Medications for Allergy

Allergic rhinitis is an IgE-mediated inflammatory disease of the nasal mucosal membranes characterized mainly by sneezing, rhinorrhea, nasal pruritis, and congestion. It is the most common form of rhinitis, affecting 20 to 40 million Americans annually, and it is considered one of the most prevalent chronic diseases in the United States. It is also well documented that allergic rhinitis can negatively impact the quality of life and contribute significantly to loss of work productivity.

Allergic rhinitis may be categorized as seasonal “hay fever” or perennial (when symptoms persist year-round). Often, patients may react to multiple allergens and have seasonal exacerbation of symptoms in addition to perennial rhinitis. Tree, grass, and weed pollens are common seasonal allergens because they become airborne in large concentrations during a particular season of the year. Important perennial allergens include house dust mites, indoor molds, animal dander, and occupational allergens.

Management overview

Treatment options for allergic rhinitis include allergen avoidance, use of pharmacological agents for prevention and control of symptoms, and allergen immunotherapy for desensitization of patients in whom avoidance strategies and pharmacotherapy have failed to produce a satisfactory response.

Allergen avoidance

Whenever possible, environmental control measures should be emphasized as a fundamental part of the treatment plan. For instance, patients with pollen or outdoor mold allergies should remain in closed environments whenever possible. Patients sensitive to dust mites should enclose all mattresses and pillows with allergen-proof casings and eliminate carpeting, if possible, to reduce exposure; bedclothes should be frequently laundered in hot water to remove allergens. Although not always feasible, patients with animal allergies should consider removal of pets from home.

Antihistamines

Antihistamines (H1-antagonists) are typically prescribed as first-line agents for allergic rhinitis. They exert their actions by competitively antagonizing histamine at the H1- receptor sites and thereby suppress symptoms attributable to histamine release, such as sneezing, rhinorrhea, nasal itching, conjunctival itching, and lacrimation.

Antihistamines, however, are generally not effective in alleviating nasal congestion.

First-generation antihistamines

Various 1st-generation antihistamines are widely available with and without prescription. Although effective and economical, the usefulness of these agents is limited by their sedative and anticholinergic properties due to penetration of the central nervous system and poor receptor specificity.

All 1st-generation antihistamines are sedating to some degree and may cause performance impairment in 10% to 40% of users. In general, the ethanolamines (e.g., diphenhydramine) and phenothiazines (e.g., promethazine) are the most sedating. The ethylenedi-amines (e.g., pyrilamine) cause moderate sedation, and the alkylamines (e.g., chlorpheniramine, brompheniramine) are considered the least sedating. The use of lst-generation antihistamines at bedtime, which are less expensive, and newer nonsedating agents during the day has been advocated as a cost-saving strategy. This therapeutic approach may not be cost-effective, however, as residual effects of the bedtime dose may result in daytime sedation and performance impairment.

The anticholinergic effects of 1st-generation antihistamines (dry mucous membranes, urinary retention, blurred vision) may preclude their use in certain patients. Elderly patients are especially sensitive to these adverse effects. These older agents should be used cautiously in patients with narrow angle glaucoma or prostatic hypertrophy or in those taking other medications that may potentiate these side effects.

Although 2nd-generation antihistamines are generally prescribed due to ease of dosing and favorable side-effects profile, clinicians should be cognizant of available non-prescription antihistamines, as many patients may be self-managing with over-the-counter products (see Table 1).

Table 1 Selected 1st-generation antihistamines

Note: available OTC, often in combination with various decongestants, analgesics, and antitussives

A woman in her early thirties wants some advice. She tells you that she has hay fever and a blocked nose and is finding it difficult to breathe. You find out that she has had the symptoms for a few days; they have gradually got worse. She gets hay fever every summer and it is usually controlled by chlorphenamine tablets, which she buys every year and which she is taking at the moment. As a child, she suffered quite badly from eczema and is still troubled by it occasionally. She tells you that she has been a little wheezy for the past day or so, but she does not have a cough, and has not coughed up any sputum. She is not taking any other medicines.

The pharmacist’s view

This woman has a previous history of hay fever, which has, until now, been dealt adequately with chlorphenamine tablets. Her symptoms have worsened over a period of a few days and she is now wheezing. It seems unlikely that she has a chest infection, which could have been a possible cause of the symptoms. She should be referred to the doctor at once since her symptoms suggest more serious implications such as asthma.

