Peptic Ulcer Bleeding Following Therapeutic Endoscopy: A New Indication for Intravenous Esomeprazole
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2. RIGD0349_12-31.qxd 12/31/09 3:28 PM Page E111
DRUG REVIEW
Peptic Ulcer Bleeding Following
Therapeutic Endoscopy: A New
Indication for Intravenous
Esomeprazole
Danial E. Baker, PharmD, FASCP, FASHP
Drug Information Center, Department of Pharmacotherapy, College of Pharmacy, Washington State University,
Spokane, WA
Intravenous (IV) administration of the esomeprazole is a faster way to
achieve gastric acid suppression than oral administration of the same agent.
Peak suppression following IV administration occurs within hours compared
with several days following oral administration. Thus, the IV administration
route offers a faster onset of gastric suppression, achievement of intragastric
pH closer to target levels, and better bioavailability. Treatment of peptic ulcer
bleeding is the newest indication for the IV formulation of esomeprazole. The
drug is effective in preventing rebleeds following endoscopic treatment when
administered within 24 hours of the procedure as an 80-mg bolus followed
by an IV infusion for 72 hours. What remains to be seen is whether oral
therapy can be substituted for all, or part, of the 72-hour IV infusion and
whether the patient can be discharged from the hospital sooner with similar
outcomes.
[Rev Gastroenterol Disord. 2009;9(4):E111-E118 doi: 10.3909/rigd0349]
© 2009 MedReviews®, LLC
Key words: Esomeprazole • Gastroesophageal reflux disease • Peptic ulcer bleeding •
Proton pump inhibitor
E
someprazole was approved as an oral capsule formulation in the United
States in February 2001 for the treatment of gastroesophageal reflux disease
(GERD), including healing of erosive esophagitis, maintenance of healing of
erosive esophagitis, and symptomatic GERD; and for Helicobacter pylori eradica-
tion to reduce the risk of duodenal ulcer recurrence. It was approved as a delayed
release suspension in October 2006; the intravenous (IV) formulation was
approved in March 2005 for the short-term (up to 10 days) treatment of GERD
patients with a history of erosive esophagitis as an alternative to oral therapy
when use of the oral formulation is not possible or appropriate. In the United
VOL. 9 NO. 4 2009 REVIEWS IN GASTROENTEROLOGICAL DISORDERS E1112. RIGD0349_12-31.qxd 12/31/09 3:28 PM Page E112
New Indication for IV Esomeprazole continued
States, the oral capsule has exclusivi- because clotting can be impaired in goal is to alter the gastric pH at the
ty applications that expired in the acidic environment and the result- site of the bleeding. The target goal is
November 2007, April 2009, and ing blood loss can be significant. The a pH ( 6.0) above the proteolytic
October 2009, whereas its various incidence of PUB is approximately 50 range for pepsin to allow stabilization
patents expire beginning in 2014 and people per 100,000 each year. Death of the clotting process.13,18
continuing through 2020. The IV for- may occur in up to 14% of patients
mulation had exclusivity through with an acute bleed and if a patient Clinical Pharmacology
March 2008, but its patents are valid experiences a rebleed the risk of death All oral PPIs are prodrugs and require
until 2014.1,2 The newest indication may be increased 3-fold.7-11 acidic activation to be effective. The
for IV esomeprazole will be for The preferred treatment of PUB is oral formulation of esomeprazole is
the treatment of peptic ulcer bleed- endoscopic therapy. The source of the acid liable and must be protected
ing (PUB) following therapeutic bleeding can be found in approxi- from premature activation. The oral
formulation is protected from gastric
The newest indication for IV esomeprazole will be for the treatment of pep- acid by filling the capsules with
enteric-coated granules or making the
tic ulcer bleeding following therapeutic endoscopy. If approved, esomepra- suspension out of enteric-coated
zole will be the only IV proton pump inhibitor approved for this indication. granules.19,20 When the unprotonated
