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Pharmacy Clinical Policy Bulletins
Aetna Non-Medicare Prescription Drug Plan
Subject: Nonsteroidal Anti-inflammatory Agents

Status Drug PR PR-QL PR-AL ST M EX‡
P diclofenac sodium          
P diclofenac potassium          
P diflunisal          
P etodolac          
P fenoprofen          
P ibuprofen (>200 mg)          
P flurbiprofen          
P indomethacin/indomethacin SR          
P ketoprofen          
P ketorolac   X      
P meclofenamate          
P meloxicam          
P naproxen/naproxen EC          
P piroxicam          
P sulindac          
P salsalate          
P choline magnesium trisalicylate          
NP Anaprox®  (naproxen sodium)          
NP Anaprox® DS  (naproxen sodium)          
NP Ansaid®  (flurbiprofen)          
NP Cataflam®  (diclofenac potassium)          
NP Clinoril®  (sulindac)          
NP Dolobid®  (diflunisal)          
NP EC-Naprosyn®  (naproxen EC)          
NP Feldene®  (piroxicam)          
NP Indocin®  (indomethacin)          
NP Indocin® SR  (indomethacin CR)          
NP Motrin®  (ibuprofen)          
NP Nalfon®  (fenoprofen)          
NP Naprosyn®  (naproxen)          
NP Toradol®  (ketorolac)   X      
P Arthrotec®  (diclofenac sodium/ misoprostal)         X
FE Celebrex®  (celecoxib) X X     X
FE Daypro®  (oxaprozin)         X
FE diclofenac XR         X
FE etodolac SR         X
FE ketoprofen SR         X
FE Lodine XL®  (etodolac SR)         X
FE mefenamic acid         X
FE Mobic®  (meloxicam)       X X
FE nabumetone         X
FE Naprelan®  (naproxen CR)       X X
FE Oruvail®  (ketoprofen SR)         X
FE oxaprozin         X
FE Ponstel®  (mefenamic acid)         X
FE Relafen®  (nabumetone)         X
FE Tolectin®  (tolmetin)         X
FE tolmetin         X
FE Voltaren XR®  (diclofenac XR)         X
FE Theraproxen™ Pak  (naproxen tab/nutritional supplement cap pack)         X


Policy:

  1. Precertification Criteria

    2. Under some plans, including plans that use an open or closed formulary, Celebrex, ketorolac and Toradol are subject to precertification. If precertification requirements apply Aetna considers Celebrex, ketorolac or Toradol to be medically necessary for those members who meet the following precertification criteria:

    (A AND C) For Celebrex 50, 100 mg and 200 mg

    C - For ketorolac and Toradol

    A.   A documented:

    • Age greater than 60 OR
    • Diagnosis of Juvenile Rheumatoid Arthritis [JRA]
    • Concomitant use of warfarin (Coumadin®) or other antiplatelet therapy OR
    • Concomitant use of chronic oral (systemic) corticosteroid therapy OR
    • Documented history of ulcer disease** or GI bleed; OR
    • Documented of an H2 receptor antagonist (cimetidine/Tagamet®, famotidine/Pepcid®, nizatidine/Axid®, ranitidine/ Zantac®) or a proton pump inhibitor (AcipHex®, Nexium®, omeprazole/Prilosec®, Prevacid®, Protonix®), or misoprostol (Cytotec®) because of history of significant GI disease** or NSAID GI adverse effects, necessitating discontinuation of NSAID therapy. Refer to the PPI CPB for list of significant GI diseases.

    For Celebrex 400mg

    B.  A Documented diagnosis of FAP (Familial Adenomatous Polyposis)

    AND

    C. Quantity Limits

    According to the manufacturer, Celebrex, ketoroloac and Toradol can be dosed up to a maximumdaily dose at the interval as indicated in the table below. A quantity of Celebrex will be considered medically necessary as indicated in the table below, if member fulfills criteria A OR B above. A quantity of ketorolac or Toradol will be considered medically necessary as indicated in the table below:

    Drug Maximum Daily Dose/ Dosing Interval Dosage Strength Quantity Limits
    Celebrex 200 mg/ once daily 50 mg, 100 mg Up to 60 capsules in 30 days
    Celebrex 200 mg/ once or twice daily 200 mg Up to 30 capsules in 30 days
    Celebrex 800 mg/ twice daily 400 mg Up to 60 capsules in 30 days
    Toradol Ketorolac 40 mg / in divided doses daily 10 mg Up to 20 tablets in 30 days


