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PL Detail-Document #280201
−This PL Detail-Document gives subscribers
additional insight related to the Recommendations published in−
PHARMACIST’S LETTER / PRESCRIBER’S LETTER
February 2012
H. Pylori Treatment: An Update
Background
Helicobacter pylori infection plays a major
role in the pathogenesis of gastric and duodenal
ulcers, gastric cancer, and gastric mucosaassociated lymphoid tissue (MALT) lymphomas.1
A triple therapy regimen with clarithromycin,
amoxicillin or metronidazole, and a PPI is often
used as a first-line therapy; however, resistance to
such a regimen is on the rise. Due the recent
shortages of clarithromycin and tetracycline and
the increased resistance rate, clinicians are
seeking effective alternatives to the standard triple
therapy regimen. Several alternative regimens
(e.g., quadruple therapy, sequential therapy, fourdrug nonbismuth-based concomitant therapy,
fluoroquinolone-based therapy, etc) have been
tried for H. pylori treatment. This document
reviews the efficacy and place in therapy for the
various treatment regimens for H. pylori. A chart
comparing the efficacy of the commonly
recommended H. pylori treatment regimens and
newer regimens is included.
Triple Therapy
The
2007
American
College
of
Gastroenterology
(ACG),
the
Canadian
Helicobacter Study Group (2004), and the
Canadian Dyspepsia Working Group (2005)
recommend proton pump inhibitor (PPI)-based
triple therapy (standard PPI dose BID +
clarithromycin 500 mg BID + amoxicillin
1000 mg BID [or metronidazole 500 mg BID if
penicillin allergic]) as first-line treatment of H.
pylori infection.2-4 The ACG recommends 14
days of treatment duration whereas the Canadian
guidelines recommend at least seven days of
treatment.4 The optimal duration of PPI-based
triple therapy with amoxicillin and clarithromycin
is an ongoing debate. A prospective, randomized
trial found no therapeutic gain from extending
standard triple therapy from seven to 14 days.5 A
meta-analysis of 21 randomized trials showed that
the eradication rate differences among the
different treatment durations (seven vs ten vs 14
days of triple therapy) to be statistically
significant with longer duration of therapy
yielding better eradication rates; however, the
clinical significance is marginal.6
Several studies and meta-analyses have shown
that triple therapy works better if the PPI is dosed
twice daily and when clarithromycin 500 mg,
rather than 250 mg, BID is used.7 The different
PPIs seem to have similar efficacy. Although
recommended as an alternative to patients who are
penicillin
allergic,
the
combination
of
clarithromycin and metronidazole should be
discouraged as there is currently no effective
salvage therapy if such a combination fails.7
Despite ongoing debate on the optimal
duration of therapy and antibiotic dosages, experts
recommend treating with higher dosages of
antibiotics (e.g., clarithromycin 500 mg BID) for
14 days unless shorter duration has been shown to
be equally effective per local susceptibility data.8
Recent data have shown the resistance rates to
metronidazole and clarithromycin are on the rise
up to 42% and 20%, respectively.9,10 In addition,
several meta-analyses have shown the cure rates
of standard triple therapy have fallen below the
acceptable rate of >80% (intention-to-treat [IT]
analysis) in many regions.8,11-13 Experts are now
discouraging the use of triple therapy as first-line
empiric therapy unless local susceptibility patterns
indicate such a treatment regimen to be highly
effective (>90% eradication rate per protocol [PP]
analysis).8,11 Based on the ACG and Canadian
Helicobacter Study Group Consensus criteria for
H. pylori protocol studies, the range for the 95%
confidence interval should remain above 80% (IT)
and above 90% (PP) for an effective regimen.2,4
Prevpac (Hp-Pac in Canada), a combo pack
containing a 14-day supply of lansoprazole 30 mg,
clarithromycin 500 mg, and amoxicillin 1 gram
dosed twice daily is available and can be used for
triple therapy in light of the current clarithromycin
shortage. In light of the current clarithromycin
More. . .
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P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
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(PL Detail-Document #280201: Page 2 of 6)
shortage, substituting clarithromycin extendedrelease for clarithromycin immediate-release may
also be considered, but is not preferred.
Theoretically, clarithromycin extended release
should be effective in the treatment of H. pylori
since clarithromycin is a time-dependent
antibiotic, where the increased exposure to the
drug may help its antimicrobial effect.14,15
However, there are no data on the use of
clarithromycin extended release in the treatment
of H. pylori.
Substitution with other macrolides (e.g.,
erythromycin or azithromycin) for clarithromycin
in triple therapy regimens is not recommended
due to low efficacy.16
Quadruple Therapy
An alternative to the triple therapy treatment
regimen is the bismuth quadruple therapy. U.S.
and Canadian guidelines both recommend the
bismuth quadruple therapy of PPI or H2-blocker
(U.S. guidelines only) + bismuth + metronidazole
+ tetracycline for ten to 14 days as a first-line
therapy for H. pylori eradication.2,4 The ACG also
recommends such quadruple therapy as a salvage
therapy in those who have failed clarithromycinbased triple therapy.2 Quadruple therapy was
previously considered a rescue regimen rather
than first-line treatment regimen due to the
perception that the dosing was too complex and
less well tolerated than PPI triple therapies.4
However, two meta-analyses concluded that the
efficacy, tolerability, and patient compliance were
similar between PPI triple therapies and quadruple
therapy.17,18
Due to the increase in clarithromycin
resistance rate, quadruple therapy regimens are
increasingly being recommended as first-line
empiric therapy.8,11
Pylera (each capsule contains bismuth
subcitrate 140 mg, metronidazole 125 mg, and
tetracycline 125 mg [three capsules per dose]) or
Helidac (bismuth subsalicylate 525 mg,
metronidazole 250 mg, tetracycline 500 mg per
dose) combo packs (doses for both given four
times daily) plus a PPI can be used for quadruple
therapy in light of the current tetracycline
shortage.
