Pantoprazole contains 20 mg pantoprazole (as pantoprazole sodium sesquihydrate 22.56 mg); 40 mg pantoprazole (as pantoprazole sodium sesquihydrate 45.12 mg).
Excipients/Inactive Ingredients: Core: Mannitol, Sodium carbonate anhydrous, Sodium starch glycolate, Crospovidone, Colloidal anhydrous silica, Calcium stearate. Sub coat: Hypromellose, Macrogol, Sodium hydroxide, Purified water. Enteric coat: Methacrylic acid ethyl acrylate copolymer, Macrogol 6000, Purified water. Film coat: Opadry AMB 80W52172: Polyvinyl alcohol (Part Hydrolyzed), Titanium Dioxide, Talc, Lecithin (Soya), Iron Oxide Yellow, Xanthan Gum, Purified water.
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 canaliculi 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 in 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 is given orally or intravenously.
Pharmacokinetics: General pharmacokinetics: Pantoprazole is rapidly absorbed and the maximal plasma concentration is achieved even after one single 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 (20 mg) and 2.3 μg/ml (40 mg) 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 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).
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.
Pantoprazole's plasma 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 in the faeces. The main metabolite in both the plasma and urine is desmethylpantoprazole, which is conjugated with sulphate. The half-life of the main metabolites (about 1.5 hours) is not much longer than that of pantoprazole.
Characteristics in patients/special groups of subjects: Although for patients with hepatic cirrhosis (classes A and B according to Child) the half-life values increased to between 3 and 6 hours and the AUC values increased by a factor of 3 to 5, the maximum plasma concentration only increased slightly by a factor of 1.3 compared with healthy subjects. Therefore the dose regimen in patients with hepatic cirrhosis should be reduced to one tablet every other day.
No dose reduction is required when pantoprazole is administered to patients with impaired kidney function (including dialysis patients). As with healthy subjects, pantoprazole's half-life is short. Only very small amounts of pantoprazole are dialysed. Although the main metabolite has a moderately delayed half-life (2-3 hours), excretion is still rapid and thus accumulation does not occur.
A slight increase in AUC and Cmax in elderly volunteers compared with younger counterparts is also not clinically relevant.
20 mg tablet: For the treatment of mild reflux disease and associated symptoms (e.g. heartburn, acid regurgitation, pain on swallowing).
For long-term management and prevention of relapse in reflux oesophagitis.
Prevention of gastroduodenal ulcers induced by non-selective, non-steroidal anti-inflammatory drugs (NSAIDs) in patients at risk with a need for continuous NSAID treatment.
40 mg tablet: For treatment of duodenal ulcer, gastric ulcer, moderate and severe reflux oesophagitis.
20 mg tablet: Mild reflux disease and associated symptoms (e.g. heartburn, acid regurgitation, pain on swallowing): The recommended oral dosage is one pantoprazole 20 mg gastro-resistant tablet per day. Symptom relief is generally accomplished within 2-4 weeks, and a 4-week treatment period is usually required for healing of associated oesophagitis.
Long-term management and prevention of relapse in reflux oesophagitis: For long-term management, a maintenance dose of one pantoprazole 20 mg gastro-resistant tablet per day is recommended, increasing to 40 mg pantoprazole per day if a relapse occurs.
Prevention of gastroduodenal ulcers induced by non-selective, non-steroidal anti-inflammatory drugs (NSAIDs) in patients at risk with a need for continuous NSAID treatment: The recommended oral dosage is one pantoprazole 20 mg gastro-resistant tablet per day.
Pantoprazole 20 mg gastro-resistant tablet must not be split, chewed or crushed, and should be swallowed whole with water 1 hour before a meal.
Special populations: Hepatic impairment: A daily dose of 20 mg pantoprazole should not be exceeded in patients with severe liver impairment.
Renal impairment: No dose adjustment is necessary in elderly patients or in those with impaired renal function.
40 mg tablet: The recommended dosage in duodenal ulcer, gastric ulcer and reflux oesophagitis is one gastro-resistant tablet per day. Pantoprazole 40 mg gastro-resistant tablet must not be split, chewed or crushed, and should be swallowed whole with water 1 hour before a meal.
Duodenal ulcer: Duodenal ulcers generally heal 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.
Gastric ulcer: 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.
Moderate and severe reflux oesophagitis: 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.
Elderly: No dose adjustment is necessary in the elderly. However, the daily dose of 40 mg pantoprazole should not be exceeded.