    For coverage of additional quantities, a member's treating physician must request prior authorization through the Pharmacy Management Precertification Unit. A prior authorization will be granted for coverage of additional quantities of ketorolac or Toradol for those members who meet the following criterion:

    For ketorolac, Toradol, or Celebrex 400 mg

    • Member's physician provides documentation (controlled clinical trial) from the peer-reviewed medical literature for use of a higher dose.


    For Celebrex 100 mg and 200 mg

    • Documented diagnosis of rheumatoid arthritis (RA)  or Juvenile Rheumatoid Arthritis [JRA] (approvable dose is 200 mg twice daily or 60 capsules (200mg) per 30 days) OR
    • Failure of 200mg QD (approvable dose is 200 mg twice daily or 60 capsules (200mg) per 30 days) OR,
    • Documented diagnosis of acute pain (approvable dose is 200 mg twice daily or 60 capsules (200 mg) per 30 days; 30 day limit) OR
    • Member's physician provides documentation (controlled clinical trial) from the peer-reviewed medical literature for use of a higher dose.

     



  2. Step Therapy Criteria

    3. Under some plans, including plans that use an open or closed formulary, Mobic and Naprelan are subject to step-therapy.  Aetna considers Mobic and Naprelan to be medically necessary for those members who meet the following step-therapy criterion:

    A documented trial of two weeks each of two preferred generic nonsteroidal anti-inflammatory agents

    If it is medically necessary for a member to be treated initially with a medication subject to step-therapy, the member's treating physician may contact the Aetna Pharmacy Management Precertification Unit to request coverage as a medical exception at 1-800-414-2386. (See criteria under section III below.)

  3. Medical Exception Criteria

    4. Arthrotec, Celebrex, Daypro, diclofenac XR, etodolac SR, ketoprofen SR, Lodine XL, mefenamic acid, Mobic, nabumetone, Naprelan, Oruvail, oxaprozin, Ponstel, Relafen, Theraproxen Pak, Tolectin, tolmetin, and Voltaren XL are currently listed on the Aetna Formulary Exclusions List.* Therefore, they are excluded from coverage for members enrolled in prescription drug benefit plans that use a closed formulary, unless a medical exception is granted.  Aetna considers Arthrotec, Celebrex, Daypro, diclofenac XR, etodolac SR, ketoprofen SR, Lodine XL, Mobic, nabumetone, Naprelan, Oruvail, oxaprozin, Ponstel, Relafen, Theraproxen Pak Tolectin, tolmetin and Voltaren XL to be medically necessary for those members who meet the following criteria:


    A.  A documented:

    For Arthrotec, Daypro, diclofenac XR, etodolac SR, ketoprofen SR, Lodine XL, mefenamic acid, Mobic, nabumetone, Naprelan, Oruvail, oxaprozin, Ponstel, Relafen, Tolectin, tolmetin, and Voltaren XL

    • Contraindication to at least two preferred nonsteroidal anti-inflammatory agents indicated for the member's condition OR
    • Intolerance to at least two preferred nonsteroidal anti-inflammatory agents indicated for the member's condition OR
    • Allergy to at least two preferred nonsteroidal anti-inflammatory agents indicated for the member's condition OR
    • Failure of an adequate trial of two weeks each of at least two preferred nonsteroidal anti-inflammatory agents indicated for the member's condition

    For Theraproxen Pak

    • Contraindication to at least two preferred nonsteroidal anti-inflammatory agents (one of which should be naproxen)indicated for the member's condition OR
    • Intolerance to at least two preferred nonsteroidal anti-inflammatory agents (one of which should be naproxen)indicated for the member's condition OR
    • Allergy to at least two preferred nonsteroidal anti-inflammatory agents (one of which should be naproxen) indicated for the member's condition OR
    • Failure of an adequate trial of two weeks each of at least two preferred nonsteroidal anti-inflammatory agents (one of which should be naproxen) indicated for the member's condition.

