Clin Drug Investig 2009; 29 Suppl.

2: 3-12
REVIEW ARTICLE 1173-2563/09/0002-0003/$49.95/0

ª 2009 Adis Data Information BV. All rights reserved.

Pantoprazole
A Proton Pump Inhibitor
Luis Moreira Dias
Médico Gastroenterologista, Porto, Portugal

Abstract Pantoprazole is a proton pump inhibitor (PPI) that binds irreversibly and
specifically to the proton pump, thereby reducing gastric acid secretion.
Pantoprazole has a relatively long duration of action compared with other
PPIs, and a lower propensity to become activated in slightly acidic body
compartments. To date, no drug-drug interactions have been identified with
pantoprazole in numerous interaction studies.
Overall, in the short-term (8–10 weeks) initial treatment of gastro-oeso-
phageal reflux disease (a condition that occurs when the reflux of gastric
contents causes troublesome symptoms and/or complications) and long-term
(6–24 months) maintenance therapy, oral pantoprazole 20 or 40 mg/day de-
monstrated similar efficacy to omeprazole, lansoprazole and esomeprazole
and greater efficacy than histamine type 2 receptor antagonists. Pantoprazole
is also effective in treating and preventing NSAID-related gastric and gas-
troduodenal injury. The optimal adult oral dose for gastric acid-related
disorders is pantoprazole 40 mg once daily. Although data are limited, panto-
prazole 20 or 40 mg/day was effective and well tolerated in the treatment of
acid-related disorders in children and adolescents. Pantoprazole was also well
tolerated in adults with acid-related disorders in short- and long-term studies.
Thus, pantoprazole is a valuable agent for the management of acid-related
disorders.

Proton pump inhibitors (PPIs) are the most
effective drug class available for the treatment of
gastric acid-related disorders. They have a well
established role in the symptomatic relief and
healing of acute gastro-oesophageal reflux dis-
ease (GORD, defined as a condition that occurs
when the reflux of gastric contents causes trou-
blesome symptoms and/or complications),[1] in
symptomatic control of non-erosive reflux dis-
ease (NERD; endoscopy-negative reflux disease),
and in the long-term maintenance of oesophageal
healing and symptom relief.[2-4] PPIs are also ef-
fective in the management of NSAID-related
gastrointestinal complications.[2,4]
Five PPIs are currently available for the man-
agement of gastro-oesophageal disorders. Ome-
prazole was the first to be introduced in Europe
in 1989, followed by pantoprazole (1994), lanso-
prazole (1994), rabeprazole (1998) and esome-
prazole (2000). All PPIs are highly effective in
providing healing and symptomatic relief in acid-
related upper gastrointestinal disorders, and
while there are some differences in their phar-
macological properties, these have not con-
sistently translated into significant therapeutic
advantages in clinical studies.[2-5]
Cochrane Database comprehensive systematic
reviews have shown that PPIs as a class are more
4 Moreira Dias
effective than histamine type 2 receptor antago-
nists (H2RAs) [e.g. ranitidine] and prokinetic
agents (e.g. metoclopramide) in controlling the
symptoms of GORD and NERD and healing the
lesions of reflux oesophagitis.[6,7] Furthermore,
