Topzole Range 20 mg, 40 mg Enteric-coated tablets

TOPZOLE u00ae 40 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, TOPZOLE u00ae 40 used in combination with appropriate antibiotics may be useful. TOPZOLE u00ae 40 is indicated for the treatment of Zollinger - Ellison Syndrome. TOPZOLE u00ae 20 is indicated for the symptomatic improvement (e.g. heartburn, acid regurgitation, pain on swallowing) and healing of mild gastro - oesophageal reflux disease. In patients with healed reflux disease, recurring symptoms can be controlled using an on - demand regimen of 20 mg once daily when required. TOPZOLE u00ae 20 is indicated for long - term management and prevention of relapse in gastro - oesophageal reflux disease. TOPZOLE u00ae 20 is indicated for the prevention of gastroduodenal lesions and dyspeptic symptoms induced by non - selective non - steroidal anti - inflammatory drugs (NSAIDu2019s) in patients at risk, and with a need for continuous NSAID treatment.

TOPZOLE u00ae 20 and TOPZOLE u00ae 40 should be swallowed whole with a little water either before or during breakfast.

Duodenal ulcer

The recommended oral dose is 40 mg TOPZOLE u00ae once daily for 2 to 4 weeks. If the duodenal ulcer has been demonstrated to be associated with Helicobacter pylori infection, TOPZOLE u00ae 40 used in combination with appropriate antibiotics may be useful.

Gastric ulcer

The recommended oral dose is 40 mg TOPZOLE u00ae 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 TOPZOLE u00ae once daily for 4 to 8 weeks.

Zollinger - Ellison Syndrome

For management of Zollinger - Ellison Syndrome patients should start their treatment with a daily dose of 80 mg (2 tablets of TOPZOLE u00ae 40). 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

The recommended oral dose is 20 mg TOPZOLE u00ae per day. A 4 - week period is usually required for healing of mild gastro - oesophageal reflux disease. If this is not sufficient, healing will usually be achieved within a further 4 weeks. In patients with healed reflux disease, reoccurring symptoms can be controlled using an on - demand regimen of 20 mg once daily when required.

Long - term management and prevention of relapse in gastro - oesophageal reflux disease

For long - term management a maintenance dose of one TOPZOLE u00ae 20 tablet per day is recommended, increasing to 40 mg TOPZOLE u00ae per day if a relapse occurs. After healing of the relapse, the dose can be reduced to 20 mg TOPZOLE u00ae. 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 (NSAIDu2019s) in patients at risk and with a need for continuous NSAID treatment, the recommended oral dose is one TOPZOLE u00ae 20 tablet per day.

Elderly patients

No dosage adjustment is necessary in the elderly.

Impaired renal function

No dosage adjustment is required in the presence of impaired renal function. In addition, TOPZOLE u00ae 40 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 TOPZOLE u00ae in combination treatment for these patients.

Impaired hepatic function

A daily dose of 20 mg TOPZOLE u00ae should not be exceeded in patients with mild to moderate liver impairment (see Section 5.2 and Section 4.4). In addition, TOPZOLE u00ae 40 must not be used in combination treatment for eradication of H. pylori in patients with mild to moderate hepatic dysfunction, since currently no data are available on the efficacy and safety of TOPZOLE u00ae in combination treatment for these patients.

Hypersensitivity to pantoprazole and any of the excipients. Safety and efficacy in children have not been established. Severely impaired liver function (see Section 4.4). TOPZOLE u00ae , should not be co - administered with nelfinavir & atazanavir (see Section 4.5).

TOPZOLE u00ae is not indicated for mild gastrointestinal complaints such as nervous dyspepsia. Further investigation is to be considered if symptoms persist despite adequate treatment. The daily dose of 40 mg TOPZOLE u00ae should not be exceeded in elderly patients or in those with impaired renal function.

Bone fracture

PPI therapy, including TOPZOLE u00ae , may be associated with an increased risk for osteoporosis - related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received daily doses, and long - term TOPZOLE u00ae therapy (a year or longer).