prodrug is released from its protected
endoscopy.3 If approved, esomepra- mately 90% of patients. The hemosta- dosage form in the duodenum, it
zole will be the only IV proton pump tic rate in these patients is high, but is rapidly absorbed. Once the
inhibitor (PPI) approved for this indi- rebleeding can occur; it is estimated orally administered esomeprazole is
cation (Table 1). to occur in 10% to 30% of these absorbed it is activated and handled
PUB occurs when the peptic ulcer patients and generally occurs within by the body just as the IV-adminis-
erodes into an underlying blood 3 days.12-17 When pharmacotherapy is tered esomeprazole. To be activated,
vessel. It is potentially life threatening added to the endoscopic procedure its the esomeprazole must penetrate the
cell membrane and transverse into the
parietal cell. There the molecule is
Table 1
protonated and trapped in the secre-
US Food and Drug Administration-Approved Indications for Injectable tory canaliculus of the parietal cell
Proton Pump Inhibitors3-6 and becomes the active moiety that
can bind to either cysteine residue
Indication Esomeprazole Lansoprazole Pantoprazole 813 within the (H/K)-adenosine
Short-term treatment (up to 7 days) X triphosphatase (ATPase) enzyme,
of all grades of erosive esophagitis resulting in inhibition of gastric acid
in patients unable to take oral secretion.4,19,21-23
therapy The IV formulation improves
Short-term treatment (up to 10 days) X X the systemic bioavailability of the
of GERD associated with a history of esomeprazole because the acidity of
erosive esophagitis in patients for the stomach and the upper duodenum
whom oral therapy is not possible is avoided. Thus, more drug is deliv-
or appropriate ered to the site of action during the
Treatment of pathologic X first few days of therapy.19,21
hypersecretory conditions associated Mean intragastric pH over a 24-
with Zollinger-Ellison syndrome or hour period was determined after 5
other neoplastic conditions days of IV esomeprazole, 20 mg, and
Treatment of acute peptic ulcer X* 40 mg once daily. The esomeprazole
bleeding following therapeutic was infused intravenously over 30
endoscopy minutes once daily. The percentage of
GERD, gastroesophageal reflux disease. time the gastric pH was 4 on day 5
*Pending. was 49.5% (95% confidence interval
[CI], 41.9-57.2) with esomeprazole,
E112 VOL. 9 NO. 4 2009 REVIEWS IN GASTROENTEROLOGICAL DISORDERS2. RIGD0349_12-31.qxd 12/31/09 3:28 PM Page E113
New Indication for IV Esomeprazole
20 mg, and 66.2% (95% CI, 62.4-70.0) doses. The higher dose used in the IV of that of IV esomeprazole.25
with esomeprazole, 40 mg.4 arm of the study may have had some Esomeprazole is 97% plasma protein
A comparison of oral and IV influence on the results observed bound. The apparent volume of distri-
esomeprazole on gastric acid suppres- within the first hour and not just the bution at steady-state is approximately
sion in patients with peptic ulcer dis- route of administration. 16 L.4
ease was conducted to evaluate the Esomeprazole is eliminated primar-
differences in pH control achieved Pharmacokinetics ily by hepatic metabolism via
with both routes of administration.24 In studies comparing the oral and CYP2C19 and CYP3A4, with the
Twenty patients were randomized to IV administration of esomeprazole, IV CYP2C19 pathway the predominant
receive either IV or oral esomeprazole administration was associated with a metabolite route.4,26 Less than 1% of
following their endoscopic examina- 2-fold higher peak concentration and the dose is excreted unchanged in the
tion. The IV group received IV
esomeprazole, 80 mg, followed by In studies comparing the oral and IV administration of esomeprazole, IV
8 mg/h for 24 hours, whereas the oral
administration was associated with a 2-fold higher peak concentration and
group received esomeprazole, 40 mg,
orally followed by a second 40-mg a 66% to 83% greater area under the plasma concentration-time curve
dose at 12 hours. Their gastric pH was compared with oral administration of the same single dose.
