Reflux oesophagitis.
- Gastric and duodenal ulcer.
- Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions.

This medicine should be administered by a healthcare professional and under appropriate medical
supervision.
Intravenous administration of Pantozol is recommended only if oral administration is not appropriate. Data
are available on intravenous use for up to 7 days. Therefore, as soon as oral therapy is possible, treatment
with Pantozol i.v. should be discontinued and 40 mg pantoprazole p.o. should be administered instead.
Recommended dose
Gastric and duodenal ulcer, reflux oesophagitis
The recommended intravenous dose is one vial of Pantozol (40 mg pantoprazole) per day.
Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions
For the long-term management of Zollinger-Ellison-Syndrome and other pathological hypersecretory
conditions patients should start their treatment with a daily dose of 80 mg Pantozol. Thereafter, the dose
can be titrated up or down as needed using measurements of gastric acid secretion to guide. With doses
above 80 mg daily, the dose should be divided and given twice daily. A temporary increase of the dose
above 160 mg pantoprazole is possible but should not be applied longer than required for adequate acid
control.
In case a rapid acid control is required, a starting dose of 2 x 80 mg Pantozol is sufficient to manage a
decrease of acid output into the target range (<10 mEq/h) within one hour in the majority of patients.

Special populations
Paediatric patients
The experience in children is limited. Therefore, Pantozol 40 mg powder for solution for injection is not
recommended for use in patients below 18 years of age until further data become available.
Hepatic Impairment
A daily dose of 20 mg pantoprazole (half a vial of 40 mg pantoprazole) should not be exceeded in patients
with severe liver impairment (see section 4.4).
Renal Impairment
No dose adjustment is necessary in patients with impaired renal function.
Elderly
No dose adjustment is necessary in elderly patients.
Method of administration
A ready-to-use solution is prepared in 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection.
For instructions for preparation see section 6.6. The prepared solution may be administered directly or
may be administered after mixing it with 100 ml sodium chloride 9 mg/ml (0.9 %) solution for injection or
glucose 55 mg/ml (5 %) solution for injection.
After preparation the solution must be used within 12 hours.
The medicinal product should be administered intravenously over 2 - 15 minutes.

Hypersensitivity to the active substance, substituted benzimidazoles, or to any of the excipients

In presence of alarm symptoms
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, as treatment with pantoprazole may alleviate symptoms and delay diagnosis.
Further investigation is to be considered if symptoms persist despite adequate treatment.
Hepatic Impairment
In patients with severe liver impairment, the liver enzymes should be monitored during therapy.
In the case of a rise of the liver enzymes, the treatment should be discontinued (see section 4.2).
Co-administration with atazanavir
Co-administration of atazanavir with proton pump inhibitors is not recommended (see section 4.5). If the
combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring
(e.g virus load) is recommended in combination with an increase in the dose of atazanavir to 400 mg with
100 mg of ritonavir. A pantoprazole dose of 20 mg per day should not be exceeded.
Gastrointestinal infections caused by bacteria
Pantoprazole, like all proton pump inhibitors (PPIs), might be expected to increase the counts of bacteria
normally present in the upper gastrointestinal tract. Treatment with Pantozol may lead to a slightly
increased risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter.

Sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. is essentially
‘sodium-free’.
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 drugs 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 the elderly 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.

Effect of pantoprazole on the absorption of other medicinal products
Because of profound and long lasting inhibition of gastric acid secretion, pantoprazole may reduce the
absorption of drugs with a gastric pH dependent bioavailability, e.g some azole antifungals as
ketoconazole, itraconazole, posaconazole and other medicine as erlotinib.
HIV medications (atazanavir)
Co-administration of atazanavir and other HIV medications whose absorption is pH-dependent with
proton-pump inhibitors, might result in a substantial reduction in the bioavailability of these HIV
medications and might impact the efficacy of these medicines. Therefore, the co-administration of proton
pump inhibitors with atazanavir is not recommended (see section 4.4).
Coumarin anticoagulants (phenprocoumon or warfarin)
Although no interaction during concomitant administration of phenprocoumon or warfarin has been
observed in clinical pharmacokinetic studies, a few isolated cases of changes in International Normalised
Ratio (INR) have been reported during concomitant treatment in the post-marketing period. Therefore, in
patients treated with coumarin anticoagulants (e.g. phenprocoumon or warfarin), monitoring of
prothrombin time / INR is recommended after initiation, termination or during irregular use of
pantoprazole.
Other interactions studies
Pantoprazole 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 drugs 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.

