APR PENTAMAAT

Pantoprazole 40mg Injection

Read all of this information carefully before you start taking this medicine because it contains important information for you.

• Keep this information. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine is prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this information.

1. COMPOSITION:

Each vial contains:

Pantoprazole – 40mg

For intravenous use only.

1. DESCRIPTION:

Pantoprazole is an antacid drug. It belongs to a class of drugs known as proton pump inhibitors (PPI’s)

1. PHARMACOLOGICAL ACTION:

Pantoprazole is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the stomach by blockade of the proton pumps of the parietal cells. It is converted to its active form in the acidic environment in the parietal cells where it inhibits the H+, K+-ATPase enzyme (final stage in the production of hydrochloric acid).

The inhibition is dose-dependent & affects both basal & stimulated acid secretion. Freedom from heartburn & acid reflux symptoms is achieved in 1 week. It reduces acidity in the stomach & thereby increases gastrin in proportion to the reduction in acidity. Increase in gastrin is reversible. Since it binds to the enzyme distal to the receptor level it can inhibit hydrochloric acid secretion independently of stimulation by other substances. The effect is the same whether the active substance is given orally/intravenously.

It increases fasting gastrin levels. They do not exceed the upper limit of normal. During long-term treatment gastrin levels double in most cases. An excessive increase occurs only in isolated cases. Mild-moderate increase in the number of specific endocrine cells in the stomach is observed in a minority of

cases during long-term treatment. The formation of carcinoid precursors (atypical hyperplasia)/gastric carcinoids have not been observed.

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.

Should be discontinued between 5 days & 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.

1. CLINICAL PHARMACOKINETICS:

Pharmacokinetics do not vary after single/repeated administration. In the dose range of 10-80 mg the plasma kinetics are linear after both oral & intravenous administration.

It is completely & rapidly absorbed after oral administration. Absolute bioavailability was found to be about 77%. On average at about 2.0- 2.5 h post administration (tmax) of a single 20 mg oral dose, the max serum concentrations (Cmax) of about 1-1.5 µg/ml are achieved. These values remain constant after multiple administration. Concomitant intake of food had no influence on bioavailability (AUC or Cmax), but increased the variability of the lag-time (tlag).

Volume of distribution is about 0.15 l/kg & serum protein binding is about 98%. It is almost exclusively metabolized in the liver.

Clearance is about 0.1 l/h/kg & terminal half-life (t1/2) about 1 h. There were a few cases of subjects with delayed elimination. Due to specific binding to the proton pumps within the parietal cell the elimination half-life does not correlate with the much longer duration of action.

Renal elimination represents the major route of excretion (~ 80%) for the metabolites; the rest is excreted with the faeces. The main metabolite in both serum & urine is desmethylpantoprazole, which is conjugated with sulphate. The half-life of the main metabolite (~ 1.5 h) is not much longer than that of pantoprazole.

1. INDICATIONS:

Pantoprazole injection is indicated for the relief of:

• Reflux oesophagitis
• Gastric & duodenal ulcer
• Zollinger-Ellison-Syndrome & other pathological hypersecretory conditions
• CONTRAINDICATIONS:
• Pantoprazole tablets are contraindicated in the following cases:
• Hypersensitivity to the active substance, substituted benzimidazoles or to any of the excipients.
• WARNINGS AND PRECAUTIONS:
• Gastric malignancy: May mask symptoms of gastric malignancy & may delay diagnosis. Further investigation is to be considered if symptoms persist despite adequate treatment.Hepatic impairment: In severe liver impairment liver enzymes should be monitored.Co-administration with HIV protease inhibitors: Co-administration is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such as atazanavir.Gastrointestinal infections caused by bacteria: May lead to a slightly increased risk of GI infections caused by bacteria such as Salmonella & Campylobacter or C. difficile.May increase the counts of bacteria normally present in the upper GI tract & may lead to a slightly increased risk of GI infections caused by bacteria such as Salmonella & Campylobacter.Hypomagnesaemia: Severe hypomagnesaemia has been reported.For patients expected to be on prolonged treatment/medicinal products that may cause hypomagnesaemia health care professionals should consider measuring magnesium levels before starting PPI treatment & periodically during treatment.Bone fractures: May modestly increase the risk of hip, wrist & spine fracture predominantly in the elderly/in presence of other recognised risk factors.

