Allergy Medications Compared

Diphenhydramine is the original antihistamine and one of the most widely recognized drug names in medicine. It blocks H1 histamine receptors, producing rapid relief of allergic symptoms including itching, urticaria (hives), and allergic rhinitis. However, it also crosses the blood-brain barrier readily, producing pronounced sedation — a consequence of both its antihistamine activity in the CNS and its potent anticholinergic effects (blocking muscarinic acetylcholine receptors). These anticholinergic effects include dry mouth, urinary retention, constipation, blurred vision, and tachycardia.

Beyond allergy, diphenhydramine is marketed under different brand names for sleep (ZzzQuil, Unisom SleepTabs) and is included in many combination cold and nighttime products. The American Geriatrics Society Beers Criteria explicitly lists diphenhydramine as a medication to avoid in adults aged 65 and older due to the risk of confusion, delirium, falls, and cognitive impairment associated with its anticholinergic properties. Tolerance to the sedative effect develops with repeated use, making it poorly suited for chronic sleep use.

Chlorpheniramine is a first-generation antihistamine with a longer half-life than diphenhydramine, allowing for less frequent dosing. It is less sedating than diphenhydramine but still crosses the blood-brain barrier and carries anticholinergic properties. Chlorpheniramine is commonly found as an ingredient in combination cold and allergy products — most notably DayQuil and many other multi-symptom formulations — where it addresses the runny nose and sneezing components.

Extended-release tablet formulations (8mg and 12mg) are available for sustained, once- or twice-daily symptom control. As a 1st-generation agent, chlorpheniramine is still subject to the Beers Criteria caution in elderly patients, though its anticholinergic burden is somewhat lower than diphenhydramine. It remains a cost-effective, widely available option for short-term allergy symptom control when non-sedating alternatives are unavailable or not tolerated.

Promethazine is a phenothiazine-class compound with potent H1 antihistamine and anticholinergic activity. Unlike most antihistamines, it also has significant dopamine receptor antagonism, which underlies its powerful antiemetic (anti-nausea and anti-vomiting) properties. It is used clinically for allergic conditions, motion sickness, nausea and vomiting, and as a sedative adjunct. Available formulations include oral tablets, syrup, suppositories, and injectable forms.

Promethazine carries an FDA black box warning against its use in children younger than 2 years of age due to the risk of potentially fatal respiratory depression. Even in older children, it should be used with extreme caution. In some states, promethazine is a Schedule V controlled substance. The IV formulation carries additional warnings about severe tissue injury if administered incorrectly. Additive CNS depression with alcohol, opioids, and other sedatives is a significant safety concern.

Hydroxyzine is a first-generation antihistamine with additional anxiolytic (anti-anxiety) properties, making it clinically distinct from other agents in the class. It is used for both allergic conditions — particularly chronic urticaria and pruritus (itching) — and for the short-term management of anxiety and tension. Its sedative properties are often leveraged for preoperative sedation and as an adjunct to anesthesia. Hydroxyzine does not cause physical dependence, which distinguishes it from benzodiazepines for anxiety management.

Two salt forms are available: hydroxyzine pamoate (Vistaril, capsules) and hydroxyzine HCl (Atarax, tablets). Both are pharmacologically equivalent after absorption. Hydroxyzine carries a QT prolongation risk, which is important to consider in patients with cardiac disease or those taking other QT-prolonging agents. Like all 1st-generation antihistamines, it is on the Beers Criteria list for older adults. Manufacturer for brand Vistaril is Pfizer.

Loratadine was among the first 2nd-generation antihistamines to reach the OTC market in the United States. By design, it has minimal CNS penetration, producing little to no sedation at standard doses and no clinically meaningful anticholinergic effects. It is indicated for the relief of seasonal and perennial allergic rhinitis symptoms and chronic idiopathic urticaria. Loratadine is metabolized to desloratadine (see below), an active compound with its own prolonged half-life of approximately 27 hours, contributing to sustained antihistamine coverage beyond the parent drug's 8-hour half-life.