    For Celebrex 50 mg, 100 mg and 200 mg

    • Age greater than 60 OR
    • Diagnosis of Juvenile Rheumatoid Arthritis [JRA]
    • Concomitant use of warfarin (Coumadin®) or other antiplatelet therapy OR
    • Concomitant use of chronic oral (systemic) corticosteroid therapy OR
    • Documented history of ulcer disease** or GI bleed; OR
    • Documented use of a H2 receptor antagonist (cimetidine/Tagamet®, famotidine/Pepcid®, nizatidine/Axid®, ranitidine/ Zantac®) OR a proton pump inhibitor (AcipHex®, Nexium®, omeprazole/Prilosec®, Prevacid®, Protonix®), OR misoprostol (Cytotec®) because member has history of significant GI disease** or NSAID GI adverse effects, necessitating discontinuation of NSAID therapy. Refer to the Proton Pump Inhibitor CPB for list of significant GI diseases.

         AND
        A documented

    • Contraindication to at least two preferred nonsteroidal anti-inflammatory agents indicated for the member's condition OR
    • Intolerance to at least two preferred nonsteroidal anti-inflammatory agents indicated for the member's condition OR
    • Allergy to at least two preferred nonsteroidal anti-inflammatory agents indicated for the member's condition OR
    • Failure of an adequate trial of two weeks each of at least two preferred nonsteroidal anti-inflammatory agents indicated for the member's condition 

    For Celebrex 400mg:

    • Documented diagnosis of FAP (Familial Adenomatous Polyposis)

     

    NOTE:
    Below is the FDA News Release about GI and CV risks associated with the NSAIDs.  More information is available on the FDA website and at: http://www.fda.gov/cder/drug/infopage/COX2/NSAIDdecisionMemo.pdf.

    FDA News
    FOR IMMEDIATE RELEASE
    P05-16
    April 7, 2005  

    Media Inquiries: Kathleen Quinn
                            301-827-6242
    Consumer Inquiries: 888-INFO-FDA

    FDA Announces Series of Changes to the Class of Marketed Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
    The Food and Drug Administration (FDA) today announced a series of important changes pertaining to the marketing of the non-steroidal anti-inflammatory class of drugs, including COX-2 selective and prescription and non-prescription (over-the-counter (OTC)) non-selective NSAID medications. A list of these products is available on the Internet at http://www.fda.gov/cder/drug/infopage/cox2/default.htm.

    "Today's actions protect and advance the health of the millions of Americans who rely on these drugs everyday," said Dr. Steven K. Galson, Acting Director of FDA's Center for Drug Evaluation and Research (CDER). "FDA is providing the public information based on the latest available scientific data to guide the careful and appropriate use of these drugs aimed at maximizing their potential benefits and minimizing their risks."

    FDA has asked Pfizer, Inc. to withdraw Bextra (valdecoxib) from the market because the overall risk versus benefit profile for the drug is unfavorable. FDA has also asked Pfizer to include a boxed warning in the Celebrex (celecoxib) label. Pfizer has agreed to suspend sales and marketing of Bextra in the U.S., pending further discussions with the agency. Pfizer has agreed to work with FDA on the boxed warning for Celebrex. FDA is asking manufacturers of all other prescription NSAIDs to revise their labels to include the same boxed warning highlighting the potential for increased risk of cardiovascular (CV) events and gastrointestinal (GI) bleeding associated with their use. Manufacturers of Celebrex and all other prescription NSAIDs will be asked to revise their labeling to include a Medication Guide for patients to help make them aware of the potential for CV and GI adverse events associated with the use of this class of drugs.

    In addition, FDA is asking the manufacturers of all OTC NSAIDs to revise their labels to include more specific information about the potential CV and GI risks, and information to assist consumers in the safe use of the drugs. FDA is also asking manufacturers of OTC NSAIDs to include a warning about potential skin reactions. The labeling of the prescription NSAIDs already addresses potential skin reactions.

    This current reexamination of the CV risks of NSAIDs began after Merck conducted a voluntary worldwide withdrawal of its COX-2 selective NSAID, Vioxx (rofecoxib), in September 2004. FDA will carefully review any proposal from Merck for resumption of marketing of Vioxx.

