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MDWISE PRIOR AUTHORIZATION CRITERIA
XOPENEX (levalbuterol) MDI: 45mcg/puff; Nebulization: 0.31mg/3mL, 0.63mg/3mL, 1.25mg/3mL
FORMULARY STATUS Non-Preferred
BACKGROUND
Levalbuterol HCl for inhalation is the R-enantiomer of the drug substance racemic albuterol. The Renantiomer of racemic albuterol is the pharmacologically active component that possesses relatively
selective beta2-adrenergic receptor agonist activity that is solely responsible for airway smooth muscle
relaxation AND in correspondence to systemic absorption: skeletal muscle tremor, headache, increased
heart rate, hypokalemia, and hyperglycemia. The side effect profile of the R-enantiomer is unaffected by the
removal if the inactive S-enantiomer in the Xopenex formulation. Clinically, in humans there is no difference
between equivalent doses of racemic albuterol and levalbuterol i.e. 0.63mg levalbuterol=1.25mg racemic
albuterol, etc. A statement of clinical equivalence appears in the most recent National Asthma Education
and Prevention Program of the National Institutes of Health (NAEPP Expert Panel Report: Guidelines for the
Diagnosis and Management of Asthma, 2007, Figure 3-23). See also Lotvall et al.
It is also important to note that albuterol in pediatrics is appropriately dosed on a mg/kg basis, as the
common practice of using 2.5mg/treatment of racemic albuterol for all circumstances leads to accentuated
beta2 adrenergic systemic effects. For routine outpatient treatments the recommended dosage given by the
NAEPP for children 0-4 starts at 0.63mg and for those ages 5-11 starts at 1.25mg.
PA CRITERIA FOR APPROVAL
INITIAL PA:
Asthma:
Hypersensitivity (atopic—i.e. difficulty breathing, urticaria, anaphylaxis, not related to acute asthma
exacerbation. Hypersensitivity does NOT include routine tachycardia and or restlessness that normally
accompanies an adrenergic receptor agonist) to racemic albuterol or one of its components.
Chronic Lung Disease:
Hypersensitivity (atopic—i.e. difficulty breathing, urticaria, anaphylaxis, not related to acute asthma
exacerbation. Hypersensitivity does NOT include routine tachycardia and or restlessness that normally
accompanies an adrenergic receptor agonist) to racemic albuterol or one of its components.
If the above criteria are met, prior authorizing entity shall approve for a period of 12 months. If the following
criteria are not met, the prior authorizing entity shall suggest utilization of racemic albuterol at a dose
equivalent to the requested dose of Xopenex (see chart below). If the requested dose of Xopenex is
equivalent to doses of albuterol already previously tried by the member, suggest the next lowest dose e.g. If
prescriber is requesting Xopenex 1.25mg and member was previously receiving 2.5mg of albuterol, suggest
1.25mg of albuterol.
Send accompanying counter detailing literature (EXHIBIT A & Weinberger article) to requesting prescriber
along with denial letter.
Dosage Conversions:
Drug
Dose
Dose
Dose
Levalbuterol (Xopenex)
0.31mg
0.62mg
1.25mg
Albuterol (Racemic)
0.62mg
1.25mg
2.5mg
Dose
45mcg/puff
2 puffs
90mcg/puff
2 puffs
FDA INDICATIONS
MDI: For the treatment or prevention of bronchospasm in adults, adolescents, and children 4 years of age
and older with reversible obstructive airway disease.
Nebulized Solution: For the treatment or prevention of bronchospasm in adults, adolescents, and children
6 years of age and older with reversible obstructive airway disease.
DOSAGE AND ADMINISTRATION
MDI:

Patients 4 years of age and older: 1-2 inhalations (45-90mcg) every 4 to 6 hours.

The safety and effectiveness in pediatric patients below the age of 4 years have not been established.
Nebulized Solution:

Children 6-11 years old: 0.31mg administered 3 times a day by nebulization, do not exceed 0.63mg
three times a day.