Multiple formulations are available OTC: standard tablets, chewable tablets for children, orally disintegrating tablets (ODT), and syrup. Loratadine is a preferred antihistamine in elderly patients because it lacks anticholinergic effects. Bayer is the manufacturer of the brand Claritin. Combination products with pseudoephedrine (Claritin-D 12 Hour, Claritin-D 24 Hour) add decongestant activity for patients with both nasal congestion and allergic rhinitis.

Cetirizine is a highly potent 2nd-generation antihistamine and is the active metabolite of hydroxyzine. While it is classified as non-sedating, clinical experience and comparative studies show that it is slightly more sedating than loratadine or fexofenadine — a meaningful distinction for patients who need to drive or operate machinery, particularly at the higher end of the OTC strength range. Despite this, it remains far less sedating than any 1st-generation antihistamine. Cetirizine is effective for seasonal and perennial allergic rhinitis and chronic idiopathic urticaria.

Its slightly higher sedation profile can be advantageous for patients with nighttime allergy symptoms who benefit from improved sleep. Multiple OTC formats are available including tablets, chewable tablets, and syrup for pediatric use. Johnson & Johnson manufactures the Zyrtec brand. Like loratadine, combination products with pseudoephedrine exist (Zyrtec-D) for patients with concurrent nasal congestion, available behind the pharmacy counter.

Fexofenadine is the least sedating antihistamine available and does not penetrate the blood-brain barrier to any clinically meaningful degree. It is the active metabolite of terfenadine, an earlier antihistamine withdrawn from the market due to cardiac arrhythmia risk — fexofenadine does not carry that risk. It is FDA-approved for seasonal allergic rhinitis in adults and children aged 2 and older, and for chronic idiopathic urticaria. Its negligible sedation profile and complete absence of anticholinergic effects make it an excellent choice for patients who cannot tolerate any impairment.

An important food-drug interaction exists: grapefruit juice, orange juice, and apple juice can significantly reduce fexofenadine absorption by inhibiting intestinal drug transporters — patients should take fexofenadine with water rather than fruit juice. The 180mg tablet is dosed once daily for allergic rhinitis; 60mg formulations are available for twice-daily use. Sanofi manufactures the Allegra brand. Allegra-D combines fexofenadine with pseudoephedrine for patients with nasal congestion.

Desloratadine is the active metabolite of loratadine, offering a long 27-hour half-life that supports once-daily dosing with consistent plasma levels. As a prescription-only agent, it does not offer advantages over OTC loratadine that are clinically compelling for most patients — it is primarily differentiated by its pediatric syrup formulation at a lower concentration and slightly greater H1 receptor affinity. FDA indications include seasonal allergic rhinitis, perennial allergic rhinitis, and chronic idiopathic urticaria. Merck manufactures the Clarinex brand.

Levocetirizine is the active R-enantiomer of cetirizine, developed to provide antihistamine efficacy with a potentially improved tolerability profile. Like desloratadine's relationship to loratadine, levocetirizine is the pharmacologically active half of the cetirizine molecule. It is available both by prescription and over the counter. FDA-approved for seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. UCB is the manufacturer of the brand Xyzal. Its sedation profile is comparable to cetirizine, and renal dose adjustments are required in patients with kidney impairment.

Fluticasone propionate (Flonase) is one of the most widely used nasal corticosteroids and is available over the counter in the United States. Delivered as 50 micrograms per spray, it is indicated for seasonal and perennial allergic rhinitis and also reduces non-allergic rhinitis symptoms. Flonase has data supporting benefit for ocular allergy symptoms as well, through a mechanism thought to involve reduced systemic histamine release. Haleon (formerly GSK Consumer Healthcare) manufactures the brand. It is typically delivered as one or two sprays per nostril once daily.

Fluticasone furoate is a distinct chemical entity from fluticasone propionate, with higher glucocorticoid receptor affinity and a different pharmacokinetic profile. Flonase Sensimist delivers 27.5 micrograms per spray in an alcohol-free, aqueous (scent-free, gentle mist) formulation that eliminates the burning or stinging sensation some patients experience with alcohol-containing sprays. It is particularly well-tolerated for patients with sensitive nasal passages or who have had difficulty using other sprays. It is also OTC for ages 2 and older.

