Levalbuterol

Levalbuterol, or levosalbuterol, is a drug used to prevent constriction of the airways in conditions such as asthma and chronic obstructive pulmonary disorder (COPD). These conditions are characterized by difficulty breathing and shortness of breath. Like all drugs that block the beta-2 receptor, levalbuterol can affect the cardiovascular system. Some of these effects include a rapid heartbeat and high blood pressure. Some physicians in their clinical use have suggested that levalbuterol is safer to use than is albuterol (Ventolin), but data from clinical trials do not support this conclusion.

Levalbuterol has the brand name Xopenex. It is marketed by Sepracor Inc. It was approved in the US March of 1999.

Uses/Indications

Lung section showing the bronchi and bronchioles (airways.)

How Levalbuterol is Taken

Levalbuterol can be inhaled through a device called a nebulizer. The nebulizer turns the liquid form of levalbuterol into a fine mist which is inhaled. Levalbuterol is also available in the traditional inhaler. Levalbuterol is available in concentrations of 0.31/3 mL 0.63/3 mL, or 1.25 mg/3 mL.

How Levalbuterol Works

Cells in the airways are one place in the body that contain receptors called a beta-2 receptors. Levalbuterol is called a beta-receptor agonist because it binds to and activates the beta-2 receptor. Activation of the receptor initiates signaling within the cell that results in the relaxation and opening of airways. Beta-2 receptors are located throughout the body. Therefore, levalbuterol can affect the function of many other body systems in addition to the lungs such as the heart. A potential side effect is rapid heart rate, which results from stimulation of beta-2 receptors in the heart (See Side Effects.)

Much like many other bronchodilators, tolerance to levalbuterol can develop. Tolerance is a gradual loss of effectiveness after many treatments. It results from a reduced responsiveness of the beta-2 receptor to Xopenex. When tolerance develops often the dose of levalbuterol is increased, or other drugs may be used in combination with levalbuterol.

How the Body Affects Levalbuterol

Most of an inhaled dose of levalbuterol is metabolized (broken down) by enzymes in the gastrointestinal tract. Levalbuterol does not stay in the body too long. The amount of time for the concentration of levalbuterol in the blood to be reduced by half, the half-life, is 1.6 hours. Levalbuterol is primarily excreted in the urine.

Side Effects

Usually levalbuterol facilitates breathing by opening the airways, but sometimes it may have the opposite effect and actually narrow the airways. This reaction is called paradoxical bronchospasm and can be serious and possibly life-threatening. In cases of paradoxical bronchospasm, other medications may be needed to help control the asthma.

Levalbuterol affects the cardiovascular system because, like the lungs, the cardiovascular system contains beta-2 receptors. Heart-related side effects, such as increased pulse and heart rate, as well as high blood pressure have been reported with levalbuterol use. The reactions may sometimes be severe enough to stop taking the drug.

Skin swelling, itching, rash, or narrowing of the airway are indicative of a hypersensitivity (allergic) reaction. If the reaction is severe, levalbuterol use may have to be stopped.

Below are some other side effects associated with the use of levalbuterol:

• Dizziness
• Tremors
• Vomiting
• Nausea
• Headache
• Heartburn
• Fever
• Cough
• Nervousness
• Diarrhea
• Severe but transient hypokalemia (low levels of potassium in the blood)

Risks and Precautions

Because of the potential interaction between levalbuterol and the heart, people with heart problems (e.g., high blood pressure, irregular heartbeat) may be prescribed a different drug to control bronchospasm. Below are some other conditions that should be discussed with a physician before taking levalbuterol:

• Diabetes
• High levels of thyroid hormone
• Seizures

Levalbuterol must be used according to a physician’s orders. Deaths have occurred when inhaled drugs similar to levalbuterol were used to excess in patients with asthma.

Levalbuterol is not used in individuals who cannot tolerate albuterol.

Most of an inhaled dose of levalbuterol is excreted by the kidneys. Accordingly, high doses should be used with caution in patients with kidney problems. Caution should also be used if using levalbuterol during labor and delivery because other drugs that act like levalbuterol are known to interfere with contraction of the uterus. In this situation, the drug should only be given if the benefits of treatment outweigh the risks.

The influence of levalbuterol on the fetus is not known. Pregnancy should be discussed with a healthcare provider. Breastfeeding should be avoided.

Drug Interactions

Below are some drugs that are more likely to interact with levalbuterol:

• Diuretics (e.g., furosemide (Lasix) or hydrochlorothiazide
• Antidepressants that are monoamine oxidase inhibitors (MAOIs) (e.g., selegiline (Eldepryl) or tricyclics (e.g., amitriptyline)
• Other drugs that affect the heart
• Drugs used for high blood pressure or after a heart attack (e.g., atenolol or metoprolol (Toprol or Lopressor))

Clinical Trials

The effectiveness of bronchodilators such as levalbuterol is often determined by measuring the forced expiratory volume of air, which is the amount of air forced out of the lungs in one breath. Levalbuterol and albuterol are equally effective in improving forced expiratory volume, and both are superior to a placebo. One study in children found that forced expiratory volume was improved by 26% with levalbuterol and 22% with albuterol.^[1] Placebo improved forced expiratory volume by 16%. This trial, similar to others, showed that the incidence of side effects is similar in patients given either levalbuterol, albuterol or placebo. In the study, 43% of levalbuterol-treated, 56% of albuterol-treated, and 51% of placebo-treated patients reported side effects. Some physicians have argued that levalbuterol use is associated with fewer side effects than is albuterol use (see “Controversy”).

Controversy

The bronchodilator albuterol is a mixture of two different forms. Levalbuterol is one of those forms. Some physicians have argued that levalbuterol is less likely to cause side effects, especially heart problems, because it is only one form of albuterol. If levalbuterol use is safer, high doses can be used to treat bronchospasm that is not responding to regular doses. However, clinical trials have not shown that levalbuterol is any safer than albuterol.^[2]

References

1. ↑ Berger WE, Milgrom H, Skoner DP, et al. Evaluation of levalbuterol metered dose inhaler in pediatric patients with asthma: a double-blind, randomized, placebo- and active-controlled trial. Curr Med Res Opin. 2006 Jun;22(6):1217-26. PMID 16846555
2. ↑ Allergy & Asthma Disease Management Center. [h ttp://www.aaaai.org/aadmc/ate/betaagonists.html Ask the Expert].

External Links

Sepracor: Xopenex Sepracor: Patient Instructions for Use eMedTV: Xopenex