PANTOL is indicated for use in adults and adolescents 12 years of age and above for:
• Symptomatic gastro-oesophageal reflux disease.
• Long-term management and prevention of relapse in reflux oesophagitis.
PANTOL is indicated for use in adults for:
• Prevention of gastroduodenal ulcers induced by non-selective non-steroidal anti-inflammatory
drugs (NSAIDs) in patients at risk with a need for continuous NSAID treatment (see section 4.4).

Posology
Adults and adolescents 12 years of age and above
Symptomatic gastro-oesophageal reflux disease
The recommended oral dose is one PANTOL 20 mg tablet per day. Symptom relief is generally
accomplished within 2-4 weeks. If this is not sufficient, symptom relief will normally be
achieved within a further 4 weeks. When symptom relief has been achieved, reoccurring
symptoms can be controlled using an on-demand regimen of 20 mg once daily, taking one tablet
when required. A switch to continuous therapy may be considered in case satisfactory symptom
control cannot be maintained with on-demand treatment.
Long-term management and prevention of relapse in reflux oesophagitis
For long-term management, a maintenance dose of one PANTOL 20 mg tablet per day is
recommended, increasing to 40 mg pantoprazole per day if a relapse occurs. PANTOL 40 mg

tablet is available for this case. After healing of the relapse the dose can be reduced again to
PANTOL 20 mg tablet.
Adults
Prevention of gastroduodenal ulcers induced by non-selective non-steroidal anti-inflammatory
drugs (NSAIDs) in patients at risk with a need for continuous NSAID treatment
The recommended oral dose is one PANTOL 20 mg tablet per day.
Patients with hepatic impairment
A daily dose of 20 mg pantoprazole should not be exceeded in patients with severe liver
impairment (see section 4.4).
Patients with renal impairment
No dose adjustment is necessary in patients with impaired renal function (see section 5.2).
Older people
No dose adjustment is necessary in older people (see section 5.2).
Paediatric population
PANTOL is not recommended for use in children below 12 years of age because of limited data
on safety and efficacy in this age group (see section 5.2).
Method of administration
Oral use
The tablets should not be chewed or crushed, and should be swallowed whole 1 hour before a
meal with some water.

Hepatic impairment
In patients with severe liver impairment the liver enzymes should be monitored regularly during
treatment with pantoprazole, particularly on long-term use. In the case of a rise of the liver
enzymes the treatment should be discontinued (see section 4.2).
Co-administration with NSAIDs
The use of PANTOL 20 mg as a preventive of gastroduodenal ulcers induced by non-selective
non-steroidal anti-inflammatory drugs (NSAIDs) should be restricted to patients who require
continued NSAID treatment and have an increased risk to develop gastrointestinal complications.

The increased risk should be assessed according to individual risk factors, e.g. high age (>65
years), history of gastric or duodenal ulcer or upper gastrointestinal bleeding.
Gastric malignancy
Symptomatic response to pantoprazole may mask the symptoms of gastric malignancy and may
delay diagnosis. In the presence of any alarm symptom (e.g. significant unintentional weight
loss, recurrent vomiting, dysphagia, haematemesis, anaemia or melaena) and when gastric ulcer
is suspected or present, malignancy should be excluded.
Further investigation is to be considered if symptoms persist despite adequate treatment.
Co-administration with HIV protease inhibitors
Co-administration of pantoprazole is not recommended with HIV protease inhibitors for which
absorption is dependent on acidic intragastric pH such as atazanavir, due to significant reduction
in their bioavailability (see section 4.5).
Influence on vitamin B12 absorption
PANTOL, as all acid-blocking medicines, may reduce the absorption of vitamin B12
(cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with
reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy or if
respective clinical symptoms are observed.
Long term treatment
In long-term treatment, especially when exceeding a treatment period of 1 year, patients should
be kept under regular surveillance.
Gastrointestinal infections caused by bacteria
Treatment with PANTOL may lead to a slightly increased risk of gastrointestinal infections
caused by bacteria such as Salmonella and Campylobacter or C. difficile.
Hypomagnesaemia
Severe hypomagnesaemia has been reported in patients treated with PPIs like pantoprazole for at
least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia
such as fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmia can occur
but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia
improved after magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with digoxin or medicinal
products that may cause hypomagnesaemia (e.g. diuretics), health care professionals should
consider measuring magnesium levels before starting PPI treatment and periodically during
treatment.
Bone fractures
Proton pump inhibitors, especially if used in high doses and over long durations (>1 year), may
modestly increase the risk of hip, wrist and spine fracture, predominantly in older people or in
presence of other recognised risk factors. Observational studies suggest that proton pump
inhibitors may increase the overall risk of fracture by 10–40%. Some of this increase may be due

