PT Novell


Prosweal Healthcare
Full Prescribing Info
Pantoprazole (as sodium sesquihydrate).
Pantoprazole Sodium Sesquihydrate equivalent to Pantoproazole, EP 40 mg.
Pantoprazole Sodium Sesquihydrate (Panvell) 40 mg Lyophilized Powder for Injection is a hygroscopic, white and clear powder. After reconstitution, the solution is colorless to yellowish.
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, and 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 notexceed 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.
Pharmacokinetics: 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 Desmethyl pantoprazole 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 metabolizers: Approximately 3% of the European population lack a functional CYP2C19 enzyme and are called poor metabolizers. In these individuals the metabolism of pantoprazole is probably mainly catalyzed 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 metabolizers than in subjects having a functional CYP2C19 enzyme (extensive metabolizers). 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 hours), 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 7 and 9 hours and the AUC values increased by a factor of 5 to 7, the maximum serum concentration only increased slightly by a factor of 1.5 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 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.
Pantoprazole is indicated for: Reflux oesophagitis; gastric and duodenal ulcer; Zollinger-Ellison Syndrome and other pathological hypersecretory conditions.
Dosage/Direction for Use
Reflux oesophagitis, gastric and duodenal ulcer: The recommended intravenous dose is one vial of Pantoprazole 40 mg 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 Pantoprazole. Thereafter, the dose 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 dose above Pantoprazole 160 mg 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 is sufficient to manage a decrease of acid output into the target range (<10 mEq/h) within one hour in the majority of patients.
Paediatric population: The safety and efficacy of Pantoprazole 40 mg Lyophilized Powder for Injection in children age under 18 years have not been established. Therefore it is not recommended for use in patients below 18 years of age.
Patients with hepatic impairment: A daily dose of 20 mg (half a vial of 40 mg) should not be exceeded in patients with severe liver impairment.
Patients with renal impairment: No dose adjustment is necessary in patients with impaired renal function.
Older people: No dose adjustment is necessary in older people.
Route of administration: A ready-to-use solution is prepared by injecting 10 mL Sodium Chloride 9 mg/mL (0.9%) solution for injection into the vial containing the Pantoprazole Lyophilized Powder for Injection. Prepared 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. After preparation the solution must be used within 12 hours. The medicinal product should be administered intravenously over 2-15 minutes.
There are no known symptoms of overdose 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 substances, substituted Benzimidazoles or to any of the ingredients in the drug.
Special Precautions
Hepatic impairment: 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.
Combination therapy: In the case of combination therapy, the summaries of product characteristics of the respective medicinal products should be observed.
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.
Co-administration with Atazanavir: Co-administration of Atazanavir with proton pump inhibitors is not recommended. If the combination of Atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring (e.g. virus load) is recommended in combination with an increase in the dose of Atazanavir to 400 mg with 100 mg of Ritonavir. A Pantoprazole dose of 20 mg per day should not be exceeded.
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.
Gastrointestinal infections caused by bacteria: Pantoprazole, like all Proton Pump Inhibitors (PPIs), 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 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 drugs 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.
Use In Pregnancy & Lactation
Pregnancy: There are no adequate data from the use of Pantoprazole in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Pantoprazole should not be used during pregnancy, unless clearly necessary.
Lactation: Animal studies have shown excretion of Pantoprazole in breast milk. Excretion into human milk has been reported. Therefore, a decision on whether to continue/discontinue breast-feeding or to discontinue/abstain from Pantoprazole therapy should be made taking into account the benefit of breast-feeding for the child, and the benefit of Pantoprazole therapy for the woman.
Adverse Reactions
Approximately 5% of patient can be expected to experience adverse drug reactions. Adverse reactions listed as follows are classified according to frequency and System Organ Class (SOC). Frequency categories are defined according to the following convention: 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), and Not Known (cannot be estimated from the ≥ available data) is spontaneous reports from the post-marketing setting.
Gastrointestinal Disorders: Common: Fundic gland polyps (benign).
Uncommon: Diarrhoea; Nausea/vomiting; Abdominal distension and bloating; Constipation; Dry mouth; Abdominal pain and discomfort.
Hepatobiliary Disorders: Common: Liver enzymes increase (transaminase, g-GT).
Uncommon: Bilirubin increased.
Not Known: Hepatocellular injury; Jaundice; Hepatocellular failure.
General Disorders and Administration Site Conditions: Uncommon: Asthenia, fatigue, and malaise.
Psychiatric Disorders: Uncommon: Sleep disorders.
Nervous System Disorders: Uncommon: Headache; Dizziness.
Skin and Subcutaneous Tissue Disorders: Uncommon: Rash/Exanthema/Eruption; Pruritus.
Musculoskeletal Connective Tissue Disorders: Uncommon: Fracture of the hip, wrist or spine.
Drug Interactions
Effect of Pantoprazole on the absorption of other medicinal products: Because of profound and long lasting inhibition of gastric acid secretion, Pantoprazole may reduce the absorption of drugs with a gastric pH dependent bioavailability, e.g. some azole antifungals such as Ketoconazole, Itraconazole, Posaconazole and other medicines such as Erlotinib.
HIV medications (Atazanavir): Co-administration of Atazanavir and other HIV medications whose absorption is pH-dependent with PPI, might result in a substantial reduction in the bioavailability of these HIV medications and might impact the efficacy of these medicines. Therefore, the co-administration of proton pump inhibitors with Atazanavir is not recommended.
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.
Other interaction 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 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 affect the metabolism of active substances metabolzed 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.
Store at temperature not exceeding 30°C. Protect from light.
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).
Powd for inj (vial) 40 mg x 1's.
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