1. Medical Exception Criteria

   Accuneb and Xopenex are currently listed on the Aetna Formulary Exclusions List* They therefore are excluded from coverage for members enrolled in prescription drug benefits plans that use a closed formulary, unless a medical exception is granted. Aetna considers Acccuneb or Xopenex to be medically necessary for those members who meet BOTH of the following criteria:

   1. Member requires a nebulized bronchodilator

      AND

   2. Member has a documented:

      • Contraindication to the preferred alternative albuterol OR,
      • Allergy to the preferred alternative albuterol OR,
      • Intolerance to the preferred alternative albuterol OR,
      • Failure of an adequate trial of one (1) week of the preferred alternative albuterol for the member's condition.

*Information regarding Aetna's Preferred Drug List, Formulary Exclusions list, Precertification and Step-Therapy lists is available on our website. In addition, members should refer to their plan documents and may call the toll-free telephone number on their ID card for information regarding their benefits. Health care professionals also may obtain information by calling the Pharmacy Management Precertification Unit at 1-800-414-2386, or if access to the Internet is available, providers may initiate the registration process to use our password-protected provider website. Visit www.aetna.com, select “Doctors & Hospitals” and choose “Physician Self-Service”.

Once registration is completed, health care professionals may utilize our online Precertification/medical exception email request form. The aforementioned lists are subject to change. Not all programs, for example Step-Therapy, Precertification and Quantity Limits, are available in all service areas (for example, Step-Therapy does not apply to fully insured New Jersey members).

Many medications on the Preferred Drug List are subject to manufacturer rebate arrangements between Aetna and the manufacturer of those medications. If the member's prescription benefits plan has copay levels based on a percentage of Aetna's contracted rate with the participating pharmacy, the contracted rate does not include or reflect any manufacturer rebate arrangements between Aetna and the medication manufacturer. In prescription plans with copayment or coinsurance tiers, use of drugs from the Preferred Drug List generally will result in lower costs to members. However, where the prescription plan utilizes copayments or coinsurance calculated on a percentage basis, there could be some circumstances in which a preferred drug would cost the member more than a non-preferred drug because (i) the negotiated pharmacy payment rate for the preferred drug may be more than the negotiated pharmacy payment rate for the non-preferred drug, and (ii) rebates received by Aetna from drug manufacturers are not reflected in the cost of a prescription drug obtained by a member. The Preferred Drug List is subject to change.

In evaluating clinically and therapeutically similar drugs for selection for the Preferred Drug List, Aetna reviews the costs of drugs and takes into account rebates negotiated between Aetna and drug manufacturers. Consequently, a drug may be included on the Preferred Drug list that is more expensive than a non-preferred alternative before any rebates Aetna may receive from a drug manufacturer are taken into account. In addition, certain drugs may be chosen for “preferred” status because of their clinical or therapeutic advantages or level of acceptance among physicians even though they cost more than non-preferred alternatives. The net cost to a self-funded plan sponsor for covered prescriptions will vary based on (i) the terms of Aetna's arrangements with participating pharmacies; (ii) the amount of the member's copayment, coinsurance or deductible obligation under the terms of the plan; and (iii) the percentage, if any, of rebates to which the plan sponsor is entitled under its agreement with Aetna. As a result, a self-funded plan sponsor's actual claim expense per prescription for a particular preferred drug may in some circumstances be higher than for a non-preferred alternative.

For members in Texas, additions to the 2005 Preferred Drug List will be effective no later than January 1, 2005. In accordance with state law, fully insured members in Texas who are receiving coverage for medications that are removed from the Preferred Drug List during the plan year will continue to have those medications covered at the same benefit level until their plan's renewal date.

This definition of Precertification is not the same as the definition used by Texas law. Our use of the term, “Precertification” relates to the prior authorization of your services by Aetna, based on our decision of whether the service is medically necessary. Precertification is not a guarantee of payment or “verification” as defined by Texas Law.

California HMO members enrolled in a closed formulary benefits plan who are receiving coverage for medications that are moved to the Formulary Exclusions List, and California HMO members who are receiving coverage for medications added to the Precertification or Step-Therapy lists, will continue to have those medications covered, for as long as the treating physician continues prescribing them. This coverage, in accordance with state law, is only provided when the drug is appropriately prescribed and is considered safe and effective for treating the member's medical condition.

Nothing in this section shall preclude the prescribing health care professional from prescribing another drug covered by the plan that is medically appropriate for the enrollee, nor shall anything in this section be construed to prohibit generic drug substitutions.