Clostridium difficile

PPI therapy, like TOPZOLE u00ae , may be associated with an increased risk of Clostridium difficile - associated diarrhoea, especially in hospitalised patients. This diagnosis should be considered for diarrhoea that does not improve (see Section 4.8).

Hypomagnesaemia

Hypomagnesaemia has been reported in patients treated with TOPZOLE u00ae for more than three months (in most cases after a year of therapy). Serious consequences of hypomagnesaemia include tetany, dysrhythmia and seizure.

HIV Protease Inhibitors

Co - administration of TOPZOLE u00ae is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such as atazanavir, nelfinavir due to a significant reduction in their bioavailability (see Section 4.5).

Methotrexate

Concomitant use with high dose methotrexate may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities (see Section 4.5).

Severe Cutaneous Adverse Reactions (SCAR)

Severe cutaneous adverse reactions, including erythema multiforme, Stevens - Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs (see Undesirable Effects, 4.8). Discontinue pantoprazole at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

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 TOPZOLE u00ae. 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, TOPZOLE u00ae 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.

TOPZOLE u00ae contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially u2018sodium - freeu2019.

Mannitol

Patients with the rare hereditary condition of mannitol intolerance should not take TOPZOLE u00ae.

Hepatic impairment

In patients with mild to moderate liver impairment the liver enzymes should be monitored regularly during treatment with 40 mg TOPZOLE u00ae, particularly on long - term use. In the case of a rise of the liver enzymes TOPZOLE u00ae should be discontinued.

Use of TOPZOLE u00ae 20 as preventative 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.

TOPZOLE u00ae is not indicated for mild gastro - intestinal complaints such as nervous dyspepsia.

Gastric malignancy

Symptomatic response to TOPZOLE u00ae does not preclude the presence of gastric malignancy. In the presence of any alarm symptoms (e.g., significant weight loss, recurrent vomiting, dysphagia, haematemesis or malaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with TOPZOLE u00ae may alleviate symptoms and delay diagnosis.

Influence on Vitamin B 12 absorption

Daily treatment with any acid blocking medicines, including TOPZOLE u00ae, over a long period of time (e.g., longer than 3 years) may lead to malabsorption of vitamin B 12 caused by hypo - or achlorhydia. Cases of vitamin B 12 deficiency under acid - blocking therapy have been reported in the literature. This should be considered when respective clinical symptoms are observed.

Concomitant intake of food has no influence on the bioavailability. The active ingredient of TOPZOLE u00ae is metabolised in the liver via the cytochrome P450 enzyme system. An interaction of TOPZOLE u00ae with other medicines or compounds which are metabolised using the same enzyme system cannot be excluded. No clinically significant interactions were, however, observed in specific tests with a number of such medicines or compounds, namely antipyrine, caffeine, carbamazepine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, metoprolol, naproxen, nifedipine, phenprocoumon, phenytoin, piroxicam, theophylline, warfarin and oral contraceptives.

Warfarin

The response to warfarin may be affected by any concomitant medication. It is therefore good practice to monitor the patient with additional PT (prothrombin time) /INR (international normalised ratio) determinations when TOPZOLE u00ae is initiated, discontinued or taken irregularly.

Due to long lasting inhibition of gastric acid secretion TOPZOLE u00ae may reduce the absorption of medicines with a gastric pH - dependent bioavailability, e.g. some azole antifungals like ketoconazole, itraconazole, posaconazole and other medicines like erlotinib.

HIV Protease Inhibitors

Co - administration of pantoprazole is contraindicated with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such as atazanavir, and nelfinavir; due to significant reduction in their bioavailability (see Contraindications, 4.3).

There were no interactions with concomitantly administered antacids.

Methotrexate

Concomitant use of TOPZOLE u00ae with methotrexate may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities (see Section 4.4).

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.

