Pantoprazole Unicorn 20/40 20mg/40mg Tablets

PANTOPRAZOLE UNICORN 40 mg is indicated for the short-term treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis. If the duodenal ulcer has been demonstrated to be associated with Helicobacter pylori infection, PANTOPRAZOLE UNICORN 40 mg used in combination with appropriate antibiotics may be useful. PANTOPRAZOLE UNICORN 40 mg is indicated for the treatment of Zollinger-Ellison Syndrome. PANTOPRAZOLE UNICORN 20 mg is indicated for the symptomatic improvement (e.g. heartburn, acid regurgitation, pain on swallowing) and healing of mild gastro-oesophageal reflux disease (GORD). PANTOPRAZOLE UNICORN 20 mg is indicated for long-term management and prevention of relapse in gastro-oesophageal reflux disease (GORD). No dosage adjustment is required in the elderly or in the presence of impaired renal and liver function.

Duodenal ulcer: The recommended oral dose is 40 mg of PANTOPRAZOLE UNICORN once daily. The total treatment with pantoprazole should be 2 to 4 weeks. If the duodenal ulcer has been demonstrated to be associated with Helicobacter pylori infection, 40 mg of PANTOPRAZOLE UNICORN used in combination with appropriate antibiotics may be useful.

Gastric ulcer: The recommended oral dose is 40 mg of PANTOPRAZOLE UNICORN once daily for 4 to 8 weeks. In the case of a suspected gastric ulcer, malignancy of the gastric ulcer should be excluded, as treatment could conceal the symptoms and may delay diagnosis.

Reflux oesophagitis: The recommended oral dose is 40 mg of PANTOPRAZOLE UNICORN once daily in the morning for 4 to 8 weeks.

Zollinger-Ellison Syndrome: For the management of Zollinger-Ellison Syndrome patients should start their treatment with a daily dose of 80 mg of PANTOPRAZOLE UNICORN (two PANTOPRAZOLE UNICORN 40 mg tablets). Thereafter, the dosage can be titrated up or down as needed using measurements of gastric acid secretion as a guide. With doses above 80 mg daily, the dose should be divided and given twice daily.

Mild Gastro-oesophageal reflux disease (GORD): The recommended oral dose is 20 mg of PANTOPRAZOLE UNICORN per day. A 4-week period is usually required. If this is not sufficient, further 4 weeks of treatment may be used.

Long-term management and prevention of relapse in GORD: For long-term management a maintenance dose of one 20 mg PANTOPRAZOLE UNICORN tablet per day is recommended, increasing to 40 mg PANTOPRAZOLE UNICORN per day if a relapse occurs. After healing of the relapse, the dose can be reduced to 20 mg of PANTOPRAZOLE UNICORN. Experience with long-term administration is limited.

For prevention of gastro-duodenal lesions and dyspeptic symptoms induced by non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in patients at risk and with a need for continuous NSAID treatment, the recommended oral dose is one 20 mg PANTOPRAZOLE UNICORN tablet per day. If symptom control has not been achieved after four weeks of treatment with the prescribed daily dose, further investigation is recommended.

Special populations: Elderly patients: No dosage adjustment is necessary in the elderly. Renal and liver function impairment: No dosage adjustment is required in the presence of impaired renal function. A daily dose of 20 mg of PANTOPRAZOLE UNICORN should not be exceeded in patients with mild to moderately severe liver impairment (see sections 5.2 and 4.4).

Method of administration: The recommended once daily dose of PANTOPRAZOLE UNICORN should be taken in the morning. PANTOPRAZOLE UNICORN should be swallowed whole with a little water either before or during breakfast.

• Hypersensitivity to pantoprazole, substituted benzimidazoles or to any of the other excipients listed in section 6.1.
• Safety and efficacy in children has not been established.
• Co-administration of PANTOPRAZOLE UNICORN is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such as atazanavir, nelfinavir; due to significant reduction in their bioavailability (see section 4.5).
• Severely impaired liver function (see section 4.4).

Influence on vitamin B12 absorption: In patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions requiring long-term treatment, PANTOPRAZOLE UNICORN, as all acid-blocking medicinal products, 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.

Co-administration with NSAIDs: The use of PANTOPRAZOLE UNICORN 20 mg as a preventive of gastroduodenal ulcers induced by non-selective non-steroidal anti-inflammatory drugs (NSAIDs) should be restricted to patients who require continued NSAID treatment and have an increased risk to develop gastrointestinal complications. The increased risk should be assessed according to individual risk factors, e.g. high age (>65 years), history of gastric or duodenal ulcer or upper gastrointestinal bleeding.

Hepatic impairment: In patients with severe liver impairment the liver enzymes should be monitored regularly during treatment with PANTOPRAZOLE UNICORN, particularly on long-term use. In the case of a rise of the liver enzymes PANTOPRAZOLE UNICORN should be discontinued (see section 4.2).

Gastric malignancy: PANTOPRAZOLE UNICORN is not indicated for mild gastrointestinal complaints such as nervous dyspepsia. 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. Diagnosis of reflux oesophagitis should be confirmed by endoscopy.