then monitored over the 24-hour
observation period. The pH study was a 66% to 83% greater area under the urine.4 The elimination half-life of
completed by 9 patients in the IV arm plasma concentration-time curve esomeprazole is 1.1 to 1.4 hours.4 Its
and 8 patients in the oral arm. The IV (AUC) compared with oral administra- metabolites are inactive.4
therapy was associated with a quicker tion of the same single dose. Polymorphism influences the rate of
onset of action and better achieve- Differences were similar, but slightly metabolism of esomeprazole via the
ment of pH levels above 4 and 6 with- less pronounced after repeated CYP2C19 isoenzyme pathway. Lack of
in the first hour of therapy and no daily administration for 5 days.25 this isoenzyme occurs in 3% of whites
differences in the intragastric acid Comparative pharmacokinetics after and 15% to 20% of the Asian popula-
profile during the subsequent 24-hour IV and oral administration of 20-mg tion. These individuals are classified
period. The results of this pH are sum- and 40-mg doses are summarized in as poor metabolizers and their AUC
marized in Table 2. The limitation of Table 3. The bioavailability of oral can be 2-fold higher than the exten-
this trial is the absence of comparable esomeprazole is approximately 78% sive metabolizers.4 The elimination
half-life is also increased with increas-
ing doses of esomeprazole.4
Table 2 The same recommendations for
Comparison of Intragastric Acid Profile Following Oral and IV dosage adjustments in special popu-
Administration of Esomeprazole in Patients with Peptic Ulcer Disease24 lations are suggested for both IV
and oral esomeprazole. With oral
Esomeprazole, Esomeprazole, esomeprazole, the AUC and peak con-
Parameter 40 mg (Oral) 80 mg (IV) P Value centration were increased slightly in
1st hour the elderly; however, dosage adjust-
ments based on age are not neces-
Intragastric pH (median) 1.5 3.7 .04
sary.4 The pharmacokinetics of oral
Percentage of time pH 4 0.1% 49% .04
and IV esomeprazole have not been
Time to achieve pH 4 (median) 102 min 25 min .01 studied in patients under age 18
Time to achieve pH 6 (median) 125 min 28 min .02 years.4 The AUC and peak concentra-
24 hours tion of esomeprazole were slightly
Intragastric pH (median) 6.2 6.6 —
increased in women compared with
men with both oral and IV adminis-
Percentage of time pH 4 85.4% 92.4% —
tration; however, dosage adjustment
Percentage of time pH 6 60.7% 91.2% — based on sex is not necessary.4
IV, intravenous. Because less than 1% of the esomepra-
zole dose is eliminated unchanged in
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New Indication for IV Esomeprazole continued
The target sample size for the study
Table 3 was 760 patients; this number was
Comparative Pharmacokinetics of IV and Oral Esomeprazole25 based on an estimated rebleed rate of
15% with placebo and 7% with
20 mg 40 mg esomeprazole. It was powered at 90%
IV Oral IV Oral for a 5% significance level and
allowed for 10% exclusion rate for
Cmax day 1 3.32 mol/L 0.78 mol/L 6.77 mol/L 2.97 mol/L protocol violations. The intent-to-
Cmax day 5 3.86 mol/L 1.57 mol/L 7.51 mol/L 4.6 mol/L treat (ITT) population consisted of all
AUC day 1 3.4 mol · h/L 1.86 mol · h/L 9.88 mol · h/L 5.94 mol · h/L patients who were enrolled and
AUC day 5 5.11 mol · h/L 3.92 mol · h/L 16.21 mol · h/L 12.55 mol · h/L received any part of an infusion of
T1/2 1.05 h 1.12 h 1.41 h 1.38 h esomeprazole or placebo. The per pro-
tocol population excluded patients
AUC, area under the curve; Cmax, maximum concentration; IV, intravenous; T1/2, elimination who discontinued the study early,
half-life.
