Preclinical Studies | XOPENEX HFA® (levalbuterol tartrate)

Preclinical Data

XOPENEX HFA® (levalbuterol tartrate) Inhalation Aerosol contains a critical molecule*

XOPENEX HFA® (levalbuterol tartrate) Inhalation Aerosol is a unique short-acting β2-agonist that contains only the active (R)-isomer*1

  • Racemic albuterol is a 1:1 mixture of the active isomer (R)-albuterol (levalbuterol; the active ingredient in XOPENEX HFA) and its enantiomer (S)-albuterol1,3
  • The (R)-isomer produces all of the bronchodilation, while the (S)-isomer produces no bronchodilation*1,2
  • XOPENEX HFA contains only the therapeutically active (R)-isomer of albuterol and does not contain (S)-albuterol*1

Only (R)-isomer activity causes bronchodilation.2

All isomers are graphical representations.

*Clinical significance of these nonclinical data is unknown.

In vitro characteristics of (R)-albuterol and (S)-albuterol4-7




Binding to the β2-receptor

High affinity4,5

Very low affinity4,5

Anti-inflammatory effects of dexamethasone§



Activity of proconstrictory and proinflammatory pathways

No effect or decreased7


Intracellular calcium



§Demonstrated by GM-CSF release from isolated human airway smooth muscle cells (hASMCs).

In isolated human bronchial smooth muscle cells (hBSMCs).

These in vitro data are provided as scientific information relevant to your understanding of levalbuterol. These data are not inclusive of all the current information available on levalbuterol. The clinical significance of these nonclinical data has not been established. These preclinical data are not—and should not be regarded by you as being—determinative of the clinical outcome that may be experienced by your patients. These preclinical studies were funded by Sunovion Pharmaceuticals Inc.


1. XOPENEX HFA Inhalation Aerosol [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals Inc.; June 2009.
2. Lötvall J, Palmqvist M, Arvidsson P, Maloney A, Ventresca GP, Ward J. The therapeutic ratio of R-albuterol is comparable with that of RS-albuterol in asthmatic patients. J Allergy Clin Immunol. 2001;108(5):726-731.
3. Proventil HFA [prescribing information]. Kenilworth, NJ: Schering Corporation; November 2010.
4. Mitra S, Ugur M, Ugur O, Goodman HM, McCullough JR, Yamaguchi H. (S)-albuterol increases intracellular free calcium by muscarinic receptor activation and a phospholipase C-dependent mechanism in airway smooth muscle. Mol Pharmacol. 1998;53(3):347-354.
5. Penn RB, Frielle T, McCullough JR, Aberg G, Benovic JL. Comparison of R-, S-, and RS-albuterol interaction with human β1- and β2- adrenergic receptors. Clin Rev Allergy Immunol. 1996;14(1):37-45.
6. Ameredes BT, Calhoun WJ. Modulation of GM-CSF release by enantiomers of β-agonists in human airway smooth muscle. J Allergy Clin Immunol. 2005;116(1):65-72.
7. Agrawal DK, Ariyarathna K, Kelbe PW. (S)-albuterol activates pro-constrictory and pro-inflammatory pathways in human bronchial smooth muscle cells. J Allergy Clin Immunol. 2004;113(3):503-510.

Important Safety Information & Indication

XOPENEX HFA is contraindicated in patients with a history of hypersensitivity to levalbuterol tartrate, racemic albuterol, or any component of the drug product. 

Patients receiving the highest dose of XOPENEX HFA should be monitored closely for adverse effects, and the risk of such effects should be balanced against the potential for improved efficacy.

XOPENEX HFA and other β-agonists can cause paradoxical bronchospasm, which may be life threatening.

XOPENEX HFA like other β-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients as measured by heart rate, blood pressure, and/or symptoms.

Potential drug interactions include: β-blockers, which can block the pulmonary effect of β-agonists and can cause severe bronchospasm in asthmatic patients; diuretics (non-potassium-sparing), whose ECG changes and/or hypokalemia side effects can worsen with administration of β-agonists; digoxin, where serum levels can decrease 16% to 22% with administration of β-agonists; monoamine oxidase inhibitors and tricyclic antidepressants, which can potentiate the action of albuterol on the vascular system. 

If additional adrenergic drugs, including other short-acting sympathomimetic bronchodilators or epinephrine, are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.

Due to the cardiovascular side effects associated with β-agonists, caution is generally recommended for patients with cardiovascular disorders (especially coronary insufficiency, cardiac arrhythmias, and hypertension), diabetes, hyperthyroidism, or convulsive disorders.

In patients aged 4 to 11 years, the most common adverse events (occurring in ≥2% of patients receiving XOPENEX HFA at 90 mcg and more frequently than patients receiving placebo) were vomiting, accidental injury, pharyngitis, and bronchitis.

In patients 12 years and older, the most common adverse events (occurring in ≥2% of patients receiving XOPENEX HFA at 90 mcg and more frequently than patients receiving placebo) were asthma, pharyngitis, rhinitis, pain, and dizziness.

For more information about XOPENEX HFA (levalbuterol tartrate) Inhalation Aerosol, please see the full Prescribing Information including Patient's Instructions for Use or visit

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit, or call 1-800-FDA-1088.

XOPENEX HFA® (levalbuterol tartrate) Inhalation Aerosol is indicated for the treatment or prevention of bronchospasm in adults, adolescents, and children 4 years of age and older with reversible obstructive airway disease.