these agents are more effective than standard-dose
H2RAs and better tolerated than misoprostol in
preventing NSAID-induced endoscopic gastro-
duodenal ulcers.[8] The greater relative efficacy of
PPIs is directly related to their potent, specific
and prolonged gastric acid suppression.[2,3]
This review summarizes the current role of
pantoprazole in the treatment and management
of upper gastrointestinal syndromes and dis-
orders.
1. Pharmacological Characteristics
Pantoprazole suppresses gastric acid secretion
via inhibition of the proton pump (H+,K+-AT-
Pase) in gastric parietal cells.[9] Like other PPIs,
pantoprazole is a prodrug and is activated and
accumulates in an acid environment. In neutral to
moderately acidic conditions in vitro, pantopra-
zole was more stable than omeprazole, lansopra-
zole or rabeprazole, suggesting that it is less likely
to accumulate or become activated in moderately
acidic body compartments (such as lysosomes).[10]
Because pantoprazole binds specifically and ir-
reversibly in vitro to a region of the proton pump
that is crucial for ATPase activity and acid
transport, it is thought that this agent may have a
longer duration of activity than other PPIs.[11]
In adults, adolescents and children, the extent
of gastric acid inhibition is similar with oral or
intravenous pantoprazole,[9,12] and optimal ac-
tivity is achieved after morning administration.[9]
In randomized, crossover trials in healthy vo-
lunteers, acid inhibition after repeated adminis-
tration of pantoprazole 40 mg/day was greater
than that with H2RAs or omeprazole 20 mg/day,
similar to that with omeprazole 40 mg/day, and
lower than or similar to that with esomeprazole
40 mg/day or lansoprazole 30 mg/day.[9]
Oral pantoprazole is rapidly absorbed,
with absolute bioavailability of 77%, and does
not accumulate after repeated administration.[9]
Pantoprazole is completely metabolized by the
ª 2009 Adis Data Information BV. All rights reserved.
cytochrome P450 (CYP) isoenzymes to inactive
metabolites. The main CYP isoenzymes involved
are CYP2C19, which exhibits polymorphism,
and CYP3A4. Metabolism is not dependent on
the route of administration. The metabolites are
eliminated primarily via the kidneys, with <20%
excreted in the faeces. Although the plasma
elimination half-life (t½) is relatively short (»1
hour), pantoprazole has a relatively long dura-
tion of acid inhibition because of the irreversible
and specific proton pump binding.[9]
The pharmacokinetic parameters of panto-
prazole are not altered to a clinically significant
extent when it is administered to elderly patients
or to those with severe renal impairment; thus,
dosage adjustments are not required in these pa-
tients.[9] In patients with moderate to severe he-
patic impairment, the pantoprazole area under
the concentration-time curve, maximum serum
concentration and t½ are increased compared
with those in healthy individuals, but drug accu-
mulation does not result and dosage reduction is
not usually required.[13]
In children, pharmacokinetic parameters with
pantoprazole were generally similar to those of
adults, although, as with other PPIs, the apparent
clearance appears faster.[14] In a single-dose
pharmacokinetics study in children aged 2–16 years,


