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SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
• Active substance: Each enteric coated tablet contains 45.10 mg of pantoprazole sodium sesquihydrate equivalent to 40 mg of pantoprazole. For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM
A yellow, oval biconvex enteric coated tablet
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
• Moderate and severe reflux oesophagitis • In combination with two appropriate antibiotics (see “Posology“) for the eradication of H. pylori in patients with peptic ulcers with the objective of reducing the recurrence of duodenal and gastric ulcers caused by this • Duodenal ulcer • Gastric ulcer • Zollinger-Ellison syndrome and other pathological hypersecretory conditions 4.2 Posology and method of administration
Adults and adolescents 12 years of age and above: Treatment of moderate and severe reflux oesophagitis
One tablet of Pantoprazole per day. In individual cases the dose may be doubled (increase to 2 tablets Pantoprazole 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. Eradication of Helicobacter Pylori
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 H. pylori: twice daily one STAMİC® 40 mg enteric coated tablet twice daily one STAMİC® 40 mg enteric coated tablet + twice daily 400 – 500 mg metronidazole + twice daily 250 – 500 mg clarithromycin twice daily one STAMİC® 40 mg enteric coated tablet + twice daily 400 – 500 mg metronidazole For further information of eradication therapy see individual cases. Gastric and Duedonal Ulcers
If combination therapy is not an option, e.g. if the patient has tested negative for Helicobacter pylori, the following dosage guidelines apply for STAMİC® 40 mg monotherapy: One tablet of STAMİC® 40 mg per day for gastric and duodenal ulcers In individual cases the dose may be doubled (increase to 2 tablets STAMİC® 40 mg daily) especially when there has been no response to other treatment. Zollinger-Ellison syndrome
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 STAMİC® 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 Treatment duration in Zollinger-Ellison syndrome and other pathological hypersecretory conditions is not limited and should be adapted according to clinical needs. Characteristics in patients/special groups of subjects
The dosage should be reduced to one tablet per day with patients who has severe hepatic No dose reduction is requested when pantoprazole is administered to patients with restricted The daily dose of 40 mg pantoprazole should not be exceeded in elderly patients. An exception is combination therapy for eradication of H. pylori, where also elderly patients should receive the usual pantoprazole dose (2x40 mg/day) during 1-week treatment. Pantoprazole is not recommended for use in children below 12 years of age due to limited data Pantoprazole tablets should not be chewed or crushed, and should be swallowed whole with water before breakfast or during breakfast. In combination therapy for eradication of Helicobacter pylori infection, the second Pantoprazole 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 oesophagitis. If this is not sufficient, healing will usually be achieved within a further 4 weeks. 4.3 Contraindications
Stamic ® 40 mg should not be used in patients who has hypersensitivity to the pantoprazole or to any of the excipients of inside it. Pantoprazole must not be used in combination treatment for eradication of H. pylori in patients with moderate to severe hepatic or renal dysfunction since currently no data are available on the efficacy and safety of Pantoprazole in combination treatment of these Pantoprazole, like other PPIs (proton pump inhibitors, should not be co-administered with 4.4 Special warnings and precautions for use
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 in patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy or if respective clinical In the presence of any alarm symptom like 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. Patient with severe hepatic impairment should be given 40 mg of pantoprazole every other day. 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 In the case of combination therapy, the summaries of product characteristics of the respective medicinal products should be observed. Further investigation is to be considered if symptoms persist despite adequate treatment. Pantoprazole, like all proton pump inhibitors, might be expected to increase the counts of bacteria normally present in the upper gastrointestinal tract. Treatment with Pantoprazole may lead to a slightly increased risk of gastrointestinal infections caused by bacteria (e.g. Salmonella, Campylobacter, and C. difficile). This medicinal product contains mannitol. It can have a mild laxative effect 4.5 Interaction with other medicinal products and other forms of interaction
Stamic ® 40 mg may reduce the absorption of medicinal products whose bioavailability is It has been shown that co-administration of atazanavir 300 mg/ritonavir 100 mg with omeprazole (40 mg once daily) or atazanavir 400 mg with lansoprazole (60 mg single dose) to healthy volunteers resulted in a substantial reduction in the bioavailability of atazanavir. The absorption of atazanavir is pH dependent. Therefore PPIs, including pantoprazole, should not be co-administered with atazanavir (see section 4.3). Pantoprazole is metabolized in the liver via the cytochrome P450 enzyme system. An interaction of pantoprazole 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 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 There were also no interactions with concomitantly administered antacids. Human kinetic interaction studies have been performed administering pantoprazole concomitantly with the respective antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically relevant interactions were found. 4.6 Pregnancy and lactation
There are no adequate data from the use of pantoprazole in pregnant women. Studies in animals have shown reproductive toxicity (see 5.3). The potential risk for humans is unknown. Pantoprazole should not be used during pregnancy unless clearly necessary. It is unknown whether pantoprazole is excreted in human breast milk. Animal studies have shown excretion of pantoprazole in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Pantoprazole should be administered taking into account the benefit of breast-feeding to the child and the benefit of Stamic ® 40 mg 4.7 Effects on ability to drive and use machines
Stamic ® 40 mg has no known influence on the ability to drive and use machines. Adverse drug reactions such as dizziness and visual disturbances may occur (see section 4.8). Under these conditions the ability to react may be decreased. 4.8 Undesirable effects
Within each frequency grouping, undesirable effects are presented in order of decreasing Frequency
Uncommon
Very rare
( 1/1,000 to
( 1/10,000 to
(<1/10,000)
System Organ
to <1/10)
<1/100)
<1/1,000)
4.9 Overdose
There are no known symptoms of overdose in man. Doses up to 240 mg intravenous were administered over 2 minutes and were well tolerated. As pantoprazole is extensively protein bound, it is not readily dialyzable. In the case of overdose with clinical signs of intoxication, the usual rules of intoxication 5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Proton pump inhibitors
ATC code: A02B C02
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 of 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 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 5.2 Pharmacokinetic properties
Absorption: 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 h p.a. the maximum serum concentrations of about 2 - 3 μg/ml are achieved, and these values remain constant after multiple administration. Distribution: Volume of distribution is about 0.15 l/kg and clearance is about 0.1 l/h/kg. Elimination: Terminal half-life is about 1 h. 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). Biotransformation: 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 h) 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. Linearity: 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. 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 moderately delayed half life (2 3h), excretion is still rapid and Although for patients with liver cirrhosis (classes A and B according to Child) the half- lifetime 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 A slight increase in AUC and Cmax in elderly volunteers compared with younger counterparts is also not clinically relevant. 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 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. 5.3 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 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 In the two-year rodent studies an increased number of liver tumors was observed in rats (in one rat study only) 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) in one 2 year study. 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 on the Investigations revealed no evidence of impaired fertility or teratogenic effects. In animal reproduction studies, signs of slight fetotoxicity were observed at doses above 5 mg/kg. 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 6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Core tablet
Tablet coating
6.2 Incompatibilities
6.3 Shelf life
6.4 Special precautions for storage
Store at room temperatures below 25°C. Product should be used in 3 months after 6.5 Nature and contents of container
6.6 Special precautions for disposal and other handling
Any unused product or waste material should be disposed of in accordance with local 7. MARKETING AUTHORISATION HOLDER
HELBA Pharmaceuticals Inc.Co.
Adress: Öveçler 68. Sok. No:5/2 Çankaya/Ankara TURKEY 8. MARKETING AUTHORISATION NUMBER(S)
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10. DATE OF REVISION OF THE TEXT

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