Subject: Proton Pump Inhibitors (PPIs)

Status	Drug	PR	PR-QL	PR-AL	ST	M EX‡
P	omeprazole	X	X
P	Prevacid®  (lansoprazole)	X	X
P	Nexium®  (esomeprazole)	X	X
FE	AcipHex®  (rabeprazole)	X	X		X	X
FE	Prilosec®  (omeprazole)	X	X		X	X
FE	Protonix®  (pantoprazole)	X	X		X	X
FE	Zegerid®  (omeprazole IR)	X	X		X	X

Policy:

1. Precertification Criteria

 (A OR B OR C) AND D

20 mg prescription Prilosec capsules are excluded from coverage for most members.  For plans where these drugs are a covered benefit, the criteria below apply.

Under some plans, including plans that use an open or closed formulary, AcipHex, Nexium, omeprazole, Prevacid, Prilosec, Protonix, and Zegerid are subject to precertification.  If precertification requirements apply Aetna considers AcipHex, Nexium, omeprazole, Prevacid, Prilosec, Protonix and Zegerid to be medically necessary for those members who meet the following precertification criteria:

A.  Member is < 6 years of age - FOR omeprazole, Prevacid, or Prilosec ONLY

OR

B.   Documented diagnosis listed below (no requirement for nonprescription Prilosec OTC)

Duodenal ulcer - active ulcer OR maintenance of healed ulcer (Aetna considers drug therapy to be medically necessary for a period of up to 12 months.)
Gastric ulcer - active benign (Aetna considers drug therapy to be medically necessary for a period of up to 12 months.); maintenance
Gastrojejunal ulcer - active; maintenance
NSAID-induced gastric ulcer - healing (Aetna considers drug therapy to be medically necessary for a period of up to 12 months.); risk reduction for recurrence
Peptic ulcer disease (Aetna considers drug therapy to be medically necessary for a period of up to 12 months.)
Stress ulcer/surgical prophylaxis
Barrett's esophagus
Crohn's disease
Erosive esophagitis - active, maintenance, healed
Reflux esophagitis -associated with GERD
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
Member is Post transplant and/or MD is a transplant specialist
Member is on chronic oral (systemic) corticosteroid therapy (> 60 days)


* Additional documentation of two concurrent antibiotics (usually amoxicillin and clarithromycin; however, metronidazole may sometimes be used) that will be used in the treatment regimen combined with the requested PPI are required.

OR

C.   Documented diagnosis of other GI condition for which Prilosec OTC is indicated (heartburn, chronic reflux), the use of a PPI is required, AND one of the below:

• Intolerance to the nonprescription Prilosec OTC 20mg OR
• Failure of an adequate trial of two weeks of the nonprescription Prilosec OTC 20mg

AND


According to the manufacturer, the proton pump inhibitors can be dosed up to a maximum daily dose at the interval(s) as indicated in the table below.  A quantity of each drug will be considered  medically necessary as indicated in the table below if member fulfills criteria A or B or C above.


Drug	Maximum Daily Dose/ Dosing Interval	Dosage Strength	Quantity Limits
AcipHex	20 mg/ Once daily	20 mg	Up to 30 tablets in 30 days
Nexium	40 mg/ Once daily	20 mg, 40 mg	Up to 30 capsules, packets in 30 days
omeprazole	40 mg/ Once daily	10 mg, 20 mg	Up to 30 capsules in 30 days
Prevacid	30 mg/ Once daily	15 mg, 30 mg	Up to 30 capsules, tablets, or packets in 30 days
Prilosec	40 mg/ Once daily	10 mg, 20 mg, 40 mg	Up to 30 capsules in 30 days
Protonix	40 mg/ Once daily	20 mg, 40 mg	Up to 30 tablets in 30 days
Zegerid	40 mg/ Once daily	20 mg, 40 mg	Up to 30 packets in 30 days