the apparent clearance of oral pantoprazole


was 0.26 – 0.20 L/h kg-1,[12] compared with
0.1 L/h kg-1 in adults.[9] This may account for
the variable and sometimes larger per-kilogram dos-
ages required in children compared with adults to
achieve similar plasma concentrations.[14] Spe-
cific data for pantoprazole in infants are limited,
but there is some evidence to suggest reduced
metabolism of PPIs in neonates.[14]
2. Drug Interactions
Overall, few clinically significant drug inter-
actions have been reported for PPIs, and none
have been reported with pantoprazole.[15-20]
However, because of the long-term treatment
often required with these agents, it is important to
understand the mechanisms for drug interactions
with PPIs and coadministered agents. All PPIs
Clin Drug Investig 2009; 29 Suppl. 2
Pantoprazole: A Proton Pump Inhibitor
increase intragastric pH and, therefore, may af-
fect the absorption of drugs that are dependent
on gastric pH (e.g. ketoconazole). Drug absorp-
tion and metabolism can also be affected by PPI
interaction with the ATPase-dependent efflux
transporter P-glycoprotein (e.g. digoxin), or with
the CYP enzyme system (e.g. diazepam), which
can lead to interference with first-pass metabo-
lism and hepatic clearance.[21]
While all PPIs have the potential for drug in-
teractions, particularly with higher dosages, the
drug-drug interaction profiles of the individual
agents differ.[21] Most reports of drug interac-
tions with PPIs have involved omeprazole, which
appears to have a greater interaction with
CYP2C19 than other PPIs.[3,21] In contrast, the
potential for pantoprazole to interact with other
agents appears to be lower. Similarly, limited
evidence suggests that there is a lower potential
for drug interactions with agents coadministered
with rabeprazole or lansoprazole than with
omeprazole.[21]
In numerous in vivo drug interaction studies,
the pharmacokinetics of pantoprazole and those
of the coadministered agent were not significantly
affected.[13] These studies included CYP2C19
substrates (e.g. diazepam and phenytoin),
CYP3A4 substrates (e.g. nifedipine, midazolam
and clarithromycin), a CYP2D6 substrate (me-
toprolol), CYP2C9 substrates (diclofenac, na-
proxen and piroxicam) and a CYP1A2 substrate
(theophylline). Furthermore, no clinically re-
levant interactions have been observed when
pantoprazole is coadministered with amoxicillin,
antacids, antipyrine, caffeine, carbamazepine,
cinacalcet, cisapride, ciclosporin, diazepam, di-
clofenac, ethanol, glibenclamide, levothyroxine
sodium, metronidazole, oral contraceptives, phena-
zone, phenprocoumon, tacrolimus or warfarin.[9,21]
3. Management of Gastro-oesophageal
Reflux Disease
3.1 Initial Healing Efficacy
PPIs are now well established as the most ef-
fective acid antisecretory agents available, pro-
viding more rapid symptom control and better
ª 2009 Adis Data Information BV. All rights reserved.
5
healing of erosive oesophagitis than H2RAs or
antacids.[22,23] As a result, treatment guidelines
recommend their use for first-line treatment of
GORD.[23] A recent review of all PPIs in patients
with GORD reported that after 8 weeks of ther-
apy, complete relief of symptoms was achieved in
65–75% of patients and endoscopic healing was
achieved in approximately 85–90%, with no sub-
stantial difference in healing rates among differ-
ent PPIs.[2]
In well designed clinical trials comparing
pantoprazole 40 mg/day with omeprazole 40 mg/
day, esomeprazole 40 mg/day or lansoprazole
30 mg/day (pantoprazole has not been compared
directly with rabeprazole) in the initial manage-
ment of GORD of varying grades of severity, the
healing rate (generally defined as the complete
epithelialization or resolution of lesions as con-
firmed by endoscopy) after 8–12 weeks of treat-
ment ranged from 90% to 97% (table I).[24-29]
Where reported, relief of symptoms (heartburn,
acid regurgitation and dysphagia) after 4 weeks
of treatment was achieved in 46–88% of patients.
Efficacy results were generally not significantly
different between PPIs, except in one study,
which reported better efficacy with esomeprazole
than with pantoprazole[27] (table I). In this large
study, subgroup analyses based on baseline
severity of erosive oesophagitis indicated that
esomeprazole may have greater relative effi-
cacy than pantoprazole in patients with more se-
vere disease, but similar efficacy in less severe
disease.[27]
Where reported, the time to resolution of
heartburn and other symptoms did not differ
significantly between treatment groups.[25,28]
However, in one study of patients with GORD
stage A–D (LA classification), symptom resolu-
tion was faster with esomeprazole 40 mg/day
(6 days) than with pantoprazole 40 mg/day (8 days)
[p < 0.001].[27] In contrast, another study of pa-
tients with GORD stage B/C reported a faster
time to the relief of GORD symptoms with pan-
toprazole 40 mg/day (3.7 days) than with esome-
prazole 40 mg/day (5.9 days) [p < 0.05].[32]
Two 4-week studies (n = 217[32] and n = 561[33])
that compared once-daily pantoprazole 40 mg
with esomeprazole 40 mg primarily based on
Clin Drug Investig 2009; 29 Suppl. 2
6 Moreira Dias

