Provider information

Proton pump inhibitor

drug list selection
Selection of proton pump inhibitors (PPIs) for our drug
list was influenced by similar efficacy rates and safety
profiles among the agents.

Provider information

Proton pump inhibitors (PPIs) are most commonly used for

prevention and treatment of gastroesophageal reflux disease
(GERD). Other FDA-approved indications include treatment of
erosive esophagitis, Helicobacter pylori (H. pylori) infection,
active duodenal or gastric ulcers, and non-steroidal
anti-inflammatory drug (NSAID)-associated ulcers.1

Summary of selected evidence for PPIs

Outcome

Products
compared

Results

H. pylori
eradication rates3

omeprazole triple therapy*

vs.
lansoprazole triple therapy

75% vs. 76%

omeprazole triple therapy

vs.
Aciphex triple therapy

78% vs. 81%

omeprazole triple therapy

vs.
Nexium triple therapy

88% vs. 89%

lansoprazole triple therapy

vs.
Aciphex triple therapy

81% vs. 86%

The PPIs are considered comparable

to each other in efficacy due to similar
clinical outcome improvements reported
in clinical trials.
As you know, the goals of GERD therapy include2:
Controlling symptoms
Healing esophagitis
Managing or preventing complications
Maintaining GERD remission
We critically evaluated studies with outcomes reflecting these
goals. These outcomes, along with safety profile information
and meta-analyses of PPI use in pregnancy, were the primary
measures used in our Pharmacy & Therapeutics Process to
select PPIs for our drug list.

Clinical review
Our clinical review focused on the efficacy and safety of PPIs for
eradication rates of H. pylori, healing rates for reflux esophagitis
and symptom control of GERD.3-11

Conclusion: No statistically significant differences in H. pylori eradication rates were

reported for omeprazole compared with lansoprazole, Aciphex or Nexium use over seven
to 10 days (P-value = not significant for all comparisons). Rates were also similar for
lansoprazole compared with Aciphex.
Reflux esophagitis
healing rates4

Nexium 40 mg
vs.
lansoprazole 30 mg
or
omeprazole 20 mg
or
pantoprazole 40 mg

Four weeks
76% vs. 70%
P-value = .0001
Eight weeks
89% vs. 85%
P-value = .0001

Conclusion: Based on one meta-analysis, Nexium provides a modest benefit over

lansoprazole, omeprazole or pantoprazole use in healing reflux esophagitis after four and
eight weeks of therapy. The absolute risk reduction for reflux esophagitis healing rates is
4% to 6% with Nexium versus other PPIs. To heal one additional patient, 17 to 25 patients
need to be treated with Nexium, instead of an alternative PPI, for four to eight weeks.
Reflux esophagitis
healing rates5

Dexilant 60 mg
vs.
lansoprazole 30 mg

Study 1
Dexilant 60 mg: 85%
lansoprazole 30 mg: 79%
P-value < .05
Study 2
Dexilant 60 mg: 87%
lansoprazole 30 mg: 85%
P-value = not significant

Conclusion: Use of Dexilant 60 mg shows similar or modestly-improved benefit in

healing erosive esophagitis compared with lansoprazole 30 mg over eight weeks,
as measured by crude rate analysis. The absolute risk reduction for reflux esophagitis
healing rates is 6% with Dexilant 60 mg versus lansoprazole. Seventeen patients need
to be treated with Dexilant, instead of a lansoprazole, for eight weeks to heal one
additional patient.
GERD symptom
control6

lansoprazole 30 mg
vs.
Nexium 40 mg

Days or nights with heartburn:

36% to 38% vs. 38% to 39%
P-value = not significant

Conclusion: No statistically significant difference in GERD symptom control was

reported for lansoprazole compared with Nexium use over two weeks (P-value = not
significant).
*Triple therapy combines a PPI with clarithromycin and amoxicillin or metronidazole.
2 | Proton pump inhibitor drug list selection

