci.2019.06.049
    27. Klimek L, Petr, C, Galffy, G, et al. Effectiveness of MP-AzeFlu in patients with different allergic rhinitis phenotypes: a German, multicentre, prospective study. In: ; 2019:TP1545.
    28. Klimek L, Petr, C, Galffy, G, et al. Asthma-related outcomes in a real world study of MP-AzeFlu to treat allergic rhinitis. In: ; 2019:TP0795.
    29. De Jong H, Voorham J, Scadding G, et al. Evaluating the Real-life Effect of MP-AzeFlu On Asthma Outcomes In Patients With Allergic Rhinitis and Asthma In UK Primary Care. J Allergy Clin Immunol Pr. 2020;Submitted.
    30. Harrow B, Sedaghat AR, Caldwell-Tarr A, Dufour R. A Comparison of Health Care Resource Utilization and Costs for Patients with Allergic Rhinitis on Single-Product or Free-Combination Therapy of Intranasal Steroids and Intranasal Antihistamines. J Manag Care Spec Pharm. 2016;22(12):1426-1436. doi:10.18553/jmcp.2016.22.12.1426
    31. Foresi A. A comparison of the clinical efficacy and safety of intranasal fluticasone propionate and antihistamines in the treatment of rhinitis. Allergy. 2000;55 Suppl 62:12-14. doi:10.1034/j.1398-9995.2000.055suppl62012.x

    Guidelines and endorsement

    Recognized by leading experts as the drug of choice
    The Journal of Allergy and clinical immunology

    Dymista® is the recommended AR therapy in next-generation guidelines1

    • Dymista® is more effective vs. INS1,2 
    • Dymista® is effective within minutes1,3 
    • Dymista® is recommended for initiation and step-up treatment1 
    • INS is recommended therapy vs. INS + OAH1

    Dymista® can be considered the drug of choice for AR4
    Allergic Rhinitis and its impact on Asthma

    References:

    1. Bousquet J et al, Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading or Recommendations Assessment, Development and Evalution (GRADE) and real-world evidence, J Allergy Clin Immunol. 2020;145:70–80.
    2. Meltzer E et al. Clinically Relevant Effect of a New Intranasal Therapy (MP29-02) in Allergic Rhinitis Assessed by Responder Analysis.Int Arch Allergy Immunol 2013;161:369–77.
    3. Bousquet J et al, Onset of Action of the Fixed Combination Intranasal Azelastine-Fluticasone Propionate in an Allergen Exposure Chamber, JACI In Practice 2018;Volume 6, Issue 5:1726-1732.
    4. Carr et al. A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis. J Allergy Clin Immunol. 2012;129(5):1282–1289.

    Patient’s Profile

    Allergic rhinitis is the most common chronic respiratory disease in the world; estimated to affect 400 million people globally.1
    Epidemiological studies estimate that allergic rhinitis affects 10-30% of adults and 40% of children.1 In children, boys outnumber girls,2 but this tendency reverses in puberty with both sexes equally affected by adulthood.2 Globally, prevalence continues on an upward trajectory,1 thought to be a consequence of increased urbanization and improved living standards, which contribute to an increased exposure to a variety of indoor and outdoor pollutants and allergens.4 The size of the allergic rhinitis population depends upon where you live in the world (Figure).4 When symptomatic, allergic rhinitis patients report a significant negative impact on their quality of life (severity of impact), can experience a worsening of co-morbid conditions (notably asthma; the link between rhinitis and asthma) and cost the economy billions every year due to lost productivity.5–10

    The allergic rhinitis world map

    World Map

    Adapted from Tong M, Lin J. 2015.

    There is very little inter-racial variation in allergic rhinitis prevalence implying that environmental factors have a greater influence than genetic differences. Indeed, climate change is measurably altering the timing, distribution, quality and quantity of allergenic plants and aeroallergens, so that the season starts earlier, lasts longer, and is more intense (i.e. higher pollen load).11,12 These changes may affect the global distribution of allergic rhinitis incidence and prevalence, as well as symptom severity.13

    Which of my patients are more at risk of developing allergic rhinitis?
    Risk factors for the development of allergic rhinitis include:2,14–16

    • Presence of other allergic disease (e.g. asthma, eczema)
    • A family history of atopic diseases
    • Parental rhinitis
      • 3 times more likely if one parent has rhinitis
      • 4 times more likely if both parents have rhinitis
    • Increased total serum IgE before 6 years of age,
    • Allergenic sensitivity to common household aeroallergens and
    • higher socio-economic class

    What are my patients allergic to?