Table I. Efficacy of pantoprazole (PAN) compared with other proton pump inhibitors in the initial treatment of gastro-oesophageal reflux
disease (GORD). Results are from randomized, double-blind,[24-27] or nonblind,[28] multicentre trials and are based on per-protocol analyses,
unless stated otherwise. GORD severity was measured at baseline according to Savary-Miller[25,26,28] or Los Angeles[24,27] systems
Study (duration) GORD severitya Dosage (mg od) No. of pts Healing rate (% of pts) Symptom relief rate (% of pts)b
4 wk endpoint 4 wk
Comparisons with ESO
Bardhan et al.[24]c (12 wk) A–D PAN 40 204 69 98 76
ESO 40 214 69 94 78
Gillessen et al.[26] (10 wk) B/C PAN 40 94 58 91 46
ESO 40 103 66 97 46
Labenz et al.[27]d (8 wk) A–D PAN 40 1562 75 92 NR
ESO 40 1589 81* 96* NR
Comparison with LAN
Dupas et al.[28] (8 wk) II–III PAN 40 187 86 97 88
LAN 30 198 86 93 86
Comparisons with OME
Bardhan et al.[25] (8 wk) I PAN 20 133 84 90 77
OME 20 131 89 95 84
Körner et al.[29] (8 wk) II/III PAN 40 282 71 NR NR
OME 40 270 73 NR NR
a Savary-Miller classification (from Nayar and Vaezi[30]): I (single erosive lesion, oval or linear, affecting 1 longitudinal fold); II (multiple
erosive lesions, non-circumferential, affecting >1 longitudinal fold, with or without confluence); III (circumferential erosive lesions). Los
Angeles classification[31]: A (‡1 mucosal breaks £5 mm long, that does not extend between the tops of 2 mucosal folds); B (‡1 mucosal
breaks >5 mm long, that does not extend between the tops of 2 mucosal folds); C (mucosal breaks that are continuous between the tops of
‡2 mucosal folds but which involve <75% of the oesophageal circumference); D (mucosal breaks which involve ‡75% of the oesophageal
circumference).
b Main symptoms were heartburn, acid regurgitation and dysphagia.
c The primary endpoint in this noninferiority study was the complete remission rate, which was defined as the percentage of pts
with endoscopically confirmed healing and relief from GORD-related symptoms at endpoint (93% for PAN and 90% for ESO). PAN
was noninferior to ESO based on the lower limit of the 97.5% CI of the 12-week treatment difference in pts with healed reflux oesophagitis
(-2.9, ¥) being between -15% and 0%.[24]
d Results are shown for the primary analysis in the intent-to-treat population.
ESO = esomeprazole; LAN = lansoprazole; NR = not reported; od = once daily; OME = omeprazole; pts = patients; * p < 0.001 vs comparator.

patient symptom assessment using diaries re-
ported similar efficacy[32] or noninferiority of
pantoprazole.[33]
Overall, GORD healing rates and symptom
relief appear to be dependent on baseline sever-
ity[28,27] and patient compliance with PPI treat-
ment,[29] and not on the PPI agent selected.
3.2 Long-Term Maintenance of Remission
Although initial PPI treatment is highly effec-
tive in achieving healing and relieving the symp-
toms of GORD, relapse often follows treatment
withdrawal.[23] In fact, in patients with more se-
vere disease (LA grades C and D), almost 80% of
patients will relapse if therapy is discontinued.[2]
Therefore, PPI maintenance therapy is recom-
mended to ensure that lesions remain healed
and symptoms are controlled and to prevent the
development of complications.[23] Furthermore,
clinical studies indicate that full healing dos-
ages of PPIs achieve greater efficacy than re-
duced dosages in the long-term management of
GORD.[34]
In well designed clinical trials, maintenance
therapy with pantoprazole 20 or 40 mg/day ef-
fectively prevented relapse of GORD for 6–24
months in the majority of patients with healed
disease (table II).[27,28,35-42] In 12-month dose

ª 2009 Adis Data Information BV. All rights reserved. Clin Drug Investig 2009; 29 Suppl. 2
Pantoprazole: A Proton Pump Inhibitor 7

comparison studies (n = 396[35] and n = 433[38]),
the difference in efficacy, as measured by the endo-
scopic relapse rate, was generally not significantly
different with pantoprazole 20 or 40 mg/day, but
in one study, pantoprazole 40 mg/day prevented
endoscopic relapse more effectively than panto-
prazole 20 mg/day (p < 0.05).[35]
Studies comparing the efficacy of pantopra-
zole with other PPIs as maintenance therapy in
patients with healed reflux oesophagitis are lim-
ited. However, conflicting results were shown in
two large (n = 1303[36] and n = 2766[27]) studies
that compared pantoprazole with esomeprazole.
One study found esomeprazole 20 mg/day to be
superior to pantoprazole 20 mg/day (87.0% vs
74.9% of patients remained in endoscopic and
symptomatic remission; p < 0.001),[27] while the
other found these agents to have similar efficacy
(85% vs 84% of patients remained in endoscopic
and symptomatic remission).[36]
As in the healing studies, PPIs are more effec-
tive in the maintenance of remission of erosive
oesophagitis than H2RAs.[23] In two randomized,
double-blind trials (n = 371[37] and n = 349[39]),
pantoprazole 20 or 40 mg/day was significantly
more effective than ranitidine 150 mg twice daily
in the maintenance of GORD healing after
12 months of treatment (p < 0.001 for both trials).
Furthermore, healing was maintained with pan-
toprazole regardless of the initial severity of
GORD.[39] In both of these trials, pantoprazole
40 mg once daily was found to be the optimal
maintenance dosage.[37,39]
4. Management of NSAID-Related
Gastrointestinal Toxicity
The association between NSAIDs and upper
gastrointestinal injury, including peptic ulceration,
is well established.[43] Similarly, the contribution

