Pantoloc

Pantoloc

pantoprazole

Manufacturer:

Takeda

Distributor:

Zuellig
Full Prescribing Info
Contents
Pantoprazole.
Description
Each 20 mg tablet contains: Pantoprazole, EP 20 mg (equivalent to Pantoprazole sodium sesquihydrate).
Each 40 mg tablet contains: Pantoprazole, EP 40 mg (equivalent to Pantoprazole sodium sesquihydrate).
Each vial contains: Pantoprazole, EP 40 mg (equivalent to Pantoprazole sodium sesquihydrate 45.1 mg).
Excipients/Inactive Ingredients: 20 mg: Sodium carbonate, mannitol, crospovidone, povidone K90, calcium stearate, hypromellose, povidone K25, propylene glycol, methylacrylic acid-ethyl acrylate copolymer (1:1), polysorbate 80, sodium lauryl sulfate, triethyl citrate, titanium dioxide E 171, yellow ferric oxide E 172, printing ink.
40 mg: Sodium carbonate, mannitol (~0.0036 BU), crospovidone, povidone K90, calcium stearate, hypromellose, povidone K25, titanium dioxide E 171, yellow iron oxide E 172, propylene glycol, methylacrylic acid-ethyl acrylate copolymer (1:1), polysorbate 80, sodium lauryl sulfate, triethyl citrate, printing ink.
IV: Edetate disodium dihydrate, sodium hydroxide.
Action
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 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.
Pharmacokinetics: Absorption: Pantoprazole is rapidly absorbed and the maximal plasma concentration is achieved even after one single 20 mg or 40 mg oral dose. On average at about 2.0 h - 2.5 h p.a. for 20 mg and 2.5 h p.a. for 40 mg the maximum serum concentrations of about 1-1.5 μg/ml for 20 mg and 2-3 μg/ml for 40 mg 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: 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 - 3h), 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 3 and 6 h (for 20 mg) and 7 and 9 h (for 40 mg) and the AUC values increased by a factor of 3-5 (for 20 mg) and 5-7 (for 40 mg), the maximum serum concentration only increased slightly by a factor of 1.3 (for 20 mg) and 1.5 (for 40 mg) 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 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.
Indications/Uses
20 mg: 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.
Adults and Adolescents aged 12 years and above: For symptomatic improvement (e.g. heartburn, acid regurgitation, pain in swallowing) and healing of mild reflux esophagitis.
For long term management and prevention of relapse in reflux esophagitis.
Children aged from 5 to 11 years old: Gastro-esophageal reflux disease (GERD), Symptomatic GERD. The treatment of heartburn and other symptoms associated with GERD.
Reflux esophagitis.
The treatment duration should not exceed 8 weeks.
40 mg: Adults: Moderate and severe reflux esophagitis; in combination with two appropriate antibiotics (see Dosage & Administration) 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 microorganism; duodenal ulcer; gastric ulcer; Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions.
Children aged from 5 to 17 years: Reflux esophagitis.
The treatment duration should not exceed 8 weeks.
IV: Duodenal ulcer; gastric ulcer, moderate and severe reflux esophagitis; Zollinger-Ellison-syndrome and other conditions associated with pathological overproduction of gastric acid; treatment of bleeding peptic ulcer and prevention of re-bleeding; prophylaxis of acute bleeding stress ulcer.
Dosage/Direction for Use
Children below 5 years of age: Pantoprazole (Pantoloc) is not recommended for use in children below 5 years of age as there is insufficient experience in children under 5 to justify a general recommendation.
20 mg: 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 gastro-resistant tablet Pantoprazole (Pantoloc) 20 mg per day.
Adults and Adolescents aged 12 years and above: For symptomatic improvement (e.g. heartburn, acid regurgitation, pain in swallowing) and healing of mild reflux esophagitis. The recommended oral dosage is one gastro-resistant tablet Pantoprazole (Pantoloc) 20 mg per day. Symptom relief is generally accomplished within 2-4 weeks, and a 4-week treatment period is usually required for healing of associated esophagitis. If this is not sufficient, healing 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, 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 esophagitis: For long term management, a maintenance dose of one gastro-resistant tablet Pantoprazole (Pantoloc) 20 mg per day is recommended, increasing to 40 mg pantoprazole per day if a relapse occurs. Pantoprazole (Pantoloc) 40 mg is available for this case. After healing of the relapse the dosage can be reduced again to 20 mg pantoprazole.
Children aged from 5 to 11 years: Symptomatic GERD (Treatment of symptomatic reflux): The recommended dosage is one Pantoprazole (Pantoloc) 20 mg tablet per day for children aged 5 to 11 years of age. If symptom control has not been achieved after four weeks treatment with Pantoprazole (Pantoloc) 20 mg tablets daily, further investigation is recommended, for example endoscopy.
Treatment of reflux esophagitis: The recommended oral dosage is one Pantoprazole (Pantoloc) 20 mg or 40 mg tablet per day.
In children aged 5 to 11 years of age, the dosage should be adjusted according to weight: Pantoprazole (Pantoloc) 20 mg (for children 19-35 kg) or Pantoprazole (Pantoloc) 40 mg (for children > 35 kg) per day.
A 4 week period is usually required for healing, however if this is not sufficient, healing will usually be achieved within a further 4 weeks.
Treatment duration in children with symptomatic GERD or reflux esophagitis should not exceed 8 weeks.
Note: A daily dose of 20 mg pantoprazole should not be exceeded in patients with severe liver impairment. No dose adjustment is necessary in elderly patients or in those with impaired renal function.