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 (see section 4.5).

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.

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 health care 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.

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 active substances 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 the elderly 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.

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 (see section 5.1). 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.

Concomitant intake of food has no influence on the bioavailability.

Medicinal products with pH-dependent absorption pharmacokinetics: Because of profound and long lasting inhibition of gastric acid secretion, PANTOPRAZOLE UNICORN 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 medicinal products such as erlotinib.

HIV protease inhibitors: Co-administration of PANTOPRAZOLE UNICORN 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 (see section 4.3).

Coumarin anticoagulants (phenprocoumon or warfarin): Co-administration of PANTOPRAZOLE UNICORN 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 UNICORN and warfarin or phenprocoumon may need to be monitored for increase in INR and prothrombin time.

Other interactions studies: PANTOPRAZOLE UNICORN is extensively metabolised 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 active substances also metabolised with these pathways, like antipyrine, carbamazepine, diazepam, glibenclamide, nifedipine, phenytoin, and an oral contraceptive containing levonorgestrel and ethinyloestradiol did not reveal clinically significant interactions. An interaction of PANTOPRAZOLE UNICORN with other medicines or compounds which are metabolized using the same enzyme system cannot be excluded. Results from a range of interaction studies demonstrate that PANTOPRAZOLE UNICORN does not affect 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, 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 Johnu00b4s wort (Hypericum perforatum) may reduce the plasma concentrations of PPIs that are metabolised through these enzyme systems.

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.

Pregnancy: Safety in pregnancy and during lactation has not been established. There are no adequate data from the use of PANTOPRAZOLE UNICORN in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. PANTOPRAZOLE UNICORN should not be used during pregnancy.

Breastfeeding: Animal studies have shown excretion of pantoprazole in breast milk. A risk to the newborns/infants cannot be excluded. Therefore, breastfeeding while on PANTOPRAZOLE UNICORN is not recommended.

Undesirable effects such as dizziness and visual disturbances may occur (see section 4.8). If affected, patients should not drive or operate machines.

Summary of the safety profile: Approximately 5 % of patients can be expected to experience undesirable effects. The most commonly reported undesirable effects are diarrhoea and headache, both occurring in approximately 1 % of patients. For all adverse reactions reported from post-marketing experience, it is not possible to apply any adverse reaction frequency and therefore they are mentioned with a u201cnot knownu201d frequency. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Adverse reactions with pantoprazole in clinical trials and post-marketing experience:

Blood and lymphatic system: Less frequent: Agranulocytosis, leucopoenia, thrombocytopenia, pancytopenia

Immune system disorders: Less frequent: Hypersensitivity (incl. anaphylactic reactions and anaphylactic shock)

Metabolism and nutrition disorders: Less frequent: Hyperlipidaemias and lipid increases (triglycerides, cholesterol), weight changes. Frequency unknown: Hyponatraemia, hypomagnesaemia (see section 4.4), hypocalcaemia, hypokalaemia (hypocalcaemia in association with hypomagnesemia)

Psychiatric disorders: Less frequent: Sleep disorders, depression (and all aggravations), disorientation (and all aggravations). Frequency unknown: Hallucination, confusion (especially in pre-disposed patients, as well as the aggravation of these symptoms in case of pre-existence)

Nervous system disorders: Less frequent: Headache, dizziness, taste disorders. Frequency unknown: Paraesthesia

Eye disorders: Less frequent: Disturbances in vision/blurred vision

Gastrointestinal disorders: Frequent: Fundic gland polyps (benign). Less frequent: Diarrhoea, nausea/vomiting, abdominal distension and bloating, constipation, dry mouth, abdominal pain and discomfort. Frequency unknown: Microscopic colitis

Hepatobiliary disorders: Less frequent: Liver enzymes increased (transaminases, u03b3-GT), bilirubin increased. Frequency unknown: Hepatocellular injury, jaundice, hepatocellular failure

Skin and subcutaneous tissue disorders: Less frequent: Rash/exanthema/eruption, pruritus, urticaria, angioedema. Frequency unknown: Stevens-Johnson syndrome, Lyell syndrome, erythema multiforme, photosensitivity, Drug reaction with eosinophilia and systemic symptoms (DRESS) and subacute cutaneous lupus erythematosus (see section 4.4)

Musculoskeletal and connective tissue disorders: Less frequent: Fracture of the hip, wrist or spine (see section 4.4), arthralgia, myalgia. Frequency unknown: Muscle spasm as a consequence of electrolyte disturbances

Renal and urinary disorders: Frequency unknown: Interstitial nephritis (with possible progression to renal failure)

Reproductive system and breast disorders: Less frequent: Gynaecomastia

General disorders and administration site conditions: Less frequent: Asthenia, fatigue and malaise, body temperature increased, oedema peripheral

There are no known symptoms of overdose in man. Systemic exposure with up to 240 mg administered intravenously over 2 minutes was well tolerated. As pantoprazole is extensively 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.