Triamcinolone acetonide (Nasacort) was approved for OTC sale in 2014, making it one of the first prescription-strength nasal corticosteroids available without a prescription. It delivers 55 micrograms per spray in an unscented, alcohol-free aqueous formulation and is indicated for seasonal and perennial allergic rhinitis in adults and children aged 2 and older. Chattem (a Sanofi company) manufactures the brand. Clinical efficacy is comparable to other OTC nasal corticosteroids.

Budesonide (Rhinocort) is an OTC nasal corticosteroid delivering 32 micrograms per spray in an alcohol-free, fragrance-free aqueous formulation. It is approved for allergic rhinitis in adults and children 6 years and older OTC. Johnson & Johnson manufactures the Rhinocort brand. Budesonide is among the most studied corticosteroids and is also used in oral, inhaled, and rectal forms for other indications including asthma and inflammatory bowel disease — the nasal formulation has minimal systemic absorption.

Mometasone furoate (Nasonex) is a prescription nasal corticosteroid delivering 50 micrograms per spray with very low systemic bioavailability (less than 0.1%). In addition to allergic rhinitis, it is FDA-approved for the treatment of nasal polyps — an indication not shared by all nasal corticosteroids. It is also available in an OTC generic form in some markets. Merck manufactures the Nasonex brand.

Beclomethasone is one of the oldest inhaled and intranasal corticosteroids, with decades of clinical use. Beconase AQ delivers 42 micrograms per spray in an aqueous formulation and is typically dosed twice daily. Qnasl is a dry propellant-based formulation available in 80mcg and 320mcg per actuation strengths for different indications and patient populations. Both require a prescription. Beclomethasone is fully metabolized to active monoester metabolites in the nasal mucosa.

Ciclesonide is a prodrug nasal corticosteroid that is pharmacologically inactive as delivered. It is cleaved by nasal mucosal enzymes to its active metabolite (des-ciclesonide) directly at the site of action, which minimizes systemic absorption and reduces potential systemic steroid effects. Omnaris delivers 50 micrograms per spray in an aqueous formulation; Zetonna is a non-aqueous (hydrofluoroalkane propellant) aerosol delivering 37 micrograms per actuation. Both are once-daily and prescription-only for seasonal and perennial allergic rhinitis.

Pseudoephedrine is a sympathomimetic amine that acts on alpha- and beta-adrenergic receptors to constrict nasal blood vessels, reducing mucosal swelling and congestion. It is the most effective oral decongestant available and is sold OTC but must be kept behind the pharmacy counter under the Combat Methamphetamine Epidemic Act (CMEA), with purchase limits and ID requirements because it can be used as a precursor to methamphetamine synthesis.

Pseudoephedrine raises blood pressure and heart rate and should be avoided in patients with hypertension, hyperthyroidism, coronary artery disease, closed-angle glaucoma, or those taking MAO inhibitors. It can also cause insomnia and restlessness. Extended-release tablets are available for 12-hour and 24-hour dosing. It is commonly combined with antihistamines in products such as Claritin-D and Allegra-D.

Phenylephrine is marketed as a decongestant in front-of-shelf OTC products. However, in September 2023, an FDA advisory committee concluded that oral phenylephrine at OTC doses is not effective as a nasal decongestant — the drug undergoes extensive first-pass metabolism in the gut and liver, leaving very little active drug to reach nasal blood vessels. The FDA is reviewing the status of oral phenylephrine products. Nasal spray formulations of phenylephrine may retain some local efficacy, but pseudoephedrine remains significantly more effective for oral decongestant use.

Oxymetazoline is a topical alpha-adrenergic agonist that produces rapid, potent nasal decongestion within minutes by constricting blood vessels in the nasal mucosa. It is highly effective for short-term relief of nasal congestion. The critical limitation is that use beyond 3 consecutive days leads to rhinitis medicamentosa — rebound congestion as each dose wears off. The nasal vasculature becomes dependent on the drug to maintain patency, and congestion upon cessation becomes worse than the original condition. Treatment of established rhinitis medicamentosa typically requires discontinuing oxymetazoline (sometimes with a nasal corticosteroid bridge).

Montelukast is a leukotriene receptor antagonist that blocks cysteinyl leukotriene receptors (CysLT1), reducing the inflammatory cascade triggered by allergen exposure. Leukotrienes — released by mast cells and eosinophils — cause bronchospasm, increased mucus production, and nasal inflammation. By blocking their action, montelukast reduces both allergic rhinitis symptoms and asthma symptoms. It is FDA-approved for seasonal and perennial allergic rhinitis and for asthma prophylaxis in patients aged 12 months and older.

