1 gastro-resistant tablet contains: Pantoprazole sodium sesquihydrate 45.1 mg (corresponding to 40 mg pantoprazole).
Pharmacotherapeutic Group: Proton pump inhibitors. ATC Code: A02BC02.
Pharmacology: Pharmacodynamics: Pantoprazole is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the stomach by specific action on 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. As with other proton pump inhibitors and H2 receptor inhibitors, treatment with pantoprazole causes a reduced acidity in the stomach and thereby an increase in 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, the substance can affect 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.
Pharmacokinetics: General pharmacokinetics: Pantoprazole is rapidly absorbed and the maximal plasma concentration is achieved even after one single 40 mg oral dose. On average at about 2.5 p.a. the maximum serum concentrations of about 2-3 μg/ml are achieved, and these values remain constant after multiple administration. Volume of distribution is about 0.15 l/kg and clearance is about 0.1 l/h/kg. Terminal half-life is about 1 h. There were a few cases of subjects with delayed elimination. Because of the specific activation of pantoprazole in the parietal cell the elimination half-life does not correlate with the much longer duration of action (inhibition of acid secretion). Pharmacokinetics do not vary after single or repeated administration. In the dose range of 10 to 80 mg, the plasma kinetics of pantoprazole are virtually linear after both oral and intravenous administration. Pantoprazole's serum protein binding is about 98%.
The substance is almost exclusively metabolized in the liver. Renal elimination represents the major route of excretion (about 80%) for the metabolites of pantoprazole, the rest are 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) is not much longer than that of pantoprazole.
Bioavailability: Pantoprazole is completely absorbed after oral 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.
Characteristics in patients/special groups of subjects: No dose reduction is requested when pantoprazole is administered to patients with restricted kidney 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 moderate 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.
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard to humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity. In a 2-year carcinogenicity study in rats-which corresponds to lifetime treatment for 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 treatment. In the two-year studies an increased number of liver tumors was observed in rats and female mice and was interpreted as being due to pantoprazole's high metabolic rate in the liver. From mutagenicity studies, cell transformation tests and a DNA binding study it is concluded that pantoprazole has no genotoxic potential. A slight increase of neoplastic changes of the thyroid was observed in the group of rats receiving the highest dose. 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 side effects to the thyroid glands are expected. 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 advance gestation. As a result, concentration of pantoprazole in the foetus is increased shortly before birth.
In combination with two appropriate antibiotics (see Dosage & Administration) for the eradication of Helicobacter pylori in patients with peptic ulcers with the objective of reducing the recurrence of duodenal and gastric ulcers caused by this microorganism.
Duodenal ulcer; Gastric ulcer; Moderate and severe reflux esophagitis; Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions.
Recommended Dosage: In Helicobacter pylori positive patients with gastric and duodenal ulcers, eradication of the germ by a combination therapy should be achieved. Depending upon the resistance pattern, the following combinations can be recommended for the eradication of Helicobacter pylori: a. 2 x 1 Pantozol 40 mg gastro-resistant tablet/day + 2 x 1000 mg amoxycillin/day + 2 x 500 mg clarithromycin/day.
b. 2 x 1 Pantozol 40 mg gastro-resistant tablet/day + 2 x 500 mg metronidazole/day + 2 x 500 mg clarithromycin/day.
c. 2 x 1 Pantozol 40 mg gastro-resistant tablet/day + 2 x 1000 mg amoxycillin/day + 2 x 500 mg metronidazole/day.
If combination therapy is not an option, e.g. if the patient has tested negative for Helicobacter pylori, the following dosage guidelines apply for Pantozol 40 mg monotherapy.
For the treatment of gastric and duodenal ulcer and reflux esophagitis: One tablet of Pantozol 40 mg gastro-resistant tablet per day. In individual cases the dose may be doubled (increase to 2 Pantozol 40 mg gastro-resistant tablets daily) especially when there has been no response to other treatment.
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 (2 tablets of Pantozol 40 mg). Thereafter, the dosage 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 dosage 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 hypersecretory conditions is not limited and should be adapted according to clinical needs.
In patients with severe liver impairment the dose has to be reduced to 1 tablet (40 mg pantoprazole) every other day. Furthermore, in these patients the liver enzymes should be monitored during Pantozol 40 mg therapy. In the case of a rise of the liver enzymes, Pantozol 40 mg should be discontinued.
