The FDA has approved Ryaltris (Hikma), a fixed-dose combination nasal spray containing the H₁-antihistamine olopatadine hydrochloride (Patanase, and generics) and the corticosteroid mometasone furoate (Nasonex 24 HR Allergy, and generics), for treatment of seasonal allergic rhinitis symptoms in persons ≥12 years old. Ryaltris is the second intranasal antihistamine/corticosteroid combination to be approved for this indication; azelastine 0.1%/fluticasone propionate (Dymista, and generics), which is approved for use in persons ≥6 years old, was the first. Both products are available only by prescription.

The 0.15% nasal spray formulation of the H₁- antihistamine azelastine hydrochloride (Astepro Allergy; Children's Astepro Allergy – Bayer) is now available over the counter (OTC) for temporary relief of nasal congestion, runny nose, sneezing, and itchy nose due to allergic rhinitis in adults and children ≥6 years old. It is the first intranasal antihistamine to be approved by the FDA for OTC use. Other drugs that are available OTC for treatment of allergic rhinitis symptoms include oral antihistamines, intranasal corticosteroids, and mast cell stabilizers.

The choice of drugs for treatment of allergic rhinitis depends on the severity of symptoms and whether they are intermittent or persistent (see Table 1).

View the Comparison Table: Some Oral Drugs for Allergic Rhinitis

View the Comparison Table: Some Nasal Sprays for Allergic Rhinitis

A 0.24% ophthalmic solution of the second-generation H₁-antihistamine cetirizine (Zerviate – Eyevance) is now available by prescription for treatment of ocular itching associated with allergic conjunctivitis in patients ≥2 years old. Oral cetirizine (Zyrtec, and others), which is used for treatment of allergic conjunctivitis and rhinitis, has been available over the counter (OTC) for years.

The FDA is requiring stronger warnings in the labeling of the leukotriene receptor antagonist montelukast (Singulair, and generics) about the risk of suicidal behavior and other serious neuropsychiatric events associated with its use.

Patients with seasonal allergies often experience nasal itching and congestion, sneezing, rhinorrhea, and itchy, watery eyes. Oral, intranasal, and ophthalmic preparations are widely available over the counter (OTC) for relief of symptoms. Prescription products for management of allergic rhinitis and allergic conjunctivitis are reviewed separately.

The FDA has approved Odactra (ALK), a sublingual allergen extract, for immunotherapy in adults 18-65 years old with house dust mite (HDM)-induced allergic rhinitis, with or without conjunctivitis. Odactra is the first sublingual allergen extract to be approved in the US for this indication. Three other sublingual allergen extracts were approved earlier (see Table 1).

Allergic rhinitis can be classified as seasonal, perennial, or episodic. It is often associated with allergic conjunctivitis, rhinosinusitis, and asthma.

H₁-ANTIHISTAMINES — Oral – Oral second-generation H₁-antihistamines are the preferred first-line treatment for relief of the itching, sneezing, and rhinorrhea that characterize mild-to-moderate allergic rhinitis. They are less effective for nasal congestion.

View the Comparison Table: Some Oral Drugs for Allergic Rhinitis

View the Comparison Table: Some Nasal Sprays for Seasonal Allergic Rhinitis

The nasal spray formulation of the corticosteroid fluticasone furoate is now available over the counter (OTC) as Flonase Sensimist Allergy Relief (GSK) in the same strength as the prescription product (Veramyst) for treatment of seasonal or perennial allergic rhinitis. It is the fourth intranasal corticosteroid to become available OTC.

In 2007, an FDA advisory committee asked that placebo-controlled, dose-ranging trials be conducted to establish the efficacy of the oral decongestant phenylephrine (Sudafed PE, and others), which is sold over the counter (OTC) as a single agent and in combination with other drugs for treatment of cold and allergy symptoms. Phenylephrine replaced pseudoephedrine (Sudafed, and others) in many OTC formulations when access to pseudoephedrine-containing products was restricted in an effort to reduce their use in the synthesis of methamphetamine.

