Medications for Allergy

1. Is there a place for antihistamines in combination with corticosteroids?

Absolutely, both alone and in combination with nasal steroids. It depends on the nature of the symptoms. For instance, a patient with a congested nose and itchy eyes would benefit from both. The steroid will be effective for the nasal obstruction but not very good at dealing with itchy eyes; while antihistamines are effective against the eye symptoms but less so against the nasal congestion. This study looked at patients with predominantly nasal symptoms. We found that the nasal steroid was better at dealing with nasal problems, particularly congestion. But antihistamines can be better for itching, eye symptoms, and possibly sneezing.

2. Would fluticasone propionate (Flonase)be safe in patients already taking corticosteroids for asthma?

We use them together often. If a patient has rhinitis and asthma, and they’re on a fairly extensive regimen for asthma which includes inhaled corticosteroids, it would still be appropriate to consider topical nasal steroids. These medicines are very effective at the low doses we use because we’re applying them directly to the affected tissues. The inhaled steroid goes directly to the lungs with very little direct application to the nasal mucus membrane. Of course, both the lungs and the nasal membrane only absorb some of the medication, and the rest is swallowed into the gastrointestinal system, from which it can be absorbed across the gut into the body. At very high doses there must be accounting for the total load to make sure you don’t overload the system. But normally we are using relatively low doses.

3. Do you think prolonged therapy with fluticasone propionate (Flonase) could lead to hypercorticism?

In this case, none of the patients’ adrenal glands were affected. In patients with moderate asthma, only low to moderate doses are required, and these are unlikely to produce adverse effects. In more severe asthma, where larger doses are needed, there are studies that have shown some risk of these symptoms developing.

4. Is fluticasone propionate a safe drug for children in view of reports of growth inhibition among children on corticosteroid therapy?

Fluticasone (Flonase) is approved at the moment only for use in children over 12. A one-year study using fluticasone in mild to moderate asthma in children showed very little if any growth suppression in the vast majority. The final answer is not yet determined as not all the data has been fully analyzed, but it appears that the low doses needed to control mild to moderate asthma in children are probably very safe.

Flonase  (Fluticasone propionate aqueous nasal spray) compared with terfenadine tablets in the treatment of seasonal allergic rhinitis.

Antihistamines are often considered the first line of defense in the treatment of rhinitis, because they are judged to be safer than other medicines and reasonably effective at relieving symptoms. Recently, low-dose corticosteroids have gained acceptance; they are generally more potent than antihistamines.

This trial compared the drugs of each type in a range of patients with rhinitis. Three hundred and forty-eight were enrolled, of whom 319 completed the course. Their average age was 30, and slightly over half were male. They were split into three groups. One group took fluticasone propionate spray each morning plus a placebo pill each morning and evening; another took terfenadine tablets morning and evening with a placebo spray each morning; the third had lookalike placebos of both drugs.

The results were clear-cut in favour of fluticasone propionate (Flonase). At the end of the month, examining physicians found that symptoms were noticeably alleviated in 52% of the fluticasone propionate patients, compared to 33% for terfenadine and 22% for placebo. The patients themselves reported similar results: 57% on fluticasone propionate had improved, as against 38% for terfenadine and 32% for placebo.

Although the beneficial effects of placebo may seem surprising, this was not unexpected by the researchers, as placebo is often found to bring reported benefits in nasal and other studies. In this case, it may well be due to the rinsing action of the placebo nasal spray. This may imply that nasal sprays have a mechanical action better suited to dealing with rhinitis-type symptoms than do pills.

Allergy-related cells in the nasal tissues were largely unchanged, except in the fluticasone propionate patients, who showed a slight drop. Nasal airflow scores showed a clear improvement in the corticosteroid group. No subjects dropped out of the fluticasone propionate trial because of lack of efficacy, but three quit in each of the other groups. Regarding drug safety, six subjects stopped their participation in the study due to adverse events, which were probably not drug-related. One of these came from the fluticasone propionate group, two from the terfenadine group, and three from the placebo group.

Fluticasone propionate (Flonase) is a corticosteroid and belongs to the family of chemicals known as glucocorticoids or steroids. In the past, oral forms of steroids were often associated with increased risk of hypercorticism. This is an excess of cortisol in the body than can interfere with the function of the adrenal gland, leading to a range of serious side effects that can include peptic ulcer disease, glaucoma, obesity, diabetes, and psychiatric problems. Tests to monitor the effect on the adrenal gland were carried out on all three groups at start and finish in an attempt to judge the safety of the two preparations. No adverse effects on adrenal gland function were noted in any of the patients.