However, due to concerns about
metronidazole
resistance,
additional
metronidazole should be added to Helidac
treatment, aiming for at least 1500 mg of
metronidazole per day. Total daily dose of
metronidazole 1400 mg to 1600 mg in bismuthbased quadruple therapy has been shown to
overcome metronidazole resistance.11
Due to the lack of data, the substitution of
doxycycline for tetracycline in standard quadruple
therapy is not recommended.
The use of doxycycline in an alternative
quadruple therapy (omeprazole 20 mg +
amoxicillin 1000 mg + doxycycline 100 mg +
bismuth subcitrate 420 mg all given BID) based
on sensitivity data has been tried in the Italian
population. This alternative quadruple therapy
regimen was shown to have eradication rates of
92% (PP) and 91% (IT).34 Preliminary data from
a randomized, open-label Chinese trial (n=160)
also suggest the addition of bismuth to standard
triple therapy regimen (omeprazole 20 mg +
amoxicillin 1000 mg + clarithromycin 500 mg +
bismuth potassium citrate 220 mg all taken BID)
for 14 days to be a promising treatment regimen
to overcome clarithromycin resistance.9 The
results of this study showed that 14-day treatment
with bismuth, in addition to standard triple
therapy, yielded higher eradication rates compared
to seven-day treatment.
Results of these preliminary findings need to
be validated in the North American population
before such regimens can be routinely
recommended.
Sequential Therapy
A 10-day sequential therapy, combining a 5day course of PPI BID with amoxicillin
1000 mg BID immediately followed by a second
course of clarithromycin 500 mg BID,
metronidazole 500 mg or tinidazole 500 mg BID,
and a PPI BID for five additional days, is another
promising regimen.1,11,12 Cure rates of such
sequential therapy has been shown to be as high
as 92% in Europe.19
Two pooled analyses of European studies
support the efficacy of sequential therapy,
especially in those infected with macrolideresistant H. pylori.20-22 Another meta-analysis
found comparable efficacy of sequential therapy
vs triple therapy.22
Trials conducted in the Asian population also
show promising results with sequential therapy.
In one study conducted in Thailand, treatment
with lansoprazole 30 mg + amoxicillin 1000 mg
BID for five days, then lansoprazole 30 mg +
metronidazole 500 mg BID + clarithromycin
More. . .
Copyright © 2012 by Therapeutic Research Center
P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
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(PL Detail-Document #280201: Page 3 of 6)
1000 mg once daily for another five consecutive
days yielded a 95% eradication rate.23
In a Chinese trial comparing standard triple
therapy, bismuth quadruple therapy, and
sequential therapy, the treatment with omeprazole
20 mg BID + amoxicillin 1000 mg BID for five
days followed by omeprazole 20 mg BID +
tinidazole 500 mg BID + clarithromycin 500 mg
BID for another five days yielded a higher
eradication rate compared to standard triple
therapy (omeprazole 20 mg BID + amoxicillin
1000 mg BID + clarithromycin 500 mg BID) and
quadruple therapy consisting of rabeprazole
20 mg BID + amoxicillin 1000 mg BID +
levofloxacin 500 mg daily + bismuth pectin
100 mg QID.24
In contrast to these positive findings, a trial
conducted in Spain, showed an eradication rate of
only 84% in patients treated with sequential
therapy.25
The web edition of Sanford Guide to
Antimicrobial Therapy recommends such
sequential treatment regimens as a first-line
treatment for H. pylori infection in patients with
gastric or duodenal ulcer.26 While sequential
therapy has been shown to be effective in the
European and Asian population, some clinicians
feel more experience with a North American
population is needed before recommending it as a
treatment option. The 2007 ACG guidelines state
that sequential therapy cannot be widely accepted
as first-line therapy in the U.S. until efficacy has
been validated in the North American population.2
A recent presentation at the Canadian Digestive
Disease Week 2010 also concluded that more data
are needed in the North American population
before sequential therapy can be widely accepted
as a treatment option in the Canadian
population.27
Four-drug
Therapy”
Nonbismuth
“Concomitant
Sequential therapy can be a complex regimen,
requiring the patient to switch from a double to
triple therapy at mid point. As an alternative to
sequential therapy, researchers proposed the same
four drugs used in sequential therapy (PPI,
clarithromycin, metronidazole, and amoxicillin) to
be given concomitantly as a nonsequential fourdrug, three-antibiotic nonbismuth containing
quadruple therapy (aka “concomitant therapy”).
A meta-analysis of five randomized controlled
trials (four European, one Japanese) showed that
concomitant therapy for three to five days
achieved higher eradication rate compared to
standard triple therapy of five to seven days (93%
vs 83%, respectively).28
A recent study in Taiwan comparing sequential
therapy vs concomitant therapy found both
therapies to be equally effective and safe for
eradication of H. pylori (92.3% vs 93%,
respectively).29
More studies comparing concomitant and
sequential therapies are needed to determine
whether the simplicity of concomitant therapy is
more effective than sequential therapy. Despite
limited clinical data in the U.S. and Canadian
population, experts now consider concomitant
therapy an option for patients who have not been
previously treated with clarithromycin or
metronidazole. However, there is concern of dual
resistance to clarithromycin and metronidazole as
such dual-resistant H. pylori strains are difficult to
eradicate.8,11,12
Salvage Therapy
For salvage therapy, a regimen that has been
studied besides quadruple therapy is the
levofloxacin-based triple therapy, which shows
eradication rates ranging from 63% to 94% in
Asian and European populations. A meta-analysis
including four randomized, controlled trials
showed that a 10-day levofloxacin-based triple
therapy regimen had a superior eradication rate
and was associated with fewer side effects
compared to a 7-day course of bismuth-based
quadruple therapy.2,30 However, these results
require validation in the North American
population.