CLINICAL STUDIES — In a randomized, open-label, dose-ranging trial in 539 patients with seasonal allergic rhinitis, phenylephrine doses up to four times the recommended dose of 10 mg were no more effective than placebo in reducing symptomatic nasal congestion.1 Other recent studies have also found oral phenylephrine no more effective than placebo in reducing nasal congestion.2-4

ALTERNATIVES – Oral pseudoephedrine reduces nasal congestion, but has no effect on other symptoms such as sneezing, itching, or rhinitis, and tolerance to its effects can occur with repeated use. Potential adverse effects include insomnia, excitability, headache, nervousness, anorexia, palpitations, tachycardia, arrhythmias, hypertension, nausea, vomiting, and urinary retention. Pseudoephedrine should be used cautiously in patients with cardiovascular disease, hypertension, diabetes, hyperthyroidism, narrow-angle glaucoma, or bladder neck obstruction.

Intranasal decongestants such as oxymetazoline (Afrin, and others) are effective and less likely than pseudoephedrine to cause systemic adverse effects, but they can cause stinging, burning, sneezing, dryness of the nose and throat, and, if used for more than 3-5 consecutive days, rebound congestion (rhinitis medicamentosa). Intranasal corticosteroids are the most effective drugs available for prevention and relief of nasal congestion and other seasonal allergic rhinitis symptoms.5

CONCLUSION — Oral phenylephrine is not effective for treatment of nasal congestion.

1. EO Meltzer et al. Oral phenylephrine HCl for nasal congestion in seasonal allergic rhinitis: a randomized, open-label, placebo-controlled study. J Allergy Clin Immunol Pract 2015; 3:702.
2. EO Meltzer at al. Phenylephrine hydrochloride modified-release tablets for nasal congestion: a randomized, placebo-controlled trial in allergic rhinitis patients. Ann Allergy Asthma Immunol 2015 November 7 (epub).
3. F Horak et al. A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber. Ann Allergy Asthma Immunol 2009; 102:116.
4. JH Day et al. Efficacy of loratadine-montelukast on nasal congestion in patients with seasonal allergic rhinitis in an environmental exposure unit. Allergy Asthma Immunol 2009; 102:328.
5. Drugs for allergic disorders. Treat Guidel Med Lett 2013; 11:43.

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The nasal spray formulation of the corticosteroid fluticasone propionate is now available over the counter (OTC) as Flonase Allergy Relief (GSK) in the same strength as the prescription product (Flonase, and generics) for patients ≥4 years old with seasonal or perennial allergic rhinitis. It is the second corticosteroid nasal spray to become available OTC; triamcinolone acetonide (Nasacort Allergy 24HR) was the first. Unlike prescription Flonase, the OTC product is FDA-approved for reduction of ocular as well as nasal symptoms. Brand-name prescription Flonase has been discontinued by the manufacturer.

The FDA has approved 3 allergen extracts for sublingual administration as immunotherapy for allergic rhinitis confirmed by a positive skin test or in vitro testing for pollen-specific IgE antibodies: Oralair (Stallergenes S.A./Greer) and Grastek (Merck) for grass pollen-induced allergic rhinitis and Ragwitek (Merck) for short ragweed pollen-induced allergic rhinitis.

The FDA has approved the over-the-counter (OTC) sale of Nasacort Allergy 24HR (Sanofi), a triamcinolone acetonide nasal spray previously available only by prescription as Nasacort AQ. The OTC product, which is scheduled to be marketed in the spring of 2014, will be the first corticosteroid nasal spray that can be purchased without a prescription in the US. Nasacort Allergy 24HR is approved for use in patients ≥2 years old with nasal allergy symptoms.

INHALATION DEVICES — Metered-dose inhalers (MDIs) require coordination of inhalation with hand-actuation of the device. Valved holding chambers (VHCs) or spacers help some patients, especially young children and the elderly, use MDIs effectively. VHCs have one-way valves that prevent the patient from exhaling into the device, minimizing the need for coordinated actuation and inhalation. Spacers are tubes or chambers placed between the canister and a face mask or mouthpiece, which also avoids the need to coordinate actuation and inhalation. Both VHCs and spacers retain the larger particles emitted from the MDI, decreasing their deposition in the oropharynx and leading to a higher proportion of small respirable particles being inhaled.