PPIs have a good overall safety profile and are well tolerated by
the majority of patients. However, overuse of these medications
is a concern. Judicious use of PPIs is advised to decrease the risk
of serious events potentially associated with PPI use. There are
conflicting reports about several possible PPI-related safety
concerns, highlighted below.
Possible PPI-related safety issues
Adverse event

Reports

Clostridium
difficile-associated
disease (CDAD)

Results of case-control studies suggest an increased

risk with PPI use, while other articles state there is no
difference in risk.12-15

Fracture risk

Three large database reviews and an analysis of

a prospective study found an increase in
osteoporosis-related fractures following one or more
years of PPI therapy.16-19 A fourth database review
found no increase in the risk of hip fractures in subjects
without major risk factors for osteoporosis who
received any PPI prescription, compared with those
with no PPI prescription.20

Drug interaction with

Plavix (clopidogrel)

The FDA recently issued a public health advisory

regarding the drug interaction between Plavix
(clopidogrel), omeprazole and Nexium. There is potential
for increased risk of cardiovascular events due to CYP
2C19 inhibition by omeprazole and Nexium. CYP 2C19
converts Plavix to an active metabolite which inhibits
platelet aggregation. Avoid concomitant use of these
medications. The FDA does not have enough information
about drug interactions between Plavix and other PPIs
to advise on their concomitant use.21

All PPIs are rated as pregnancy category B, with the exception

of omeprazole-containing products (omeprazole, Prilosec,
Zegerid) and Prevpac, which are pregnancy category C.
The most documented data and clinical experience
during pregnancy are with use of omeprazole.22
Based on critical appraisal of the clinical data, the Clinical
Review Committee determined that all PPIs are safe, effective
and comparable to each other at equivalent doses. The PPIs are
considered comparable in their efficacy due to similar clinical
outcome improvements reported in clinical trials. These agents
are also well tolerated by the majority of patients.

Value assessment
Internal analyses revealed the most prescribed PPIs are23:
Nexium
Generic omeprazole
Prevacid
The least costly PPIs for Anthem Blue Cross and Blue Shield
include:
Generic lansoprazole
Nexium
Generic omeprazole
Generic pantoprazole

Tier placement
Final placement of the PPI products on our drug list was
determined based on the clinical review conclusions, followed
by considerations from the value assessment, to make evidencebased, informed tier placement decisions. The lower, moderate
and higher tiers of our PPI coverage are outlined below.
PPI coverage on the Drug List
Lower
member cost

Moderate
member cost

Higher
member cost

lansoprazole 30 mg
capsules*
omeprazole capsules*
pantoprazole tablets

Nexium

D exilant (formerly Kapidex)

Aciphex
Prevacid solutab
Prilosec suspension
P rotonix injection &
suspension
P revpac
Zegerid*

*Lansoprazole 15 mg capsules, omeprazole 20 mg tablets and Zegerid 20 mg/1100 mg capsules

are available over the counter.

Prevpac contains lansoprazole, amoxicillin and clarithromycin and is only indicated for H. pylori
eradication.

Zegerid contains omeprazole and sodium bicarbonate.

To learn more about our Pharmacy & Therapeutics Process, visit

anthem.com and select Providers on the bottom right. On the
Provider landing page, under Formulary click Rx Search. Click
the Drug List Selection tab, then scroll down and select the
How is our Drug List selection process unique? link.

Proton pump inhibitor drug list selection | 3

References
1. Drug Facts and Comparisons eAnswers. Available at

11. Wang X, Fang JY, Lu R, Sun DF. A meta-analysis: comparison of

http://www.factsandcomparisons.com Accessed on

esomeprazole and other proton pump inhibitors in eradicating

February 6, 2011.

Helicobacter pylori. Digestion. 2006;73:178-86.

2. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al, American

12. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-

Gastroenterological Association (AGA) Institute Medical Position

suppressive agents and the risk of community-acquired

Panel. American Gastroenterological Association Medical Position

Clostridium difficile-associated disease. JAMA. 2005;294:2989-95.

Statement on the management of gastroesophageal reflux disease.