subjects who received less than 70%
of the planned infusion doses, and
the urine, renal impairment is not of hospitalization following the endo- individuals with major deviations
expected to significantly affect the scopic treatment were similar in both from the protocol.28
pharmacokinetics of esomeprazole.4 groups.27 Patients were randomized to post-
The pharmacokinetics of oral The pivotal trial for the use of IV endoscopic prophylaxis with a bolus
esomeprazole were not altered in esomeprazole in the treatment of dose of the study drug followed by a
patients with mild to moderate PUB was a randomized, multicenter, maintenance infusion. The study
hepatic impairment (Child Pugh double-blind, placebo-controlled study. drug bolus (375 treated with placebo
Classes A and B). In patients with This study was conducted in 91 cen- and 389 treated with esomeprazole,
severe hepatic insufficiency (Child ters in 16 countries. It enrolled 767 80 mg) was administered as an
Pugh Class C), the AUC of esomepra- high-risk patients who had undergone IV infusion over 30 minutes. The
zole was 2- to 3-fold higher than endoscopic hemostasis for PUB. The maintenance infusion (placebo or
what is observed in subjects with nor- patients had to be older than age 18 esomeprazole, 8 mg/h) was initiated
mal hepatic function. In patients with years, have an upper gastrointestinal immediately after the bolus dose and
severe hepatic impairment (Child (GI) bleeding within the last 24 hours, continued for 71.5 hours. All patients
Pugh Class C), a dose of 20 mg once 1 endoscopically confirmed bleeding were then switched to oral therapy
daily should not be exceeded.4 gastric or duodenal ulcer 5 mm in with esomeprazole, 40 mg, once daily,
diameter, and successful hemostasis before breakfast, for 27 days.28
Clinical Efficacy following the endoscopic treatment. The primary endpoint was the inci-
A small pilot study was conducted in Patients were excluded for various dence of rebleeding from the peptic
China to evaluate the potential use of medical reasons associated with ulcer within the first 72 hours of ther-
oral esomeprazole for the prevention bleeding, GI abnormalities, major apy using the ITT population. If
of rebleed from a bleeding peptic cardiovascular event within the last 3 hematemesis occurred, the patient
ulcer following endoscopic treatment. months, or severe hepatic or renal underwent an endoscopic examina-
This study enrolled 70 patients with disease. They were also excluded if tion to confirm the source of the
bleeding peptic ulcers. The bleeding they had received an IV PPI within 24 bleeding. Rebleeding within 72 hours
was first handled with endoscopic hours of study enrollment or required of therapy initiation in the ITT popu-
treatment and the patients were then treatment with H2-receptor antago- lation was 5.9% in the IV esomepra-
randomized to receive oral esomepra- nists, sucralfate, prostaglandins, non- zole group, and 10.3% in the placebo
zole, 40 mg, or placebo twice daily for steroidal anti-inflammatory agents, group (P .026).30 This represented a
3 days. The primary endpoint was the aspirin, clopidogrel, somatostatin, 43% risk reduction for rebleeding and
incidence of rebleeding within 30 tranexamic acid, heparin, warfarin, the number needed to treat (NNT)
days. Rebleeding occurred in 5.7% of phenytoin, clarithromycin, itracona- with IV esomeprazole to avoid a
the esomeprazole group and 8.6% of zole, ketoconazole, cisapride, rebleed was 23.7. Rebleeding within
the placebo group (P .999). The atazanavir, or ritonavir during the 72 hours of therapy initiation in the
number of transfusions and duration first 7 days after study enrollment.28,29 per protocol population was 4.8% in
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New Indication for IV Esomeprazole
in the prevention of bleeding peptic
Table 4 ulcers postendoscopic treatment or
Secondary Endpoint From the IV Esomeprazole Versus Placebo information on the impact of convert-
Treatment of PUB (ITT Population)29,30 ing IV esomeprazole therapy to oral
esomeprazole earlier in the course of
Esomeprazole IV Placebo therapy in an attempt to decrease
Parameter (n 375) (n 389) P Value the duration of hospitalization.