    Allergic rhinitis may be triggered by several different allergens. It is important to link allergen exposure and symptoms when making a diagnosis. Allergens or triggers are commonly divided into seasonal triggers (i.e. those present during a specific time of the year or season – e.g. pollen) and perennial triggers (i.e. those present during the whole year – e.g. house dust mite) (classification of allergic rhinitis).14 The relative prevalence of seasonal AR (SAR) and perennial AR (PAR) also varies by country, depending upon the most common prevailing allergens.14

    Seasonal triggers

    The duration of the pollen season varies from year to year and from country to country.17 The season is usually divided into different periods, since different types of pollen are released at different times (Table).
    Table: temporal trends for common seasonal triggers

    Tree,Grass, Sea grass

    Individuals may be sensitized to many different types of allergen (i.e. poly-sensitized) and in this instance can experience a very prolonged hay fever season.
    Perennial triggers
    The most common perennial triggers are house dust mite (HDM), pet dander and indoor mould (Table).14 Patients with perennial allergic rhinitis present to clinic throughout the year.
    Table: common perennial triggers

    sherb,Pet house,Bears

    On average, 3 out of every 10 of your patients could have allergic rhinitis, and this number is set to rise in the future1
    Climate change and urbanization means that more and more people are developing allergic rhintis. Are you ready to meet the challenge? 2-3
    The scale of the allergy epidemic means that symptoms cannot be avoided, but they can be treated!

    References:

    1. Pawankar R, Canonica GW, Holgate ST, Lockey RF, Blaiss MS. WAOJ White Book on Allergy. Published online 2013. https://www.worldallergy.org/UserFiles/file/WhiteBook2-2013-v8.pdf
    2. Kellberger J, Dressel H, Vogelberg C, et al. Prediction of the incidence and persistence of allergic rhinitis in adolescence: a prospective cohort study. J Allergy Clin Immunol. 2012;129(2):397-402, 402.e1-3. doi:10.1016/j.jaci.2011.08.016
    3. Global Atlas of Allergic Rhinitis & Chronic Rhinosinusitis. Eur Acad Allergy Clin Immunol. http://webcast.eaaci.cyim.com/mediatheque/media.aspx?mediaId=60232&channel=8518
    4. Tong M, Lin J. Epidemiology of allergic rhinitis throughout the world. Glob Atlas Allerg Rhinitis Chronic Rhinosinusitis. http://webcast.eaaci.cyim.com/mediatheque/media.aspx?mediaId=60232&channel=8518
    5. Price D, Scadding G, Ryan D, et al. The hidden burden of adult allergic rhinitis: UK healthcare resource utilisation survey. Clin Transl Allergy. 2015;5:39. doi:10.1186/s13601-015-0083-6
    6. Valovirta E, Myrseth S-E, Palkonen S. The voice of the patients: allergic rhinitis is not a trivial disease. Curr Opin Allergy Clin Immunol. 2008;8(1):1-9. doi:10.1097/ACI.0b013e3282f3f42f
    7. Bousquet PJ, Demoly P, Devillier P, Mesbah K, Bousquet J. Impact of allergic rhinitis symptoms on quality of life in primary care. Int Arch Allergy Immunol. 2013;160(4):393-400. doi:10.1159/000342991
    8. Cardell L-O, Olsson P, Andersson M, et al. TOTALL: high cost of allergic rhinitis-a national Swedish population-based questionnaire study. NPJ Prim Care Respir Med. 2016;26:15082. doi:10.1038/npjpcrm.2015.82
    9. Lamb CE, Ratner PH, Johnson CE, et al. Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective. Curr Med Res Opin. 2006;22(6):1203-1210. doi:10.1185/030079906X112552
    10. Clatworthy J, Price D, Ryan D, Haughney J, Horne R. The value of self-report assessment of adherence, rhinitis and smoking in relation to asthma control. Prim Care Respir J J Gen Pract Airw Group. 2009;18(4):300-305. doi:10.4104/pcrj.2009.00037
    11. Zhang Y, Bielory L, Mi Z, Cai T, Robock A, Georgopoulos P. Allergenic pollen season variations in the past two decades under changing climate in the United States. Glob Change Biol. 2015;21(4):1581-1589. doi:10.1111/gcb.12755
    12. Ziska LH, Makra L, Harry SK, et al. Temperature-related changes in airborne allergenic pollen abundance and seasonality across the northern hemisphere: a retrospective data analysis. Lancet Planet Health. 2019;3(3):e124-e131. doi:10.1016/S2542-5196(19)30015-4
    13. Fuertes E. Allergic rhinitis prevalence and climate change: a global ecological analysis. Glob Atlas Allerg Rhinitis Chronic Rhinosinusitis. http://webcast.eaaci.cyim.com/mediatheque/media.aspx?mediaId=60232&channel=8518
    14. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63 Suppl 86:8-160. doi:10.1111/j.1398-9995.2007.01620.x
    15. Baumann LM, Romero KM, Robinson CL, et al. Prevalence and risk factors for allergic rhinitis in two resource-limited settings in Peru with disparate degrees of urbanization. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2015;45(1):192-199. doi:10.1111/cea.12379
    16. Shaaban R, Zureik M, Soussan D, et al. Rhinitis and onset of asthma: a longitudinal population-based study. Lancet Lond Engl. 2008;372(9643):1049-1057. doi:10.1016/S0140-6736(08)61446-4
    17. Smith M, Jäger S, Berger U, et al. Geographic and temporal variations in pollen exposure across Europe. Allergy. 2014;69(7):913-923. doi:10.1111/all.12419
    18. Cho S-H, Reponen T, Bernstein DI, et al. The effect of home characteristics on dust antigen concentrations and loads in homes. Sci Total Environ. 2006;371(1-3):31-43. doi:10.1016/j.scitotenv.2006.09.001
    19. Chan SK, Leung DYM. Dog and Cat Allergies: Current State of Diagnostic Approaches and Challenges. Allergy Asthma Immunol Res. 2018;10(2):97-105. doi:10.4168/aair.2018.10.2.97
    20. WHO Guidelines for indoor air quality. https://www.euro.who.int/__data/assets/pdf_file/0017/43325/E92645.pdf?ua=1