to other risk factors. Patients at risk of osteoporosis should receive care according to current
clinical guidelines and they should have an adequate intake of vitamin D and calcium.
Subacute cutaneous lupus erythematosus (SCLE)
Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions occur,
especially in sun exposed areas of the skin, and if accompanied by arthralgia, the patient should
seek medical help promptly and the healthcare professional should consider stopping PANTOL.
SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with
other proton pump inhibitors.
Interference with Laboratory Tests
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine
tumours. To avoid this interference, PANTOL treatment should be stopped for at least 5 days
before CgA measurements (see section 5.1). If CgA and gastrin levels have not returned to
reference range after initial measurement, measurements should be repeated 14 days after
cessation of proton pump inhibitor treatment.

Medicinal products with pH-Dependent Absorption Pharmacokinetics
Because of profound and long lasting inhibition of gastric acid secretion, pantoprazole may
interfere with the absorption of other medicinal products where gastric pH is an important
determinant of oral availability, e.g. some azole antifungals such as ketoconazole, itraconazole,
posaconazole and other medicines such as erlotinib.
HIV protease inhibitors)
Co-administration of pantoprazole is not recommended with HIV protease inhibitors for which
absorption is dependent on acidic intragastric pH such as atazanavir due to significant reduction
in their bioavailability (see section 4.4).
If the combination of HIV protease inhibitors with a proton pump inhibitor is judged
unavoidable, close clinical monitoring (e.g virus load) is recommended. A pantoprazole dose of
20 mg per day should not be exceeded. Dosage of the HIV protease inhibitor may need to be
adjusted
Coumarin anticoagulants (phenprocoumon or warfarin)
Co-administration of pantoprazole with warfarin or phenprocoumon did not affect the
pharmacokinetics of warfarin, phenprocoumon or INR. However, there have been reports of
increased INR and prothrombin time in patients receiving PPIs and warfarin or phenprocoumon
concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding, and even
death. Patients treated with pantoprazole and warfarin or phenprocoumon may need to be
monitored for increase in INR and prothrombin time.
Methotrexate

Concomitant use of high dose methotrexate (e.g. 300 mg) and proton -pump inhibitors has been
reported to increase methotrexate levels in some patients. Therefore in settings where high-dose
methotrexate is used, for example cancer and psoriasis, a temporary withdrawal of pantoprazole
may need to be considered.
Other interactions studies
PANTOL is extensively metabolized in the liver via the cytochrome P450 enzyme system. The
main metabolic pathway is demethylation by CYP2C19 and other metabolic pathways include
oxidation by CYP3A4.
Interaction studies with medicinal products also metabolized with these pathways, like
carbamazepine, diazepam, glibenclamide, nifedipine, and an oral contraceptive containing
levonorgestrel and ethinyl oestradiol, did not reveal clinically significant interactions.
An interaction of pantoprazole with other medicinal products or compounds, which are
metabolized using the same enzyme system, cannot be excluded.
Results from a range of interaction studies demonstrate that pantoprazole does not affect the
metabolism of active substances metabolised by CYP1A2 (such as caffeine, theophylline),
CYP2C9 (such as piroxicam, diclofenac, naproxen), CYP2D6 (such as metoprolol), CYP2E1
(such as ethanol), or does not interfere with p-glycoprotein related absorption of digoxin.
There were no interactions with concomitantly administered antacids.
Interaction studies have also been performed by concomitantly administering pantoprazole with
the respective antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically relevant
interactions were found.
Medicinal products that inhibit or induce CYP2C19:
Inhibitors of CYP2C19 such as fluvoxamine could increase the systemic exposure of
pantoprazole. A dose reduction may be considered for patients treated long-term with high doses
of pantoprazole, or those with hepatic impairment.
Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin and St John´s wort
(Hypericum perforatum) may reduce the plasma concentrations of PPIs that are metabolized
through these enzyme systems.

