XOPENEX HFA is different from racemic albuterol HFA…
because XOPENEX HFA contains only the (R)-isomer.
XOPENEX HFA is indicated for the treatment or prevention of bronchospasm in adults, adolescents, and children 4 years of age or older with reversible obstructive airway disease.
Compare the preclinical characteristics of (R)- and (S)-albuterol*
(S)-isomer:
Very limited binding to the beta2-receptor1,2
Produces no bronchodilation3
Diminishes the effects of steroids4
Augments inflammatory stimuli4-6
(R)-isomer:
Potent binding to the beta2-receptor1,2
Produces all of the bronchodilation3
Enhances the effects of steroids4
Has no effect on or reduces inflammatory stimuli4,5
*Clinical significance of these preclinical findings is not known.
Does the (R)-isomer need to be combined with the (S)-isomer?
No. The (R)-isomer is effective with or without the (S)-isomer and, in fact, is responsible for the clinical bronchodilation. When racemic albuterol is inhaled and traverses the airway bronchioles, (R)-albuterol has a high affinity for and binds to the beta2-adrenergic receptors on the surface of bronchiolar smooth muscle cells1-6. (R)-albuterol binding to these beta-receptors results in a conformational change in the receptor, thus inducing intracellular signaling. The complex cascade of signaling pathways causes activation of adenylate cyclase, increased cyclic AMP, and eventually activation of regulatory proteins. This in turn leads to a sequestering of calcium. The net effect is a decrease in intracellular calcium and ultimately smooth muscle relaxation, or bronchodilation. It is (R)-albuterol that produces all the bronchodilation.
References:
1. Mitra S, Ugur M, Ugur O, et al. (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.
2. Penn RB, Frielle T, McCullough JR, et al. Comparison of
R-, S-, and RS-albuterol interaction with human β1- and β2-adrenergic receptors. Clin Rev Allergy Immunol. 1996;14(1):37-45.
3. Lötvall J, Palmqvist M, Arvidsson P, et al. 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.
4. Ameredes BT, Calhoun WJ. Modulation of GM-CSF release by enantiomers of beta-agonists in human airway smooth muscle. J Allergy Clin Immunol. 2005;116(1):65-72.
5. 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.
6. Volcheck GW, Kelkar P, Bartemes KR, et al. Effects of (R)- and
(S)-isomers of β-adrenergic agonists on eosinophil response to interleukin-5. Clin Exp Allergy. 2005;35(10):1341-1346.
XOPENEX HFA® (levalbuterol tartrate) Inhalation Aerosol is contraindicated in patients with a history of hypersensitivity to levalbuterol, racemic albuterol, or any component of XOPENEX HFA. XOPENEX HFA and other β-agonists can produce paradoxical bronchospasm, which may be life threatening. 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. Do not exceed the recommended dose. Fatalities have been reported in association with excessive use of sympathomimetic drugs in patients with asthma. Please refer to the full prescribing information regarding potential drug interactions with β-blockers, diuretics, digoxin, or MAOI and tricyclic antidepressants.
XOPENEX HFA Inhalation Aerosol
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.