Adults and Adolescents 12 years of age and older: 0.63mg administered three times a day, every 6 to 8
hours by nebulization. Patients who do not respond adequately to this dose may benefit from a dosage
of 1.25mg three times a day. Closely monitor patients receiving the higher dose for adverse systemic
effects and balance the risks of such effects against the potential for improved efficacy.

The safety and effectiveness in pediatric patients below the age of 6 years have not been established.
REFERENCES
1. National Asthma Education and Prevention Program. Expert panel report-3, 2007: Guidelines for the
Diagnosis and Management of Asthma. Washington, DC: US Department of Health and Human
Services, National Institutes of Health, 2007.
2. Asmus MJ, Hendeles L. Levalbuterol Nebulizer Solution: Is It Worth Five Times the Cost of Albuterol?
Pharmacotherapy 2000;20(2):123-9.
3. Weinberger M. Is There Any Advantage to Using Levalbuterol in the Treatment of Asthma? Clinical
Pulmonary Medicine. May 2004;11(3):129-34.
4. Lotvall 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;108:726-31.
5. Mazzoni L, Naef R, Chapman ID, et al. Hyperresponsiveness of the airways following exposure of
guinea-pigs to racemic mixtures and isomers of beta2 selective sympathomimetics. Pulm Pharmacol.
1994;7:367-76.
6. Leff RA, Herrrnreiter A, Naclerio RM, et al. Effect of enantiomeric forms of albuterol on stimulated
secretion of granular protein from human eosinophils. Pulm Pharmacol Ther. 1997;10:97-104.
7. Handley DA, McCullough JR, Crowther SD, et al. Sympathomimetic enantiomers and asthma. Chirality.
1998;10:262-72.
8. Waldek B. Enantiomers of bronchodilating beta2 adrenoceptor agonists: is there a cause for concern?
J Allergy Clin Immunol. 1999;103:742-8.
9. Nelson HS. Clinical experience with levalbuterol. J Allergy Clin Immunol.1999;104:S77-84.
10. Handley D. The asthma-like pharmacology and toxicology of (S)-isomers of beta agonists. J Allergy Clin
Immunol. 1999;104(pt 2):S69-76.
11. Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levalbuterol compare with
racemic albuterol in patients with asthma. J Allergy Clin Immunol. 1998;102:943-52.
12. Ahrens RC. On comparing beta adrenergic agonists. Ann Allergy. 1991;67:296-8.
13. Facts and Comparisons, St. Louis, 2010 eFacts CliniSphere Version ISBN 1-57439-0368.
14. Xopenex HFA. Prescribing Information. Sepracor. June 2009.
15. Xopenex Inhalation Solution. Prescribing Information. Sepracor. February 2009.
Revision/Review Date: 10/12/2011
Associated Policy: Prior Authorization of Medications 236.200
EXHIBIT A
XOPENEX (levalbuterol) MDI: 45mcg/puff; Nebulization: 0.31mg/3mL, 0.63mg/3mL, 1.25mg/3mL
FORMULARY STATUS Non-Preferred
SUMMARY
Xopenex appears to have no clinically significant advantage over albuterol.
BACKGROUND
Levalbuterol HCl for inhalation is the R-enantiomer of the drug substance racemic albuterol. The Renantiomer of racemic albuterol is the pharmacologically active component that possesses relatively
selective beta2-adrenergic receptor agonist activity that is solely responsible for airway smooth muscle
relaxation AND in correspondence to systemic absorption: skeletal muscle tremor, headache, increased
heart rate, hypokalemia, and hyperglycemia. The side effect profile of the R-enantiomer is unaffected by the
removal if the inactive S-enantiomer in the Xopenex formulation. Clinically, in humans there is no difference
between equivalent doses of racemic albuterol and levalbuterol i.e. 0.63mg levalbuterol=1.25mg racemic
albuterol, etc. A statement of clinical equivalence appears in the most recent National Asthma Education
and Prevention Program of the National Institutes of Health (NAEPP Expert Panel Report: Guidelines for the
Diagnosis and Management of Asthma, 2007, Figure 3-23). See also Lotvall et al.
It is also important to note that albuterol in pediatrics is appropriately dosed on a mg/kg basis, as the
common practice of using 2.5mg/treatment of racemic albuterol for all circumstances leads to accentuated
beta2 adrenergic systemic effects. For routine outpatient treatments the recommended dosage given by the
NAEPP for children 0-4 starts at 0.63mg and for those ages 5-11 starts at 1.25mg.
Dosage Conversions:
Drug
Dose
Dose
Dose
Dose
Levalbuterol
(Xopenex)
Albuterol
(Racemic)
0.31mg
$1.04 each dose
0.62mg
$0.16 each dose
0.62mg
$1.02 each dose
1.25mg
$0.33 each dose
1.25mg
$1.09 each dose
2.5mg
$0.41-$0.65 each dose
45mcg/puff (2 puffs)
$50/inhaler
90mcg/puff (2 puffs)
$20-$30/inhaler
FDA INDICATIONS
MDI: For the treatment or prevention of bronchospasm in adults, adolescents, and children 4 years of age
and older with reversible obstructive airway disease.
Nebulized Solution: For the treatment or prevention of bronchospasm in adults, adolescents, and children
6 years of age and older with reversible obstructive airway disease.
DOSAGE AND ADMINISTRATION
MDI:

Patients 4 years of age and older: 1-2 inhalations (45-90mcg) every 4 to 6 hours.

The safety and effectiveness in pediatric patients below the age of 4 years have not been established.
Nebulized Solution:

Children 6-11 years old: 0.31mg administered 3 times a day by nebulization, do not exceed 0.63mg
three times a day.

Adults and Adolescents 12 years of age and older: 0.63mg administered three times a day, every 6 to 8
hours by nebulization. Patients who do not respond adequately to this dose may benefit from a dosage
of 1.25mg three times a day. Closely monitor patients receiving the higher dose for adverse systemic
effects and balance the risks of such effects against the potential for improved efficacy.

The safety and effectiveness in pediatric patients below the age of 6 years have not been established.
REFERENCES
1. National Asthma Education and Prevention Program. Expert panel report-3, 2007: Guidelines for the
Diagnosis and Management of Asthma. Washington, DC: US Department of Health and Human
Services, National Institutes of Health, 2007.
2. Asmus MJ, Hendeles L. Levalbuterol Nebulizer Solution: Is It Worth Five Times the Cost of Albuterol?
Pharmacotherapy 2000;20(2):123-9.
3. Weinberger M. Is There Any Advantage to Using Levalbuterol in the Treatment of Asthma? Clinical
Pulmonary Medicine. May 2004;11(3):129-34.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Lotvall 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;108:726-31.
Mazzoni L, Naef R, Chapman ID, et al. Hyperresponsiveness of the airways following exposure of
guinea-pigs to racemic mixtures and isomers of beta2 selective sympathomimetics. Pulm Pharmacol.
1994;7:367-76.
Leff RA, Herrrnreiter A, Naclerio RM, et al. Effect of enantiomeric forms of albuterol on stimulated
secretion of granular protein from human eosinophils. Pulm Pharmacol Ther. 1997;10:97-104.
Handley DA, McCullough JR, Crowther SD, et al. Sympathomimetic enantiomers and asthma. Chirality.
1998;10:262-72.
Waldek B. Enantiomers of bronchodilating beta2 adrenoceptor agonists: is there a cause for concern?
J Allergy Clin Immunol. 1999;103:742-8.
Nelson HS. Clinical experience with levalbuterol. J Allergy Clin Immunol.1999;104:S77-84.
Handley D. The asthma-like pharmacology and toxicology of (S)-isomers of beta agonists. J Allergy Clin
Immunol. 1999;104(pt 2):S69-76.
Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levalbuterol compare with
racemic albuterol in patients with asthma. J Allergy Clin Immunol. 1998;102:943-52.
Ahrens RC. On comparing beta adrenergic agonists. Ann Allergy. 1991;67:296-8.
Xopenex HFA. Prescribing Information. Sepracor. September 2005.
Xopenex Inhalation Solution. Prescribing Information. Sepracor. August 2007.
Revision/Review Date: MAC 9/8/2010
Associated Policy: Prior Authorization of Medications 236.200