Pantakind-40 40 mg Delayed release tablet

PANTAKIND-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, PANTAKIND-40 used in combination with appropriate antibiotics may be useful. PANTAKIND-40 is indicated for the treatment of Zollinger-Ellison Syndrome.

Posology

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

Gastric ulcer
The recommended oral dose is 40 mg PANTAKIND-40 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 PANTAKIND-40 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 PANTAKIND-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.

Long-term management and prevention of relapse in gastro-oesophageal reflux disease
For long-term management a maintenance dose of one 20 mg pantoprazole tablets per day is recommended, increasing to 40 mg PANTAKIND-40 per day if a relapse occurs. After healing of the relapse, the dose can be reduced to 20 mg pantoprazole tablets. Experience with long-term administration is limited.

Special population

Elderly patients
No dosage adjustment is necessary for the elderly.

Impaired renal and liver function
No dosage adjustment is required in the presence of impaired renal function. A daily dose of 20 mg PANTAKIND-40 should not be exceeded in patients with mild to moderately severe liver impairment (see sections 4.4 and 5.2).

Method of administration
For oral administration PANTAKIND-40 should be swallowed whole with a little water either before or during breakfast.

PANTAKIND-40 is contraindicated in:

• Hypersensitivity to pantoprazole sodium.
• Severely impaired liver function (see section 4.4).
• Safety and efficacy in children have not been established.
• PANTAKIND-40 should not be co-administered with atazanavir and nelfinavir (see section 4.4).

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 in the liver enzymes, the treatment should be discontinued (see section 4.2).

Combination therapy
In the case of combination therapy, the Professional Information of the respective medicines 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 a significant reduction in their bioavailability (see section 4.5).

Influence on vitamin B12 absorption
In patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions requiring long-term treatment, pantoprazole, like 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 rarely reported in patients treated with proton pump inhibitors (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. Hypomagnesaemia may lead to hypocalcaemia and/or hypokalaemia (see section 4.8). In most affected patients, hypomagnesaemia (and hypomagnesaemia associated with hypocalcaemia and/or hypokalaemia) improved after magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who takes PPIs with digoxin or medicines 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 the presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10 to 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.

Sub-acute 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. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

Acute tubulointerstitial nephritis
Acute Tubulointerstitial Nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. TIN is characterised by an inflammatory reaction within the tubulointerstitial space of the kidney. Acute interstitial inflammatory reactions are associated with damage to the tubulointerstitium, leading to acute kidney injury. TIN may be drug-related, infectious, systemic, autoimmune, genetic, and idiopathic with the most common cause being related to a medication or drug exposure. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decrease renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extrarenal manifestations (e.g., fever rash or arthralgia). Discontinue PANTAKIND-40 and evaluate patients with suspected acute TIN.

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 the reference range after the initial measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor treatment.

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

Interference with Antiretroviral Therapy
Concomitant use of atazanavir or nelfinavir with proton pump inhibitors is not recommended. Coadministration of atazanavir or nelfinavir with proton pump inhibitors is expected to substantially decrease atazanavir or nelfinavir plasma concentrations and may result in a loss of therapeutic effect and development of medicine resistance. 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
Study reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including PANTAKIND-40, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly should be monitored for increases in INR and prothrombin time.

Clopidogrel
In a study concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel induced platelet inhibition. No dose adjustment of clopidogrel is necessary when administered with an approved dose of PANTAKIND-40.

Medicines for which gastric pH can affect bioavailability
Pantoprazole causes long-lasting inhibition of gastric acid secretion. Therefore, pantoprazole may interfere with the absorption of medicines where gastric pH is an important determinant of their bioavailability (e.g., ketoconazole, ampicillin esters, and iron salts).

False positive urine tests for THC
There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving proton pump inhibitors. An alternative confirmatory method should be considered to verify positive results.

Methotrexate
Studies published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose, see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted (see section 4.4).

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 metabolised through these enzyme systems.

Pregnancy
The safety in pregnant women has not been established. Animal studies have shown reproductive toxicity.

Breastfeeding
Safety during lactation has not been established. Animal studies have shown the 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 breastfeeding or to discontinue/abstain from Pantoprazole therapy takes into account the benefit of breastfeeding for the child and the benefit of Pantoprazole therapy for the woman.

Fertility
There was no evidence of impaired fertility following the administration of pantoprazole in animal studies.

Pantoprazole has no or negligible influence on the ability to drive and use machines. Adverse drug reactions, such as dizziness and visual disturbances may occur (see section 4.8). If affected, patients should not drive or operate machines.

Adverse reactions are listed according to MedDRA primary system organ class. Within each system organ class, adverse reactions are ranked by frequency. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Blood and lymphatic system disorders
Less frequent: Agranulocytosis, thrombocytopenia, leukopenia, pancytopenia.

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

Metabolism and nutrition disorders
Less frequent: Hyperlipidaemias and lipid increases (triglycerides, cholesterol, generalized edema, weight changes. Frequency unknown: Hyponatremia, hypomagnesemia, hypocalcaemia, hypokalemia.

Psychiatric disorders
Less frequent: Sleep disorders, depression, 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
Frequent: Headache. Less frequent: dizziness, taste disorders, vertigo. Frequency unknown: Paraesthesia.

Eye Disorders
Less frequent: Vision disturbances (blurred vision).

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

Hepato-biliary disorders
Less frequent: Increased liver enzymes (transaminases, y-GT), Increased bilirubin. Frequency unknown: Hepatocellular damage leading to jaundice and hepatic failure.

Skin and subcutaneous tissue disorders
Less frequent: Rash/exanthema/eruption, pruritus, urticaria, angioedema. Frequency unknown: Stevens-Johnson syndrome, Lyell syndrome, severe dermatologic reactions (some fatal), including erythema multiforme, toxic epidermal necrolysis (TEN, some fatal), photosensitivity reaction Sub-acute cutaneous lupus erythematosus (see section 4.4). Drug reaction with eosinophilia and systemic symptoms (DRESS)

Musculoskeletal, connective tissue and bone disorders
Less frequent: Fracture of the hip, wrist or spine, arthralgia, myalgia. Frequency unknown: Rhabdomyolysis, muscle spasm.

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

Reproductive system and breast disorders
Less frequent: Gynaecomastia.

General disorders and administrative site conditions
Less frequent: Asthenia, fatigue, malaise, Increased body temperature, Peripheral oedema.

Investigations
Less frequent: elevated triglycerides.

Description of selected adverse reactions
1. Hypocalcemia and/or hypokalemia may be related to the occurrence of hypomagnesemia in association with hypomagnesemia (see section 4.4) 2. Muscle spasm as a consequence of electrolyte disturbance.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine are important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care 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.

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