Subject: Ulcerative Colitis Agents

Status	Drug	PR	PR-QL	PR-AL	ST	M EX‡
P	balsalazide		X
P	mesalamine enema
P	prednisolone
P	prednisone
P	sulfasalazine		X
P	Apriso™  (mesalamine sr oral)		X
P	Asacol®  (mesalamine oral)		X
P	Asacol® HD  (mesalamine oral)		X
P	Canasa®  (mesalamine supp)		X
P	Lialda®  (mesalamine delayed release oral)		X
NP	Azulfidine®  (sulfasalazine)		X
FE	Colazal®  (balsalazide)		X			X
FE	Dipentum®  (olsalazine)		X			X
FE	Entocort EC®  (budesonide oral)					X
FE	Pentasa®  (mesalamine oral)		X			X
FE	Rowasa®  (mesalamine enema)					X
FE	Rowasa Kit®  (mesalamine rectal enema & cleanser wipe kit)					X

Policy:

1. Precertification Criteria

Under some plans, including plans that use an open or closed formulary, Apriso, Asacol, Azulfidine, balsalazide, Canasa, Colazal, Dipentum, Lialda, Pentasa and sulfasalazine are subject to precertification.  If precertification requirements apply Aetna considers Apriso, Asacol, Azulfidine, balsalazide, Canasa, Colazal, Dipentum, Lialda, Pentasa, and sulfasalazine to be medically necessary for those members who meet the following precertification criteria:

According to the Ulcerative Colitis Practice Guidelines from the American College Gastroenterology (ACG), these agents may be dosed up to a maximum dose as indicated below. A quantity of each drug will be considered medically necessary as indicated in the table below:


Drug	Maximum Daily Dose/ Dosing Interval	Dosage Strength	Quantity Limits
Apriso	1.5 grams	0.375 g	Up to 120 capsules in 30 days (4/day)
Asacol	4.8 grams	400 mg	Up to 360 tablets in 30 days (12/day)
Asacol HD	4.8 grams	800 mg	Up to 180 tablets in 30 days (6/day)
Azulfidine	6 grams	500 mg	Up to 360 tablets in 30 days (12/day)
Canasa	1500 mgs	500 mg	Up to 90 suppositories in 30 days (3/day)
Canasa	1500 mgs	1000 mg	Up to 60 suppositories in 30 days (2/day)
balsalazide; Colazal	6.75 grams	750 mg	Up to 270 capsules in 30 days (9/day)
Dipentum	3 grams	250 mg	Up to 360 capsules in 30 days (12/day)
Lialda	4.8 grams	1.2 grams	Up to 120 tablets in 30 days (4/day)
Pentasa	4.8 grams	250 mg	Up to 600 capsules in 30 days (20/day)
Pentasa	4.8 grams	500 mg	Up to 300 capsules in 30 days (10/day)
sulfasalazine	6 grams	500 mg	Up to 360 tablets in 30 days (12/day)





For coverage of additional quantities, a member's treating physician must request prior authorization through the Pharmacy Management Precertification Unit. Additional quantities of ulcerative colitis agents will be considered medically necessary for those members who meet ANY of the following criteria:

• Member's dose is being titrated by physician (3-month limit) OR
• Member's physician provides documentation (controlled clinical trial) from the peer-reviewed medical literature for use of a higher dose.
  



2. Medical Exception Criteria

Colazal, Dipentum, Entocort EC, Pentasa, Rowasa, and Rowasa Kit are currently listed on the Aetna Formulary Exclusions List.* Therefore, they 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 Colazal, Dipentum, Entocort EC, Pentasa, Rowasa and Rowasa Kit to be medically necessary for those members who meet ANY of the following criteria:

A. A documented

• Contraindication to one preferred alternative agent indicated for the member's condition OR
• Intolerance to one preferred alternative agent indicated for the member's condition OR
• Allergy to one preferred alternative agent indicated for the member's condition OR
• Failure of an adequate trial of one month of one preferred alternative agent indicated for the member's condition OR
• Members has Crohn's disease located in the small (top) intestine (Pentasa-only )
  

Special Notes:

For treatment of active ulcerative colitis with  balsalazide/ Colazal, the usual dose in adults is three 750mg capsules to be taken three times a day for a total daily dose of 6.75 gms (9 capsules) for a duration of 8 weeks.  Some patients in the clinical trials required treatment for up to 12 weeks.  Safety and effectiveness of Colazal beyond 12 weeks has not been established.

Entocort EC is indicated for the treatment of mild to moderate active Crohn's disease involving the ileum and/or the ascending colon.  It is said to be "locally active" in the colon.  The active ingredient in Entocort EC is released in the intestines and is then quickly and extensively metabolized, preventing the majority of the drug from entering the systemic circulation.  This leads to fewer systemic side effects (compared with other corticosteroids, such as prednisolone) and improved tolerability. 

The recommended adult dosage for Entocort EC is 9 mg taken once daily in the morning for up to 8 weeks.  For recurring episodes of active Crohn's Disease, a repeat 8 week course of Entocort EC can be given.  Treatment with Entocort EC capsules can be tapered to 6 mg daily for 2 weeks prior to complete cessation.  Patients have been switched from oral prednisolone to Entocort EC with no reported episodes of adrenal insufficiency.  Since prednisolone should not be stopped abruptly, tapering should begin concomitantly with initiating Entocort EC treatment.