Rebleed 7 days 7.2% 12.9% .0096 Several investigators have attempted
to evaluate the possible differences
Rebleed 30 days 7.7% 13.6% .0092
between IV and oral treatment with a
All-cause mortality 30 days 0.8% 2.1% .22 PPI when used as postendoscopic
Surgery 30 days 2.7% 5.4% .059 treatment in patients with acute non-
Endoscopic retreatment 30 days 6.4% 11.6% .012 variceal upper GI bleeding. A retro-
No. of blood units transfused 30 days 589 935 .034 spective evaluation conducted in
No. of days hospitalized due to rebleed Canada found no difference in the
30 days 284 500 .008 incidence of rebleeding, surgery, mor-
tality, readmission for upper GI bleed-
ITT, intent-to-treat; IV, intravenous; PUB, peptic ulcer bleeding. ing, and transfusions in patients
treated with IV and oral PPIs. The IV
PPI group received various agents via
the IV esomeprazole group, and prazole; the PPI used in the study was continuous infusion or intermittent
10.4% in the placebo group (P determined by the investigator based IV boluses, whereas the oral group
.0093).29,30 This represented a 54% on local availability. Patients admitted received at least 40 mg of omeprazole
risk reduction for rebleeding and the with overt GI bleeding, recent history per day or an equipotent dose of an
NNT with IV esomeprazole to avoid a ( 24 h before presentation) of alternative PPI. These authors believe
rebleed was 17.9. The results for the hematemesis and/or melena, or ulcer these results are suggestive that oral
secondary endpoints from this study hemorrhage beginning after hospital- therapy may be an effective alterna-
are summarized in Table 4. ization for an unrelated medical or tive to IV therapy.33
A decision-tree model was devel- surgical condition were eligible. They
oped with the data from this pivotal were then randomized to receive IV
Contraindications
study to determine the cost- treatment with either high- (n 243)
Use of any of the injectable PPIs is
effectiveness of IV esomeprazole in or low-dose (n 239) PPI therapy for
contraindicated in patients with
the follow-up treatment of PUB. The 72 hours postprocedure. The high-
known hypersensitivity to the drug,
model used a 30-day time horizon dose group was treated with an 80-mg
other substituted benzimidazoles (eg,
using a US third-party payor perspec- bolus of the PPI followed by 8 mg/h
omeprazole, pantoprazole, lansopra-
tive. The costs used in the model were as a continuous infusion for 72 hours;
zole, rabeprazole), or any of the
extracted from national US databases the low-dose group was treated with a
formulation ingredients.4-6
and expressed in 2007 American dol- 40-mg bolus daily followed by saline
lars. The estimated cost associated infusion for 72 hours. After 72 hours
with the esomeprazole therapy was both groups were converted to 20-mg Warnings and Precautions
$14,290 and the cost associated with oral therapy twice daily until dis- Treatment with the IV formulation
the placebo therapy was $14,240. charge. The primary endpoint was the should be discontinued as soon as the
Thus, the incremental cost-effective- occurrence of rebleeding during the patient is able to resume treatment
ness ratio was $913 per rebleed avert- hospitalization. Rebleeds occurred in with an oral esomeprazole.4
ed with the esomeprazole therapy.31 11.8% of the high-dose group and in Symptomatic response to therapy
Whether esomeprazole doses this 8.1% of the low-dose group (P .18). with any esomeprazole does not
high are necessary for all patients is Most of the rebleeds occurred within preclude the presence of gastric
unknown because dose-ranging stud- the first 72 hours (6.7% and 9.3%, malignancy.4
ies were not conducted. However, a respectively; P .32).32 The safety and effectiveness of any
