Do levosalbutamol (Levalbuterol) and terbutaline increase the risk of tachycardia?

From the Guidelines

Levosalbutamol is generally preferred over terbutaline due to its lower risk of tachycardia, as it has greater selectivity for beta-2 adrenergic receptors in the lungs with less activity on cardiac beta-1 receptors that influence heart rate. According to the most recent and highest quality study available, 1, tachycardia was noted with albuterol, but the increase in heart rate was less when albuterol was delivered through a metered dose inhaler compared with delivery by nebulizer.

Key Points to Consider

• Levosalbutamol (also known as levalbuterol) is the R-enantiomer of salbutamol and has greater selectivity for beta-2 adrenergic receptors in the lungs, with less activity on cardiac beta-1 receptors that influence heart rate.
• Terbutaline is a non-selective beta-agonist with more pronounced effects on both beta-1 and beta-2 receptors, leading to potentially more cardiac side effects including tachycardia.
• Typical dosing for levosalbutamol is 0.63-1.25 mg via nebulizer every 6-8 hours or 45-90 mcg via metered-dose inhaler (2 puffs) every 4-6 hours, while terbutaline is typically given as 2.5-5 mg orally every 6-8 hours or 0.25-0.5 mg subcutaneously.
• For patients with cardiovascular conditions or those prone to tachycardia, levosalbutamol would generally be preferred, as supported by studies such as 1 and 1, which discuss the potential for beta-2 agonists to induce tachycardia and other cardiac side effects.

Monitoring and Precautions

• Monitoring heart rate after administration is recommended, especially in patients with cardiovascular disease, the elderly, or those on other medications that might affect heart rate, as noted in 1.
• Individual patient responses vary, and some patients may experience tachycardia with either medication, highlighting the need for personalized care and monitoring.

From the FDA Drug Label

The incidence of systemic beta-adrenergic adverse effects (e.g., tremor, nervousness) was low and comparable across all treatment groups, including placebo. Postmarketing In addition to the adverse events reported in clinical trials, the following adverse events have been observed in postapproval use of levalbuterol inhalation solution These events have been chosen for inclusion due to their seriousness, their frequency of reporting, or their likely beta-mediated mechanism: angioedema, anaphylaxis, arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles), asthma, chest pain, cough increased, dyspnea, nausea, nervousness, rash, tachycardia, tremor, urticaria The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/‌or occurrence or exaggeration of any of the symptoms listed under ADVERSE REACTIONS, e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and insomnia.

Tachycardia Risk:

• Levosalbutamol and terbutaline may have a higher risk of tachycardia due to their beta-adrenergic agonist properties.
• The FDA drug labels for levosalbutamol and terbutaline list tachycardia as a potential adverse event associated with their use 2, 3, and 3.
• The risk of tachycardia is likely due to the beta-mediated mechanism of these drugs.
• It is essential to monitor patients for signs of tachycardia and other systemic beta-adrenergic adverse effects when using these medications.

From the Research

Tachycardia Risk with Levosalbutamol and Terbutaline

• The risk of tachycardia associated with levosalbutamol and terbutaline is a concern in the treatment of respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD) 4, 5.
• A study published in 2011 found that nebulized albuterol and ipratropium did not cause significant tachycardia or tachyarrhythmias in critically ill adult patients, and substitution of levalbuterol for albuterol to avoid tachycardia and tachyarrhythmias was unwarranted 4.
• Another study published in 2019 found that combination of nebulized ipratropium bromide and terbutaline did not reduce hospital admission and need for ICU care in patients with acute exacerbation of COPD requiring noninvasive ventilation 6.
• Terbutaline has been shown to increase heart rate, systolic blood pressure, and plasma glucose, while decreasing diastolic pressure and serum potassium 5.
• A systematic review of the clinical pharmacokinetics of terbutaline in humans found that the drug's pharmacokinetics are affected by routes of administration, stereoisomerism, disease states, smoking, age, exercise, and chronobiology 7.

Comparison with Other Bronchodilators

• A study published in 2013 found that combination of inhaled ipratropium bromide and salbutamol provided greater bronchodilatation than monotherapy with salbutamol alone in acute severe asthma 8.
• The same study found that the combination group had a greater increase in peak flow at 30 and 60 minutes after treatment compared to the salbutamol group 8.

Pharmacokinetics and Pharmacodynamics

• The pharmacokinetics of terbutaline are affected by various factors, including routes of administration, disease states, and patient characteristics 7.
• The drug's pharmacodynamics, including its effects on heart rate, blood pressure, and glucose metabolism, are also important considerations in its use 5.