Furthermore,
the
optimal
levofloxacin
dose
(250
mg
BID
vs
500 mg daily vs 500 mg BID) and duration of
therapy has yet to be determined (seven day vs
ten day). However, another meta-analysis did
find a higher eradication rate with the 10-day over
7-day regimen.31 Unfortunately, resistance to
fluoroquinolones is rapidly increasing. Experts
now recommend using fluoroquinolone therapy
only when susceptibility data are available.11
Rifabutin-based salvage therapy (rifabutin
150 mg + amoxicillin 1000 mg + PPI BID for 14
days) has also been tried in patients who have
failed other therapies. Due to concerns of adverse
drug effects and increased mycobacterium
More. . .
Copyright © 2012 by Therapeutic Research Center
P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
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(PL Detail-Document #280201: Page 4 of 6)
resistance to rifabutin, such therapy should be
reserved as a last resort for patients who have
failed at least two courses of first-line
therapy.7,8,11,12
LOAD Therapy
An investigational four-drug regimen known
as LOAD therapy (levofloxacin 250 mg daily with
breakfast + omeprazole 40 mg daily before
breakfast + nitazoxanide 500 mg BID +
doxycycline 100 mg daily at dinner) was found to
be an effective regimen with eradiation rates of
88.9% (10-day therapy) and 89.4% (7-day
therapy) in an open-label study.32 A larger
randomized controlled trial is warranted to further
evaluate the efficacy of this treatment regimen.
Sequential-Concomitant Hybrid Therapy
A hybrid of sequential and concomitant
therapy with seven days of PPI plus amoxicillin
treatment followed by amoxicillin, clarithromycin,
metronidazole or tinidazole, and PPI for an
additional seven days is currently being
investigated. Treatment success with such hybrid
therapy has been shown to be >95%.8 Some
experts consider such hybrid therapy a reasonable
alternative to quadruple therapy for patients who
have not recently been treated with clarithromycin
and/or metronidazole.8,11,12
Dual Therapy
Although dual therapy (e.g., PPI + amoxicillin)
for ten to 14 days is an FDA–approved regimen,
such regimens should not be recommended since
the eradication rate falls below 80%.2
Commentary
In treating H. pylori infection, it is important to
achieve a high eradication rate in order to reduce
symptoms and complications of the infection.2
The eradication rate of H. pylori is highly
dependent on patient compliance to the treatment
regimen. An ideal treatment regimen should be
simple, well tolerated, cost effective, encourage
patient compliance, and provide a bacterial
eradication rate of >80% (IT) or >90% (PP).2 See
our PL Chart, H. Pylori Treatment Regimens, for
regimens and their efficacy. To avoid repeated
treatments of dyspepsia symptoms not attributable
to H. pylori, follow-up testing with urea breath
test or fecal antigen test is recommended.1 For
both urea breath test and fecal antigen test, the
patient should stop taking proton pump inhibitors
two weeks before testing or stop H2-receptor
antagonists for 24 hours before testing. Patients
should also avoid taking antimicrobial agents for
four weeks before testing. These agents can
reduce the sensitivity of testing.1
The choice of regimen should be based on
local susceptibility patterns.8 Standard triple
therapy is considered the first-line therapy in areas
where the clarithromycin resistance rate is <20%
[Evidence level A, high quality RCTs].1-4 In areas
with high prevalence for clarithromycin-resistant
H. pylori (>20%) or in patients who have failed
standard triple therapy, consider quadruple
therapy with PPI + bismuth + metronidazole +
tetracycline for ten to 14 days [Evidence level A,
high quality RCTs].1,2,4 If the local H. pylori
antimicrobial resistance information is not readily
available, it is reasonable to consider bismuthbased quadruple therapy with a PPI in individuals
who have previously been treated with either a
macrolide or metronidazole for any reason, since
prior exposure significantly increases the
likelihood of H. pylori resistance to these agents
[Evidence level C; Consensus].2 In patients who
have not been recently treated with clarithromycin
and/or metronidazole, concomitant therapy can be
considered an alternative, especially in those who
are not able to adhere to the QID dosing schedule
of quadruple therapy regimens [Evidence level C;
Expert opinion].8,11,12 There are data suggesting
concomitant therapy and sequential therapy are
equally effective; therefore, sequential therapy can
also be considered in areas where efficacy of
triple therapy has fallen below the acceptable
level [Evidence level C, expert opinion].8,11,12
Experts also consider hybrid therapy a reasonable
alternative to standard quadruple therapy in
patients who have not recently been treated with
clarithromycin and/or metronidazole [Evidence
level C, expert opinion].8,11,12 A 10-day course of
levofloxacin-based triple therapy has been shown
to be effective in treatment of persistent H. pylori
infections in non-North American populations
[Evidence level A; quantitative systematic
review].30
However, it should not be
recommended routinely as a first-line therapy.33
More data with a North American population are
needed for its routine use; however, it can be
considered as a salvage therapy [Evidence level C,
Consensus].2
More. . .