high- versus low-dose study was con- There are no direct comparisons of of these PPIs has not been established
ducted using omeprazole and panto- the efficacy of oral and IV esomeprazole in pediatric patients.4
VOL. 9 NO. 4 2009 REVIEWS IN GASTROENTEROLOGICAL DISORDERS E1152. RIGD0349_12-31.qxd 12/31/09 3:28 PM Page E116
New Indication for IV Esomeprazole continued
Esomeprazole is a Pregnancy tional normalized ratio and pro- or appropriate.4 Treatment with the IV
Category B drug. Esomeprazole should thrombin time in patients receiving formulation should be discontinued
only be used during pregnancy if concomitant esomeprazole and war- as soon as the patient is able to
clearly needed.4 Esomeprazole excre- farin. Monitoring is recommended in resume treatment with an oral
tion in breast milk has not been patients receiving this combination.4 esomeprazole.4
assessed; however, omeprazole con- Esomeprazole may interfere The dose of esomeprazole used for
centrations have been measured in with CYP2C19. Administration of the treatment of PUB following ther-
breast milk following omeprazole ther- esomeprazole, 30 mg, with diazepam, apeutic endoscopy is 80-mg IV over
apy. Discontinuation of either nursing a CYP2C19 substrate, resulted in a 30 minutes followed by an IV infu-
or esomeprazole is recommended in 45% reduction in diazepam clearance sion of 8 mg/h for 71.5 hours.28-30
breastfeeding mothers due to the and increased diazepam plasma lev- Esomeprazole should not be admin-
potential risks of adverse effects.4 els. This drug interaction is not istered concomitantly with any other
believed to be clinically important.4 medications through the same site or
Adverse Reactions Concomitant administration with tubing. The line should always be
All PPIs are well tolerated.4 Common inhibitors of CYP2C19 and CYP3A4 flushed with either 0.9% Sodium
adverse effects associated with (eg, voriconazole) may cause a 2-fold Chloride Injection USP, Lactated
esomeprazole therapy include increase in the esomeprazole expo- Ringer’s Injection USP, or 5%
headache, flatulence, nausea, dyspep- sure. Dosage adjustments are not Dextrose Injection USP (Hospira, Inc.,
sia, and abdominal pain. required, but the prescriber may con- Lake Forest, IL) prior to and after
Reactions specific to the IV route sider adjustments in patients requir- administration of the esomeprazole.4
have included mild itching at the ing higher doses of esomeprazole.4 A dose of 20 mg should not be
injection site and mild focal erythema Concomitant use with atazanavir exceeded in patients with severe hepat-
at the IV insertion site. The incidence and nelfinavir is not recommended ic impairment (Child Pugh Class C).
and nature of adverse effects did not because the serum levels of these No dosage adjustments are necessary
appear to differ between oral and IV drugs may be decreased to ineffective in the elderly, patients with renal
administration.4,20 levels.4 Although concomitant use dysfunction, or based on sex.4
with saquinavir/ritonavir may be
Drug Interactions associated with elevated saquinavir Conclusions
Changes in pH may influence the levels and toxicity, a reduction in IV administration of esomeprazole is
absorption of some drugs from the saquinavir dose may be appropriate.4 a faster way to achieve gastric acid
stomach. PPIs may decrease the The pharmacokinetics of esomepra- suppression than oral administration
absorption of ketoconazole, ampi- zole were not altered by concomitant of the same agent. Peak suppression
cillin esters, and iron salts, and may administration of diazepam, pheny- following IV administration occurs
increase the absorption of benzyl toin, oral contraceptives, or quini- within hours compared with several
penicillin by raising the pH of the dine.4 Concomitant administration days following oral administration.
