Panpriva

Panpriva

pantoprazole

Manufacturer:

Pharmaniaga LifeScience

Distributor:

Pharmaniaga Logistics
Full Prescribing Info
Contents
Pantoprazole sodium.
Description
Each vial contains: Active ingredient: Pantoprazole Sodium Sesquihydrate 45.11mg is equivalent to Pantoprazole 40mg.
The compatible reconstitution solution for intravenous use is as follow: 0.9% Sodium Chloride.
The compatible infusion solutions for intravenous use are as follows: 0.9% Sodium Chloride; 5% Dextrose.
Before reconstitute: Hygroscopic white to off-white solid.
After reconstitute: A clear solution.
The solution should be a clear solution after reconstituted. Do not use if there is any precipitates in the solution. The solution will remain stable for 12 hours at room temperature (30°C) after reconstitution and dilution.
Excipients/Inactive Ingredients: Sodium Hydroxide and Water For Injection.
Action
Pharmacotherapeutic group: Proton pump inhibitors. ATC code: A02BC02.
Pharmacology: Pharmacodynamics:
Pantoprazole is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the stomach by specific 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.
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).
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: General pharmacokinetics: Pharmacokinetics do 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.
Distribution: Pantoprazole's serum protein binding is about 98%. Volume of distribution is about 0.15 l/kg.
Elimination: The substance is almost exclusively metabolized in the liver. The main metabolic pathway is demethylation by CYP2C19 with subsequent sulphate conjugation, other metabolic pathway include oxidation by CYP3A4. 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.
Indications/Uses
Short term use for symptomatic improvement and healing of gastrointestinal diseases which require a reduction in acid secretion: Duodenal ulcer; Gastric ulcer; Moderate and severe reflux oesophagitis; Zollinger-Ellison syndrome and other pathological hypersecretory conditions.
Dosage/Direction for Use
The intravenous administration of panpriva is recommended only if oral application is not appropriate.
The recommended dose for gastric and duodenal ulcer and moderate and severe reflux esophagitis is one vial of 40mg panpriva per day.
For the long-term management of Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions the recommended daily dose at the beginning of the treatment is 80mg panpriva. Thereafter, the dosage can be titrated up or down as needed using measurements of gastric acid secretion to guide.
With doses above 80mg 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 × 80 mg panpriva is sufficient to manage a decrease of acid output into the target range (<10mEq/h) within one hour in the majority of patients. Transition from panpriva to the oral formulation of pantoprazole should be performed as soon as it is clinically justified. The recommended intravenous dosage is one vial (40 mg Pantoprazole) panpriva per day.
Instructions for use / handling: 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. panpriva should not be prepared or mixed with solvents other than those stated. After preparation the solution must be used within 12 h. From a microbiological point of view the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 12 hours at not more than 30°C after reconstitution and dilution. The drug should be administered intravenously over 2 -15 minutes.
Special Patient Populations: Impaired Hepatic function: A daily dose of 20 mg pantoprazole half a vial of 40 mg pantoprazole I.V.) should not be exceeded in patients with severe liver impairment (See Precautions).
Impaired renal function: No dose adjustment is necessary in patients with impaired renal function.
Type and duration of the treatment: As soon as oral therapy is possible, treatment with panpriva should be discontinued and 40mg pantoprazole p.o. should be administered instead.
ROUTE OF ADMINISTRATION: For intravenous (IV) use only.
Overdosage
There are no known symptoms of overdosage in man.
Systematic exposure with up to 240 mg administered intravenously over 2 minutes were well tolerated. As pantoprazole is excessively protein bound, it is not readily dialysable.
In the case of overdose with clinical signs of intoxication, apart from symptomatic and supportive treatment, no specific therapeutic recommendations can be made.
Contraindications
Hypersensitivity to the active substance, substituted benzimidazoles, or to any of the excipients.
Special Precautions
Regular Surveillance: Patients on proton pump inhibitor treatment (particularly those treated for long term) should be kept under regular surveillance.
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.
Gastrointestinal infections caused by bacteria: 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 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 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.
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. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.
Clostridium Difficile Diarrhea: Published observational studies suggest that PPI therapy may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
Vitamin B12 Deficiency: Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.
Interference with Laboratory Tests: Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. If the patient(s) are due to have a test on Chromogranin A level, pantoprazole treatment should be stopped for at least 5 days before CgA measurements to avoid this interference (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 of machines: Adverse drug reactions such as dizziness and visual disturbances may occur. If affected, patients should not drive or operate machines.