General instructions: Pantoprazole (Pantoloc) 20 mg tablets should not be chewed or crushed, and should be swallowed whole with liquid before a meal.
40 mg: Adults: Treatment of moderate and severe reflux esophagitis: One tablet of Pantoprazole 40 mg (Pantoloc) per day. In individual cases the dose may be doubled (increase to 2 tablets Pantoprazole 40 mg (Pantoloc) daily) especially when there has been no response to other treatment.
Eradication of H. pylori in combination with two appropriate antibiotics: 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 40 mg tablet Pantoprazole (Pantoloc) + twice daily 1000 mg amoxicillin + twice daily 500 mg clarithromycin.
Twice daily one 40 mg tablet Pantoprazole (Pantoloc) + twice daily 500 mg metronidazole + twice daily 500 mg clarithromycin.
Twice daily one 40 mg tablet Pantoprazole (Pantoloc) + twice daily 1000 mg amoxicillin + twice daily 500 mg metronidazole.
If combination therapy is not an option, e.g. if the patient has tested negative for Helicobacter pylori, the following dosage guidelines apply for Pantoprazole (Pantoloc) monotherapy: Treatment of gastric and duodenal ulcer: One 40 mg tablet of Pantoprazole (Pantoloc) per day.
In individual cases the dose may be doubled (increase to 2 tablets of 40 mg Pantoprazole (Pantoloc) daily especially when there has been no response to other treatment.
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 (2 tablets of "Pantoprazole (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 hypersecretory conditions is not limited and should be adapted according to clinical needs.
Children aged from 5 to 17 years: Treatment of reflux esophagitis: The recommended oral dosage is one Pantoprazole (Pantoloc) 20 mg or 40 mg tablet per day.
In children 5 to 17 years of age, the dosage should be adjusted according to weight: Pantoprazole (Pantoloc) 20 mg (for children 19-35 kg) or Pantoprazole (Pantoloc) 40 mg (for children > 35 kg) per day. A 4 week period is usually required for healing, however if this is not sufficient, healing will usually be achieved within a further 4 weeks. This dosage may be increased up to 80 mg pantoprazole per day in adolescents 12 years of age and above. Treatment duration in children aged 5 to 17 years with reflux esophagitis should not exceed 8 weeks.
Special populations: 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 Pantoprazole (Pantoloc) therapy. In case of a rise of the liver enzymes, Pantoprazole (Pantoloc) should be discontinued.
The daily dose of 40 mg pantoprazole should not be exceeded in elderly patients or in those with impaired renal function. 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.
General instructions: Pantoprazole (Pantoloc) 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 Pantoprazole (Pantoloc) 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.
IV: The intravenous administration of Pantoprazole (Pantoloc) IV is recommended only if oral application is not appropriate.
As soon as oral treatment becomes possible, intravenous administration of Pantoprazole (Pantoloc) IV should be discontinued, and the treatment should be continued with oral doses of 40 mg pantoprazole.
Recommended dosage: Duodenal ulcer, gastric ulcer, moderate and severe reflux esophagitis: The recommended intravenous dosage is one vial (40 mg pantoprazole) Pantoprazole (Pantoloc) IV per day.
Long-term management of Zollinger-Ellison Syndrome and other pathological: Hypersecretory conditions: Patients should start their treatment with a daily dose of 80 mg Pantoprazole (Pantoloc) IV. 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 Pantoprazole (Pantoloc) IV is sufficient to manage a decrease of acid output into the target range (<10 mEq/h) within one hour in the majority of patients. Transition from Pantoprazole (Pantoloc) to the oral formulation of Pantoprazole (Pantoloc) should be performed as soon as it is clinically justified.
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: No dose adjustment is necessary in older patients (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: The safety and efficacy of Pantoprazole (Pantoloc) 40 mg powder for solution for injection in children aged under 18 years have not been established. Therefore, Pantoprazole (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.
Treatment of upper digestive hemorrhage (complimentary to endoscopic therapy), and prevention of rebleeding. Bolus administration of 80 mg Pantoprazole (Pantoloc) IV followed by infusion of 8 mg/h Pantoprazole (Pantoloc) IV during 72 hours is recommended.
Prophylaxis of acute bleeding due to stress ulcer: The following dosage schedules are recommended: 40 mg to 80 mg Pantoprazole (Pantoloc) IV, once to twice daily.
The solution may be given as a bolus (for at least 2 minutes), or as an infusion, after dilution of the reconstituted solution in 100 mL of saline or 100 mL of 5% or 10% dextrose solution, in which case, a time of 15 minutes is recommended for administration.
General instructions: A ready-to-use solution is prepared by injecting 10 mL of physiological sodium chloride solution into the vial containing the dry substance. This solution may be administered directly or may be administered after mixing with 100 mL physiological sodium chloride solution or 5% Glucose.
After preparation the solution must be used within 12 hours. Pantoprazole (Pantoloc) IV should not be manufactured or mixed with solvents other than those stated.
As soon as oral therapy is possible, treatment with Pantoprazole (Pantoloc) IV should be discontinued and 40 mg pantoprazole p. o. should be administered instead. The drug should be administered intravenously over 2-15 minutes.
