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Comparing Levalbuterol vs Albuterol for Respiratory Conditions
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Albuterol and levalbuterol are both inhaled medications used to prevent and treat symptoms of asthma and COPD, such as difficulty breathing, shortness of breath, wheezing, cough, and chest tightness.
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Levalbuterol and albuterol are both effective in preventing and treating asthma attacks. Most reviews find no clear advantage for one over the other. However, albuterol is considered a drug of choice to treat acute bronchospasm.
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Levalbuterol may have a more pronounced effect in patients with moderate to severe asthma. Levalbuterol is also usually more expensive than albuterol, especially for nebulized formulations.
Levalbuterol vs Albuterol: Overview
Levalbuterol and albuterol are both prescription medications that are used to treat bronchospasm (narrowing of the airways) caused by lung conditions such as asthma and chronic obstructive pulmonary disease (COPD). They are short-acting beta-agonists used to prevent and treat acute asthma exacerbations.
Mechanism of Action
Albuterol and levalbuterol belong to a drug class called short-acting beta-2-receptor agonists (SABAs), also called bronchodilators. These beta agonists are used for asthma treatment because they attach to beta receptors in the air passages and cause smooth muscle relaxation. This helps the airways to relax and open up, thereby making breathing easier.
Year Introduced to Market
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Albuterol: 1968
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Levalbuterol: 1999
Chemical Structure and Active Ingredient in Levalbuterol and Racemic Albuterol
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Albuterol (also called salbutamol) is a racemic mixture of R-enantiomers and S-enantiomers in equal parts (think of enantiomers as a pair of molecules that are a mirror image of each other).
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Levalbuterol (also called (R)-Salbutamol) contains only the active R-enantiomer of the albuterol racemic mixture.
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One thing to keep in mind is that the R-enantiomer is the one that is responsible for the bronchodilating effects (opening the airway, alleviating shortness of breath and wheezing) and less unpleasant side effects like tremors, nausea, and tachycardia (fast heart rate).
Age Range
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Albuterol is approved for use in infants, children, and adults.
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Levalbuterol is approved for use in children 4 years of age and older and adults.
Side Effects
Both albuterol and levalbuterol can cause similar side effects. Studies that have compared the two drugs have found that albuterol may cause a slightly greater increase in heart rate than levalbuterol, especially in children. However, most researchers don't consider these differences clinically significant.
Safety Profile
Levalbuterol may have a more favorable safety profile than racemic albuterol, but both drugs are generally safe.
Dosage Forms
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Albuterol is available as an oral tablet, oral solution, nebulizer solution, and metered-dose inhaler (MDI).
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Levalbuterol comes as a nebulizer solution and metered-dose inhaler (MDI).
Standard Dose
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Albuterol: 2.5 milligrams (mg) by nebulizer or 90 micrograms (mcg) by MDI every 4-6 hours.
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Levalbuterol: 0.63 mg by nebulizer or 45 mcg by MDI every 4-6 hours.
Brand Names
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Albuterol: Accuneb, Proair HFA, Proair Respiclick, Proventil HFA, Ventolin HFA
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Levalbuterol: Xopenex HFA
Cost
Levalbuterol is more expensive than albuterol. The cost gap between levalbuterol and albuterol metered-dose inhalers has narrowed with the adoption of the hydrofluoroalkane formulation; however, the cost gap remains for nebulized formulations.
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Effectiveness in Treating Respiratory Conditions
Clinical Uses and Indications
Albuterol and levalbuterol are used to prevent and treat symptoms of asthma and COPD, such as difficulty breathing, shortness of breath, wheezing, cough, and chest tightness. They are also used to prevent breathing problems during exercise and treat asthma exacerbations in patients with moderate to severe asthma.
Efficacy in Treating Bronchospasm Related to Asthma and COPD
Levalbuterol may have a more pronounced effect in patients with moderate to severe asthma, especially if they have overused racemic albuterol.
Is Levalbuterol Stronger Than Albuterol?
As mentioned, albuterol is a 50:50 racemic mixture of the active enantiomer (R)-albuterol and the inactive enantiomer (S)-albuterol. In contrast, levalbuterol contains only the active enantiomer (R)-albuterol.
(R)-albuterol has a 100-fold stronger binding to beta-2 adrenergic receptors compared to (S)-albuterol.
However, albuterol continues to be the most commonly prescribed inhaled beta-2 agonist and is considered a drug of choice to treat acute bronchospasm.
What Are The Benefits Of Levalbuterol?
Levalbuterol and albuterol are both effective in preventing and treating asthma attacks. Most reviews find no clear advantage for one over the other.
Side Effects Comparison
Common Side Effects
Potential unwanted effects of albuterol include headache, uncontrolled shaking, nervousness, throat irritation, cough, nausea, vomiting, muscle pain, and back pain.
Potential side effects of levalbuterol include headache, dizziness, uncontrolled shaking, nervousness, cough, heartburn, diarrhea, vomiting, fever, weakness, leg cramps, and muscle pain.
Does Levalbuterol Have Less Cardiac Side Effects Than Albuterol?
Traditionally, racemic albuterol has been linked to poorer cardiac outcomes because it contains both the S-isomer and the R-isomer. Levalbuterol, which contains only the active R-isomer, has been thought to have fewer cardiac side effects, such as tachycardia (increased heart rate).
However, research suggests that the effects on the heart of levalbuterol and albuterol are dose-dependent. Both bronchodilators have similar cardiac side effects when used at equivalent doses. Findings of studies that compared an albuterol group and a levalbuterol group are summarized below:
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Critically ill patients: In one clinical trial, patients in the intensive care unit who received either albuterol or levalbuterol had similar heart rate changes and arrhythmia incidence.