Table II. Efficacy of pantoprazole (PAN) for the maintenance of healing after initial treatment of gastro-oesophageal reflux disease. Results
are from randomized, double-blind,[27,35-39] or open-label trials[40,41]
Study (duration) Dosage (mg/day) No. of pts Remission rate (% of pts)
Noncomparative
Escourrou et al.[35] (12 mo) PAN 20 203 71
PAN 40 193 81
Mossner et al.[40] (12 mo) PAN 40 222 94a
Plein et al.[38] (12 mo) PAN 20 221 75
PAN 40 212 78
Van Rensburg et al.[41] (24 mo) PAN 40 157 76
Comparisons with ESO
Labenz et al.[27] (6 mo) PAN 20 1389 74.9
ESO 20 1377 87.0**
Goh et al.[36] (6 mo) PAN 20 636 84
ESO 20 667 85
Comparisons with RAN
Metz and Bochenek[37] (12 mo) PAN 10 89 40**
PAN 20 93 68**
PAN 40 94 82**
RAN 300 95 33
Richter et al.[39] (12 mo) PAN 10 88 46*
PAN 20 88 55**
PAN 40 85 78**
RAN 300 88 21
a Estimated rate (Kaplan-Meier survival analysis).
ESO = esomeprazole; pts = patients; RAN = ranitidine; * p < 0.01, ** p < 0.001 vs comparator.

ª 2009 Adis Data Information BV. All rights reserved. Clin Drug Investig 2009; 29 Suppl. 2
8 Moreira Dias
of gastric acid to NSAID-related injury makes
the use of acid-suppressing agents a rational ap-
proach to the management of NSAID-induced
gastrointestinal toxicity.[43] Both traditional
NSAIDs and selective cyclo-oxygenase (COX)-2
inhibitors (coxibs) increase the risk of gastro-
intestinal complications, with concomitant use
of aspirin further increasing gastrointestinal
toxicity.[44]
PPIs are very effective in treating NSAID-re-
lated complications, including healing gastric and
duodenal ulcers, and in reducing ulcer recurrence
in NSAID users.[4] They are more effective than
H2RAs and better tolerated than misoprostol
and, thus, are considered the treatment of choice
in short- and long-term prevention of NSAID-
related mucosal lesions.[4,8,43] Furthermore, PPIs
appear to be more effective than misoprostol in
preventing duodenal ulcers, although mis-
oprostol is slightly more effective than PPIs at
preventing gastric ulcers.[4,8]
When pantoprazole was compared with pla-
cebo in a randomized, double-blind, 12-week trial
in patients with osteoarthritis or rheumatoid ar-
thritis without severe lesions (Lanza grade 0–2)
who continued receiving NSAIDs, the prob-
ability of remaining ulcer free was 72% in the
pantoprazole 40 mg/day group (n = 65) compared
with 59% in the placebo group (n = 30) [life-table
analysis; difference did not reach significance].[45]
In a subgroup analysis of those with normal
gastroduodenal mucosa at baseline (Lanza grade
0; n = 66), the cumulative rate of being free from
peptic ulcers in the respective treatment groups
was 82% versus 55% (p < 0.05).[45]
Few studies have compared pantoprazole with
other PPIs in the management of NSAID-related
gastrointestinal toxicity, but in one randomized,
double-blind study in rheumatic patients con-
tinuing to receive NSAIDs with no more than a
moderate level of severity of gastrointestinal
symptoms, efficacy with pantoprazole 20 (n = 196)
or 40 mg/day (n = 199) or omeprazole 20 mg/day
(n = 200) was similar.[46] After 6 months of treat-
ment, the probability of remaining in remission
without therapeutic failure (calculated by life-
table analysis) was 90%, 93% and 89%, respec-
tively (figure 1).[46]
ª 2009 Adis Data Information BV. All rights reserved.
PAN 20 mg od
PAN 40 mg od
OME 20 mg od
100
90
80
Patients in remission (%)
70
60
50
40
30
20
10
0
3 months 6 months
Fig. 1. The proportion of rheumatic patients remaining in remission
after 3 or 6 months of treatment with pantoprazole (PAN) 20 or 40 mg
once daily (od) or omeprazole (OME) 20 mg od. Results are from a
randomized, double-blind study in patients (n = 505) receiving con-
tinuous NSAID therapy with no more than a moderate level of se-
verity of gastrointestinal symptoms at baseline.[46]
These results are consistent with those reported
in a review of PPIs, which found that in short-term
studies of up to 1 month, PPIs protect between
89% and 100% of patients against NSAID-
induced erosions, and in long-term studies of
3 months or longer, PPIs significantly reduced
overall ulcer rates and provided effective protec-
tion in patients receiving NSAIDs.[4]
Pantoprazole 20 mg once daily was more ef-
fective than misoprostol 200 mg twice daily in
preventing therapeutic failure and endoscopic
failure in rheumatic patients (n = 515) receiving
NSAIDs in a randomized, double-blind, multi-
centre, 6-month study.[47] Estimated remission
rates at 6 months (Kaplan Meier life-table ana-
lysis) were 89% with pantoprazole compared with
70% with misoprostol (p < 0.01).[47]
5. Role of Pantoprazole in Paediatric
Gastro-oesophageal Reflux Disease
Although GORD is a common condition in
children, of the five PPIs currently marketed in
Europe, only omeprazole has a formal indication
for paediatric use in children aged 2 years or
Clin Drug Investig 2009; 29 Suppl. 2
Pantoprazole: A Proton Pump Inhibitor 9