The daily dose of 40 mg pantoprazole should not be exceeded in elderly patients or in patients with impaired renal function. An exception is combination therapy for eradication of Helicobacter pylori, where also elderly patients should receive the usual pantoprazole dose (2 x 40 mg per day) during 1-week treatment.
In the case of a rise of the liver enzymes, Pantozol 40 mg should be discontinued.
General Instructions: Pantozol 40 mg tablets should not be chewed or crushed, and should be swallowed whole with water 1 hour before breakfast. In combination therapy for eradication of Helicobacter pylori infection, the second Pantozol 40 mg tablet should be taken before the evening meal. The combination therapy is implemented for 7 days in general and can be prolonged to up to two weeks maximum. If to ensure healing of the ulcers, further treatment with pantoprazole is indicated, the dosage recommendations for duodenal and gastric ulcers should be considered. 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. A 4-week period is usually required for the treatment of gastric ulcers and reflux esophagitis. If this is not sufficient, healing will usually be achieved within a further 4 weeks.
There are no known symptoms of overdosage in man.
In the case of overdosage with clinical signs of intoxication, the usual rules of intoxication apply. If the patient has been taken too little Pantozol 40 mg or have forgotten to take the Pantozol 40 mg, do not take the dose late, but continue with the next regular dose on the dosing schedule.
Talk to the doctor if the patient wants to interrupt or prematurely discontinue of treatment is considered with Pantozol 40 mg.
Pantozol 40 mg should generally not be used in cases of known hypersensitivity to one of the constituents of Pantoprazole 40 mg or of the combination partners. Pantozol 40 mg must not be used in combination treatment for eradication of Helicobacter pylori in patients with moderate to severe hepatic or renal dysfunction since currently no data are available on the efficacy and safety of Pantozol 40 mg in combination treatment of these patients.
Pantoprazole is not indicated for mild gastrointestinal complaints, such as nervous dyspepsia. In the case of combination therapy, the summaries of product characteristics of the respective drugs should be observed. Prior to treatment the possibility of malignancy of gastric ulcer or a malignant disease of the esophagus should be excluded as the treatment with pantoprazole may alleviate the symptoms of malignant ulcers and can thus delay diagnosis. Diagnosis of reflux esophagitis should be confirmed by endoscopy.
To date there has been no experience with treatment in children.
In patients with Zollinger-Ellison-Syndrome and other pathological hypersecretory 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 if respective clinical symptoms are observed.
Effect on the ability to drive and to use machines: There are no known effects on the ability to drive and use of machines.
Pregnancy and lactation: Clinical experience in pregnant women is limited. In animal reproduction studies, signs of slight fetotoxicity were observed at doses above 5 mg/kg. There is no information on the excretion of pantoprazole into human breast milk. Pantoprazole tablets should only be used when the benefit to the mother is considered greater than the potential risk to the foetus/baby.
Clinical experience in pregnant women is limited. In animal reproduction studies, signs of slight fetotoxicity were observed at doses above 5 mg/kg. There is no information on the excretion of pantoprazole into human breast milk. Pantoprazole tablets should only be used when the benefit to the mother is considered greater than the potential risk to the foetus/baby.
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Pantozol 40 mg may reduce the absorption of drugs whose bioavailability is pH-dependent (e.g. ketoconazole).
Pantoprazole is metabolized in the liver via the cytochrome P450 enzyme system. An interaction with other drugs or compounds which are metabolized using the same enzyme system cannot be excluded. No clinically significant interactions were, however, observed in specific tests with a number of such drugs or compounds, namely carbamazepine, caffeine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, metoprolol, naproxen, nifedipine, phenytoin, piroxicam, theophylline, and an oral contraceptive.
Although no interaction during concomitant administration of phenprocoumon or warfarin has been observed in clinical pharmacokinetic studies, a few isolated cases of changes in INR have been reported during concomitant treatment in the post-marketing period. Therefore, in patients being treated with coumarin anticoagulants, monitoring of prothrombin time/INR is recommended after initiation, termination or during irregular use of pantoprazole. There were also no interactions with concomitantly administered antacids.
Human kinetic interaction studies have been performed administering pantoprazole concomitantly with the respective antibiotics (chlarithromycin, metronidazole, amoxicillin).
No clinically interactions were found.
A02BC02 - pantoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).
Gastro-resistant tab 40 mg x 1 x 7's.