Symbicort: Fast-Acting Combination for Long-Term Asthma Control

The twice-daily asthma therapy that combines the inhaled corticosteroid budesonide (Pulmicort) with the long-acting beta₂-agonist formoterol (Foradil) in a single inhaler (Symbicort; AstraZeneca) was approved in July 2006 for long-term maintenance in patients aged ≥12 years. Symbicort is expected to become available in the United States by mid-2007.

“Symbicort offers something that other available asthma therapies do not, and that is a fast-acting combination therapy for the long-term maintenance treatment of asthma,” says Kevin R. Murphy, MD, FAAP. “And it comes in a very familiar delivery device—a metered-dose inhaler [MDI] that is similar to what all asthma patients use when taking short-acting beta₂-agonists such as albuterol [AccuNeb, Proventil].”

Having a preventive antiinflammatory agent and a controller/reliever agent in a single inhaler simplifies treatment—and thus may improve compliance—in a patient population that recent estimates from the Agency for Healthcare Research and Quality (AHRQ) suggest includes 9.3% of American adults. The AHRQ reports that 30.9% of Americans with active asthma use quick-relief medications, but only 13.5% use long-term preventive medications.

“We’ll have to wait and see, but certainly having this new fast-acting combination therapy may well have a significant impact on compliance. It’s also been shown to be effective for excellent control of asthma symptoms and improved lung function over time,” says Dr Murphy, clinical professor of pediatrics, University of Nebraska Medical Center, Omaha. “Compliance with medications in a very serious chronic disease is important,” he emphasizes.

The Evidence

Symbicort has been available in Europe since 2000 and has been approved in more than 90 countries outside of the United States, where there have been more than 5 million patient-years of experience.

The FDA approval was based on data from 2 large, double-blind, placebo-controlled trials in the United States that included more than 1000 patients.

Drugs

The first study enrolled 596 adults and adolescents (aged ≥12 years) with moderate-to-severe persistent asthma who had been previously treated with an inhaled corticosteroid (. 2006; 66:2235-2254).

Participants were randomized to 1 of 4 groups: (1) budesonide/formoterol pressurized MDI, 160 μg/4.5 μg, 2 inhalations; (2) budesonide pressurized MDI 160 μg, 2 inhalations, plus formoterol dry-powder inhaler (DPI) 4.5 μg, 2 inhalations; (3) budesonide pressurized MDI 160 µg, 2 inhalations; formoterol DPI 4.5 μg, 2 inhalations; or (4) placebo twice daily.

The 2 primary efficacy end points were mean change from baseline in morning predose forced expiratory volume in 1 second (FEV₁) and mean change from baseline in 12-hour FEV₁. At the end of the 12-week treatment period, greater improvements in both end points were evident in patients randomized to budesonide and formoterol, whether combined in the same inhaler or administered in separate inhalers (Table). In addition, fewer patients receiving both agents met the criteria for worsening asthma, compared with the monotherapy and placebo groups.

Results of the second study were presented at the recent annual meeting of the American College of Allergy, Asthma & Immunology. This 12-week study included 480 adults and adolescents (≥12 years) with persistent asthma who had been previously treated with an inhaled corticosteroid. Treatment with the combination of budesonide/formoterol 80 μg/4.5 μg via pressurized MDI outperformed treatment with either agent alone or with placebo.

In both studies, all treatments were well-tolerated.

Adverse Events, Contraindications

The most common adverse events reported in the clinical studies (by >5% of patients) were nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, influenza, back pain, nasal congestion, and stomach discomfort.

Symbicort should not be used for:

• Patients who can successfully manage their asthma with inhaled corticosteroids and the occasional use of inhaled, short-acting beta₂-agonists

• Patients who are having rapidly deteriorating or potentially life-threatening episodes of asthma

• Patients who are transferring from systemic corticosteroid therapy

• Relief of acute bronchospasm

• Prevention of exercise-induced bronchospasm

• Primary treatment of status asthmaticus or other acute episodes of asthma that require intensive measures.

Prescribing Symbicort

Symbicort is indicated for long-term maintenance therapy of asthma in adults and adolescents ≥12 years.

It is available in 2 strengths: 80 μg/ 4.5 μg and 160 µg/4.5 μg budesonide and formoterol, respectively. Each dose should be administered as 2 inhalations twice daily, once in the morning and once in the evening. Instruct patients to rinse their mouth after every dose.

For patients currently receiving medium-to-high doses of inhaled cortico-steroids, the recommended starting dose of Symbicort is 160 μg/4.5 μg, 2 inhalations twice daily. For those currently receiving low-to-medium doses of inhaled corticosteroids, the starting dose of Symbicort is 80 μg/4.5 μg, 2 inhalations twice daily. Either dosage strength can be used in patients not currently taking inhaled corticosteroids.

Since long-acting beta₂-adrenergic agonists, such as formoterol, may increase the risk of asthma-related death, Symbicort should only be prescribed to patients whose asthma is not adequately controlled with other asthma-controlling agents, such as low- to medium-dose inhaled corticosteroids; and to those whose disease severity warrants treatment with 2 maintenance therapies.

Who Is a Candidate?

Physicians must understand the significance of the problem of asthma in the United States, Dr Murphy emphasizes. “More than 30 million Americans suffer from this disease. Appropriate treatment is crucial. It’s very important for all patients to talk to their doctor and discuss which medication is correct for them.”

The National Institutes of Health asthma guidelines recommend using an inhaled corticosteroid and a long-acting inhaled beta₂-agonist—the 2 agents in Symbicort—for the long-term maintenance of symptom control in adults and children aged ≥5 years with moderate-to-severe persistent asthma.

“I think that any patient with moderate-to-severe asthma should be considered for Symbicort,” Dr Murphy says, adding that “primary care physicians and specialists alike should consider its use, especially in the patient who wakes up and needs a beta₂-agonist in the morning or who is having recurring episodes of worsening.”

The 2 Combination Inhalers

Fluticasone/salmeterol (Advair Diskus), a combination of the inhaled corticosteroid fluticasone (Flovent) and the long-acting beta₂-agonist salmeterol (Serevent Diskus) was approved by the FDA in 2000 for long-term maintenance therapy for asthma as well as for chronic obstructive pulmonary disease associated with chronic bronchitis. Advair Diskus is delivered in a DPI. The FDA recently approved an MDI version, Advair HFA Inhaler.

“Both Symbicort and Advair Diskus are indicated for patients with moderate-to-severe asthma. They both are combination products, and they have an inhaled steroid and a long-acting beta₂-agonist,” Dr Murphy explains. “The difference is that Symbicort has a rapid onset of action—within 15 minutes of beginning treatment,” compared with the 30- to 60-minute onset of action of the 2 Advair formulations.