Presentation and Status in Health Basket
14 X 40 mg
28 X 40 mg
Adults and adolescents 12 years of age and above
Reflux oesophagitis: One tablet of 40 mg per day. In individual cases the dose may be doubled (increase to 2 tablets of 40 mg daily) especially when there has been no response to other treatment. A 4-week period is usually required for the treatment of reflux oesophagitis. If this is not sufficient, healing will usually be achieved within a further 4 weeks.
Eradication of H. pylori in combination with two appropriate antibiotics: In H. pylori positive patients with gastric and duodenal ulcers, eradication of the germ by a combination therapy should be achieved. Considerations should be given to official local guidance (e.g. national recommendations) regarding bacterial resistance and the appropriate use and prescription of antibacterial agents. Depending upon the resistance pattern, the following combinations can be recommended for the eradication of H. pylori:
a. twice daily one tablet of 40 mg
+ twice daily 1000 mg amoxycillin
+ twice daily 500 mg clarithromycin
b. twice daily one tablet of 40 mg
+ twice daily 400-500 mg metronidazole (or 500 mg tinidazole)
+ twice daily 250-500 mg clarithromycin
c. twice daily one tablet of 40 mg
+ twice daily 1000 mg amoxycillin
+ twice daily 400-500 mg metronidazole (or 500 mg tinidazole)
In combination therapy for eradication of H. pylori infection, the second 40 mg tablet should be taken 1 hour before the evening meal. The combination therapy is implemented for 7 days in general and can be prolonged for a further 7 days to a total duration of up to two weeks. If, to ensure healing of the ulcers, further treatment with pantoprazole is indicated, the dose recommendations for duodenal and gastric ulcers should be considered. If combination therapy is not an option, e.g. if the patient has tested negative for H.pylori, the following dose guidelines apply for 40 mg monotherapy:
Treatment of gastric ulcer: One tablet of 40 mg per day. In individual cases the dose may be doubled (increase to 2 tablets 40 mg daily) especially when there has been no response to other treatment. A 4 week period is usually required for the treatment of gastric ulcers. If this is not sufficient, healing will usually be achieved within a further 4 weeks.
Treatment of duodenal ulcer: One tablet of 40 mg per day. In individual cases the dose may be doubled (increase to 2 tablets 40 mg daily) especially when there has been no response to other treatment. 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.
Zollinger-Ellison-Syndrome: For the long-term management of Zollinger-Ellison-Syndrome patients should start their treatment with a daily dose of 80 mg (2 tablets of 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 is not limited and should be adapted according to clinical needs.
Patients with hepatic impairment: A daily dose of 20 mg pantoprazole (1 tablet of 20 mg pantoprazole) should not be exceeded in patients with severe liver impairment. Pantoprazole must not be used in combination treatment for eradication of H. pylori in patients with moderate to severe hepatic dysfunction since currently no data are available on the efficacy and safety of Pantoprazole in combination treatment of these patients.
Patients with Renal Impairment: No dose adjustment is necessary in patients with impaired renal function. Pantoprazole must not be used in combination treatment for eradication of H. pylori in patients with impaired renal function since currently no data are available on the efficacy and safety of Pantoprazole in combination treatment for these patients .
Older People: No dose adjustment is necessary in elderly patients.
Children below 12 years of age: Pantoprazole is not recommended for use in children below 12 years of age due to limited data on safety and efficacy in this age group.
Method of administration
Oral use: The tablets should not be chewed or crushed, and should be swallowed whole 1 hour before a meal with some water.
Short term treatment of acute duodenal ulcer. Acute gastric ulcer. Moderate and severe reflux esophagitis. Eradication of the Helicobacter pylori in combination with clarithromycin and amoxycillin or clarithromycin and metronidazole or amoxycillin and metronidazole in cases of duodenal ulcer and gastric ulcer with the objective of reducing the recurrence of duodenal and gastric ulcers caused by this microorganism. Zollinger-Ellison-Syndrome.
Hypersensitivity to the active substance, substituted benzimidazoles or to any of the other excipients. Combination therapy for the eradication of H. pylori in patients with renal impairment or severe hepatic impairment.
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.
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.
Influence on vitamin B12 absorption: In patients with Zollinger-Ellison-Syndrome 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: 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 medications such as 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 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 Controloc 20 mg or 40 mg. 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. 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 are diarrhoea and headache, both occurring in approximately 1 % of patients. Additional undesirable effects: fundic gland polyps (benign), sleep disorders, dizziness, nausea /vomiting, abdominal distension and bloating, constipation, dry mouth, abdominal pain and discomfort, liver enzymes increased (transaminases, γ-GT), rash /exanthema/ eruption, pruritus, fracture of the hip, wrist or spine, asthenia, fatigue and malaise.
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 availability, 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, 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 eaffect 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, amoxycillin). 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 Pantoprazole. Animal studies have shown reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of Pantoprazole 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 Pantoprazole therapy should take into account the benefit of breast-feeding for the child, and the benefit of Pantoprazole therapy for the woman.
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 dialyzable. In the case of an overdose with clinical signs of intoxication, apart from symptomatic and supportive treatment, no specific therapeutic recommendations can be made.
Storage: Store below 25ºC.