Patients with impaired renal function: No dose adjustment is necessary in patients with impaired renal function. However, the daily dose of 40 mg pantoprazole should not be exceeded.
Hepatic Impairment: In patients with severe liver impairment the dose has to be reduced to 1 tablet every other day. Furthermore, in these patients the liver enzymes should be monitored during pantoprazole therapy. In the case of a rise of the liver enzymes, pantoprazole should be discontinued.
Children: There is no information on the use of pantoprazole in children. Therefore pantoprazole tablets should not be used in children.
There are no known symptoms of overdosage in man. In the case of overdosage with clinical signs of intoxication, the usual rules of intoxication therapy apply.
Hypersensitivity to the active substance or to any of the excipients. Pantoprazole, like other proton pump inhibitors (PPIs), should not be co-administered with atazanavir.
To date, there has been no experience with treatment in children.
Pantoprazole is not indicated for mild gastrointestinal complaints such as nervous dyspepsia.
Hepatic Impairment: In patients with severe liver impairment, particularly those on long-term use, liver enzymes should be monitored regularly during treatment with pantoprazole. In the case of a rise in liver enzymes, pantoprazole 40 mg gastro-resistant tablets should be discontinued.
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.
Clostridium difficile-associated diarrhoea: Published observational studies suggest that proton pump inhibitor (PPI) therapy like pantoprazole may be associated with an increased risk of Clostridium difficile-associated diarrhoea (CDAD), especially in hospitalized patients. This diagnosis should be considered for diarrhoea that does not improve.
Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
Hypomagnesemia: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.
Bone Fracture: Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines (see Dosage & Administration and Adverse Reactions).
Concomitant use of Pantoprazole with Methotrexate: Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be considered in some patients (see Interactions).
Note: Prior to treatment a malignant disease of the oesophagus or stomach should be excluded as the treatment with pantoprazole may alleviate the symptoms of malignant diseases and can thus delay diagnosis. Patients who do not respond after 4 weeks should be investigated.
20 mg: Co-administered with NSAIDS: The use of Pantoprazole 20 mg gastro-resistant tablets as a preventive of gastroduodenal ulcers induced by non-selective, 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 gastro-intestinal bleeding.
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.
Pregnancy: There are no adequate data from the use of pantoprazole in pregnant women. Studies in animals have shown reproductive toxicity. Preclinical studies revealed no evidence of impaired fertility or teratogenic effects. The potential risk for humans is unknown. Pantoprazole should not be used during pregnancy.
Breast-feeding: Animal studies have shown excretion of pantoprazole in breast milk. Excretion into human milk has been reported. Pantoprazole should not be used during breast-feeding.
Approximately 5% of patients can be expected to experience adverse drug reactions (ADRs). The most commonly reported ADRs are diarrhoea and headache, both occuring in approximately 1% of patients.
The table as follows lists adverse reactions reported with pantoprazole , ranked under following frequency classification: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000), 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. (See table as follows.)
Click on icon to see table/diagram/image
Pantoprazole gastro-resistant tablet may reduce or increase the absorption of drugs whose bioavailability is pH-dependent (e.g. ketoconazole).
HIV medications (atazanavir): 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 PPI's, including pantoprazole must not be co-administered with atazanavir (see Contraindications).
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.
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.
Case reports, published, population pharmacokinetic studies and retrospective analyses suggest that concomitant administration of PPls and methotrexate (primarily at high dose) may elevate andprolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug Interaction studies of methotrexate with PPls have been conducted (see Precautions).
Other Interactions studies: Pantoprazole is 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.
An interaction of pantoprazole with other drugs or compounds which are metabolized using the same enzyme system cannot be ruled out. However, in targeted studies involving a range of such drugs and substances, no clinically significant interactions were observed; studies have been carried out on carbamazepine, caffeine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, metoprolol, naproxen, nifedipine, phenytoin, piroxicam, theophylline and all oral contraceptive.
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 metabolized by CYP1A2 (such as caffeine, theophylline), CYP2C9 (such as piroxicam, diclofenac, naproxen). CYP2D6(such asmetoprolol). CYP2E1 (such as ethanol), or does not interfere with p-glycoprotein relatedabsorption of digoxin.
There were also no interactions with concomitantly administered antacids.
Interaction studies have also been performed by concomitantly administering pantoprazole with the respective antibiotics (clarithromycin, metronidazole, amoxycillin). No clinically relevant interactions were found.
Store at or below 30°C, protect from light.
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 (yellow, oval, biconvex enteric coated, plain on both the sides) 20 mg x 3 x 10's. 40 mg x 3 x 10's.