    Patient’s Materials

    Patient’s Material

    How to use a Nasal Spray
    Patient’s Material 

    What does uncontrolled AR mean?

    Classification of AR symptoms

    Current AR guidelines define uncontrolled AR as--≥5.1-3

    What does uncontrolled mean?
    Allergic symptoms bothering you today

    New guidelines state VAS as a useful tool to assess symptom control in AR.2

    Patients’ AR symptom control status1,*
    VAS > 5

    MCAVIA clinical decision algorithm

    Dymista® recommended first-line treatment for AR patients with a VAS ≥51,*

    References:

    *In patients previously treated or self-medicated. Modified from Bousquet J, et al. 2016.

    1. Bousquet J, et al. MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis. J allergy clin immunol. 2016;138(2):367–74.
    2. EAACI, Global Atlas of Allergic Rhinitis and Chronic Rhinosinusitis. 2015.
    3. Bousquet J, et al, Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence. J Allergy Clin Immunol. 2020;145:70–80.

    Abbreviated Prescribing Information

    [Dymista]® abbreviated prescribing information

    PRESENTATION: Bottle Nasal Spray, with 23g (17ml) of suspension in 25 mL bottles (at least 120 actuations).

    One actuation (0.14 g) delivers 137 micrograms azelastine hydrochloride (= 125 micrograms azelastine) and 50 micrograms fluticasone propionate.

    INDICATIONS: Relief of symptoms of moderately severe to severe seasonal and perennial allergic rhinitis if monotherapy with either intranasal antihistamine or glucocorticoid is not considered sufficient.

    DOSAGE AND ADMINISTRATION: Adults and adolescents (12 years and older): One actuation in each nostril twice daily (morning and evening). Children below 12 years: Dymista Nasal Spray is not recommended for use in children below 12 years of age, as safety and efficacy has not been established in this age group. Elderly patients: No dose adjustment is required in this population. Patients with renal and hepatic impairment: There are no data on patients with renal or hepatic impairment. Duration of treatment: Dymista Nasal Spray is suitable for long-term use. The duration of treatment should correspond to the period of allergenic exposure. Pregnancy: There are no, or only limited, data from the use of azelastine hydrochloride and fluticasone propionate in pregnant women. Therefore, Dymista Nasal Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Breast-feeding: It is unknown whether nasally administered azelastine hydrochloride/metabolites or fluticasone propionate/metabolites are excreted in human breast milk. Dymista Nasal Spray should be used during lactation only if the potential benefit for the mother is higher than the potential risk to the newborn/infant. Method of administration: Dymista Nasal Spray is for nasal use only. Instruction for use Preparing the spray:The bottle should be shaken well before use for about 5 seconds by tilting it upwards and downwards. Then remove the protective cap. Prior to first use, Dymista Nasal Spray must be primed by pressing down and releasing the pump 6 times. If Dymista Nasal Spray has not been used for more than 7 days it must be reprimed by pressing down and releasing the pump once. Using the spray: The bottle should be shaken well before use for about 5 seconds by tilting it upwards and downwards. Then remove the protective cap. After blowing one's nose the suspension is sprayed once into each nostril keeping the head tilted downward . After use, wipe the spray tip and replace the protective cap.

