Provider information
The PPIs are considered comparable to each other in efficacy due
to similar clinical outcome improvements reported in clinical
trials.
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
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 reviewOur 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
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%
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
orpantoprazole 40 mg
Four weeks76% vs. 70%P-value = .0001
Eight weeks89% 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 mgvs.lansoprazole 30 mg
Study 1Dexilant 60 mg: 85% lansoprazole 30 mg: 79%P-value <
.05
Study 2Dexilant 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 mgvs.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 assessmentInternal 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 placementFinal 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
evidence-
based, 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 Dexilant (formerly Kapidex) Aciphex Prevacid solutab
Prilosec suspension Protonix injection &
suspension Prevpac
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
19514ANPENABS Rev. 10/11 F0072276
References1. Drug Facts and Comparisons eAnswers. Available
at
http://www.factsandcomparisons.com Accessed on
February 6, 2011.
2. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al, American
Gastroenterological Association (AGA) Institute Medical
Position
Panel. American Gastroenterological Association Medical
Position
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
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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
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9. Lightdale CJ, Schmitt C, Hwang C, Hamelin B. A
multicenter,
randomized, double-blind, 8 week comparative trial of low
dose
esomeprazole (20 mg) and standard dose omeprazole (20 mg) in
patients with erosive esophagitis. Dig Dis Sci. 2006;
51:852-7.
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.
11. Wang X, Fang JY, Lu R, Sun DF. A meta-analysis: comparison
of
esomeprazole and other proton pump inhibitors in eradicating
Helicobacter pylori. Digestion. 2006;73:178-86.
12. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric
acid-
suppressive agents and the risk of community-acquired
Clostridium difficile-associated disease. JAMA.
2005;294:2989-95.
13. Dial S, Delaney JA, Schneider V, Suissa S. Proton pump
inhibitor
use and risk of community-acquired Clostridium difficile-
associated 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
Clopidogrel Bisulfate (marketed as Plavix) to alert
healthcare
professionals about a drug interaction with omeprazole
(marketed
as Prilosec and Prilosec OTC). FDA Center for Drug Evaluation
and
Research (CDER). Available at: fda.gov. Accessed January 20,
2011.
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23. Data on file. WellPoint, Inc.; 2009.
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