Presentation and Status in Health Basket
1 X 40 mg
This medicine should be administered by a healthcare professional and under appropriate medical supervision. Intravenous administration of Controloc I. V. is recommended only if oral administration is not appropriate. Data are available on intravenous use for up to 7 days. Therefore, as soon as oral therapy is possible, treatment with Controloc I.V. should be discontinued and 40 mg pantoprazole p.o. should be administered instead.
Duodenal ulcer, gastric ulcer, moderate and severe reflux oesophagitis: The recommended intravenous dose is one vial of Controloc I.V. (40 mg pantoprazole) per day.
Zollinger-Ellison-Syndrome: For the long-term management of Zollinger-Ellison-Syndrome patients should start their treatment with a daily dose of 80 mg Controloc I.V. 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 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 Controloc 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.
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.
Patients with renal Impairment: no dose adjustment is necessary in patients with impaired renal function.
Older people: no dose adjustment is necessary in older patients.
Paediatric population: the safety and efficacy of Controloc I.V. in children aged under 18 years have not been established. Therefore, Controloc I.V. is not recommended for use in patients below 18 years of age.
Method of 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, 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.
Duodenal ulcer, gastric ulcer, moderate and severe reflux oesophagitis, Zollinger-Ellison-Syndrome.
Hypersensitivity to the active substance, substituted benzimidazoles, or to any of the excipients.
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.
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.
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.
Sodium: this medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. is essentially ‘sodium-free’.
Hypomagnesemia: 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 hypomagnesemia (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 the elderly or in 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 Controloc I.V. 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, Controloc® I.V. treatment should be stopped for at least 5 days before CgA measurements. 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.
See prescribing information for full details.
Approximately 5% of patients can be expected to experience adverse drug reactions (ADRs). The most commonly reported ADRs is injection site thrombophlebitis. Diarrhoea and headache occurred in approximately 1% of patients.
See prescribing information for full details.
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, 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. 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, phenoprocoumon or INR. However, there have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin or phenoprocoumon 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 metabolized 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 administering pantoprazole concomitantly 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.
Pregnancy and Lactation
Pregnancy: A moderate amount of data on pregnant women (between 300-1000 pregnancy outcomes) indicate no malformative or feto/ neonatal toxicity of Controloc I.V. Animal studies have shown reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of Controloc I.V. during pregnancy.
Lactation: 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 Controloc I.V. therapy should take into account the benefit of breast-feeding for the child, and the benefit of Controloc I.V. therapy for the women.
There are no known symptoms of over dosage 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 overdosage with clinical signs of intoxication, apart from symptomatic and supportive treatment, no specific therapeutic recommendations can be made.
Shelf life: After reconstitution, or reconstitution and dilution, chemical and physical in-use stability has been demonstrated for 12 hours at 25°C.
Storage: Do not store above 25°C. Keep the vial in the outer carton in order to protect from light.