Results from a range of interaction studies demonstrate that pantoprazole does not effect 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.

Pregnancy
Pregnancy category B
Intravenous reproduction studies have been performed in rats and rabbits and have revealed no evidence
of impaired fertility or harm to the fetus due to Pantoprazole at doses up to 4-6 times the human dose
(based on body surface area), however studies in animals above this dose have shown reproductive
toxicity (see section 5.3). There are, however, no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, this drug should be
used in pregnancy only if clearly needed’
Lactation
Animal studies have shown excretion of pantoprazole in breast milk. Excretion into human milk has been
reported. Therefore, a decision on whether to continue/discontinue breast-feeding or to
continue/discontinue therapy with Pantozol should be made taking into account the benefit of breastfeeding
to the child, and the benefit of Pantozol therapy to women.

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 ADR is injection site thrombophlebitis. Diarrhoea and headache occurred 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.

 

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
Pantoprazole 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.
Pantoprazole 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.
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 longterm
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.

General pharmacokinetics
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.
Distribution
Pantoprazole's serum protein binding is about 98 %. Volume of distribution is about 0.15 l/kg.
Elimination
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. 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.
Characteristics in patients/special groups of subjects
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.
No dose reduction is recommended when pantoprazole is administered to patients with impaired renal
function (incl. 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 - 3 h), excretion is still rapid and thus accumulation does not occur.

Although for patients with liver cirrhosis (classes A and B according to Child) the half-life values
increased to between 7 and 9 h and the AUC values increased by a factor of 5 - 7, the maximum serum
concentration only increased slightly by a factor of 1.5 compared with healthy subjects.
A slight increase in AUC and Cmax in elderly volunteers compared with younger counterparts is also not
clinically relevant.
Children
Following administration of single intravenous 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.

Preclinical 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 forestomach 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 highdose
treatment. In the two-year rodent studies an increased number of liver tumors 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 animal reproduction studies, signs of slight fetotoxicity were observed at doses above 5 mg/kg.
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.

Disodium edetate
Sodium hydroxide (for pH adjustment)

This medicinal product must not be mixed with other medicinal products except those mentioned in
section 6.6.

Unopened vial: 2 years After reconstitution, or reconstitution and dilution, chemical and physical in use stability has been demonstrated for 12 hours at 25 °C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Do not store above 25 °C.
Keep the vial in the outer carton in order to protect from light.
For storage conditions of the reconstituted and diluted medicinal product see section 6.3.

10 ml clear glass (type I) vial with aluminum cap and grey rubber stopper containing 40 mg powder for
solution for injection.
Pack sizes of 1 vial and 5 (5x1) vials with powder for solution for injection.
Hospital packs: 1 vial, 5 (5x1) vials, 10 (10x1) vials and 20 (20x1) vials with powder for solution for
injection.
Not all pack sizes may be marketed.

A ready-to-use solution is prepared by injecting 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for
injection into the vial containing the powder. The appearance of the product after reconstitution is a clear
yellowish solution. This solution may be administered directly or may be administered after mixing it with
100 ml sodium chloride 9 mg/ml (0.9 %) solution for injection or glucose 55 mg/ml (5 %) solution for
injection. Glass or plastic containers should be used for dilution.
After reconstitution, or reconstitution and dilution, chemical and physical in use stability has been
demonstrated for 12 hours at 25 °C.
From a microbiological point of view, the product should be used immediately.
Pantozol should not be prepared or mixed with solvents other than those stated.
The medicine should be administered intravenously over 2-15 minutes.
The contents of the vial are for single use only. Any product that has remained in the container or the visual
appearance of which has changed (e.g. if cloudiness or precipitation is observed) should be disposed of in
accordance with local requirements.