Pregnancy
A moderate amount of data on pregnant women (between 300-1000 pregnancy outcomes)
indicate no malformative or feto/ neonatal toxicity of PANTOL.
Animal studies have shown reproductive toxicity (see section 5.3).
As a precautionary measure, it is preferable to avoid the use of PANTOL during pregnancy.
Breast-feeding

Animal studies have shown excretion of pantoprazole in breast milk. There is insufficient
information on the excretion of pantoprazole in human milk but excretion into human milk has
been reported. A risk to the newborns/infants cannot be excluded. Therefore, a decision on
whether to discontinue breast-feeding or to discontinue/abstain from PANTOL therapy should
take into account the benefit of breast-feeding for the child, and the benefit of PANTOL therapy
for the woman.
Fertility
There was no evidence of impaired fertility following the administration of pantoprazole in
animal studies (see section 5.3).

PANTOL has no or negligible influence on the ability to drive and use machines.
Adverse drug reactions, such as dizziness and visual disturbances may occur (see section 4.8). If
affected, patients should not drive or operate machines.

Approximately 5 % of patients can be expected to experience adverse drug reactions (ADRs).
The most commonly reported ADRs are diarrhoea and headache, both occurring in
approximately 1 % of patients.
The table below lists adverse reactions reported with pantoprazole, ranked under the following
frequency classification:
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare
(≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the
available data).
For all adverse reactions reported from post-marketing experience, it is not possible to apply any
Adverse Reaction frequency and therefore they are mentioned with a “not known” frequency.
Within each frequency grouping, adverse reactions are presented in order of decreasing
seriousness.
Table 1. Adverse reactions with pantoprazole in clinical trials and post-marketing experience

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via:

There are no known symptoms of overdose in man.
Systemic exposure with up to 240 mg administered intravenously over 2 minutes, were well
tolerated.

As pantoprazole is extensively protein bound, it is not readily dialysable.
In the case of an overdose with clinical signs of intoxication, apart from symptomatic and
supportive treatment, no specific therapeutic recommendations can be made.

Pharmacotherapeutic group: proton pump inhibitors, ATC code: A02BC02
Mechanism of action
PANTOL is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the
stomach by specific blockade of the proton pumps of the parietal cells.
PANTOL is converted to its active form in the acidic environment in the parietal cells where it
inhibits the H+, K+-ATPase enzyme, i.e. the final stage in the production of hydrochloric acid in
the stomach. The inhibition is dose-dependent and affects both basal and stimulated acid
secretion. In most patients, freedom from symptoms is achieved within 2 weeks. As with other
proton pump inhibitors and H2 receptor inhibitors, treatment with pantoprazole reduces acidity
in the stomach and thereby increases gastrin in proportion to the reduction in acidity. The
increase in gastrin is reversible. Since pantoprazole binds to the enzyme distal to the cell receptor
level, it can inhibit hydrochloric acid secretion independently of stimulation by other substances
(acetylcholine, histamine, gastrin). The effect is the same whether the product is given orally or
intravenously.
Pharmacodynamic effects
The fasting gastrin values increase under pantoprazole. On short-term use, in most cases they do
not exceed the upper limit of normal. During long-term treatment, gastrin levels double in most
cases. An excessive increase, however, occurs only in isolated cases. As a result, a mild to
moderate increase in the number of specific endocrine (ECL) cells in the stomach is observed in
a minority of cases during long-term treatment (simple to adenomatoid hyperplasia). However,
according to the studies conducted so far, the formation of carcinoid precursors (atypical
hyperplasia) or gastric carcinoids as were found in animal experiments (see section 5.3) have not
been observed in humans.
An influence of a long term treatment with pantoprazole exceeding one year cannot be
completely ruled out on endocrine parameters of the thyroid according to results in animal
studies.
During treatment with antisecretory medicinal products, serum gastrin increases in response to
the decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased
CgA level may interfere with investigations for neuroendocrine tumours.
Available published evidence suggests that proton pump inhibitors should be discontinued
between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might
be spuriously elevated following PPI treatment to return to reference range.