older. However, the off-label or unlicensed use of mean composite symptom score improved sig-
other PPIs is widespread, and it has been sug- nificantly from baseline after 8 weeks of treat-
gested that existing clinical evidence for this drug ment with pantoprazole 20 or 40 mg once daily
class is sufficient to justify extending PPI use in (p < 0.001 in both groups).[52] Furthermore, pan-
paediatric patients not currently covered by a toprazole 20 mg once daily effectively reduced
formal indication.[48] intra-oesophageal and intragastric acid (p < 0.01)
Although limited data are available compar- and improved symptoms after 28 days of treat-
ing the efficacy of different PPIs in children, evi- ment in a small nonblind study in 15 children
dence suggests that these agents are highly effec- aged 6–13 years with endoscopically confirmed reflux
tive and well tolerated.[49] However, long-term oesophagitis.[50] Endoscopically confirmed heal-
tolerability studies are needed, particularly if ing was achieved in 47% of patients by day 28.[50]
prolonged treatment is indicated where child-
hood reflux disorders continue into adulthood. 6. Safety and Tolerability
In clinical studies in children and adolescents
with GORD, oral pantoprazole was effective and PPIs are generally well tolerated with few ad-
well tolerated.[50-52] In 53 children aged 5–11 verse events. The most common adverse events
years, pantoprazole 10, 20 or 40 mg once daily associated with this class of agent include head-
effectively improved endoscopically proven ache, nausea, diarrhoea, abdominal pain, fatigue
symptomatic GORD compared with baseline and dizziness,[2,3,53] and these events occur with a
(p < 0.001 for each treatment group) in a rando- similar frequency with each agent.[53] The long-
mized, double-blind, multicentre study.[51] The term tolerability of PPIs has been established
mean composite symptom score improved sig- with over 15 years’ experience with omeprazole.[2]
nificantly throughout 8 weeks of treatment, and Early concerns about an increased risk of gas-
in the pantoprazole 20 and 40 mg/day groups, tric cancer with prolonged PPI use have not ma-
improvement in symptoms was evident as early as terialized, although ongoing debate continues
week 1.[51] In a similarly designed trial in adoles- regarding the possible effects of chronic hypo-
cents (n = 136) aged 12–16 years with GORD, the chlorhydria and gastric atrophy.[3]