Place of Service:

Outpatient

The above policy is based on the following references:

1. Ind PW. Salbutamol enantiomers: Early clinical evidence in humans. Thorax 1997;52:839-40.
2. Bakale RP, et al. Albuterol: A pharmaceutical chemistry review of R-, S-, and RS-albuterol. Clin Rev Allergy Immunol 1996;14:7-35.
3. Penn RB, et al. Comparison of R-, S-, and RS-albuterol interaction with human ß1-and ß2-adrenergic receptors. Clin Rev Allergy Immunol 1996;14:37-45.
4. Cockcroft DW, Swystun VA. Effect of single doses of S-salbutamol, R-salbutamol, racemic salbutamol, and placebo on the airway response to methacholine. Thorax 1997;52:845-8.
5. Perrin-Fayolle M, et al. Differential responses of asthmatic airways to enantiomers of albuterol: Implications for clinical treatment of asthma. Clin Rev Allergy Immunol 1996;14:139-47.
6. Xopenex Product Information. Sepracor Inc., Marlborough, MA. January 2002.
7. Accuneb Product Information. Dey, Napa, CA. September 2001.
8. National Institutes of Health, National Heart, Lung and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report Number 2: Guidelines for the Diagnosis and Management of Asthma. Clinical Practice Guidelines. NIH Publication No. 97-4051. Bethesda, MD: NIH, July 1997.
9. National Institutes of Health, National Heart, Lung and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma - Update on Selected Topics 2002. Clinical Practice Guidelines. NIH Publication No. 02-5075. Bethesda, MD: NIH, July 2002. http://www.nhlbi.nih.gov/guidelines/asthma/index.htm
10. Drugs for asthma. Med Lett Drugs Ther. 2000;42(1073):19-24.
11. Busse WW, Lemanske RF. Asthma. N Engl J Med. 2001;344:350-62.
12. ICSI Health Care Guideline: Diagnosis and management of asthma. Rochester, MN: Institute for Clinical Systems Improvement. May 2002. http://www.icsi.org/knowledge/detail.asp?catID=29&itemID=162. accessed March 1, 2003.
13. Apter AJ. Clinical advances in adult asthma. J Allergy Clin Immunol. 2003;111:S780-4.
14. Lemanske Jr FR, Busse WW. Asthma. J Allergy Clin Immunol. 2003;111:S502-19.
15. Spahn JD, Szefler SJ. Childhood asthma: New insights into management. J Allergy Clin Immunol. 2002;109:3-13.
16. Jenne JW. The debate on S-enantiomers of ß-agonists: Tempest in a teapot or gathering storm? J Allergy Clin Immunol. 1998;102(6 part 1):893-5.
17. Ahrens R, Weinberger M. Levalbuterol and recemic albuterol: Are there therapeutic differences? J Allergy Clin Immunol. 2001;108:681-4.
18. Baramki D, Koester J, Anderson AJ, Borish L. Modulation of T-cell function by (R)- and (S)-isomers of albuterol: Anti-inflammatory influences of (R)-isomers are negated in the presence of the (S)-isomer. J Allergy Clin Immunol. 2002;109:449-54.
19. 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.
20. Rodenberg H. Effect of levalbuterol on prehospital patient parameters. Am J Emerg Med. 2002;20:481-83.
21. Milgrom H, Skoner DP, Bensch G, et al. Low-dose levalbuterol in children with asthma: Safety and efficacy in comparison with placebo and racemic albuterol. J Allergy Clin Immunol. 2001;108:938-45.
22. Asmus MJ, Hendeles L, Weinberger M, et al. Levalbuterol has not been established to have therapeutic advantage over racemic albuterol. J Allergy Clin Immunol. 2002;110:325.
23. Chowdhury BA. Comparative efficacy of levalbuterol and racemic albuterol in the treatment of asthma. J Allergy Clin Immunol. 2002;110:324.
24. Milgrom H, Skoner D, Bensch, et al. Reply: Levalbuterol has not been established to have therapeutic advantage over racemic albuterol. J Allergy Clin Immunol. 2002;110:325-27.
25. Slattery D, Wong SW, Colin AA. Levalbuterol hydrochloride. Pediatr Pulmonol. 2002;33:151-7.
26. Truitt T, Witko J, Halpern M. Levalbuterol compared to racemic albuterol: Efficacy and outcomes in patients hospitalized with COPD or asthma. Chest. 2003;123:128-35.
27. Richard M.Nowak, Charles L. Emarman, et al. Levalbuterol Compared with racemic Albuterol in the treatment of Acute Asthma: Results of a Pilot Study. Am J Emerg Med 2004;22:29-36.
28. John C. Carl, Timothy R. Myeres, et, al. Comparison of racemic albuterol and levalbuterol for treatment of acute asthma. J Pediatr 2003; 143:731-6.
29. USPDI Drug Information for the HealthCare Professional (online). Thomson MICROMEDEX, Greenwood Village, Colorado; 2004.
30. McEvoy GK, editor. AHFS Drug Information (online). American Society of Health-Systems Pharmacists, Bethesda, Maryland; 2004.
31. Olin BR, editor. Drugs Facts and Comparisons (electronic online version). St. Louis: J.B. Lippincott Company, 2004.

Property of Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.