Place of Service:

Outpatient

The above policy is based on the following references:

1. DrugPoints® System ( www.statref.com) Thomson Micromedex, Greenwood Village, CO. Updated periodically.
2. AHFS Drug Information® with AHFSfirstReleases®. ( www.statref.com), American Society Of Health-System Pharmacists®,Bethesda, MD. Updated periodically.
3. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
4. Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. Updated periodically.
5. PDR® Electronic Library™ [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
6. Hanauer SB and Sandborn W. Management of Crohn’s disease in adults. Am J Gastroenterol 2001;96:635-43.
7. Stein RB and Hanauer SB. Comparative tolerability of treatments for inflammatory bowel disease. Drug Safety 2000;23 (5):429-48.
8. Lochs H, Mayer M, Fleig WE, et al. Prophylaxis of postoperative relapse in Crohn’s disease with mesalamine: European Cooperative Crohn’s Disease Study VI. Gastroenterology 2000;118:264-73.
9. Marshall JK and Irvine EJ. Putting rectal 5-aminosalicylic acid in its place: the role in distal ulcerative colitis. Am J Gastroenterol 2000;95(7):1628-36.
10. De Vos M. Clinical pharmacokinetics of slow release mesalamine. Clin Pharmacokinet 2000;39(2):85-97.
11. Clemett D and Markham A. Prolonged-Release mesalamine. A review of its therapeutic potential in ulcerative colitis and Crohn’s disease. Drugs 2000;59:929-56.
12. Cohen RD. A meta-analysis and overview of the literature on treatment options for left-sided ulcerative colitis and ulcerative proctitis. Am J Gastroenterol 2000;95(5):1263-76.
13. Mahmud N, Kamm MA, Dupas JL, et al. Olsalazine is not superior to placebo in maintaining remission of inactive Crohn’s colitis and ileocolitis: a double blind, parallel, randomized, multicentre study. Gut 2001;49:552-6.
14. Green JRB, Mansfield JC, Gibson JA, et al. A double-blind comparison of balsalazide, 6.75 g daily, and sulfasalazine, 3 g daily, in patients with newly diagnosed or relapsed active ulcerative colitis. Aliment Pharmacol Ther 2002;16(1):61-68.
15. Mansfield JC, Giaffer MH, Cann PA, et al. A double-blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis. Aliment Pharmacol Ther 2002;16(1):69-77.
16. Pruitt R, Hanson J, Safdi M, et al. Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute ulcerative colitis. Gastroenterology. 2000;118(4,Pt 1):A756.
17. Pruitt R, Hanson J, Safdi M, Wruble L, et al. Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of actue  mild-to-moderate ulcerative colitis. Am J Gastroenterol 2002:;97:12:3078-86.
18. Levine DS, Riff DS, Pruitt R, et al. A randomized, double blind, dose-response comparison of balsalazide (6.75 g), balsalazide (2.25 g), and mesalamine (2.4 g) in the treatment of active, mild-to-moderate ulcerative colitis. Am J Gastroenterol 2002;97(6):1398-1407.
19. Cortot A, Colombel JF, Rutgeerts P, et al. Switch from systemic steroids to budesonide in steroid dependent patients with inactive Crohn's disease. Gut 2001;48:186-90.
20. Papi C, Luchetti R, Gili L, et al. Budesonide in the treatment of Crohn's disease: a meta-analysis. Aliment Pharmacol Ther 2000;14:1419-28.
21. Kendhal P, Zachos M, Holmes JL, and Griffiths AM. Controlled ileal release budesonide in pediatric Crohn disease: Efficacy and effect on growth. J Pediatr Gastroenterol Nutr 2001;33:75-80.
22. Kornbluth A, Sachar DB. Ulcerative Colitis Practice Guideline in Adults (Update): American College of Gastroenterology, Practice Parameters Committee.  Am J Gastroenterol. 2004;99(7):1371-85.
23. Loftus EV Jr, Kane SV, Bjorkman D. Systematic review: short-term adverse effects of 5-aminosalicylic acid agents in the treatment of ulcerative colitis. Aliment Pharmacol Ther. 2004;19(2):179-89.
24. Akobeng AK, Gardener E. Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's Disease. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD003715.
25. Hanauer SB, Stromberg U. Oral Pentasa in the treatment of active Crohn's disease: A meta-analysis of double-blind, placebo-controlled trials. Clin Gastroenterol Hepatol. 2004;2(5):379-88.
26. Sutherland L, Macdonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000544.
27. Bergman R, Parkes M. Systematic review: the use of mesalazine in inflammatory bowel disease. Aliment Pharmacol Ther. 2006;23(7):841-55.
28. Kane SV. Systematic review: adherence issues in the treatment of ulcerative colitis. Aliment Pharmacol Ther. 2006;23(5):577-85.
29. Caprilli R, Gassull MA, Escher JC, et al; European Crohn's and Colitis Organisation. European evidence based consensus on the diagnosis and management of Crohn's disease: special situations. Gut. 2006;55 Suppl 1:i36-58.
30. Lialda production information  internet site accessed at http://lialda.com/
31. Rowasa Kit Product information internet site accessed 9-3-08 at http://rowasa.com/
32. Apriso Product information internet site accessed 12-29-08 at http://www.salix.com/assets/pdf/prescribe_info/aprisopi.pdf.
33. Asacol HD Product information internet site accessed 5-22-09 at http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021830s002lbl.pdf.

 

 

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.

July 31, 2009