Copyright © 2012 by Therapeutic Research Center
P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com
(PL Detail-Document #280201: Page 5 of 6)
In light of the current clarithromycin and
tetracycline shortages, quadruple therapy using
PPI + bismuth + metronidazole + tetracycline for
ten to 14 days or Helidac dose pack with
additional metronidazole dose aiming for at least
1500 mg metronidazole per day as first-line
empiric therapy can be considered.2-4 Pylera plus
a PPI is also an option. However, cost can be a
limiting factor when using the brand combo
products.
If necessary, H. pylori treatment can be
delayed until appropriate antibiotics are available.
In general, there is no urgency in treating H.
pylori since H. pylori is typically acquired in
childhood and most patients have been infected
for decades.8
Users of this PL Detail-Document are cautioned to use
their own professional judgment and consult any other
necessary or appropriate sources prior to making
clinical judgments based on the content of this
document.
Our editors have researched the
information with input from experts, government
agencies, and national organizations. Information and
internet links in this article were current as of the date
of publication.
Project Leader in preparation of this PL DetailDocument: Wan-Chih Tom, Pharm.D.
Levels of Evidence
In accordance with the trend towards Evidence-Based
Medicine, we are citing the LEVEL OF EVIDENCE
for the statements we publish.
Level
A
B
C
D
Definition
High-quality randomized controlled trial (RCT)
High-quality meta-analysis (quantitative
systematic review)
Nonrandomized clinical trial
Nonquantitative systematic review
Lower quality RCT
Clinical cohort study
Case-control study
Historical control
Epidemiologic study
Consensus
Expert opinion
Anecdotal evidence
In vitro or animal study
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Adapted from Siwek J, et al. How to write an evidence-based
clinical review article. Am Fam Physician 2002;65:251-8.
References
1.
2.
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Chey WD, Wong BC; Practice Parameters
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Veldhuyzen van Zanten SJ, Bradette M, Chiba N,
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Zagari RM, Bianchi-Porro G, Fiocca R, et al.
Comparison of 1 and 2 weeks of omeprazole,
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Helicobacter pylori eradication: the HYPER Study.
Gut 2007;56:475-9.
Fuccio L, Minardi ME, Zagari RM, et al. Metaanalysis: duration of first-line proton-pump inhibitor
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Calvet X. Helicobacter pylori infection: treatment
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Graham DY, Fischbach L. Helicobacter pylori
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resistance. Gut 2010;59:1143-53.
Sun Q, Liang X, Zheng Q, et al. High efficacy of
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Malfertheiner P. Infection: bismuth improves PPIbased triple therapy for H. pylori eradication. Nat
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Rimbara E, Fischbach LA, Graham DY. Optimal
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Chuah SK, Tsay FW, Hsu PI, Wu DC. A new look
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grade Helicobacter pylori therapy. Helicobacter
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Rapp RP, Nogid B, Goldberg T. Principles of
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Silva FM, Eisig JN, Teixeira AC, et al. Short-term
triple therapy with azithromycin for Helicobacter
pylori eradication: low cost, high compliance, but
low efficacy. BMC Gastroenterol 2008;8:20.
More. . .
Copyright © 2012 by Therapeutic Research Center
P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com
(PL Detail-Document #280201: Page 6 of 6)
17. Gene E, Calvet X, Azagra R, Gisbert JP. Triple vs.
quadruple therapy for treating Helicobacter pylori
infection: a meta-analysis. Aliment Pharmacol
Ther 2003;17:1137-43.
18. Luther J, Higgins PD, Schoenfeld PS, et al.
Empiric quadruple vs. triple therapy for primary
treatment of Helicobacter pylori infection:
systematic review and meta-analysis of efficacy
and tolerability. Am J Gastroenterol 2010;105;6573.
19. Vaira D, Zullo A, Hassan C, et al. Sequential
therapy for Helicobacter pylori eradication; the time
is now! Therap Adv Gastroenterol 2009;2:317-22.
20. Zullo A, De Francesco V, Hassan C, et al. The
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Am J Gastroenterol 2009;104:3069-79.
23. Sirimontaporn N, Thong-Ngam D, Tumwasorn S,
Mahachai V.
Ten-day sequential therapy of
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24. Gao XZ, Qiao XL, Song WC, et al. Standard triple,
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25. Sanchez-Delgado J, Calvet X, Bujanda L, et al.
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26. Chambers HF, Eiopoulos GM, Gilber DN, et al.
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http://webedition.sanfordguide.com/.
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Sequential therapy eradicates
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Aklavik Natives: Presented at CDDW. March 2,
2010.
Doctor’s
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28. Essa AS, Kramer JR, Graham DY, Treiber G.
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29. Wu DC, Hsu PI, Wu JY, et al. Sequential and
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Gastroenterol Hepatol 2010;8:36-41.
30. Saad RJ, Schoenfeld P, Kim HM, Chey WD.
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31. Jodlowski TZ, Lam S, Ashby CR Jr. Emerging
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32. Basu PP, Rayapudi K, Pacana T, et al.
A
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triple therapy for the eradication of Helicobacter
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33. Liou JM, Lin JT, Chang CY, et al. Levofloxacinbased and clarithromycin-based triple therapies as
first-line
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34. Cammarota G, Martino A, Pirozzi G, et al. High
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Cite this document as follows: PL Detail-Document, H. Pylori Treatment:
Letter/Prescriber’s Letter. February 2012.
An Update.
