⚠️ Warnings
Hepatic impairment. Patients with severe hepatic impairment should have their liver enzyme levels monitored regularly, particularly during long-term treatment. If liver enzyme levels increase, treatment with the medicinal product should be discontinued.
Combination therapy. During combination therapy, the instructions for use of the respective co-administered medicinal products must be followed.
Gastric malignancy. The symptomatic response to pantoprazole therapy may mask the symptoms of gastric malignancy and delay its diagnosis. In the presence of alarm symptoms (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia, melaena), and when gastric ulcer is suspected or present, malignancy should be excluded.
If symptoms persist despite adequate treatment, further investigation should be considered.
HIV protease inhibitors. Co-administration of pantoprazole with HIV protease inhibitors (such as atazanavir), the absorption of which depends on intragastric pH, is not recommended due to a significant reduction in their bioavailability (see section "Interactions with other medicinal products and other forms of interaction").
Effect on vitamin B12 absorption.
Pantoprazole may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with reduced body weight or risk factors for decreased vitamin B12 (cyanocobalamin) absorption, particularly during long-term treatment or when corresponding clinical symptoms are present.
Long-term treatment. During long-term treatment, especially exceeding 1 year, patients should be kept under regular medical supervision.
Gastrointestinal infections caused by bacteria.
Treatment with the medicinal product may slightly increase the risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter or C. difficile.
Hypomagnesaemia. Rare cases of severe hypomagnesaemia have been reported in patients treated with PPIs such as pantoprazole for at least 3 months, and in most cases for a year. Serious clinical manifestations of hypomagnesaemia may develop insidiously and include: fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmia. Hypomagnesaemia may lead to hypocalcaemia and/or hypokalaemia (see section "Special warnings and precautions for use"). In the majority of cases of hypomagnesaemia (and associated hypocalcaemia and/or hypokalaemia), patients improved after replacement magnesium therapy and discontinuation of PPI treatment.
For patients expected to require prolonged treatment or those taking PPIs concomitantly with digoxin or medicinal products that may cause hypomagnesaemia (e.g. diuretics), magnesium levels should be measured prior to initiation of PPI therapy and periodically during treatment.
Bone fractures. Long-term treatment (more than 1 year) with high doses of proton pump inhibitors may moderately increase the risk of hip, wrist, and spine fractures, predominantly in elderly patients or in the presence of other risk factors. Observational studies indicate that PPI use may increase the overall risk of fractures by 10–40%. Some of these may be attributable to other risk factors. Patients at risk of osteoporosis should receive treatment according to current clinical guidelines and should have an adequate intake of vitamin D and calcium.
Severe cutaneous adverse reactions (SCARs).
Severe cutaneous adverse reactions have been reported with pantoprazole use, including erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which may be life-threatening or fatal. The frequency of these reactions is not known (see section "Adverse reactions").
When prescribing pantoprazole, patients should be informed of the signs and symptoms and closely monitored for cutaneous reactions. If signs or symptoms suggestive of these severe cutaneous reactions appear, pantoprazole should be discontinued immediately and alternative treatment should be considered.
Subacute cutaneous lupus erythematosus. The use of proton pump inhibitors has been associated with very rare cases of subacute cutaneous lupus erythematosus. If lesions occur, especially in sun-exposed areas of the skin, accompanied by arthralgia, the patient should promptly seek medical attention, and the physician should consider discontinuing Nolpaza®. The occurrence of subacute cutaneous lupus erythematosus during prior PPI therapy may increase the risk of its development with other proton pump inhibitors.
Effect on laboratory test results.
Elevated chromogranin A (CgA) levels may interfere with investigations for neuroendocrine tumours. To avoid such interference, treatment with Nolpaza® should be temporarily discontinued at least 5 days prior to CgA level assessment (see section "Pharmacodynamics"). If CgA and gastrin levels have not returned to the normal range after the initial measurement, repeat measurements should be performed 14 days after discontinuation of PPI therapy.
Information regarding excipients.
Nolpaza® contains sorbitol. Patients with rare hereditary fructose intolerance should not take this medicinal product.