stomach.4 with naproxen or rofecoxib did not Thus, the IV administration route
Esomeprazole is extensively metab- result in changes in the pharmacoki- offers a faster onset of gastric sup-
olized in the liver via CYP2C19 and netics of esomeprazole or either of pression, achievement of intragastric
CYP3A4.4 the nonsteroidal anti-inflammatory pH closer to target levels, and better
Esomeprazole is not likely to drugs.4 bioavailability. Treatment of PUB is
inhibit CYPs 1A2, 2A6, 2C9, 2D6, the newest indication for the IV for-
2E1, or 3A4. Drug interactions are not Dosing mulation of esomeprazole. The drug is
anticipated with substrates of these The recommended dose of injectable effective in preventing rebleeds fol-
enzymes. Drug-interaction studies esomeprazole is 20 mg or 40 mg once lowing endoscopic treatment when
have shown that esomeprazole does daily by IV injection (no less than administered within 24 hours of the
not have any clinically important 3 min) or IV infusion (10-30 min) for procedure as an 80-mg bolus fol-
interactions with phenytoin, warfarin, the treatment of GERD patients with a lowed by an IV infusion for 72 hours.
quinidine, clarithromycin, or amoxi- history of erosive esophagitis as an What remains to be seen is whether
cillin. However, postmarketing reports alternative to oral therapy when use oral therapy can be substituted for all,
have described increases in interna- of the oral formulation is not possible or part, of the 72-hour IV infusion
E116 VOL. 9 NO. 4 2009 REVIEWS IN GASTROENTEROLOGICAL DISORDERS2. RIGD0349_12-31.qxd 12/31/09 3:28 PM Page E117
New Indication for IV Esomeprazole
and whether the patient can be dis- 6. Protonix® I.V. (pantoprazole sodium) for injec- bleeding peptic ulcer after successful endoscopic
tion [package insert]. Philadelphia, PA: Wyeth therapy. Arch Intern Med. 1998;158:54-58.
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February 10, 2009. omeprazole prevents rebleeding in patients with 2005;39:1667-1677.
Main Points
• The intravenous (IV) formulation of esomeprazole was approved in March 2005 for the short-term treatment of gastroesophageal
reflux disease (GERD) patients with a history of erosive esophagitis as an alternative when use of the oral formulation is not pos-
sible or not appropriate.
• The IV route of esomeprazole allows for the fastest onset of gastric suppression, achievement of intragastric pH closer to target
levels, and better bioavailability. The newest indication is for the treatment of peptic ulcer bleeding, and if approved, it will be the
only IV proton pump inhibitor approved for this indication.
• In a comparison study, the IV esomeprazole therapy was associated with a better onset of action and achievement of pH levels
above 4 and 6 within the first hour of therapy with no differences observed in the intragastric acid profile for the subsequent
24-hour period.
• The pivotal trial for IV esomeprazole use in the treatment of PUB was a randomized, multicenter, double-blind, placebo-controlled
study where the primary endpoint was the incidence of rebleeding from the peptic ulcer within the first 72 hours of therapy using
the intent-to-treat (ITT) population. Rebleeding within 72 hours of therapy initiation in the ITT population was 5.9% in the IV
esomeprazole group, and 10.3% in the placebo group—a 43% risk reduction for rebleeding and the number needed to treat (NNT)
with IV esomeprazole to avoid a rebleed was 23.7. Rebleeding within 72 hours of therapy initiation in the per protocol population
was 4.8% in the IV esomeprazole group, and 10.4% in the placebo group, representing a 54% risk reduction for rebleeding and
the NNT with IV esomeprazole to avoid a rebleed was 17.9.
• All proton pump inhibitors are well tolerated with the incidence and nature of adverse effects not appearing to differ between oral
and IV administration. Common adverse effects associated with esomeprazole include headache, flatulence, nausea, dyspepsia,
and abdominal pain. Reactions specific to the IV route include mild itching at the injection site and mild focal erythema at the IV
insertion site.
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New Indication for IV Esomeprazole continued
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agement of bleeding peptic ulcer. Dig Dis Sci. scopic treatment of bleeding peptic ulcers. J Finland.
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