Subject: Ranexa -- Antiangina

Status	Drug	PR-B/D	PR	PR-QL	PR-AL	ST	M EX‡	TOC§
C	Ranexa™  (ranolazine)			X		X	X

Policy:

1. Precertification Criteria

According to the manufacturer, Ranexa can be dosed up to a maximum daily dose at the interval(s) as  indicated in the table below. A quantity of this drug will be considered medically necessary as indicated in the table below:

Drug	Maximum Daily Dose/ Dosing Interval	Dosage Strength	Quantity Limits
Ranexa	2000 mg/x 2 per day	500 mg	Up to 120 tablets in 30 days
Ranexa	2000 mg/x 2 per day	1000 mg	Up to 60 tablets in 30 days





For coverage of additional quantities, a member's treating physician must request prior authorization through the Aetna Pharmacy Management Precertification Unit. Additional quantities of Ranexa 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
• Special diagnosis/situation 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

Under some plans, including plans that use an open or closed formulary, Ranexa is subject to step-therapy.  Aetna considers Ranexa to be medically necessary for those members who meet the following step-therapy criteria:

Use of Norvasc (amlodipine), a beta-blocker (BUT NOT sotalol AF, sotalol, sorine, Betapace, or Betapace AF), and a nitrate. (See list of drugs below)

Beta-Blocker Examples

acebutolol	Inderal LA	Propranolol, Propranolol ER
atenolol	Innopran XL	Sectral
betaxolol	Kerlone	Timolol maleate
Bisoprolol	Levatol	Tenormin
Blocadren	labetalol	Toprol XL
carvedilol/Coreg/Coreg CR	Lopressor	Zebeta
Corgard	Metoprolol, metoprolol ER
Cartrol	Nadolol
Inderal	Pindolol

Nitrate Examples

Dilatrate SR	Monoket	Nitrolingual
Imdur	Nitrek	Nitroquick
Ismo	Nitrobid	Nitrostat
Isochron	Nitro-dur	Nitrotab
Isordil	Nitrogard	Nitro-time
Isosorbide dinitrate	Nitroglycerin	Nitro-transderm
Isosorbide mononitrate	Nitroglycerin SL
minitran	Nitroglycerin SR

3. Medical Exception Criteria

Ranexa is currently a Covered Part D drug under the Aetna Medicare Prescription Drug Plan.* 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 Brand Names to be medically necessary for those members who meet ANY of the following criteria:

A. A documented:

• Contraindication to three preferred alternatives (Norvasc (amlodipine), beta-blockers (BUT NOT sotalol AF, sotalol, sorine, Betapace, or Betapace AF), and nitrates) indicated for the member's condition OR,
• Intolerance to three preferred alternatives alternatives (Norvasc (amlodipine), beta-blockers (BUT NOT sotalol AF, sotalol, sorine, Betapace, or Betapace AF), and nitrates) indicated for the member's condition OR,
• Allergy to three preferred alternatives alternatives (Norvasc (amlodipine), beta-blockers (BUT NOT sotalol AF, sotalol, sorine, Betapace, or Betapace AF), and nitrates)  indicated for the member's condition OR,
• Failure of an adequate trial of two-weeks of three preferred alternatives alternatives (Norvasc (amlodipine), beta-blockers (BUT NOT sotalol AF, sotalol, sorine, Betapace, or Betapace AF), and nitrates) indicated for the member's condition.
  

Beta-Blocker Examples

acebutolol	Inderal LA	Propranolol
atenolol	Innopran XL	Sectral
betaxolol	Kerlone	Timolol maleate
Bisoprolol	Levatol	Tenormin
Blocadren	labetalol	Toprol XL
carvedilol/Coreg/Coreg CR	Lopressor	Zebeta
Corgard	Metoprolol, metoprolol ER
Cartrol	Nadolol
Inderal	Pindolol

Nitrate Examples

Dilatrate SR	Monoket	Nitrolingual
Imdur	Nitrek	Nitroquick
Ismo	Nitrobid	Nitrostat
Isochron	Nitro-dur	Nitrotab
Isordil	Nitrogard	Nitro-time
Isosorbide dinitrate	Nitroglycerin	Nitro-transderm
Isosorbide mononitrate	Nitroglycerin SL
minitran	Nitroglycerin SR

Place of Service:

Outpatient

The above policy is based on the following references:

1.       Olin BR, editor. Drugs Facts and Comparisons (electronic online version).St. Louis: J.B. Lippincott Company, 2004.

2.       USPDI Drug Information for the HealthCare Professional (online through Stat!Ref). Thomson MICROMEDEX, Greenwood Village, Colorado; 2004.

3.       McEvoy GK, editor. AHFS Drug Information (online through Stat!Ref). American Society of Health-Systems Pharmacists, Bethesda, Maryland; 2004.

4.       Medical Economics, Inc., PDR Electronic Library. Thomson Medical Economics, Montvale, NJ; 2003.

5.       Fick DM, Cooper JW, Wade WE, et al.  Updating the Beers criteria for potentially inappropriate medication use in older adults.  Arch Intern Med. 2003;163:2716-24.

6.       Zahn C, Sangl J, Bierman AS, et al.  Potentially inappropriate medication use in the community-dwelling elderly.  JAMA.  2001;286:2823-29.

7.       Klasco RK (Ed): DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com (cited: April 14, 2005).

8.       Chaitman BR, Pepine CJ, Parker JO, et al. Effects of ranolazine with atenolol, amlodipine, or diltiazepam on exercise tolerance and angina frequency in patients with severe chronic angina. JAMA 2004;291(3):309-16.

9.       Stone PH, Gratsiansky NA, Blokhin A, et al. Antianginal efficacy of ranolazine when added to maximal treatment with a conventional therapy: the efficacy of ranolazine in chronic angina (ERICA) trial. Circulation 2005;112 (17) Supplement II Abstract 3491.

10.   Chaitman BR, Skettino SL, Parker JO, et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43:1375-82.

11. Jerling M, Huan Bl, Leung K, et al. Studies to investigate te pharmacokinetic interactions between ranolazine and ketoconazole, diltiazem, or simvastatin during comobined administration I healthy subjects. J Clin Pharmacol 2005;45:422-33

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.

October 2, 2007