  Subacute cutaneous lupus erythematosus: Associated with very infrequent cases of SCLE.

  Interference with laboratory tests: Increased Chromogranin A level may interfere with investigations for neuroendocrine tumours.

• ADVERSE EFFECTS:
• Common side effects include
• Injection site thrombophlebitis
• Fundic gland polyps
• Sleep disorders
• Headache/dizziness
• Diarrhoea, nausea, vomiting, abdominal distension, constipation, dry mouth, abdominal pain/discomfort
• Rash/pruritis
• Increased risk of fractures
• DRUG INTERACTIONS:
• May reduce the absorption of active substances whose bioavailability is dependent on the gastric pH (e.g. ketoconazole).Co-administration of atazanavir/ritonavir with omeprazole resulted in a substantial reduction in the bioavailability of atazanavir. The absorption is pH-dependent. Must not be co-administered with atazanavir.No interaction during concomitant administration of phenprocoumon/warfarin has been observed in clinical pharmacokinetic studies. A few isolated cases of changes in INR have been reported during concomitant treatment.Concomitant use of high dose methotrexate & proton-pump inhibitors has been reported to increase methotrexate levels.There were no interactions with concomitantly administered antacids.
• DOSAGE:
• Gastric & duodenal ulcer, reflux oesophagitis: The recommended IV dose is one vial per day.Zollinger-Ellison-Syndrome & other pathological hypersecretory conditions: For the long-term management of Zollinger-Ellison-Syndrome & other pathological hypersecretory conditions patients should start their treatment with a daily dose of 80mg. Thereafter dose can be titrated up/down as needed using measurements of gastric acid secretion to guide. With doses above 80mg daily, the dose
• Diarrhoea, nausea, vomiting, abdominal distension, constipation, dry mouth, abdominal pain/discomfort
• Rash/pruritis
• Increased risk of fractures
• DRUG INTERACTIONS:
• May reduce the absorption of active substances whose bioavailability is dependent on the gastric pH (e.g. ketoconazole).Co-administration of atazanavir/ritonavir with omeprazole resulted in a substantial reduction in the bioavailability of atazanavir. The absorption is pH-dependent. Must not be co-administered with atazanavir.No interaction during concomitant administration of phenprocoumon/warfarin has been observed in clinical pharmacokinetic studies. A few isolated cases of changes in INR have been reported during concomitant treatment.Concomitant use of high dose methotrexate & proton-pump inhibitors has been reported to increase methotrexate levels.There were no interactions with concomitantly administered antacids.
• DOSAGE:
• Gastric & duodenal ulcer, reflux oesophagitis: The recommended IV dose is one vial per day.Zollinger-Ellison-Syndrome & other pathological hypersecretory conditions: For the long-term management of Zollinger-Ellison-Syndrome & other pathological hypersecretory conditions patients should start their treatment with a daily dose of 80mg. Thereafter dose can be titrated up/down as needed using measurements of gastric acid secretion to guide. With doses above 80mg daily, the dose should be divided & given twice daily. A temporary increase of the dose above 160mg 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 within 1 hour in the majority of patients.Hepatic Impairment: A daily dose of 20 mg should not be exceeded in patients with severe liver impairment.
• ADMINISTRATION:
• A ready-to-use solution is prepared in 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection. The 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/glucose monohydrate 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.
• PRESENTATION:
• STORAGE:
• Store below 25°C in a cool & dry pace. Protect from direct sunlight. Keep away from the reach of children.
• MANUFACTURED BY:
• MARKETED BY:
• This leaflet was last revised on May 2019.