Pantol is indicated for use in adults and adolescents 12 years of age and above for:
- Reflux oesophagitis.
Pantol is indicated in adults for:
- Eradication of Helicobacter pylori (H. pylori) in combination with appropriate antibiotic therapy
in patients with H. pylori associated ulcers.
- Gastric and duodenal ulcer.
- Zollinger-Ellison-Syndrome and other pathological hyper secretory conditions.

Posology
Adults and adolescents 12 years of age and above
Reflux oesophagitis
One tablet of Pantol per day. In individual cases the dose may be doubled (increase to 2 tablets
Pantol 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 Pantol
+ twice daily 1000 mg amoxicillin +
twice daily 500 mg clarithromycin
b) Twice daily one tablet Pantol
+ twice daily 400 - 500 mg metronidazole (or 500 mg tinidazole) +
twice daily 250 - 500 mg clarithromycin
c) Twice daily one tablet Pantol
+ 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 Pantol 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 Pantol 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 Pantol monotherapy:
Treatment of gastric ulcer
One tablet of Pantol per day. In individual cases the dose may be doubled (increase to 2 tablets of
Pantol 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 Pantol per day. In individual cases the dose may be doubled (increase to 2 tablets of
Pantol 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.
Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions
For the long-term management of Zollinger-Ellison-Syndrome and other pathological hyper
secretory conditions patients should start their treatment with a daily dose of 80 mg (2 tablets of
Pantol 40 mg). 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.
Treatment duration in Zollinger-Ellison syndrome and other pathological hyper secretory
conditions is not limited and should be adapted according to clinical needs.

Patients with 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. Pantol 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 Pantol in combination treatment of these patients
(see section 4.4).
Patients with renal impairment
No dose adjustment is necessary in patients with impaired renal function. Pantol 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 Pantol in combination treatment for
these patients (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 the 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).
Combination therapy
In the case of combination therapy, the summaries of product characteristics of the respective
medicinal products should be observed.

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
In patients with Zollinger-Ellison syndrome and other pathological hyper secretory conditions
requiring long-term treatment, 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
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 the
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.
Sub-acute 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 medicine 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 inhibitors 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 taking 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:

To report any side effect(s):
The National Pharmacovigilance and Drug Safety Centre (NPC)
o Fax: +966-11-205-7662 o Call NPC at +966-11-2038222, Exts:
2317-2356-2340. o Reporting hotline: 19999.
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc

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
40 mg oral dose. On average at about 2.5 h p.a. the maximum serum concentrations of about 2 - 3
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 - 3 h), 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 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.
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.

Pantoprazole sodium is dispensed based on the potency and the difference is compensated
mannitol BP.

Not applicable.

Do not store above 30°C.

Pantol is distributed in or ALU/ALU blisters packed in carton boxes of 14 & 28 tablets.

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