Pharmacist’s
Evidence and Recommendations You Can Trust…
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Copyright  2012 by Therapeutic Research Center
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PL Detail-Document #280201
−This Detail-Document accompanies the related article published in−
PHARMACIST’S LETTER / PRESCRIBER’S LETTER
February 2012
H. Pylori Treatment Regimens for Adults
Abbreviations: ACG=American College of Gastroenterology; AMOX=amoxicillin; BID=twice daily; BIS=bismuth subcitrate potassium;
BSS=bismuth subsalicylate (Pepto-Bismol Regular Strength); CLAR=clarithromycin; DOX=doxycycline; DU=duodenal ulcer;
ESOMP=esomeprazole; GU=gastric ulcer; IT=intention-to-treat; LANS=lansoprazole; LEV=levofloxacin; MET=metronidazole; NIT=nitazoxanide;
OMP=omeprazole; PANT=pantoprazole; PP=per protocol; PPI=proton pump inhibitor; QID=four times daily; RAB=rabeprazole; RIF=rifabutin;
TCN=tetracycline; TID=three times daily; TIN=tinidazole; TPD=Therapeutic Products Directorate (Health Canada).
NOTE: Not all FDA- or TPD-approved regimens have maximum efficacy. Only Regimens with >80% (IT) or >90% (PP) are considered effective.1,2
PPI or
Antibiotic 1
Antibiotic 2
Bismuth
Duration Comments
Efficacyb,c FDATPDa,f,g
1-3
H2-Blocker
Compound
Approvedd Approvede
(U.S.)
(Canada)
Recommended Oral Regimens per ACG Guidelines (2007), Canadian Helicobacter Study Group Consensus (2004), or Dyspepsia Working Grp (2005)1-3
ESOMP 20 mg
CLAR 500 mg
AMOX 1 gm
14 days1 10-day regimen is FDA
10-day
Yes
Yes
2,3
4
BID
BID
BID
U.S.
approved.
regimen
84% (PP)
or
ESOMP 40 mg
7 or 10
FDA-approved Nexium
77% (IT)
days3
40 mg once daily dosing
once daily1
Canada
rather than 20 mg BID.4 7-day
regimen5
7-day regimen is TPD
86% (PP)
approved.
89% (IT)
This regimen is known
as Nexium
1-2-3 A in Canada.
ESOMP 20 mg
BID2,3
or
ESOMP 40 mg
once daily1
CLAR 500 mg
BID
MET 500 mg
BID
14 days1
U.S.
--
No
No
7 or 10
days3
Canada
More. . .
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(PL Detail-Document #280201: Page 2 of 15)
PPI or
H2-Blockera,f,g
Antibiotic 1
Antibiotic 2
Bismuth
Compound
Duration Comments
Efficacyb,c
FDATPDApprovedd Approvede
(U.S.)
(Canada)
Recommended Oral Regimens per ACG Guidelines (2007), Canadian Helicobacter Study Group Consensus (2004), or Dyspepsia Working Grp (2005)1-3
Yes
Yes
LANS 30 mg
CLAR 500 mg
AMOX 1 gm
14 days
Both 10-day and 14-day 7-day
regimen
BID1-3
BID
BID
U.S.
regimens are FDA
90% (PP)
approved.6,7
85% (IT)
7 or 10
days
7-day, 10-day, and 1410-day
Canada
day regimens are TPD
6-8
regimen
approved.8
84% (PP)
1-3
81% (IT)
Available as Prevpac in
U.S. and Hp-Pac in
Canada.
LANS 30 mg
BID1-3
CLAR 500 mg
BID
MET 500 mg
BID
14 days
U.S.
7 or 10
days
Canada
14-day
regimen6,7
85-92%
(PP)
82-86%
(IT)
≥90%
(PP)1
≥80%
(IT)1
More. . .
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No
No
(PL Detail-Document #280201: Page 3 of 15)
PPI or
H2-Blockera,f,g
Antibiotic 1
PANT 40 mg
BID1-3
CLAR 500 mg
BID
Antibiotic 2
Duration Comments
Efficacyb,c
FDATPDApprovedd Approvede
(U.S.)
(Canada)
Recommended Oral Regimens per ACG Guidelines (2007), Canadian Helicobacter Study Group Consensus (2004), or Dyspepsia Working Grp (2005)1-3
OMP 20 mg
10-day regimen is FDA
10-day
Yes
Yes
CLAR 500 mg
AMOX 1 gm
14 days
BID1-3
BID
BID
U.S.
approved.9
regimen
77-90%
7-day regimen is TPD
10
7 or 10
(PP)9
approved.
days
69-83%
Also known as Losec 1- (IT)9
Canada
2-3 A in Canada.
7-day
Give additional 18 days
regimen
of OMP 20 mg daily for 95-98%
ulcer healing and
(PP)10
symptom relief.9 Give
94%-96%
additional OMP 20 mg
(IT)10
daily for up to 3 wks for
active DU and OMP 2040 mg daily for up to 12
wks for active GU.10
CLAR 250 mg or MET 500 mg
14 days
7-day regimen with
No
Yes
OMP 20 mg
91–94%
500 mg BID
BID
U.S.
CLAR 250 mg BID is
(PP)10
BID1-3
TPD approved.10
87-95%
7 or 10
(IT)10
days
Also known as Losec
(with
Canada
1-2-3 M in Canada (with CLAR
CLAR 250 mg).
250 mg
BID)
AMOX 1 gm
BID
Bismuth
Compound
1-3
14 days
U.S.