Effects of Other Medicines on Pantoprazole

Drugs that Inhibit or Induce CYP2C19 Inhibitors of CYP2C19, such as fluvoxamine, would likely increase the systemic exposure to pantoprazole. Inducers of CYP2C19 may decrease the systemic exposure to pantoprazole.

Safety in pregnancy and during lactation has not been established.

Pantoprazole is not expected to adversely affect the ability to drive or use machines. However, adverse drug reactions such as dizziness and visual disturbances (e.g., blurred vision) may occur (see Section 4.8). If affected, patients should not drive or operate machines.

SIDE EFFECTS

Very common (u22651/10); common (u22651/100, < 1/10); uncommon (u22651/1000, < 1/100); rare (u2265 1/10 000, < 1/1000) very rare (u2264 1/10 000) including isolated cases, not known (cannot be estimated from the available data).

Frequency MEDRASystem Organ Class Common Uncommon Rare Very rare Not known Blood and lymphatic system disorders Agranulocytosis Thrombocytopenia; Leukopenia; Pancytopenia Immune system disorders Hypersensitivity (including anaphylactic reactions and anaphylactic shock) Metabolism and nutrition disorders Hyperlipidaemias and lipid increases (triglycerides, cholesterol); Weight changes Hyponatraemia; Hypomagnesaemia (see section 4.4); Hypocalcaemia (1); Hypokalaemia (1) Psychiatric disorders Sleep disorders Depression (and all aggravations) Disorientation (and all aggravations) Hallucination; Confusion (especially in pre - disposed patients, as well as the aggravation of these symptoms in case of pre - existence) Nervous system disorders Headache; Dizziness Taste disorders Paraesthesia

Eye disorders Disturbances in vision / blurred vision Gastrointestinal disorders Fundic gland polyps (benign) Diarrhoea; Nausea / vomiting; Abdominal distension and bloating; Constipation; Dry mouth; Abdominal pain and discomfort Microscopic colitis Hepatobiliary disorders Liver enzymes increased (transaminases, u03b3 - GT) Bilirubin increased Hepatocellular injury; Jaundice; Hepatocellular failure Skin and subcutaneous tissue disorders Rash / exanthema / eruption; Pruritus Urticaria; Angioedema Stevens - Johnson syndrome; Toxic epidermal Necrolysis; Lyell syndrome; Drug reaction with eosinophilia and systemic symptoms; Acute generalized exanthematous pustulosis; Erythema multiforme; Photosensitivity; Subacute cutaneous lupus erythematosus (see section 4.4); Drug reaction with eosinophilia and systemic symptoms (DRESS)

Musculoskeletal and connective tissue disorders Fracture of the hip, wrist or spine (see section 4.4) Arthralgia; Myalgia Muscle spasm (2) Renal and urinary disorders Tubulointerstitial nephritis (TIN) with possible progression that may lead to chronic renal failure) Reproductive system and breast disorders Gynaecomastia General disorders and administration site conditions Asthenia, fatigue and malaise Body temperature increased; Oedema peripheral

1. Hypocalcaemia and/or hypokalaemia may be related to the occurrence of hypomagnesaemia (see section 4.4) 2. Muscle spasm as a consequence of electrolyte disturbance

Post - marketing reports: Hepatobiliary disorders : Hepatocellular injury, jaundice, hepatocellular failure Psychiatric disorders : Hallucination, confusion (especially in pre - disposed patients, as well as the aggravation of these symptoms in case of pre - existence) Renal and urinary disorders : Interstitial nephritis Skin and subcutaneous tissue disorders : Stevens - Johnson syndrome, Lyell syndrome (Toxic epidermal necrolysis), erythema multiforme, photosensitivity Infections and infestations : Clostridium difficile - associated diarrhoea.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who umc.org) found on SAHPRA website. Additionally, suspected adverse reactions can be reported to [email protected] or on the 24 hours contact number: 082 525 3040

There are no known symptoms of overdosage in man. No specific therapeutic recommendation can be made in cases of overdosage.