Moderate & sever cases of inflammation of the esophagus (Reflux oesophagitis).
- Eradication of Helicobacter pylori (H. pylori) in combination with appropriate
antibiotic therapy in patients with H. pylori associated ulcers.
- Gastric and duodenal ulcer
 

Tablets should not be chewed or crushed, and should be swallowed whole 1 hour before a
meal with some water.
Recommended dose
Reflux oesophagitis
One tablet of Pantomax per day. In individual cases the dose may be doubled (increase to 2
tablets Pantomax daily) especially when there has been no response to other treatment. A
4-week period is usually required for the treatment of reflux oesophagitis. If this is not
sufficient, healing will usually be achieved within a further 4 weeks.
Adults
Eradication of H. pylori in combination with two appropriate antibiotics
In H. pylori positive patients with gastric and duodenal ulcers, eradication of the germ by a
combination therapy should be achieved. Considerations should be given to official local
guidance (e.g. national recommendations) regarding bacterial resistance and the
appropriate use and prescription of antibacterial agents. Depending upon the resistance
pattern, the following combinations can be recommended for the eradication of H. pylori:
a) twice daily one tablet Pantomax
+ twice daily 1000 mg amoxicillin
+ twice daily 500 mg clarithromycin
b) twice daily one tablet Pantomax
+ twice daily 400 - 500 mg metronidazole (or 500 mg tinidazole)
+ twice daily 250 - 500 mg clarithromycin
c) twice daily one tablet Pantomax
+ twice daily 1000 mg amoxicillin
+ twice daily 400 - 500 mg metronidazole (or 500 mg tinidazole)
In combination therapy for eradication of H. pylori infection, the second Pantomax tablet
should be taken 1 hour before the evening meal. The combination therapy is implemented
for 7 days in general and can be prolonged for a further 7 days to a total duration of up to
two weeks. If, to ensure healing of the ulcers, further treatment with pantoprazole is
indicated, the dose recommendations for duodenal and gastric ulcers should be considered.
If combination therapy is not an option, e.g. if the patient has tested negative for H. pylori,
the following dose guidelines apply for Pantomax monotherapy:
Treatment of gastric ulcer
One tablet of Pantomax per day. In individual cases the dose may be doubled (increase to 2
tablets Pantomax daily) especially when there has been no response to other treatment. A
4-week period is usually required for the treatment of gastric ulcers. If this is not sufficient,
healing will usually be achieved within a further 4 weeks.
Treatment of duodenal ulcer
One tablet of Pantomax per day. In individual cases the dose may be doubled (increase to 2
tablets Pantomax daily) especially when there has been no response to other treatment. A
duodenal ulcer generally heals within 2 weeks. If a 2-week period of treatment is not
sufficient, healing will be achieved in almost all cases within a further 2 weeks.
Special populations
Children below 12 years of age
Pantomax is not recommended for use in children below 12 years of age due to limited data
on safety and efficacy in this age group.
Hepatic Impairment
A daily dose of 20 mg pantoprazole (1 tablet of 20 mg pantoprazole) should not be exceeded
in patients with severe liver impairment. Pantomax must not be used in combination
treatment for eradication of H. pylori in patients with moderate to severe hepatic
dysfunction since currently no data are available on the efficacy and safety of Pantomax in
combination treatment of these patients (see section 4.4).
Renal Impairment
No dose adjustment is necessary in patients with impaired renal function. Pantomax must
not be used in combination treatment for eradication of H. pylori in patients with impaired
renal function since currently no data are available on the efficacy and safety of Pantomax in
combination treatment for these patients.
Elderly
No dose adjustment is necessary in elderly patients.
 

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 Pantomax 20 mg as a preventive of gastroduodenal ulcers induced by nonselective 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.
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.
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.
Influence on vitamin B12 absorption
Pantoprazole, 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
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
Pantomax may lead to a slightly increased risk of gastrointestinal infections caused by
bacteria such as Salmonella and Campylobacter.
 

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 pHdependent 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
There are no adequate data from the use of pantoprazole in pregnant women. Studies in
animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is
unknown. Pantomax should not be used during pregnancy, unless clearly necessary.
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 breastfeeding or to continue/discontinue therapy with Pantomax should be made taking into
account the benefit of breast-feeding to the child, and the benefit of Pantomax 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 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

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 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.
 

Absorption
Pantoprazole 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 is
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
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 (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.
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.
A slight increase in AUC and Cmax in elderly volunteers compared with younger counterparts
is also not clinically relevant.
Children
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.
Absorption
Pantoprazole 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 is
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
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 (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.
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.
A slight increase in AUC and Cmax in elderly volunteers compared with younger counterparts
is also not clinically relevant.
Children
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.
 

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 high-dose
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.
 

Mannitol , Crospovidone,Sodium Carbonate Anhydrous,Hyreromellose,Calcium Stearate,
Opadry,Acryl eze.
 

Not applicable.
 

Do not store above 30°C.
Store in the original package
 

How supplied
Packs of 15, 30 enteric coated tablets: Each enteric coated tablet contains Pantoprazole
Sodium Sesquihydrate equivalent to 40 mg Pantoprazole.
 

No special requirements.