In 2020, the FDA added a black box warning for serious neuropsychiatric events including agitation, aggression, depression, anxiety, sleep disturbances, and suicidal thoughts and behaviors. These events have occurred in patients with no prior psychiatric history. The FDA recommends reserving montelukast for patients who do not respond adequately or cannot tolerate other allergy treatments. Merck manufactures the Singulair brand.

Zafirlukast is a leukotriene receptor antagonist indicated for the prophylaxis and chronic treatment of asthma in patients aged 5 and older. Unlike montelukast, zafirlukast must be taken on an empty stomach (food significantly reduces absorption) and is dosed twice daily. It inhibits CYP2C9 and can increase the effects of warfarin — INR monitoring is recommended in patients on anticoagulation. Hepatic function monitoring is advisable given rare reports of hepatotoxicity. AstraZeneca manufactures Accolate.

Cromolyn sodium stabilizes mast cells and prevents them from releasing histamine and other inflammatory mediators when triggered by allergens. It is unique among allergy medications in being entirely preventive — it has no therapeutic effect once an allergic reaction has already begun. Patients must start using cromolyn before allergen exposure (ideally 1–2 weeks before allergy season) and continue regular dosing throughout the exposure period. It has an excellent safety profile with virtually no systemic absorption and no known significant side effects, making it a particularly good option for patients who cannot tolerate other agents. Prestige Brands manufactures NasalCrom. Nedocromil is a related mast cell stabilizer available as an inhaled formulation (1.75mg per actuation) for asthma prevention.

Olopatadine is a selective H1 antihistamine and mast cell stabilizer formulated as eye drops for the treatment of allergic conjunctivitis. It is available in three concentrations for different dosing needs: Patanol (0.1%) twice daily, Pataday (0.2%) once daily, and Pazeo (0.7%) once daily for more severe symptoms. The 0.2% formulation (Pataday) is now available over the counter. Alcon manufactures all branded formulations. Olopatadine is generally considered the preferred ophthalmic antihistamine due to its dual mechanism (antihistamine + mast cell stabilization) and once-daily convenience at the higher concentrations.

Ketotifen ophthalmic solution combines H1 antihistamine activity with mast cell stabilizing properties, providing both immediate symptom relief and preventive benefit with regular use. Available OTC at 0.025% concentration, it is dosed twice daily and indicated for itchy eyes due to allergic conjunctivitis. Alcon manufactures both the Zaditor and Alaway brand names. Ketotifen eye drops are generally well-tolerated with minimal systemic absorption.

Omalizumab is a humanized monoclonal antibody that binds to free immunoglobulin E (IgE) in the bloodstream, preventing IgE from attaching to mast cells and basophils. By blocking the initial trigger of the allergic cascade, omalizumab dramatically reduces allergic reactions in patients with severe, IgE-mediated allergic disease. It is FDA-approved for moderate-to-severe persistent allergic asthma that is inadequately controlled with inhaled corticosteroids, and for chronic idiopathic urticaria (chronic hives) in patients 12 and older who remain symptomatic despite antihistamine therapy.

Omalizumab is administered as a subcutaneous injection every 2–4 weeks in a clinical setting (due to anaphylaxis risk requiring 30-minute post-injection monitoring). It is not appropriate as initial or first-line therapy — it is reserved for patients with confirmed severe allergic disease that has not responded to standard treatments. Genentech and Novartis co-market Xolair in the United States.

Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 (IL-4) and interleukin-13 (IL-13), two cytokines central to type 2 (Th2) inflammatory responses that drive atopic disease. It has a broad and rapidly expanding set of FDA approvals: moderate-to-severe atopic dermatitis, moderate-to-severe asthma (with an eosinophilic phenotype or oral corticosteroid-dependent asthma), chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, and allergic bronchopulmonary aspergillosis. Dupilumab is self-injected subcutaneously every 2 weeks (after an initial loading dose for some indications) and is among the most commercially successful biologics in recent years. Regeneron and Sanofi co-market Dupixent.