Omalizumab (Xolair) is a recombinant humanized monoclonal anti-IgE antibody currently approved by the FDA for treatment of moderate to severe persistent allergic asthma. It has been used off-label for treatment of allergic rhinitis and food allergies. Recently the results of a phase III clinical trial indicated that omalizumab may be effective in treating chronic urticaria as well.

The use of drugs to prevent and control symptoms of allergic disorders can be optimized when patients avoid exposure to specific allergens and/or environmental conditions that trigger or worsen their symptoms.

The FDA has approved a nasal spray fixed-dose combination (Dymista – Meda) of the H₁-antihistamine azelastine (Astelin, Astepro, and generics) and the corticosteroid fluticasone propionate (Flonase, and generics) for treatment of seasonal allergic rhinitis (SAR) in patients ≥12 years old who need both medications for symptomatic relief. It is the first nasal spray to be approved in the US that contains both an H₁-antihistamine and a corticosteroid.

The FDA has approved 2 intranasal HFA (hydrofluoroalkane) aerosols of the corticosteroids beclomethasone dipropionate (Qnasl – Teva Respiratory) and ciclesonide (Zetonna – Sunovion) for once-daily treatment of seasonal and perennial allergic rhinitis. They are the first HFA nasal steroids to become available in the US (HFA propellants do not deplete the ozone layer). Both drugs are already available for these indications as aqueous nasal sprays. Aqueous ("wet") formulations can cause adverse effects such as postnasal drip, moist feeling in the nose, strong odor, and bitter aftertaste, which could reduce patient compliance and may lead to discontinuation of the medication; the new pressurized, odorless, non-aqueous ("dry") HFA formulations may be better tolerated.

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Inhalation is the preferred route of delivery for most asthma drugs. Chlorofluorocarbons (CFCs), which have ozone-depleting properties, are being phased out as propellants in metered-dose inhalers. Non-chlorinated hydrofluoroalkane (HFA) propellants, which do not deplete the ozone layer, are being used instead.

A new formulation of the H1-antihistamine azelastine hydrochloride 0.1% nasal spray (Astepro - Meda) has been approved by the FDA for treatment of seasonal allergic rhinitis (SAR) in patients ≥12 years old and is being heavily advertised to the public on radio, television and the Internet. All azelastine products require a prescription.

Olopatadine 0.6% nasal spray (Patanase - Alcon) has been approved by the FDA for treatment of seasonal allergic rhinitis in patients ≥ 12 years old. An H1-antihistamine with mast-cell stabilizing activity, olopatadine is already marketed for treatment of allergic conjunctivitis in a 0.1% solution as Patanol and in a 0.2% solution as Pataday. Azelastine (Astelin), another H1-antihistamine with mast-cell stabilizing activity, has been available for intranasal treatment of allergic rhinitis since 1997.

Ciclesonide (Omnaris - Sepracor/Nycomed), a once daily corticosteroid nasal spray, is now available for treatment of seasonal allergic rhinitis (SAR) in adults and children ≥6 years old and for perennial allergic rhinitis (PAR) in those ≥12 years old. An orally inhaled formulation of ciclesonide (Alvesco) was recently approved by the FDA for maintenance treatment of asthma, and will be reviewed in a future issue of The Medical Letter

Cetirizine (Zyrtec, and others) and cetirizine/pseudoephedrine (Zyrtec-D) are becoming available without a prescription this month for treatment of allergic rhinitis and urticaria in adults and children. Cetirizine is the second of the second-generation H1-antihistamines to become available over the counter. Loratadine (Claritin, and others) was the first.

Cetirizine has been shown to be more effective than loratadine in suppressing histamine-induced wheals in healthy volunteers (W Carey et al. Drugs Exp Clin Res 2002; 28:243), but no well-controlled clinical trials have established that any second-generation H1-antihistamine is more effective overall than any other (M Plaut and MD Valentine. N Engl J Med 2005; 353:1934).

Cetirizine may be mildly sedating in some patients, but it is significantly less sedating than first-generation H1-antihistamines such as diphenhydramine (Benadryl, and others) or chlorpheniramine (Chlor-Trimeton, and others), which have been available without a prescription for many years. Its safety in young children is better documented than that of any other first- or second-generation H1-antihistamine (Treat Guidel Med Lett 2007; 5:71).