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

• Member has a diagnosis of a pathological hypersecretory condition OR
• Member is being treated for Barrett's esophagus OR
• Member is being treated for laryngopharyngeal reflux OR
• Member is Post transplant and/or MD is a transplant specialist OR
• Member is being treated for a GI bleed (3-month duration) OR
• Member is being treated for eradication of H. pylori (triple therapy only; 30-day duration) OR
• Member has gastroesophageal reflux disease (GERD) and meets ALL the following criteria:
   a. Member has had at least 4 wks of once daily PPI therapy taken 30-60 min
       before a meal (any meal)
   b. Member is experiencing acid breakthrough  OR
• If Member is <11 years of age and has gastroesophageal reflux disease (GERD) or erosive esophagitis and meets ALL the following criteria ( for Prevacid, omeprazole and Prilosec ):
   a. Member has had at least 4 wks of once daily PPI therapy taken 30-60 min before 
       a meal (any meal)
   b. Member is experiencing acid breakthrough
  
  NOTE:  Aetna does NOT consider prescription PPIs to be medically necessary for members with the following indications:

1. Uncomplicated heartburn of greater than 1-month duration, with a frequency of at least 2 heartburn episodes per week when all of the following criteria are met:

a. The heartburn can be controlled by use of OTC medications AND
b. There is no diagnosis of more complicated acid reflux disease, such as erosive esophagitis AND
c. There are no symptoms of a more complicated GI condition.*  

*  Symptoms of a more complicated GI condition may include any of the following:
trouble or pain swallowing food
vomiting with blood
bloody or black stools
heartburn of > 3 months duration
heartburn with lightheadedness, sweating, dizziness
chest pain or shoulder pain with shortness of breath, sweating, pain spreading to arms, neck, shoulders
frequent chest pain
frequent wheezing, particularly with heartburn
unexplained weight loss
nausea or vomiting
stomach pain

OR

2. Uncomplicated heartburn with a frequency of < 1 episode/week that can be controlled by use of OTC medications

OR

3. Any of the following diagnoses when NOT in combination with a diagnosis listed under B above:
Dyspepsia
Gastritis or duodenitis
Gastroparesis
Gastric bypass surgery(surgical prophylaxis only)
Hiatal hernia
Schatzki's ring (esophagogastric ring)





2. Step Therapy Criteria

20 mg prescription Prilosec capsules are excluded from coverage for most members.  For plans where these drugs are a covered benefit, the criteria below apply.

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

A documented trial of one month each of both lansoprazole (Prevacid) AND esomeprazole (Nexium) - alternatives on the Preferred Drug List.

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

A OR [(B OR C) ANDD]

20 mg prescription Prilosec capsules are excluded from coverage for most members.  For plans where these drugs are a covered benefit, the criteria below apply.

Aciphex, Prilosec, Protonix and Zegerid 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 Aciphex, Prilosec, Protonix and Zegerid to be medically necessary for those members who meet the following criteria:

A.  Member is < 6 years of age AND is intolerant to OR has failed an adequate trial of two (2) weeks of the formulary alternative Prevacid - FOR Prilosec ONLY

OR

B.   Documented diagnosis listed below (no requirement for nonprescription Prilosec OTC)

Duodenal ulcer - active ulcer OR maintenance of healed ulcer (Aetna considers drug therapy to be medically necessary for a period of up to 12 months.)
Gastric ulcer - active benign (Aetna considers drug therapy to be medically necessary for a period of up to 12 months.); maintenance
Gastrojejunal ulcer - active; maintenance
NSAID-induced gastric ulcer - healing (Aetna considers drug therapy to be medically necessary for a period of up to 12 months.); risk reduction for recurrence
Peptic ulcer disease (Aetna considers drug therapy to be medically necessary for a period of up to 12 months.)
Stress ulcer/surgical prophylaxis
Barrett's esophagus
Crohn's disease
Erosive esophagitis - active, maintenance, healed
Reflux esophagitis -associated with GERD
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
Member is Post transplant and/or MD is a transplant specialist
Member is on chronic oral (systemic) corticosteroid therapy (> 60 days)

* Additional documentation of two concurrent antibiotics (usually amoxicillin and clarithromycin; however, metronidazole may sometimes be used) that will be used in the treatment regimencombined with the requested PPI are required


          OR

C.   Documented diagnosis of other GI condition for which Prilosec OTC is indicated (heartburn, chronic reflux), the use of a PPI is required, AND one of the below:

• Intolerance to the nonprescription Prilosec OTC 20mg OR
• Failure of an adequate trial of two weeks of the nonprescription Prilosec OTC 20mg

AND

D.    A documented

• Contraindication to the preferred alternatives lansoprazole (Prevacid) AND esomeprazole (Nexium) OR
• Intolerance to the preferred alternatives lansoprazole (Prevacid) AND esomeprazole (Nexium) OR
• Allergy to the preferred alternatives lansoprazole (Prevacid) AND esomeprazole (Nexium) OR
• Failure of an adequate trial of one month each of the preferred alternatives lansoprazole (Prevacid) AND esomeprazole (Nexium)

NOTE:  Aetna does NOT consider prescription PPIs to be medically necessary for members with the following indications:

1.   Uncomplicated heartburn of greater than 1-month duration, with a frequency of at least 2 heartburn episodes per week when all of the following criteria are met:

a. The heartburn can be controlled by use of OTC medications AND
b. There is no diagnosis of more complicated acid reflux disease, such as erosive esophagitis AND
c. There are no symptoms of a more complicated GI condition.*   

*  Symptoms of a more complicated GI condition may include any of the following:
trouble or pain swallowing food
vomiting with blood
bloody or black stools
heartburn of > 3 months duration
heartburn with lightheadedness, sweating, dizziness
chest pain or shoulder pain with shortness of breath, sweating, pain spreading to arms, neck, shoulders
frequent chest pain
frequent wheezing, particularly with heartburn
unexplained weight loss
nausea or vomiting
stomach pain

OR

2. Uncomplicated heartburn with a frequency of < 1 episode/week that can be controlled by use of OTC medications

OR

3. Any of the following diagnoses when NOT in combination with a diagnosis listed under B above:

Dyspepsia
Gastritis or duodenitis
Gastroparesis
Gastric bypass surgery(surgical prophylaxis only)
Hiatal hernia
Schatzki's ring (esophagogastric ring)

Special Notes:

Prilosec OTC is used to treat frequent heartburn, defined as heartburn that occurs two or more days per week.  Prilosec OTC is not for people who have heartburn infrequently, defined as one episode of heartburn a week or less, or those that want immediate relief of heartburn.  Other nonprescription heartburn treatments, antacids and acid reducers, are indicated for infrequent heartburn.

Both prescription Prilosec and Prilosec OTC contain the same active ingredient, omeprazole, which effectively stops acid production.  Prescription Prilosec treats diseases that require diagnosis and supervision by a doctor.  Prilosec OTC treats only symptoms of frequent heartburn.  Used as directed, Prilosec OTC will not treat the conditions that prescription Prilosec treats.

Prilosec OTC is a delayed-release 20mg tablet, taken once a day (every 24 hours) for 14 days before eating. It should not be taken for more than 14 days or a 14-day course repeated more often than every 4 months unless directed by a physician.  The FDA based its approval of Prilosec OTC on the results of various studies. Two clinical studies demonstrated that it was effective in increasing the proportion of patients with no heartburn over 24 hours; the effectiveness of Prilosec OTC increases from day 1 to day 14.