    CONTRAINDICATIONS: Hypersensitivity to the active substances or to any of the excipients.

    WARNING AND PRECAUTIONS: Clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side- effects. Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods. Potential systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and, more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Dymista Nasal Spray undergoes extensive first-pass metabolism, therefore the systemic exposure of intranasal fluticasone propionate is likely to be increased in patients with severe liver disease. This may result in a higher frequency of systemic adverse events. Caution is advised when treating these patients. Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery. In general the dose of intranasal fluticasone formulations should be reduced to the lowest level at which effective control of the symptoms of rhinitis is maintained. Higher doses than the recommended one have not been tested for Dymista. As with all intranasal corticosteroids, the total systemic burden of corticosteroids should be considered whenever other forms of corticosteroid treatment are prescribed concurrently. Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses. Since adolescents may also still be growing, it is recommended that the growth of adolescents receiving prolonged treatment with nasal corticosteroids is regularly monitored, too. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid, if possible, to the lowest dose at which effective control of symptoms is maintained. Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids. Close monitoring is required in patients with a change in vision or with a history of increased ocular pressure, glaucoma and/or cataracts. If there is any reason to believe that adrenal function is impaired, care must be taken when transferring patients from systemic steroid treatment to Dymista Nasal Spray. In patients who have tuberculosis or any other type of untreated infection, or have had a recent surgical operation or injury to the nose or mouth, the possible benefits of the treatment with Dymista Nasal Spray should be weighed against possible risk. Upper respiratory tract infections should be treated with antibacterial or antimycotic drugs, but do not constitute a specific contraindication to treatment with Dymista Nasal Spray. Dymista contains benzalkonium chloride. It may cause irritation of the nasal mucosa and bronchospasm. The preservative contained in Dymista (benzalkonium chloride) can cause swelling of the nasal mucosa, especially with prolonged use. If there is reason to suspect such a reaction (persistent blocked nose), a medicinal product that does not contain any preservative should be used in the nose if possible. If such preservative-free medicinal products for intranasal use are not available, a different pharmaceutical form should be considered.

    INTERACTIONS: Fluticasone propionate: Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after intranasal dosing. Co-treatment with other CYP 3A4 inhibitors, including cobicistat-containing products is also expected to increase the risk of systemic side- effects. other inhibitors of cytochrome P450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. Nevertheless, care is advised when co-administering potent cytochrome P450 3A4 inhibitors (e.g. ketoconazole), as there is potential for increased systemic exposure to fluticasone propionate. Azelastine hydrochloride: No specific interaction studies with azelastine hydrochloride nasal spray have been performed. Nevertheless, care should be taken when administering azelastine hydrochloride in patients taking concurrent sedative or central nervous medications because the sedative effect may be strengthened. Alcohol may also enhance this effect.

    OVERDOSING: With the nasal route of administration, overdose reactions are not anticipated. Administration of doses higher than those recommended over a long period of time may lead to temporary suppression of adrenal function. In these patients, treatment with Dymista Nasal Spray should be continued at a dose that is just sufficient to control symptoms; the adrenal function will recover in a few days and can be verified by measuring plasma cortisol. In the event of overdose after accidental oral uptake, disturbances of the central nervous system (including drowsiness, confusion, coma, tachycardia and hypotension) caused by azelastine hydrochloride are to be expected, based on the results of animal experiments.

    ADVERSE REACTION: Very Common adverse reactions (≥1/10): Epistaxis. Common adverse reactions (≥1/100 to <1/10): Headache, dysgeusia (unpleasant taste), unpleasant smell

    PHARMACEUTICAL PRECAUTIONS: Shelf life: 24 months.

    Special precautions for storage: Store below 30°C Do not refrigerate or freeze.

    Special precautions for disposal and other handling: No special requirements for disposal.

    REFERENCE: Dymista [SmPC]. MEDA Pharma GmbH & Co. KG; Bad Homburg. January 2019

    Date of This Document: 22 August 2021

    FULL PRESCRIBING INFORMATION IS AVAILABLE UPON REQUEST

    DYM-2022-0248

    Full Prescribing information