Gastroenterology. 2008;135: 1383-91.
3. Vergara M, Vallve M, Gisbert JP, Calvet X. Meta-analysis: comparative
efficacy of different proton pump inhibitors in triple therapy for
Helicobacter pylori eradication. Aliment Pharmacol Ther.
2003;18:647-54.
4. Edwards SJ, Lind T, Lundell L. Systematic review: proton
pump inhibitors (PPIs) for the healing of reflux oesophagitis a comparison of esomeprazole with other PPIs. Aliment
Pharmacol Ther. 2006; 24:743-50.
5. Sharma P, Shaheen NJ, Perez MC, et al. Clinical trials: healing of
erosive oesophagitis with dexlansoprazole MR, a proton pump
inhibitor with a novel dual delayed-release formulation--results
from two randomized controlled studies. Aliment Pharmacol Ther.
2009;29:731-41.
6. Chey W, Huang B, Jackson RL. Lansoprazole and esomeprazole in
symptomatic GERD. Clin Drug Invest. 2003; 23:69-84.
7. Bardhan KD, Achim A, Riddermann T, Pfaffenberger B. A clinical trial
comparing pantoprazole and esomeprazole to explore the concept
of achieving complete remission in gastro-oesophageal reflux
disease. Aliment Pharmacol Ther. 2007;25:1461-9.
8. Fennerty MB, Johanson JF, Hwang C, Sostek M. Efficacy of
esomeprazole 40 mg vs. lansoprazole 30 mg for healing moderate
to severe erosive esophagitis. Aliment Pharmacol Ther. 2005;
21:455-63.
9. Lightdale CJ, Schmitt C, Hwang C, Hamelin B. A multicenter,
randomized, double-blind, 8 week comparative trial of low dose

13. Dial S, Delaney JA, Schneider V, Suissa S. Proton pump inhibitor

use and risk of community-acquired Clostridium difficileassociated disease defined by prescription for oral vancomycin
therapy. CMAJ. 2006; 175:745-8.
14. Lowe DO, Mamdani MM, Kopp A, et al. Proton pump inhibitors and
hospitalization for Clostridium difficile-associated disease: a
population-based study. Clin Infect Dis. 2006;43:1272-6.
15.Pepin J, Saheb N, Coulombe MA, et al. Emergence of
fluoroquinolones as the predominant risk factor for Clostridium
difficile-associated diarrhea: a cohort study during an epidemic
in Quebec. Clin Infect Dis. 2005; 41:1254.
16. Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of
proton pump inhibitors and risk of osteoporosis-related fractures.
CMAJ. 2008;179(4):319-26.
17. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump
inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947-53.
18. Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors,
histamine H2 receptor antagonists, and other antacid medications
and the risk of fracture. Calcif Tissue Int. 2006;79:76-83.
19. Yu EW, Blackwell T, Ensrud KE, et al. Acid-suppressive medications
and risk of bone loss and fracture in older adults. Calcif Tissue Int.
2008;83:251-9.
20. Kaye JA, Jick H. Proton pump inhibitor use and risk of hip fractures
in patients without major risk factors. Pharmacotherapy.
2008;28:951-9.
21. Information for Healthcare Professionals: Update to the labeling of

esomeprazole (20 mg) and standard dose omeprazole (20 mg) in

Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare

patients with erosive esophagitis. Dig Dis Sci. 2006; 51:852-7.

professionals about a drug interaction with omeprazole (marketed

10. Mulder CJ, Dekker W, Gerretsen M. Lansoprazole 30 mg versus

omeprazole 40 mg in the treatment of reflux oesophagitis grade II,
III and IVa (a Dutch multicentre trial). Eur J Gastroenterol Hepatol.
1996; 8:1101-6.

as Prilosec and Prilosec OTC). FDA Center for Drug Evaluation and
Research (CDER). Available at: fda.gov. Accessed January 20, 2011.
22. Gill SK, OBrien L, Einarson TR, Koren G. The safety of proton pump
inhibitors (PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol.
2009;104:1541-5.
23. Data on file. WellPoint, Inc.; 2009.

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