7-day regimen is TPD
approved.11
86%-93%
(IT)11
7 or 10
days
Canada
More. . .
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No
Yes
(PL Detail-Document #280201: Page 4 of 15)
PPI or
H2-Blockera,f,g
Antibiotic 1
Antibiotic 2
Bismuth
Compound
Duration Comments
Efficacyb,c
FDATPDApprovedd Approvede
(U.S.)
(Canada)
Recommended Oral Regimens per ACG Guidelines (2007), Canadian Helicobacter Study Group Consensus (2004), or Dyspepsia Working Grp (2005)1-3
PANT 40 mg
83%-96% No
Yes
CLAR 500 mg
MET 500 mg
14 days
7-day regimen is TPD
BID1-3
(IT)11
BID
BID
U.S.
approved.11
1-3
7 or 10
days
Canada
RAB 20 mg
BID1-3
CLAR 500 mg
BID
AMOX 1 gm
BID
14 days
U.S.
7 or 10
days
Canada
RAB 20 mg
BID1-3
CLAR 500 mg
BID
MET 500 mg
BID
14 days
U.S.
7-day regimen is FDA
and TPD approved.12,13
7-day regimen is not
recommended per 2007
U.S. H. pylori treatment
guidelines due to lower
eradication rates
compared to 10- and 14day treatment regimens.1
7-day
regimen
84%
(PP)12
77%
(IT)12
10-day
regimen
86%
(PP)12
78%
(IT)12
--
7 or 10
days
Canada
More. . .
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Yes
Yes
No
No
(PL Detail-Document #280201: Page 5 of 15)
PPI or
H2-Blockera,f,g
TCN 500 mg
QID
Antibiotic 2
MET 250 mg to
500 mg QID
Bismuth
Compound
BSS 525 mg
QID
Duration Comments
Efficacyb,c
FDATPDApprovedd Approvede
(U.S.)
(Canada)
Recommended Oral Regimens per ACG Guidelines (2007), Canadian Helicobacter Study Group Consensus (2004), or Dyspepsia Working Grp (2005)1-3
ESOMP 20 mg
BSS/MET/TCN
-No
No
TCN 500 mg
MET 250 mg
BSS 525 mg 10 or 14
BID or ESOMP
combination is available
QID
QID
QID
days1
40 mg once daily
in U.S. as Helidac.14
or LANS 30 mg
Experts recommend total
or
OMP 20 mg or
daily dose of MET to be
PANT 40 mg or
at least 1500 mg/day for
RAB 20 mg BID1
better efficacy and to
overcome MET
resistance.15 Consider
additional MET 250 mg
TID with meals when
using Helidac.
ESOMP 20 mg
BID or
LANS 30 mg
BID or
OMP 20 mg BID
or PANT 40 mg
BID or
RAB 20 mg BID3
Antibiotic 1
1-3
10 or 14
days
Considered a first-line
therapy per 2007 U.S.
H. pylori treatment
guidelines.1
Considered the
preferred therapy for
H. pylori treatment
failures per 2005
Canadian dyspepsia
treatment guidelines.3
---
No
More. . .
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No
(PL Detail-Document #280201: Page 6 of 15)
PPI or
H2-Blockera,f,g
Antibiotic 1
Antibiotic 2
Bismuth
Compound
Duration Comments
Efficacyb,c
FDATPDApprovedd Approvede
(U.S.)
(Canada)
Recommended Oral Regimens per ACG Guidelines (2007), Canadian Helicobacter Study Group Consensus (2004), or Dyspepsia Working Grp (2005)1-3
Ranitidine
MET 250 mg
TCN 500 mg
BSS 525 mg 10 or 14
BSS/MET/TCN combo
71%
Yes
No
150 mg BID or
QID
QID
days
is available in U.S. as
QID
(PP)14
standard dose
Helidac.14
72%
H2-blockers
Experts recommend total (IT)14
(Famotidine
daily dose of MET to be
40 mg/day, or
at least 1500 mg/day for
Nizatidine
better efficacy and to
300 mg/day
overcome MET
[given as single
resistance.15 Consider
or divided
additional MET 250 mg
doses]).1
TID with meals when
using Helidac.
Ranitidine-based
regimen is considered a
first-line therapy per
2007 U.S. H. pylori
guidelines, but not listed
as an option in the
Canadian guidelines.1
Give BSS, antibiotics
and H2-blocker together
for 14 days. Then give
H2-blocker alone for an
additional 14 days. H2blocker may be given
QD at bedtime or in two
equally divided doses
BID. Avoid cimetidine
to reduce risk of drugdrug interactions.14
1-3
More. . .
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(PL Detail-Document #280201: Page 7 of 15)
PPI or
H2-Blockera,f,g
Antibiotic 1
Antibiotic 2
Bismuth
Compound
Duration Comments
Efficacyb,c
FDATPDApprovedd Approvede
(U.S.)