    These actions are based on the available scientific data, including data accumulated since the drugs were approved. The FDA has carefully considered the presentations, discussions, and recommendations from the joint meeting of the Agency's Arthritis and Drug Safety and Risk Management Advisory Committee held on February 16-18, 2005.

    To inform the public and healthcare community of its decisions, FDA today issued a Public Health Advisory (PHA) and updated patient and healthcare practitioner fact sheets.

    Additional information about today's announcements is available on FDA's Web site at www.fda.gov/cder. Information can also be obtained by calling 1-888-INFO-FDA (888-463-6332).


Special Notes:

**NOTE: Examples of Significant GI diseases can include:

Barrett's esophagus
Crohn's disease
Erosive esophagitis - active, maintenance, healed
Gastric residual reduction
Gastrointestinal bleed
GERD - moderate to severe with symptoms (treatment, maintenance, screening)
H. pylori, treatment
Hypersecretory conditions, including Zollinger-Ellison Syndrome
Laryngopharyngeal reflux

Ulcer disease Specific
Duodenal ulcer - active ulcer; maintenance of healed ulcer
Gastric ulcer - active benign; maintenance
Gastrojejunal ulcer - active; maintenance
NSAID-induced gastric ulcer - healing; risk reduction for recurrence
Peptic ulcer disease
Stress ulcer/surgical prophylaxis



Place of Service:

Outpatient

The above policy is based on the following references:
  1. Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. 2006.
  2. USP DI® Drug Information For The Health Care Professional - 26th Ed. (online from www.statref.com) Thomson Micromedex, Greenwood Village, CO. 2006.
  3. AHFS Drug Information® with AHFSfirstReleases®. (online from www.statref.com), American Society Of Health-System Pharmacists®, Bethesda, MD. 2006.
  4. DRUGDEX® System: Klasco RK (Ed):DRUGDEX® System. Online edition. Thomson Micromedex, Greenwood Village, CO.
  5. PDR® Electronic Library, Thomson Micromedex, Greenwood Village, Colorado (Edition expires 2006).
  6. Subcommittee on Osteoarthritis Guidelines, Recommendations for the Medical Management of Osteoarthritis of the HIP and Knee, Arthritis & Rheumatism, September 2000; Vol 43(9):1905-1915.
  7. Bloom BJ.  New drug therapies for the pediatric rheumatic diseases.  Current Opinion in Rheumatology.  2001;13:410-4.
  8. Jackson, LM, Hawkey, CJ, COX-2 Selective Nonsteroidal Anti-inflammatory Drugs, Do They Really Offer Any Advantages, ADIS Drugs, 2000 Jun;59(6):1207-1216.
  9. Creamer P, Osteoarthritis Pain and Its Treatment, Current Opinion in Rheumatology 2000;12:450-455.
  10. Feldman, M, McMahon, AT, Do Cyclooxygenase-2 Inhibitors Provide Benefits Similar to Those of Traditional Nonsteroidal Anti-Inflammatory Drugs, with Less Gastrointestinal Toxicity, Ann Intern Med. 2000;132:132-143.
  11. NICE Appraisal Team, on behalf of the National Institutes of Clinical Excellence, The Clinical Effectiveness and Cost Effectiveness of Celecoxib, Rofecoxib, Meloxicam and Etodolac (COX-2 Inhibitors) For Rheumatoid Arthritis and Osteoarthritis, November 1, 2000.
  12. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines, Guidelines for the Management of Rheumatoid Arthritis, February 2002 Update, Arthritis & rheumatism; 46(2):328-346.
  13. Yuan Y, Hunt RH.  Assessment of the safety of selective cyclo-oxygenase-2 inhibitors: where are we in 2003?  Inflammopharmacology. 2003;11:337-54.
  14. Cheng HF, Harris RC.  Cyclooxygenases, the kidney, and hypertension.  Hypertension.  2004;43:525-30.
  15. FitzGerald GA.  Cardiovascular pharmacology of nonselective nosteroidal anti-inflammatory drugs and coxibs: clinical considerations.  Am J Cardiol. 2002;89(suppl):26D-32D.
  16. Frishman WH.  Effects of nonsteroidal anti-inflammatory drug therapy on blood pressure and peripheral edema.  Am J Cardiol. 2002;89(suppl):18D-25D.
  17. Armstrong EP, Malone DC.  The impact of nosteroidal anti-inflammatory drugs on blood pressure, with an emphasis on newer agents.  Clin Ther.  2003;25:1-18.
  18. Creamer P, Osteoarthritis Pain and Its Treatment, Current Opinion in Rheumatology 2000;12:450-455.
  19. Feldman, M, McMahon, AT, Do Cyclooxygenase-2 Inhibitors Provide Benefits Similar to Those of Traditional Nonsteroidal Anti-Inflammatory Drugs, with Less Gastrointestinal Toxicity, Ann Intern Med. 2000;132:132-143.
  20. Lanas, A, et al., Nitrovasodilators, Low-dose Aspirin, Other Nonsteroidal Anti-inflammatory Drugs, and the Risk of Upper Gastrointestinal Bleeding, N Engl J Med 2000;343(12):834-9.
  21. Lapane, KL, The Effect of Nonsteroidal Anti-Inflammatory Drugs on the Use of Gastroprotecive Medication in People with Arthritis, Am J. Managed Care 2001; 7:402-408.
  22. Meagher EA.  Balancing gastroprotection and cardioprotection with selective cyclo-oxygenase-2 inhibitors.  Drug Safety.  2003;26:913-24.
  23. Deeks JJ, et al, Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systemic review of randomised controlled trials, BMJ, September 21, 2002; 325:619-627.
  24. Fitzgerald, GA, Patrono, C, The COXIBs, Selective Inhibitors of Cyclooxygenase-2, N EnglJ Med, August 9, 2001;345(6):433-442.
  25. Bombardier C, Laine L, Reicin A, et al, for the VIGOR Study Group.  Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.  N Engl J Med.  2000;343:1520-8.
  26. Garner S, Fidan D, Frankish R, et al. Celecoxib for rheumatoid arthritis. Cochrane Database Syst Rev. 2002;(4):CD003831.
  27. Simon LS, Lipman AG, Jacox AK, Caudill-Slosberg M, Gill LH, Keefe FJ, Kerr KL, Minor MA, Sherry DD, Vallerand AH, Vasudevan S. Pain in osteoarthritis, rheumatoid arthritis and juvenile chronic arthritis. 2nd ed. Glenview (IL): American Pain Society (APS); 2002
  28. Ofman JJ, MacLean CH, Straus WL, et al. A metaanalysis of severe upper gastrointestinal complications of nonsteroidal antiinflammatory drugs. J Rheumatol. 2002;29(4):804-12.
  29. Moore RA, Derry S, Makinson GT, McQuay HJ. Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: information from company clinical trial reports. Arthritis Res Ther. 2005;7(3):R644-65.
  30. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004257.
  31. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006 Oct 4;296(13):1633-44.
  32. Tannenbaum H, Bombardier C, Davis P, Russell AS; Third Canadian Consensus Conference Group. An evidence-based approach to prescribing nonsteroidal antiinflammatory drugs. Third Canadian Consensus Conference. J Rheumatol. 2006;33(1):140-57.
  33. Zhang W, Doherty M, Arden N, et al; EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2005;64(5):669-81.
  34. Ruperto N, Nikishina I, Pachanov ED, et al; Pediatric Rheumatology International Trials Organization. A randomized, double-blind clinical trial of two doses of meloxicam compared with naproxen in children with juvenile idiopathic arthritis: short- and long-term efficacy and safety results. Arthritis Rheum. 2005 Feb;52(2):563-72.
  35. Cheng JW. Use of non-aspirin nonsteroidal antiinflammatory drugs and the risk of cardiovascular events. Ann Pharmacother. 2006;40(10):1785-96.
  36. Pham T, Gossec L, Constantin A, et al. Cardiovascular risk and rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion. Joint Bone Spine. 2006;73(4):379-87.
  37. Koren G, Florescu A, Costei AM, Boskovic R, Moretti ME. Nonsteroidal antiinflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis. Ann Pharmacother. 2006;40(5):824-9.
  38. Tannenbaum H, Bombardier C, Davis P, Russell AS; Third Canadian Consensus Conference Group. An evidence-based approach to prescribing nonsteroidal antiinflammatory drugs. Third Canadian Consensus Conference. J Rheumatol. 2006;33(1):140-57.

Copyright 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.

January 01, 2007
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