0.20
0.18
0.16
Incidence (% of patients)

0.14
0.12
0.10
0.08
0.06
0.04
0.02
0
a

ed

ng

ss

de

in

ce

ed

ce
oe

in

as

io

pa
e

en

an
ifi

iti

itu

ifi
ra

ns
in

R
rrh

om

c
ss

al

ul

r
ig
pe

pe
te

le
iz
ia

in

at
/m

/la
v

to
ns

ns
D
D

a/

di

Fl
he

In
se
U

Iu
se

do
al
ac

ai

in
au

G
Ab
al
d

m
N

ea

do
H

Ab

Fig 2. Tolerability profile of pantoprazole. Incidence of the most common adverse events reported (107 events in 80 patients) in a pharma-
covigilance surveillance study of 11 541 patients treated with pantoprazole in general practice (most patients had oesophageal reflux or
dyspepsia).[54] GI = gastrointestinal.

ª 2009 Adis Data Information BV. All rights reserved. Clin Drug Investig 2009; 29 Suppl. 2
10
Pantoprazole has been well tolerated in clin-
ical trials of up to 4 years’ duration.[9] In short-
term (£8-week) trials for the initial treatment of
GORD, oral pantoprazole 40 mg/day was as well
tolerated as omeprazole 20 mg/day, lansoprazole
30 mg/day or ranitidine 300 mg/day.[9] Adverse
events associated with pantoprazole 40 mg/day in
a 12-month study included diarrhoea (4.5%),
nausea (2.7%), vomiting (2.3%) and dizziness
(1.8%).[9]
Data from a postmarketing surveillance study
including 11 541 patients in the UK further sup-
port the generally favourable tolerability profile
of pantoprazole.[54] Overall, 107 adverse events
(i.e. <1%) in 80 patients were reported by general
practitioners as being attributable to pantopra-
zole. A summary of these results is illustrated in
figure 2.[54]
7. Conclusions
Pantoprazole is a PPI that effectively inhibits
gastric acid secretion in adults, adolescents and
children. Comparisons of the various PPIs in
pharmacodynamics and pharmacokinetics studies
have demonstrated only minor differences of ques-
tionable clinical significance. The main differences
associated with pantoprazole are its irreversible and
specific proton pump binding leading to greater
bioavailability and longer duration of action than
other PPIs. In addition, pantoprazole is more stable
in neutral to moderately acidic conditions than
omeprazole, lansoprazole or rabeprazole, suggest-
ing a lower propensity to become activated in
slightly acidic body compartments. To date, no
drug-drug interactions have occurred with panto-
prazole, which is an important consideration for
elderly patients, who are often taking several drugs.
Overall in clinical trials, pantoprazole has shown
similar efficacy to other PPIs and greater efficacy
than H2RAs in the initial healing of oesophagitis
and relief of associated symptoms and in the long-
term maintenance therapy of healed GORD. Pan-
toprazole is also very effective in treating and pre-
venting NSAID-related gastroduodenal injury.
The optimal adult oral dose for gastric acid-related
disorders is pantoprazole 40 mg once daily. Limited
ª 2009 Adis Data Information BV. All rights reserved.
Moreira Dias
data also suggest that pantoprazole is effective and
well tolerated in treating gastric acid-related dis-
orders in children and adolescents.
Substantial evidence from clinical studies and
postmarketing surveillance studies has demon-
strated that pantoprazole is well tolerated in
adults when used for initial short-term treatment
and long-term maintenance of GORD. Thus,
pantoprazole is a valuable agent for the man-
agement of gastric acid-related disorders.
Acknowledgements
Funding for the preparation of this manuscript was pro-
vided by Tecnimede Portugal. Medical writing assistance was
provided by Ray Hill and Kate McKeage of Wolters Kluwer.
The author reports no conflicts of interest and did not receive
any funding for this paper.
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Correspondence: Dr Luis Moreira Dias, Rua Conde Campo
Belo, 105-3G, 4200-603, Porto, Portugal.
E-mail: l.md@clix.pt
Clin Drug Investig 2009; 29 Suppl. 2