(Canada)
Recommended Oral Regimens per ACG Guidelines (2007), Canadian Helicobacter Study Group Consensus (2004), or Dyspepsia Working Grp (2005)1-3
ESOMP 20 mg
>80%
No
No
MET 375 mg or
TCN 375 or
BSS 525 mg 10 or 14
Considered a first-line
BID or
(IT)2
500 mg QID
500 mg QID
QID
days2
therapy per 2004
LANS 30 mg
Canadian Helicobacter
BID or
Study Group.2
OMP 20 mg BID
or PANT 40 mg
BID or
RAB 20 mg BID2
1-3
Other Oral Regimens
AMOX 1 gm
BID
(Days 1-5)
RAB 20 mg
BID16
(Days 1-10)
May use PPIs
other than
RAB.15
Followed by:
CLAR 500 mg
BID
(Days 6-10)
10 days
TIN 500 mg
BID
(Days 6-10)
Sequential therapy for
total of 10 days. Start
with RAB + AMOX for
5 days followed by RAB
+ CLAR + TIN for
another 5 days.16
92%
(PP)17
90%
(IT)16
(in
European
population)
Recommended as a
first-line therapy for H.
pylori infected patients
with DU or GU per
Sanford Guide to
Antimicrobial Therapy
web edition.16
Experts now consider
sequential therapy an
acceptable first-line
therapy in those who
have not been exposed
clarithromycin or
metronidazole
recently.15,19,20
More. . .
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No
No
(PL Detail-Document #280201: Page 8 of 15)
PPI or
H2-Blockera,f,g
Antibiotic 1
Antibiotic 2
Bismuth
Compound
Duration Comments
Efficacyb,c
FDAApprovedd
(U.S.)
TPDApprovede
(Canada)
95%18
(not
specified
PP or IT)
No
No
90-99%17
(not
specified
PP or IT)
No
No
--
No
No
1-3
Other Oral Regimens
10 days18
AMOX 1 gm
BID (Days 1-5)
LAN 30 mg BID
(Days 1-10)18
OMP 20 mg
BID16
ESOMP 20 mg
BID or
LANS 30 mg
BID or
OMP 20 mg BID
or PANT 40 mg
BID or
RAB 20 mg BID
CLAR 1 gm
Daily (Days 610)
TCN 500 mg
QID
TCN 500 mg
QID
MET 500 mg
BID (Days 6-10)
MET 250 mg
QID
BSS 525 mg
QID
14 days16
MET 500 mg
TID or
MET 400 mg
QID or
TIN 500 mg
TID
BSS 525 mg
QID
10 or 14
days15,19,
20
CLAR and MET
combination should not
be routinely
recommended as there
are no effective salvage
therapies if such
combination failed.1
Considered an
alternative to sequential
therapy for H. pylori
infected patients with
DU or GU per Sanford
Guide to Antimicrobial
Therapy Web Edition.16
Experts now consider
sequential therapy an
acceptable first-line
therapy in those who
have not been exposed
to clarithromycin or
metronidazole
recently.15,19,20
Experts recommend total
daily dose of MET to be
at least 1500 mg/day for
better efficacy and to
overcome MET
resistance.15
MET taken TID with
meals may cause
confusion while other
drugs are taken QID.
(in Asian
population)
More. . .
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(PL Detail-Document #280201: Page 9 of 15)
PPI or
H2-Blockera,f,g
Antibiotic 1
OMP 20 mg BID
AMOX 1 gm
BID
OMP 20 mg
BID21
OMP 40 mg once
daily9
Antibiotic 2
Bismuth
Compound
Duration Comments
Efficacyb,c
FDAApprovedd
(U.S.)
TPDApprovede
(Canada)
1-3
Other Oral Regimens
7 days
Efficacy needs to be
validated in North
American population.28
92%
(PP)
91%
(IT)
No
No
BIS 140 mg MET 125 mg TCN 125 mg (Pylera)
3 capsules QID
10 days
Each Pylera capsule
contains BIS 140 mg,
MET 125 mg, and TCN
125 mg.
93%
(PP)21
88%
(IT)21
Yes
CLAR 500 mg
TID
14 days
Give CLAR and OMP
together for 14 days.
Then give only OMP
20 mg daily for an
additional 14 days for
ulcer healing and
symptom relief.22
64-74%
(PP)22
Yes
Yes (as
Helizide in
2003,
reapproved
as Pylera in
2011, but
not
marketed)
Yes
DOX 100 mg
BID
BIS 420 mg
BID
55-60%
(IT)23
Regimens containing
clarithromycin as a
single antimicrobial
agent are more likely to
develop clarithromycin
resistance among
patients who fail
treatment.22
More. . .
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(PL Detail-Document #280201: Page 10 of 15)
PPI or
H2-Blockera,f,g
Antibiotic 1
Antibiotic 2
Bismuth
Compound
ESOMP 20 mg
BID or
LANS 30 mg
BID or
OMP 20 mg BID
or PANT 40 mg
BID or
RAB 20 mg
BID21
ESOMP 20 mg
BID or
LANS 30 mg
BID or
OMP 20 mg BID
or PANT 40 mg
BID or
RAB 20 mg BID1
RIF 150 mg BID
AMOX 1 gm
BID
10 or 14
days
LEV 500 mg
once daily
AMOX 1 gm
BID
10 or 14
days15
Efficacyb,c
FDAApprovedd
(U.S.)
TPDApprovede
(Canada)
Reserve rifabutin based
therapy as salvage
therapy for patients who
have failed two different
first-line therapies.1
70-85%
(IT)24
No
No
May be considered as
salvage therapy for
patients with persistent
H. pylori who have
failed other treatment
regimens.1
10-day
regimen1
63-94%
(not
specified
PP or IT)1
No
No
No
No
Duration Comments
1-3
Other Oral Regimens
ESOMP 20 mg
BID or
LANS 30 mg
BID or
OMP 20 mg BID
or PANT 40 mg
BID or
RAB 20 mg
BID19
LEV 500 mg
once daily
AMOX 500 mg
QID
BSS 525 mg
QID
10 days
The 2007 U.S. guideline
states that such regimen
requires efficacy
validation in the North
American population
before it can be accepted
as first-line therapy.1
Efficacy of levofloxacin- -based quadruple therapy
needs to be validated.19
More. . .