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. Katz PO, Anderson C, Khoury R, & Castell DO.  Gastro-aesophageal reflux associated with nocturnal gastric acid breakthrough on proton pump inhibitors.  Aliment Pharmacol Ther 1998:  12:  1231-1234.
7. Robinson, M.  Clinical Relevance and Management of 'Occasional Acid Breakthrough' on Proton Pump Inhibitor Therapy.  Pract Gastroenterol November 1999:  55 - 57.
8. Peghini P, Castell DO, Decktor D.  Understanding Nocturnal Acid Breakthrough on Proton Pump Inhibitors.  Pract Gastroenterol May 2000:  60 - 67.
9. Earnest D.  Symptomatic Occasional Acid Breakthrough During Proton Pump Inhibitor Therapy is Common.  Ask Your Patients.  Pract Gastroenterol February 2000:  51 - 54.
10. Peghini PL, Katz, PO, Bracy NA, & Castell DO.  Nocturnal Recovery of Gastric Acid Secretion with Twice-Daily Dosing of Proton Pump Inhibitors.  Am J Gastroenterol  1998:  93: (5) 763 - 767.
11. Kahrilas et al., Esomeprazole Improves Healing Symptoms Resolution as Compared with Omeprazole in Reflux Oesophagitis Patients: a Randomized Controlled Trial.  The Esomperazole Study Investigator, Aliment Pharmacol Ther 2000;14(10):1249-1258.
12. Richter et al., abstract - Esomerprazole is Superior to Omeprazole for the Healing of Erosive Esophagitis in GERD Patients, Gastroenterology, 2000;118:A20.
13. Vakil et al., abstract - Esomeprazole is Effective as Maintenance Therapy in GERD Patients with Healed Erosive Esophagitis (EE), Gastroenterology, 2000;118:A22.
14. Lind et al., Esomeprazole Provides Improved Acid Control vs. Omeprazole In Patients with Symptoms of Gastro-esophageal Reflux Disease, Aliment Pharmacol Ther., 2000;14:861-867. 
15. Pan T, Wang Y, Guo Z, et al.  Additional bedtime H2-receptor antagonist for the control of nocturnal gastric acid breakthrough.  The Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD004275.pub2. DOI: 10.1002/14651858.CD004275.pub2.
16. Rostom A, Dube C, Wells G, et al.  Prevention of NSAID-induced gastroduodenal ulcers. The Cochrane Database of Systematic Reviews 2022, Issue 4. Art.: CD00296. DOI: 10.1002/14651858.CD002296.
17. Labenz J, Armstrong D, Lauritsen K, et al. Esomeprazole 20mg vs. pantoprazole 20mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study. Aliment Pharmacol Ther. 2005;22(9):803-11.
18. Rohss K, Lind T, Wilder-Smith C. Esomeprazole 40mg provides more effective intragastric acid control than lansoprazole 30mg, omeprazole 20mg, pantoprazole 40mg and rabeprazole 20mg in patients with GERD symptoms. Eur J Clin Pharmacol. 2004;60(8):531-9.
19. Richter JE, Fraga P, Mack M, et al. Prevention of erosive oesophagitis relapse with pantoprazole. Aliment Pharmacol Ther. 2004;20(5):567-75.
20. Conrad SA, Gabrielli A, Margolis B, et al. Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med. 2005;33(4):760-5.
21. DeVault KR et al.  Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease.  Am J Gastroenterology 2005; 100: 190-200.
22. Gillesen A, Beil W, Modlin IM, et al.  40mg pantoprazole and 40mg esomeprazole are equivalent in the healing of esophageal lesions and relief from GERD-related symptoms. J Clin Gastroenterol. 2004;38(4):332-40.
23. Fennerty MB, Johanson JF, Hwang C, Sostek M.  Efficacy of esomeprazole 40mg vs. lansoprazole 30mg for healing moderate to severe erosive esophagitis. Aliment Pharmacol Ther. 2005;21(4):455-63.
24. Caos A, Breiter J, Perdomo C, Barth J. Long-term prevention of erosive or ulcerative GERD relapse with rabeprazole 10 or 20 mg vs. placebo: results of a 5-year study in the United States. Aliment Pharmacol Ther. 2005;22(3):193-202.
25. Bour B, Staub JL, Chousterman M, et al.  Long-term treatment of GERD patients with frequent symptomatic relapses using rabeprazole: on-demand treatment compared with continuous treatment.  Aliment Pharmacol Ther. 2005;21(7):805-12.
26. Scholten T, Dekkers CP, Schulze K, et al. On-demand therapy with pantoprazole 20 mg as effective as long-term management of reflux disease in patients with mild GERD: the ORION trial. Digestion. 2005;72(2-3);76-85.
27. Tsai HH, Chapman R, Shepherd A, et al. Esomeprazole 20 mg on-demand is more acceptable to patients than continuous lansoprazole 15 mg in the long-term maintenance of endoscopy-negative gastroesophageal reflux patients: the COMMAND study. Aliment Pharmacol Ther. 2004;20(6):657-65.
28. Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101(4):701-10.

 

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 9, 2007