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Levocetirizine (Xyzal - UCB/Sanofi-aventis), the active enantiomer of the second-generation H₁-antihistamine cetirizine (Zyrtec), has been approved by the FDA for treatment of seasonal and perennial allergic rhinitis (SAR and PAR) and chronic idiopathic urticaria in adults and children 6 years of age and older. Cetirizine has been approved by the FDA for over-the-counter use and may also become available generically in the US. Levocetirizine has been available in Europe since 2001.

Fluticasone furoate nasal spray (Veramyst - GSK) is now available for once-daily treatment of seasonal and perennial allergic rhinitis in adults and children ≥2 years old. It is similar to fluticasone propionate nasal spray (Flonase, and others), which is now available generically.

Allergic rhinitis, allergic conjunctivitis, atopic dermatitis, urticaria, anaphylaxis and asthma (reviewed in Treatment Guidelines 2005; 3:33 and not included here), are prevalent worldwide, especially in industrialized countries. Pharmacologic treatment of these disorders continues to improve in efficacy and safety. In addition to using drugs to prevent and control the symptoms of their allergic diseases, patients should also be instructed to avoid, if possible, specific allergens and/or environmental conditions that trigger or worsen their symptoms.

Montelukast (Singulair - Merck) is an oral cysteinyl leukotriene D₄ receptor antagonist originally marketed for treatment of asthma. It was approved by the FDA in 2003 for treatment of seasonal allergic rhinitis and recently for use in perennial allergic rhinitis in adults and children ≥ 6 months old. Intranasal corticosteroids have generally been considered the most effective drugs available for prevention and treatment of allergic rhinitis.

Allergic rhinitis, allergic conjunctivitis, atopic dermatitis, urticaria and anaphylaxis, along with asthma (reviewed in Treatment Guidelines 2002; 1:7 and not included here), have increased in prevalence during the past 30 years and are now epidemic worldwide, especially in industrialized countries. Many safe and effective drugs are currently available for prevention and relief of symptoms in these disorders, but pharmacological treatment alone may not be sufficient. Patients should also be instructed to avoid specific allergens or environmental conditions that trigger their symptoms. Allergen-specific immunotherapy, parenteral administration of gradually increasing doses of the allergen ("allergy shots"), has been effective in allergic rhinitis, allergic conjunctivitis and allergic asthma, and also in prevention of anaphylaxis triggered by stings from bees, yellow jackets, hornets and wasps. It has not been effective in food allergy, atopic dermatitis or urticaria.

The FDA has approved release of omalizumab (oh mah lye zoo mab; Xolair - Genentech, Novartis), a humanized monoclonal antibody given subcutaneously that binds to immunoglobulin E (IgE). The drug is labeled for patients at least 12 years old with moderate to severe persistent asthma who have shown reactivity to an allergen and whose symptoms are inadequately controlled by an inhaled corticosteroid. The manufacturer claims the drug can help stop allergic reactions before they begin.

Montelukast (Singulair - Merck), a leukotriene receptor antagonist already marketed for asthma (Treatment Guidelines from The Medical Letter 2002; 1:11), has been approved by the FDA for treatment of seasonal allergic rhinitis in adults and children more than 2 years old.

Desloratadine (des lor at' a deen; Clarinex - Schering), an active metabolite of the H1-receptor antagonist loratadine (Claritin), has been approved by the FDA for oral treatment of allergic rhinitis and chronic urticaria in patients at least 12 years old. The patent for loratadine expires in December 2002, and generic or over-the-counter versions are expected.

Advertisements for clemastine (Tavist-1 - Sandoz), an ethanolamine oral antihistamine, have recently appeared on television and in major newspapers in the USA. Clemastine is an old drug (Medical Letter, 21:24, 1979) that has now become available without a prescription.

Astemizole (Hismanal - Janssen), a new antihistamine, was recently marketed in the USA for treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. Like terfenadine (Seldane - Medical Letter, 27:65, 1985), astemizole is claimed to be no more sedating than placebo, but the new drug offers the advantage of a once-daily dosage schedule.