The use of intranasal corticosteroids is increasingly becoming first-line therapy for many patients with allergic rhinitis, especially those with moderate to severe symptoms or those with perennial allergic rhinitis in which nasal symptoms predominate. Intranasal corticosteroids specifically inhibit the allergic inflammatory processes that contribute to the late-phase response of nasal congestion. When used prophylactically, they can also inhibit the early-phase response to allergens. Overall, they are effective in relieving sneezing, nasal itching, rhinorrhea, and congestion.

Table 3 lists available intranasal corticosteroids, along with dosing information and comparative costs. In general, these agents are considered more cost-effective for use as monotherapy than 2nd-generation antihistamines. A recent meta-analysis found intranasal corticosteroids to be more effective than oral antihistamines in reducing nasal blockage, nasal discharge, sneezing, nasal itch, postnasal drip, and total nasal symptoms. No significant difference was detected for nasal discomfort, nasal resistance, and eye symptoms. No particular product has demonstrated clinical superiority, selection of drug should be based on factors such as response, ease of administration, cost, and formulation.

Table 3 Intranasal corticosteroids

Application site irritation (e.g., nasal irritation, burning, or sneezing after administration) is the most commonly encountered side effect. Patients complaining of local irritation may be switched to various aqueous formulations. Although rare, mucosal erosion and septal perforations have been reported with long-term use. To minimize septal irritation, patients should be instructed to direct the spray upwards and toward the lateral portion of the nose. Periodic examination of the nasal septum should be performed.

Although systemic effects from intranasal corticosteroids at recommended doses are considered minimal, there are some concerns regarding long-term exposure. Reports of posterior subcapsular cataract formation have been linked with the use of intranasal or inhaled corticosteroids; however, more recent prospective trials did not reveal evidence of posterior subcapsular cataract formation or elevation in intraocular pressure.

In 1998, the FDA’s advisory committees on pulmonary and allergy drugs and on metabolic endocrine drugs convened to assess data suggesting that intranasal corticosteroids may have an effect on growth velocity in children. Consequently, a new class labeling for pediatric use of inhaled and intranasal corticosteroids was mandated. At this time, the long-term significance of growth velocity reduction on final adult height is unknown. The FDA recommends routine monitoring of growth in pediatric patients using intranasal corticosteroids and titration to the lowest effective dose to minimize systemic risks.

Patient education is essential in ensuring proper use and compliance to intranasal corticosteroid therapy. Patients should be instructed on instillation techniques and informed about the possible delay in symptomatic response. Assessment of maximal response may require a therapeutic trial of several weeks. The drug should be administered regularly on a daily basis, rather than as needed for rescue relief.

For patients with severe disease, the combined use of intranasal corticosteroids and antihistamines may be necessary to control symptoms. The use of oral corticosteroids should be reserved for patients with severe exacerbations or intractable disease due to high risk of systemic adverse effects.

Most intranasal corticosteroids (CS) take a few days to work with the exception of the newer, more potent agents fluticasone and mometasone. Regardless, the maximum effect requires 1-2 weeks and possibly up to 3 weeks. Patients should be encouraged to contact their healthcare provider if no benefit is seen in this time. Often anti-allergy therapy is prescribed on a presumptive basis. Patients may be on intranasal CS therapy and not be aware of which allergens they are sensitive to. Skin prick allergy testing can easily assess allergy status. Once specific allergens are identified, appropriate environmental controls can be instituted.

When a patient exhibits intolerance to a specific intranasal corticosteroids product, an excipient in the formulation may be the cause. A suggested intervention would be to switch to an alternative product. For example, an alcohol-free product could be recommended over a product containing alcohol. Additional reinforcement should target instructions on proper nasal CS administration, and nasal conditioning (moisturizing). Often overlooked are patient-specific nasal behaviors. For example, a patient may be reporting nosebleeds, and through further inquiry reveals he is a frequent nose-picker; another patient may irrigate the nose with hydrogen peroxide. If nosebleeds remain problematic for the patient, referral to an Ear, Nose and Throat Specialist may be warranted. To facilitate tailoring patient therapy, Table 8 compares various intranasal corticosteroids available in the U.S.

Conclusion

Allergic rhinitis is characterized by acute and late phase reactions. Inflammation plays a dominant role in maintaining the late phase and contributes to the increased risk of complications. Intranasal steroids have been proven effective treatment for allergic rhinitis and are superior to oral antihistamines. Therefore, first-line treatment of allergic rhinitis should be intranasal steroids in patients with allergic rhinitis of perennial or seasonal pattern with persistent or moderate symptoms. Environmental control measures should target allergens relevant to the individual. Pharmacists are in a unique position to provide balanced information and take patient-specific factors into consideration when evaluating an individual patient for specific therapy for allergic rhinitis.