Absorption
PANTOL is rapidly absorbed and the maximal plasma concentration is achieved even after one
single 20 mg oral dose. On average at about 2.0 h - 2.5 h p.a. the maximum serum concentrations
of about 1-1.5 μg/ml are achieved, and these values remain constant after multiple
administration. Pharmacokinetics does not vary after single or repeated administration. In the
dose range of 10 to 80 mg, the plasma kinetics of pantoprazole are linear after both oral and
intravenous administration.
The absolute bioavailability from the tablet was found to be about 77 %. Concomitant intake of
food had no influence on AUC, maximum serum concentration and thus bioavailability. Only the
variability of the lag-time will be increased by concomitant food intake.
Distribution
PANTOL's serum protein binding is about 98 %. Volume of distribution is about 0.15 l/kg.
Biotransformation
The substance is almost exclusively metabolized in the liver. The main metabolic pathway is
demethylation by CYP2C19 with subsequent sulphate conjugation; other metabolic pathway
includes oxidation by CYP3A4.
Elimination
Terminal half-life is about 1 hour and clearance is about 0.1 l/h/kg. There were a few cases of
subjects with delayed elimination. Because of the specific binding of pantoprazole to the proton
pumps of the parietal cell the elimination half-life does not correlate with the much longer
duration of action (inhibition of acid secretion).
Renal elimination represents the major route of excretion (about 80 %) for the metabolites of
pantoprazole, the rest is excreted with the faeces. The main metabolite in both the serum and
urine is desmethylpantoprazole which is conjugated with sulphate. The half-life of the main
metabolite (about 1.5 hours) is not much longer than that of pantoprazole.
Special populations
Poor metabolisers
Approximately 3 % of the European population lack a functional CYP2C19 enzyme and are
called poor metabolisers. In these individuals the metabolism of pantoprazole is probably mainly
catalysed by CYP3A4. After a single-dose administration of 40 mg pantoprazole, the mean area
under the plasma concentration-time curve was approximately 6 times higher in poor
metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers).
Mean peak plasma concentrations were increased by about 60 %. These findings have no
implications for the posology of pantoprazole.
Renal impairment

No dose reduction is recommended when pantoprazole is administered to patients with impaired
renal function (including dialysis patients). As with healthy subjects, pantoprazole's half-life is
short. Only very small amounts of pantoprazole are dialyzed. Although the main metabolite has a
moderately delayed half-life (2 - 3h), excretion is still rapid and thus accumulation does not
occur.
Hepatic impairment
Although for patients with liver cirrhosis (classes A and B according to Child) the half-life
values increased to between 3 and 6 h and the AUC values increased by a factor of 3 - 5, the
maximum serum concentration only increased slightly by a factor of 1.3 compared with healthy
subjects.
Older people
A slight increase in AUC and Cmax in elderly volunteers compared with younger counterparts is
also not clinically relevant.
Paediatric population
Following administration of single oral doses of 20 or 40 mg pantoprazole to children aged 5 -
16 years AUC and Cmax were in the range of corresponding values in adults.
Following administration of single i.v. doses of 0.8 or 1.6 mg/kg pantoprazole to children aged 2
- 16 years there was no significant association between pantoprazole clearance and age or
weight. AUC and volume of distribution were in accordance with data from adults.

Non-clinical data reveal no special hazard to humans based on conventional studies of safety
pharmacology, repeated dose toxicity and genotoxicity.
In the two-year carcinogenicity studies in rats neuroendocrine neoplasms were found. In
addition, squamous cell papillomas were found in the fore stomach of rats. The mechanism
leading to the formation of gastric carcinoids by substituted benzimidazoles has been carefully
investigated and allows the conclusion that it is a secondary reaction to the massively elevated
serum gastrin levels occurring in the rat during chronic high-dose treatment. In the two-year
rodent studies an increased number of liver tumours was observed in rats and in female mice and
was interpreted as being due to pantoprazole's high metabolic rate in the liver.
A slight increase of neoplastic changes of the thyroid was observed in the group of rats receiving
the highest dose (200 mg/kg). The occurrence of these neoplasms is associated with the
pantoprazole-induced changes in the breakdown of thyroxine in the rat liver. As the therapeutic
dose in man is low, no harmful effects on the thyroid glands are expected.
In a peri-postnatal rat reproduction study designed to assess bone development, , signs of
offspring toxicity (mortality, lower mean body weight, lower mean body weight gain and
reduced bone growth) were observed at exposures (Cmax) approximately 2x the human clinical
exposure. By the end of the recovery phase, bone parameters were similar across groups and
body weights were also trending toward reversibility after a drug-free recovery period. The

increased mortality has only been reported in pre-weaning rat pups (up to 21 days age) which is
estimated to correspond to infants up to the age of 2 years old. The relevance of this finding to
the paediatric population is unclear. A previous peri-postnatal study in rats at slightly lower
doses found no adverse effects at 3 mg/kg compared with a low dose of 5 mg/kg in this study.
Investigations revealed no evidence of impaired fertility or teratogenic effects.
Penetration of the placenta was investigated in the rat and was found to increase with advanced
gestation. As a result, concentration of pantoprazole in the foetus is increased shortly before
birth.

Not applicable.

Do not store above 30°C.
This medicinal product does not require any special storage conditions.

14 and 28/pack
Reel PVC/PVDC and aluminium foil lid

No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.