Hepatic impairment: In patients with severe liver impairment, the liver enzymes should be monitored during therapy. In the case of a rise of the liver enzymes, the treatment should be discontinued.
Use In Pregnancy & Lactation
Pregnancy: The potential risk for humans is unknown. Pantoprazole should not be used during pregnancy unless clearly necessary.
Lactation: Excretion of pantoprazole into human milk has been reported. Therefore, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with pantoprazole should be made taking into account the benefit of breast-feeding to the child and the benefit of pantoprazole therapy to women.
Side Effects
The most commonly reported ADRs are diarrhoea and headache.
Blood and lymphatic system disorders: Rare: Agranulocytosis.
Very rare: Thrombocytopenia; Leukopenia, Pancytopenia.
Immune system disorders: Rare: Hypersensitivity (including anaphylactic reactions and anaphylactic shock).
Metabolism and nutrition disorders: Vitamin B12 deficiency.
Rare: Hyperlipidaemia as and lipid increases (triglycerides, cholesterol); Weight changes.
Not known: Hyponatraemia, Hypomagnesaemia, Hypocalcaemia in association with hypomagnesemia; Hypokalaemia.
Psychiatric disorders: Uncommon: Sleep disorders.
Rare: Depression (and all aggravations).
Very rare: Disorientation (and all aggravations).
Not known: Hallucination; Confusion (especially in pre-disposed patients, as well as the aggravation of these symptoms in case of pre-existence).
Nervous system disorders: Uncommon: Headache; Dizziness.
Rare: Taste disorders.
Not known: Paraesthesia.
Eye disorders: Rare: Disturbances in vision / blurred vision.
Gastrointestinal disorders: Uncommon: Diarrhoea; Nausea / vomiting; Abdominal distension and bloating; Constipation; Dry mouth; Abdominal pain and discomfort.
Common: Fundic Gland Polyps (Benign).
Hepatobiliary disorders: Uncommon: Liver enzymes increased (transaminases, γ-GT).
Rare: Bilirubin increased.
Not known: Hepatocellular injury; Jaundice; Hepatocellular failure.
Skin and subcutaneous tissue disorders: Uncommon: Rash/exanthema/eruption; Pruritus.
Rare: Urticaria; Angioedema.
Not known: Stevens-Johnson syndrome; Lyell syndrome; Erythema multiforme; Photosensitivity; Subacute cutaneous lupus erythematosus.
Musculoskeletal and connective tissue disorders: Uncommon: Fracture of the hip, wrist or spine.
Rare: Arthralgia; Myalgia.
Not known: Muscle spasm as a consequence of electrolyte disturbances.
Renal and urinary disorders: Unknown: Interstitial nephritis (with possible progression to renal failure).
Reproductive system and breast disorders: Rare: Gynaecomastia.
General disorders and administration site conditions: Common: Injection site thrombophlebitis.
Uncommon: Asthenia, fatigue and malaise.
Rare: Body temperature increased; Oedema peripheral.
Infection/ infestations: Clostridium Difficile associated Diarrhea.
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 as ketoconazole, itraconazole, posaconazole and other medicine as erlotinib.
HIV medications (atazanavir): Co-administration of atazanavir and other HIV medications whose absorption is pH-dependent with proton-pump inhibitors 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): A few isolated cases of changes in INR have been reported during concomitant administration of phenprocoumon or warfarin. Therefore, in patients being treated with coumarin anticoagulants, 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 interactions: 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.
No clinically significant interactions with other drugs metabolized with these pathways, like carbamazepine, diazepam, glibenclamide, nifedipine, and an oral contraceptive containing levonorgestrel and ethinyl oestradiol.
Pantoprazole does not effect 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.
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.
There were also no interactions with concomitantly administered antacids.
No clinically relevant interactions were found when administering pantoprazole concomitantly with the respective antibiotics (clarithromycin, metronidazole, amoxicillin).
Incompatibilities: This medicinal product should not be mixed with solvents other than those stated in sections Instruction for Use under Cautions for Usage.
Caution For Usage
Instructions and use/handling: 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 infusion solution or 5% Dextrose intravenous infusion.
panpriva should not be prepared or mixed with solvents other than stated.
After preparation the solution must be used within 12 hours.
From a microbiological point of view the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 12 hours at not more than 30°C after reconstitution and dilution.
The drug should be administered intravenously over 2-15 minutes.
Storage
Store below 30°C.
Protect from light.
Do not freeze.
Retain in carton until time of use.
The solution will remain stable for 12 hours at room temperature (30°C) after reconstitution and dilution. From a microbiological point of view the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. (See Table 1.)

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Shelf-Life: 2 years.
The solution will remain stable for 12 hours at room temperature (30°C) after reconstitution and dilution. From a microbiological point of view the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. (See Table 2.)

Click on icon to see table/diagram/image
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
Powd for inj (vial) 40 mg x 10 mL x 10's.
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