Gastro-resistant tablet: Yellow, oval, biconvex film-coated tablet imprinted with "P20" or "P40" in brown ink on one side.
Each gastro-resistant tablet contains 20 mg or 40 mg of pantoprazole (as sodium sesquihydrate).
Powder for solution for injection: White to off-white powder.
Each vial contains 40 mg of pantoprazole (as pantoprazole sodium).
Excipients with known effect: Each vial contains 1 mg disodium edetate and 0.24 mg sodium hydroxide.
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'.
Excipients/Inactive Ingredients: Gastro-resistant tablet: Core: Anhydrous sodium carbonate, Mannitol (E421), Crospovidone, Povidone K90, Calcium stearate.
Coating: Hypromellose, Povidone K25, Titanium dioxide (E171), Yellow iron oxide (E172), Propylene glycol, Methacrylic acid-ethyl acrylate copolymer (1:1), Polysorbate 80, Sodium laurilsulfate, Triethyl citrate.
Printing ink: Shellac, Red iron oxide (E172), Black iron oxide (E172), Yellow iron oxide (E172), Concentrated ammonia solution.
Powder for solution for injection: Disodium edetate, Sodium hydroxide (for pH adjustment).
Pharmacotherapeutic group: Proton pump inhibitors. ATC code: A02BC02.
Pharmacology: Pharmacodynamics: 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.
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 Toxicology: Preclinical safety data as follows) 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 inhibitor 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.
Pharmacokinetics: General pharmacokinetics: Powder for solution for injection: 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.
Absorption: Gastro-resistant tablet 20 mg: 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 are linear after both oral and intravenous administration.
Gastro-resistant tablet 40 mg: 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.
Gastro-resistant tablet 20 mg and 40 mg: 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.
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: Gastro-resistant tablet 20 mg: 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.
Gastro-resistant tablet 40 mg & Powder for solution for injection: 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/Elderly: 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 intravenous 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.
Gastro-resistant tablet 20 & 40 mg: 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.
Toxicology: Preclinical safety data: 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 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 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.
Gastro-resistant tablet 20 mg: Pantoprazole is indicated for use in adults and adolescents 12 years of age and above for: Symptomatic gastro-oesophageal reflux disease; Long-term management and prevention of relapse in reflux oesophagitis.
Pantoprazole is indicated for use in adults for: 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 (see Precautions).
Gastro-resistant tablet 40 mg: Pantoprazole is indicated for use in adults and adolescents 12 years of age and above for: Reflux oesophagitis.
Pantoprazole 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 hypersecretory conditions.
Powder for solution for injection: Pantoloc i.v. is indicated for use in adults for: Reflux oesophagitis; Gastric and duodenal ulcer; Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions.
Posology: Gastro-resistant tablet 20 mg: Adults and adolescents 12 years of age and above: Symptomatic gastro-oesophageal reflux disease: The recommended oral dosage is one Pantoloc 20 mg tablet per day. Symptom relief is generally accomplished within 2-4 weeks. If this is not sufficient, symptom relief will normally be achieved within a further 4 weeks. When symptom relief has been achieved, reoccurring symptoms can be controlled using an on-demand regimen of 20 mg once daily, taking one tablet when required. A switch to continuous therapy may be considered in case satisfactory symptom control cannot be maintained with on-demand treatment.
Long-term management and prevention of relapse in reflux oesophagitis: For long-term management, a maintenance dose of one Pantoloc 20 mg tablet per day is recommended, increasing to 40 mg pantoprazole per day if a relapse occurs. Pantoloc 40 mg tablet is available for this case. After healing of the relapse the dosage can be reduced again to Pantoloc 20 mg tablet.
Adults: 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 Pantoloc 20 mg tablet per day.
Special populations: Patients with hepatic impairment: A daily dose of 20 mg pantoprazole should not be exceeded in patients with severe liver impairment (see Precautions).
Patients with renal impairment: No dose adjustment is necessary in patients with impaired renal function (see Pharmacology: Pharmacokinetics under Actions).
Elderly: No dose adjustment is necessary in the elderly (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: Pantoloc is not recommended for use in children below 12 years of age because of limited data on safety and efficacy in this age group (see Pharmacology: Pharmacokinetics under Actions).