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(PL Detail-Document #280201: Page 11 of 15)
PPI or
H2-Blockera,f,g
Antibiotic 1
Antibiotic 2
Antibiotic 3
OMP 20 mg BID
or LANS 30 mg
BID25
CLAR 250 mg
BID
MET 400 mg
BID
AMOX 1gm
BID
5 days
ESOMP 40 mg
BID26
CLAR 500 mg
BID
MET 500 mg
BID or
TIN 500 mg
BID
AMOX 1 gm
BID
10 days26
Efficacyb,c
FDAApprovedd
(U.S.)
TPDApprovede
(Canada)
The efficacy of this
concomitant therapy for
5-day duration needs
further validation.25
90-96%
(PP)25
88-91%
(IT)25
No
No
The efficacy of this fourdrug concomitant
therapy given for 10
days appears to be
equivalent to sequential
therapy of same four
drugs given in sequential
manner.26
10-day
regimen26
93% (PP
and IT)
(ESOMP
40 mg
BID)26
No
No
Duration Comments
1-3
Other Oral Regimens
More. . .
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(PL Detail-Document #280201: Page 12 of 15)
PPI or H2 Blockera,f,g
Antibiotic 1
ESOMP 20 mg
BID or
LANS 30 mg
BID or
OMP 20 mg BID
or PANT 40 mg
BID or
RAB 20 mg
BID15
(Days 1-14)
AMOX 1 gm
BID (Days 1-7)
Antibiotic 2
Antibiotic 3
Duration Comments
Efficacyb,c
FDAApprovedd
(U.S.)
TPDApprovede
(Canada)
99%
(PP)15
97%
(IT)15
No
No
77%
(PP)6
70%
(IT)6
Yes
No
--
No
No
Other Oral Regimens
AMOX 1 gm
BID (Days 8-14)
14 days
CLAR 500 mg
BID
(Days 8-14)
MET 500 mg
BID or
TIN 500 mg
BID
(Days 8-14)
LANS 30 mg
TID6
AMOX 1 gm
TID
14 days
OME 40 mg or
LAN 30 mg QID
AMOX 500 mg
QID
14 days
Although there are
limited data, experts
now consider such
hybrid of concomitant
and sequential therapy
as acceptable for those
who have not been
exposed to
clarithromycin or
metronidazole
recently.15,19,20
Use only in
clarithromycin
allergy/intolerance or in
known/suspected
clarithromycin
resistance.6
Considered a salvage
therapy. High dose PPI
can maintain intragastric
pH above 6, where H.
pylori is susceptible to
amoxicillin.20
Efficacy of this high
dose dual therapy needs
to be validated.20
OME 40 mg once LEV 250 mg
NIT 500 mg
DOX 100 mg 7 or 10
Efficacy of this regimen 89% (IT)27 No
No
27
daily
once daily
BID
once daily
days
needs to be validated.
a. The U.S. and Canadian guidelines were published prior to the approval of dexlansoprazole (Dexilant). There are limited data on the use of
dexlansoprazole for the treatment of H. pylori infection.29 However, it is the general consensus that PPIs are interchangeable (at equipotent
More. . .
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(PL Detail-Document #280201: Page 13 of 15)
b.
c.
d.
e.
f.
g.
dose) for H. pylori regimens. Dexlansoprazole is not approved by the FDA or TPD for the treatment of H. pylori infection. To help with PPI
dose comparisons, see our PL Chart, Proton Pump Inhibitor Dose Comparison (U.S. subscribers #250801; Canadian subscribers #250820).
Efficacy reported as cure rate (eradication rate) by intention-to-treat (IT) analysis or by per protocol (PP) analysis. IT means that outcomes
were analyzed for all patients, based on the treatment to which they were randomized, regardless of whether they dropped out. PP means that
outcomes were analyzed for all patients who completed the study and complied with protocol. Based on the American College of
Gastroenterology and Canadian Helicobacter Study Group Consensus criteria, the range for the 95% confidence interval should remain above
80% (IT) and above 90% (PP) for an effective regimen.1,2
H. pylori resistance to clarithromycin is on the rise. Recent data suggest that cure rates for first-line triple therapy (PPI + CLAR + AMOX [or
MET]) fall below 80%.20
Treatment regimen is approved by the FDA.
Treatment regimen is approved by the Therapeutic Products Directorate (Health Canada).
For guideline recommendations, efficacy of all PPIs (excluding dexlansoprazole; see footnote “a”) appear comparable.1,3 For regimens with
only one PPI listed, the listed regimen is the specific regimen studied or listed in product labeling.
The 2007 U.S. guidelines provide specific dosing for PPIs.1 The Canadian guidelines do not provide specific PPI dosing,2,3 but the 2005
Canadian guidelines state that all PPIs (excluding dexlansoprazole; see footnote “a”), dosed twice daily have similar efficacy in curing H.
pylori.3
Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making
clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national
organizations. Information and Internet links in this article were current as of the date of publication.
More. . .
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(Detail-Document #280201: Page 14 of 15)
Project Leader in preparation of this PL DetailDocument: Wan-Chih Tom, Pharm.D.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Chey WD, Wong BC; Practice Parameters
Committee
of
the
American
College
of
Gastroenterology.
American
College
of
Gastroenterology guideline on the management of
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Cite this document as follows: PL Detail-Document, H. Pylori Treatment Regimens for Adults. Pharmacist’s
Letter/Prescriber’s Letter. February 2012.
More. . .
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