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Pediatric patients: A systematic review of clinical trials found that levalbuterol and albuterol had similar effects on the heart rate in asthmatic children.
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Tachyarrhythmias: Patients with tachyarrhythmias (rapid heart rhythm abnormalities) are at an increased risk of harmful or fatal cardiac side effects from these drugs. There's a lack of evidence for using either drug in these patients.
Serious Side Effects
You should seek emergency medical care if you develop the following signs and symptoms after using albuterol or levalbuterol:
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Fast, pounding, or irregular heartbeat
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Worsening breathing problems
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Swelling of the face, lips, tongue, throat, hands, or feet
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Skin rash, hives, itching
Long-Term Safety Profiles
Both albuterol and levalbuterol can be safely used long-term to prevent and treat asthma and COPD. Comparative studies published in medical literature, such as the Journal of Allergy and Clinical Immunology (J Allergy Clin Immunol), have found that levalbuterol and racemic albuterol are equally safe for long-term use in patients 12 years or older without serious detrimental effects. Other studies have shown that levalbuterol is better than or comparable to racemic albuterol at improving lung function in children with acute exacerbations of asthma.
Cost and Availability
Pricing Comparison
Levalbuterol, which is a newer drug, is more expensive than albuterol. The cost gap between the two drugs is closing for metered-dose inhalers (MDIs) due to the availability for newer formulas, but remains for nebulized levalbuterol and albuterol.
In general, studies have shown that while clinical outcomes are similar with the use of levalbuterol versus albuterol for treating COPD and asthma exacerbations, treatment costs are significantly higher with levalbuterol, and patients receiving levalbuterol have longer and more costly hospital stays.
Availability in Different Regions
Albuterol has been available for over five decades and is widely available in generic and brand name forms. Levalbuterol first became available in 1999 as a brand name drug, and the generic form became available in 2016.
Insurance Coverage
Levalbuterol and albuterol are typically covered by health insurance, Medicare, and Medicaid. However, coverage varies depending on the type of insurance plan. Copay costs also vary by plan. The insurance company may impose restrictions on the quantity and/or require prior authorization.
Patient Suitability
Ideal Patient Profile for Levalbuterol
The ideal patient profile for levalbuterol is a patient with moderate to severe asthma and racemic albuterol overuse.
Frequent use of albuterol (which contains equal amounts of (R)- and (S)-enantiomers) can lead to an accumulation of (S)-albuterol over time and have the opposite effect to the desired bronchodilation.
Studies have shown that levalbuterol is clinically comparable to 4-8 times higher doses of albuterol in such patients with a more favorable safety profile.
Therefore, doctors recommend the use of (R)-albuterol (levalbuterol) during asthma exacerbations in patients who are likely to need repeated doses of bronchodilator.
Contraindications: Who Should Not Take Levalbuterol and Albuterol?
Asthma treatment with bronchodilators such as levalbuterol and albuterol may not be safe for people with certain medical conditions such as high blood pressure, irregular heart rhythm, heart disease, hyperthyroidism (overactive thyroid gland), diabetes, seizures, and kidney disease.
Considerations for Pediatric and Elderly Patients
Comparison of levalbuterol and albuterol in children and adults has shown that there is no difference between albuterol and levalbuterol in terms of effectiveness and outcomes in acute exacerbation of asthma, including in terms of asthma scores, forced expiratory volume, respiratory rate, oxygen saturation, length of care in the emergency department, and hospitalization rates for acute pediatric asthma and adult asthma. However, some of these studies had a small sample size, so further research is needed.
Choosing Between Levalbuterol and Albuterol
Both levalbuterol and albuterol are prescription drugs that act as bronchodilators to open airways. They can be used to treat bronchospasm related to acute asthma exacerbations and COPD exacerbations and to prevent exercise-induced bronchospasm.
Levalbuterol is usually more expensive than albuterol, especially for nebulized formulations. However, the general consensus is that albuterol is just as effective as levalbuterol and is more cost-effective.
Here are some of the factors your healthcare provider and clinical pharmacist will keep in mind when choosing between albuterol and levalbuterol:
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Use: Albuterol is usually the first-line therapy for acute asthma, while levalbuterol is used for patients who have a poor response to or are intolerant to albuterol.
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Side effects: Levalbuterol may cause fewer side effects than albuterol, but this may not be true for everyone.
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Individual response: The individual response to a medication can vary, so what works best for one person may not work best for another. Your doctor may try you on albuterol versus levalbuterol based on your response to either medication.
Healthcare Professional Recommendations
The consensus among healthcare professionals is that there is no significant difference between the two drugs. Both are similarly effective in terms of clinical efficacy, but levalbuterol comes at a higher cost. In other words, the good old fashioned beta-agonist albuterol works just as well in asthmatic patients as the newer more expensive drug, levalbuterol, at a considerably lower cost.
References:
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https://www.sciencedirect.com/science/article/abs/pii/S1058981324000237
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https://www.jwatch.org/jw201201310000009/2012/01/31/levalbuterol-isnt-more-beneficial-albuterol
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https://www.jacionline.org/article/S0091-6749(99)70233-2/fulltext
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https://www.annallergy.org/article/S1081-1206(10)60384-5/abstract#:
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https://www.sciencedirect.com/topics/medicine-and-dentistry/levalbuterol
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https://www.jacionline.org/article/S0091-6749(01)42570-X/fulltext
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