Is levoalbuterol (albuterol's R-enantiomer) a better option for patients who experience tachycardia with albuterol?

From the Guidelines

Levoalbuterol may be considered for patients who experience tachycardia with albuterol, but its clinical benefit is modest at best. Levoalbuterol (the R-enantiomer) is the active bronchodilator component of racemic albuterol, while the S-enantiomer has been theorized to contribute to side effects like tachycardia 1. However, real-world clinical studies have shown only minimal differences in cardiovascular side effects between the two medications. If a patient experiences troublesome tachycardia with albuterol, switching to levoalbuterol (typically dosed at 0.63 mg or 1.25 mg via nebulizer every 6-8 hours, or 45-90 mcg via metered-dose inhaler) might be worth trying, as suggested by the guidelines for the diagnosis and management of asthma 1.

Key Considerations

• The higher cost of levoalbuterol compared to albuterol should be considered, as insurance coverage varies 1.
• Alternative approaches for patients with tachycardia include using the lowest effective dose of albuterol, ensuring proper inhaler technique to minimize systemic absorption, or considering alternative bronchodilators like ipratropium bromide.
• The theoretical advantage of levoalbuterol stems from the pharmacology of enantiomers - the R-form provides bronchodilation while potentially avoiding some of the cardiac stimulation attributed to the S-form, though this separation of effects is not as clear-cut in clinical practice as once hoped.

Clinical Evidence

• Studies have shown that levalbuterol administered in half the milligram dose of albuterol provides comparable efficacy and safety 1.
• The effectiveness and side effect profile of levalbuterol is indistinguishable from that of the racemic mixture of molecules in albuterol, but it is more expensive 1.

Recommendations

• For patients experiencing tachycardia with albuterol, consider switching to levoalbuterol as an alternative, taking into account the higher cost and insurance coverage.
• Ensure proper inhaler technique and consider alternative bronchodilators for patients with persistent tachycardia.

From the FDA Drug Label

5.4 Cardiovascular Effects Levalbuterol Inhalation Solution, USP, like other beta-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by heart rate, blood pressure, and symptoms Although such effects are uncommon after administration of Levalbuterol Inhalation Solution, USP at recommended doses, if they occur, the drug may need to be discontinued.

Table 2: Mean Changes from Baseline Heart Rate at 15 Minutes and Glucose and Potassium at 1 Hour after First Dose (Day 1) in Adults and Adolescents ≥ 12 Years Old Mean Changes (Day 1) TreatmentHeart Rate (bpm) Levalbuterol Inhalation Solution, USP 0.63 mg, n = 722.4 Levalbuterol Inhalation Solution, USP 1.25 mg, n = 736.9 Racemic albuterol 2.5 mg, n = 745.7 Placebo, n = 75-2.8

The cardiovascular effects of levoalbuterol and albuterol are similar, with both medications capable of producing clinically significant cardiovascular effects in some patients. However, the data from the clinical trials suggest that the incidence of tachycardia may be slightly lower with levoalbuterol compared to racemic albuterol.

• The mean change in heart rate at 15 minutes after administration was 2.4 bpm for levoalbuterol 0.63 mg, 6.9 bpm for levoalbuterol 1.25 mg, and 5.7 bpm for racemic albuterol 2.5 mg.
• The incidence of tachycardia was reported in 2.7% of patients receiving levoalbuterol 1.25 mg, 2.8% of patients receiving levoalbuterol 0.63 mg, and 2.7% of patients receiving racemic albuterol 2.5 mg. Based on the available data, it appears that levoalbuterol may be a better option for patients who experience tachycardia with albuterol, although the difference in incidence is small and the clinical significance is unknown 2, 2, 2.

From the Research

Comparison of Levoalbuterol and Albuterol

• Levoalbuterol is the R-enantiomer of albuterol, and it has been suggested as a potential alternative for patients who experience tachycardia with albuterol.
• Studies have compared the effects of levoalbuterol and albuterol on heart rate and arrhythmias in various patient populations.

Effects on Heart Rate

• A study published in 2011 3 found that nebulized albuterol and levalbuterol did not cause significant tachycardia or tachyarrhythmias in critically ill adult patients.
• Another study published in 2003 4 found that short-term use of nebulized albuterol and levalbuterol was associated with similar changes in heart rate in intensive care patients with or without baseline tachycardia.
• A study published in 2014 5 noted that there is a lack of data on the comparison of levalbuterol and albuterol in patients with baseline tachyarrhythmias.

Pediatric Population

• A study published in 2011 6 found that levalbuterol and racemic albuterol produced similar effects on heart rate in pediatric patients.
• Another study published in 2021 7 found that supraventricular tachycardia (SVT) is rare during hospital-based treatment for acute asthma using inhaled short-acting beta agonists (SABAs), including levalbuterol and albuterol.

Conclusion on Tachycardia

• The available evidence suggests that levoalbuterol may not be significantly better than albuterol in reducing the risk of tachycardia in patients.
• However, more research is needed to fully understand the effects of levoalbuterol and albuterol on heart rate and arrhythmias in different patient populations, particularly those with baseline tachyarrhythmias.