Gastro-resistant tablet 40 mg: Adults and adolescents 12 years of age and above: Reflux oesophagitis: One tablet of Pantoloc 40mg per day. In individual cases the dose may be doubled (increase to 2 tablets Pantoloc 40mg 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 Pantoloc 40 mg gastro-resistant tablet/day + twice daily 1000 mg amoxicillin/day + twice daily 500 mg clarithromycin /day.
b) Twice daily one Pantoloc 40 mg gastro-resistant tablet/day + twice daily 400-500 mg metronidazole (or 500 mg tinidazole)/day + twice daily 250-500 mg clarithromycin/day.
c) Twice daily one Pantoloc 40 mg gastro-resistant tablet/day + twice daily 1000 mg amoxicillin/day + twice daily 400-500 mg metronidazole (or 500 mg tinidazole)/day.
In combination therapy for eradication of H. pylori infection, the second Pantoloc 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 dosage guidelines apply for Pantoloc 40 mg monotherapy: Treatment of gastric ulcer: One tablet of Pantoloc 40mg per day. In individual cases the dose may be doubled (increase to 2 tablets of Pantoloc 40mg 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 Pantoloc 40mg per day. In individual cases the dose may be doubled (increase to 2 tablets of Pantoloc 40mg 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 Pantoloc 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 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. Pantoloc 40mg 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 Pantoloc 40mg in combination treatment of these patients (see Precautions).
Patients with renal impairment: No dose adjustment is necessary in patients with impaired renal function. Pantoloc 40mg 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 Pantoloc 40mg in combination treatment for these patients (see Pharmacology: Pharmacokinetics under Actions).
Older people: No dose adjustment is necessary in older people (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: Pantoloc 40mg 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 Pharmacology: Pharmacokinetics under Actions).
Powder for solution for injection: This medicine should be administered by a healthcare professional and under appropriate medical supervision.
The intravenous administration of Pantoloc i.v is recommended only if oral application is not appropriate. Data are available on intravenous use for up to 7 days. Therefore, as soon as oral therapy is possible, treatment with Pantoloc i.v. should be discontinued and 40 mg pantoprazole p.o. should be administered instead.
Gastric and duodenal ulcer, reflux oesophagitis: The recommended intravenous dosage is one vial (40 mg pantoprazole) Pantoloc i.v. per day.
Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions: 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 Pantoloc i.v.. 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.
In case a rapid acid control is required, a starting dose of 2 x 80 mg Pantoloc i.v. is sufficient to manage a decrease of acid output into the target range (<10 mEq/h) within one hour in the majority of patients.
Special populations: Patients with hepatic impairment: A daily dose of 20 mg pantoprazole (half a vial of 40 mg pantoprazole) should not be exceeded in patients with severe liver impairment (see Precautions).
Patients with renal impairment: No dose adjustment is necessary in patients with impaired renal function (see Pharmacology: Pharmacokinetics under Actions).
Older people/Elderly: No dose adjustment is necessary in older patients/elderly (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: The safety and efficacy of Pantoloc 40 mg powder for solution for injection in children aged under 18 years have not been established. Therefore, Pantoloc 40 mg powder for solution for injection is not recommended for use in patients below 18 years of age. Currently available data are described in Pharmacology: Pharmacokinetics under Actions but no recommendation on a posology can be made.
Method of administration: Gastro-resistant tablet: Oral use.
The tablets should not be chewed or crushed, and should be swallowed whole 1 hour before a meal with some water.
Powder for solution for injection: A ready-to-use solution is prepared in 10 mL of sodium chloride 9 mg/mL (0.9%) solution for injection. For instructions for preparation see Special precautions for disposal under Cautions for Usage. The prepared solution may be administrated directly or may be administrated after mixing it with 100 mL sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 55 mg/mL (5%) solution for injection.
After preparation the solution must be used within 12 hours.
The medicinal product should be administrated intravenously over 2-15 minutes.
There are no known symptoms of overdose/overdosage 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.
Hypersensitivity to the active substance, substituted benzimidazoles, or to any of the other excipients listed in Description.
Hepatic impairment: In patients with severe liver impairment, the liver enzymes should be monitored regularly during treatment with pantoprazole, particularly on long-term use (Gastro-resistant tablet 20 & 40 mg). In the case of a rise of the liver enzymes, the treatment should be discontinued (see Dosage & Administration).
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 Interactions).
Gastrointestinal infections caused by bacteria: Decreased gastric acidity due to any means, including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella, and Campylobacter and possibly Clostridium difficile.
Hypomagnesaemia: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with proton pump inhibitors (PPIs) for at least three months, in most cases after a year of therapy.
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), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.