The experience in children is limited. Therefore, Pantoprazole (Pantoloc) IV 40 mg powder for solution for injection is not recommended for use in patients below 18 years of age until further data become available.
Overdosage
There are no known symptoms of 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.
Contraindications
Pantoprazole (Pantoloc) should generally not be used in cases of known hypersensitivity to the active substance, substituted benzimidazoles, any of the other excipients listed.
40 mg: Pantoprazole (Pantoloc) 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 (Pantoloc) in combination treatment of these patients.
Special Precautions
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.
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 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.
Treatment with Pantoprazole (Pantoloc) 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 recognized 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.
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 Pantoprazole (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, pantoprazole 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.
20 mg: The use of Pantoprazole (Pantoloc) 20 mg as a preventive of gastroduodenal ulcers induced by non-selective nonsteroidal 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. age (>65 years), history of gastric or duodenal ulcer or upper gastrointestinal bleeding.
Pantoprazole, as all acid blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorydria. 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.
In long term treatment, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.
Note: 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. Patients who do not respond after 4 weeks should be investigated.
40 mg: 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.
In the presence of any alarm symptom (eg significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded.
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 vit B12 (cyanocobalamin) due to hypo- or achlorydia. 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.
In long-term treatment, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.
IV: Gastric malignancy: The intravenous administration of Pantoprazole (Pantoloc) IV is recommended only if oral application is not appropriate.
Pantoprazole (Pantoloc) IV is not indicated for mild gastrointestinal complaints such as nervous dyspepsia. Symptomatic response to pantoprazole may mask the symptoms of gastric malignancy and may delay diagnosis.
In the presence of any alarm symptom (eg 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.
Hepatic impairment: The daily dose of 40 mg pantoprazole should not be exceeded in elderly patients or in those with impaired renal functions.
In patients with severe liver impairment the daily dose has to be reduced to 20 mg pantoprazole.
Furthermore, in these patients the liver enzymes should be monitored during Pantoprazole (Pantoloc) IV therapy. In case of a rise of the liver enzymes Pantoprazole (Pantoloc) IV should be discontinued.
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: Treatment with Pantoprazole (Pantoloc) may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter or C.difficile.
Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. is essentially 'sodium-free'.
Effects on ability to drive and use of 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.
Use in Children: To date there is insufficient experience with treatment in children under 5 to justify a general recommendation.
Use In Pregnancy & Lactation
Pregnancy: A moderate amount of data on pregnant women (between 300-1000 pregnancy outcomes) indicate no malformative or feto/ neonatal toxicity of Pantoprazole (Pantoloc).
Animal studies have shown reproductive toxicity.
As a precautionary measure, it is preferable to avoid the use of Pantoprazole (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 Pantoprazole (Pantoloc) therapy should take into account the benefit of breast-feeding for the child, and the benefit of Pantoprazole (Pantoloc) therapy for the woman.
Fertility: There was no evidence of impaired fertility following the administration of pantoprazole in animal studies.
Adverse Reactions
The assessment of side effects is based on the following frequencies: 20 & 40 mg: See Table 1.

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IV: See Table 2.

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Drug Interactions
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 medicines 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.
20 mg: 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 contraceptive.
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: 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.
Please make sure to inform the doctor if patient is taking drugs affecting blood coagulation. Additional checks of blood coagulation values may be necessary.
Caution For Usage
Special precautions for disposal: IV: 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.
Pantoprazole 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.
Storage
Store at temperature not exceeding 30°C.
IV: Store at temperatures not exceeding 25°C and protect from light.
Shelf life: 20 mg & 40 mg: 3 years.
IV: 24 months.
The reconstituted solution must be used within 12 hours after preparation.
ATC Classification
A02BC02 - pantoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).
Presentation/Packing
EC tab 20 mg (yellow, oval, biconvex film-coated imprinted with "P 20" in brown ink on one side) x 14's. 40 mg (yellow, oval, biconvex film-coated imprinted with "P 40" in brown ink on one side) x 14's. Powd for inj 40 mg (vial, white to almost white dry substance) x 1's.
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