The doctor’s view

This woman should be referred to her doctor directly. She almost certainly has seasonal asthma. In addition to the hay fever treatment recommended by her pharmacist, it is likely that she would benefit from a steroid inhaler such as beclometasone. Depending on the severity of her symptoms, she would probably be prescribed a beta-agonist, such as a salbutamol inhaler, as well. This consultation is a complex one for a doctor to manage in the usual 10 min available in view of the time required for information-giving, explanation about the nature of the problem, the rationale for the treatments and the technique of using inhalers.

After seven-and-one-half long years under FDA review, Pfizer’s antihistamine cetirizine (Zyrtec) has received marketing approval for the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic hives. Cetirizine, a metabolite of hydroxyzine, is a selective inhibitor of peripheral histamine-1 receptors. This selectivity reportedly improves the potency and reduces the side effects of cetirizine (Zyrtec) relative to other antihistamines. According to the manufacturer, cetirizine has been used in more than 2.3 billion patient-days of therapy in more than 90 countries, and is the most frequently prescribed antihistamine in Europe.

In multicenter, randomized, double-blind trials involving adults and children (aged 12-16 years) treated for up to eight weeks, cetirizine significantly reduced symptoms of seasonal and perennial allergic rhinitis (nine trials, 5-10 mg/day) and of chronic idiopathic urticaria (two trials, 5-20 mg/day). Generally, the 10 mg dose was superior to the 5 mg dose, and the 20 mg dose gave no added benefit.

In comparative trials, cetirizine proved to be at least as effective as, and in most cases superior to, chlorpheniramine (Chlor-Trimeton, Piriton, Chlor-Tripolon), hydroxyzine (Vistaril, Atarax), astemizole, terfenadine, and loratidine (Claritin) for reducing symptoms of allergic rhinitis (nasal itching and congestion, sneezing, postnasal discharge, and redness, itching and watering of the eyes. In asthmatics with allergic rhinitis, cetirizine safely reduced allergic symptoms without exacerbating the asthma. Indeed, in healthy volunteers cetirizine actually blocked bronchoconstriction when histamine was given by nebulizer.

In clinical trials involving patients with hives, cetirizine was more effective than placebo and at least as effective as terfenadine, hydroxyzine, and aztemizole for alleviating wheal, pruritus, and erythema. Volunteers given histamine by intradermal injection responded to a single 10- mg dose of cetirizine; skin wheal and flare reaction was inhibited within 20 minutes in 50% of subjects and within one hour in 95% of subjects. This activity persisted for at least 24 hours. In studies conducted for up to 12 hours following cutaneous challenge, cetirizine inhibited the allergic inflammatory response (late phase recruitment of eosinophils, neutrophils, and basophils).

Cetirizine (Zyrtec) is well tolerated. The most common side effects in clinical trials were somnolence, fatigue, dry mouth, pharyngitis, and dizziness. These effects were mild or moderate and, except for sedation, their incidence was not significantly different from placebo. Because some of the newer antihistamines can cause adverse cardiac effects, cetirizine has been evaluated extensively for eletcrophysiologic activity and drug interactions. Terfenadine (Seldane/Dow) and astemizole (Hismanal/Janssen) can cause conduction abnormalities when administered concurrently with a variety of drugs. By contrast, cetirizine did not demonstrate any clinically significant effects on the QTc interval, even in high doses (60 mg, six times the recommended dose) and in combination with ketoconazole, erythromcyin, or azithromycin. No pharmacokinetic interactions were observed with pseudoephedrine, antipyrine, ketoconazole, erythromycin or azithromycin. The only drug interaction found was with theophylline, which reduced cetirizine clearance by 16%. Cetirizine had no effect on theophylline pharmacokinetics.

Cetirizine (Zyrtec) is rapidly absorbed orally, with peak serum concentrations achieved within one hour. Food delays absorption and reduces the peak blood concentration, but has no effect on the extent of absorption. The mean elimination half-life is about eight hours. Cetirizine undergoes minimal hepatic metabolism and is excreted primarily in the urine; 70% of the dose is recovered in the urine and 10% in the feces, for a combined total recovery of about 80%. Approximately 50% of the dose is excreted in the urine as unchanged drug. Because of low first-pass metabolism and extended half-life, cetirizine can be given once daily. The drug is available in 5 and 10 mg tablets, but most patients respond best to the 10 mg, given once daily with or without food. Since cetirizine (Zyrtec) has the potential to cause somnolence, patients should be cautioned against driving or operating dangerous machinery. Concurrent use with alcohol or other CNS depressants should be avoided.