Gastro-resistant tablet 20 mg: Serious adverse events include fatigue, delirium, convulsions, dizziness, tetany, arrhythmias, and seizures can occur but they may begin insidiously and be overlooked. Hypomagnesaemia may lead to hypocalcaemia and/or hypokalaemia (see Adverse Reactions). In most patients, treatment of hypomagnesemia (and hypomagnesaemia associated hypocalcaemia and/or hypokalaemia) required magnesium replacement and discontinuation of the PPI.
Gastro-resistant tablet 40 mg: Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.
Powder for solution for injection: Serious adverse events include fatigue, delirium, convulsions, dizziness, tetany, arrhythmias, and seizures can occur but they may begin insidiously and be overlooked. Hypomagnesaemia may lead to hypocalcaemia and/or hypokalaemia (see Adverse Reactions). In most patients, treatment of hypomagnesemia (and hypomagnesaemia associated hypocalcaemia and/or hypokalaemia) required magnesium replacement and discontinuation of the PPI.
Bone fractures: Long term (a year or longer) and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine, predominantly in the elderly/older people or in 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. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
Subacute 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 Pantoloc. 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, Pantoloc treatment should be stopped for at least 5 days before CgA measurements (see Pharmacology: Pharmacodynamics under Actions). 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.
Effects on ability to drive and use machines: Pantoprazole 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 Adverse Reactions). If affected, patients should not drive or operate machines.
Gastro-resistant tablet: Influence on vitamin B12 absorption: 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 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.
Gastro-resistant tablet 20 mg: Co-administration with NSAIDs: The use of Pantoloc 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.
Pantoprazole contains sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium free'.
Gastro-resistant tablet 40 mg: Combination therapy: In the case of combination therapy, the summaries of product characteristics of the respective medicinal products should be observed.
Powder for solution for injection: Pantoloc i.v. contains sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'.
Pregnancy: A moderate amount of data on pregnant women (between 300-1000 pregnancy outcomes) indicate no malformative or feto/neonatal toxicity of Pantoloc.
Animal studies have shown reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions).
As a precautionary measure, it is preferable to avoid the use of Pantoloc 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 Pantoloc therapy should take into account the benefit of breast-feeding for the child, and the benefit of Pantoloc therapy for the woman.
Fertility: There was no evidence of impaired fertility following the administration of pantoprazole in animal studies (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Approximately 5% of patients can be expected to experience adverse drug reactions (ADR). The most commonly reported ADRs for Pantoloc 40 mg tablet are diarrhoea and headache, both occurring in approximately 1% of patients.
The following table 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 form 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.)
Click on icon to see table/diagram/image
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 bioavailability/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 Precautions).
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 inhibitor 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.
Concomitant use of Proton Pump Inhibitors (PPIs) with Methotrexate: Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. A temporary withdrawal of the PPI may be considered in some patients receiving treatments with high dose methotrexate.
Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted.
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 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.
Special precautions for disposal: Gastro-resistant tab: No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Powder for solution for injection: A ready-to-use solution is prepared by injecting 10 mL of sodium chloride 9 mg/mL (0.9%) solution for injection into the vial containing the powder. The appearance of the product after reconstitution is a clear yellowish solution. This solution may be administered directly or may be administered after mixing it with 100 mL sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 55 mg/mL (5%) solution for injection. Glass or plastic containers should be used for dilution.
After reconstitution, or reconstitution and dilution, chemical and physical in use stability has been demonstrated for 12 hours at 25°C.
From a microbiological point of view, the product should be used immediately.
Pantoloc i.v. should not be prepared or mixed with solvents other than those stated.
The medicine should be administered intravenously over 2-15 minutes.
The contents of the vial are for single use only. Any product that has remained in the container or the visual appearance of which has changed (e.g. if cloudiness or precipitation is observed) should be disposed of in accordance with local requirements.
Incompatibilities: This medicinal product must not be mixed with other medicinal products except those mentioned in Special precautions for disposal as previously mentioned.
Powder for solution for injection: Do not store above 25°C.
Keep the vial in the outer carton in order to protect from light.
For storage conditions of the reconstituted and diluted medicinal products, see Shelf life as follows.
Shelf life: Gastro-resistant tab: Blister packs: 3 years.
Powder for solution for injection: After reconstitution, or reconstitution and dilution, chemical and physical in use stability has been demonstrated for 12 hours at 25°C.
From a microbiological point of view, the product should be used immediately.
If not used immediately, in-use storage times and conditions are the responsibility of the user.
A02BC02 - pantoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).
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