Pantocid 20 40 20 mg & 40 mg Enteric coated tablets.

PANTOCID 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. PANTOCID u00ae 40 used in combination with appropriate antibiotics may be useful. PANTOCID u00ae 40 is indicated for the treatment of Zollinger-Ellison syndrome. PANTOCID u00ae 20 is indicated for the symptomatic improvement (e.g. heartburn, acid regurgitation, pain on swallowing) and healing of mild gastro-esophageal reflux disease (GERD). In patients with healed reflux disease, recurring symptoms can be controlled using an on-demand regimen of 20 mg once daily when required. PANTOCID u00ae 20 is indicated for long-term management and prevention of relapse in gastro-esophageal reflux disease (GERD). PANTOCID 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.

Posology

Duodenal ulcer

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

Gastric ulcer

The recommended dose is PANTOCID u00ae 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 dose is PANTOCID u00ae 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 PANTOCID 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 PANTOCID u00ae per day. A 4-week period is usually required for healing of mild gastro-oesophageal reflux disease. If symptom control has not been achieved after four weeks of treatment with the prescribed daily dose, further investigation is recommended. 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 PANTOCID u00ae 20 tablet per day is recommended, increasing to PANTOCID u00ae 40 mg per day if a relapse occurs. After healing of the relapse, the dose can be reduced to PANTOCID u00ae 20. Experience with long-term administration is limited.

For prevention of gastro-duodenal lesions and dyspeptic symptoms induced by non-selective nonsteroidal anti-inflammatory drugs (NSAIDu2019s) in patients at risk and with a need for continuous NSAID treatment, the recommended oral dose is one PANTOCID u00ae 20 tablet per day.

Special populations

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.

Impaired liver function

A daily dose of 20 mg PANTOCID u00ae should not be exceeded in patients with mild to moderately severe liver impairment (see Section 4.4 and 5.2).

Method of administration

PANTOCID u00ae should be swallowed whole with a little water either before or during breakfast.

• Hypersensitivity to pantoprazole, or to any of the ingredients of PANTOCID u00ae (see Section 6.1).
• Severely impaired liver function (see Section 4.4).
• Safety and efficacy in children has not been established.
• PANTOCID u00ae should not be co-administered with atazanavir (see Section 4.5).

Liver failure

In patients with severe liver impairment the liver enzymes should be monitored regularly during treatment with PANTOCID u00ae, particularly on long-term use. In the case of a rise of the liver enzymes PANTOCID u00ae should be discontinued (see Section 4.3).

Mild gastro-intestinal complaints

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

Clostridium difficile-associated diarrhoea

Published observational studies suggest that proton pump inhibitor therapy, like PANTOCID 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)

Gastrointestinal infections caused by bacteria

Treatment with PANTOCID u00ae may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter. PANTOCID u00ae, like all proton pump inhibitors (PPIs), might be expected to increase the counts of bacteria normally present in the upper gastrointestinal tract.

Co-administration with NSAIDs

The use of PANTOCID u00ae 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.

Co-administration with HIV protease inhibitors

Co-administration of PANTOCID u00ae 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).

Gastric malignancy

Prior to treatment the possibility of malignancy of gastric ulcer or a malignant disease of the oesophagus should be excluded, as the treatment with PANTOCID u00ae may alleviate the symptoms of malignant ulcers and can thus delay diagnosis. Diagnosis of reflux oesophagitis should be confirmed by endoscopy.

Cyanocobalamin (Vitamin B12) deficiency

Daily treatment with any acid-blocking medicines over a long period of time (e.g. longer than 3 years) may lead to malabsorption of cyanocobalamin caused by hypo- or achlorhydria. Rare cases of cyanocobalamin deficiency under acid-blocking therapy have been reported in the literature. This should be considered when respective clinical symptoms are observed.

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 hypocalcaemia and/or hypokalaemia) improved after magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with digoxin or medicinal products that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.

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.

Renal failure

Interstitial nephritis may progress to chronic renal inflammation and renal failure as it is not necessarily reversed when treatment is discontinued.

Long term treatment

In long-term treatment, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.

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.

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.

Lactose

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take this medicine.

Concomitant intake of food has no influence on the bioavailability.

Medicinal products with pH dependent absorption pharmacokinetics

PANTOCID u00ae may reduce or increase the absorption of medicines whose absorption is pH-dependent, e.g. ketoconazole.

HIV protease inhibitors

Atazanavir: It has been shown that co-administration of atazanavir/ritonavir with omeprazole or atazanavir with lansoprazole resulted in a substantial reduction in the bioavailability of atazanavir. The absorption of atazanavir is pH-dependent. Therefore, pantoprazole must not be co-administered with atazanavir.

Other interaction studies

The active ingredient of PANTOCID u00ae is 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. An interaction of PANTOCID 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, phenytoin, piroxicam, theophylline, warfarin and oral contraceptives. However, the response to anti-coagulants, such as warfarin, may be affected by any concomitant medication. Therefore, monitoring the patient with additional PT (prothrombin time) / INR (international normalised ratio) determinations when PANTOCID u00ae is initiated, discontinued or taken irregularly would be a good practice.

Pregnancy

Safety in pregnancy has not been established.

Breastfeeding

Safety during lactation has not been established.

Fertility

No available data

PANTOCID u00ae has no or negligible influence on the ability to drive and use machines. Adverse medicine reactions such as dizziness and visual disturbances may occur (see section 4.8). If affected patients should not drive or operate machines.

Tabulated list of adverse reactions

Table 1

System Organ Class

Frequent

Less Frequent

Frequency Unknown

Infections and infestations

Clostridium difficile Associated diarrhoea.

Blood and the lymphatic system disorders

Agranulocytosis.

Leukopenia, thrombocytopenia, pancytopenia.

Immune system disorders

Hypersensitivity reactions including anaphylactic reactions and anaphylactic shock.

Metabolism and nutrition disorders

Increased liver enzymes (transaminases, u03b3 -GT), elevated triglycerides and increased body temperature, weight changes.

Hyponatraemia, Hypomagnesaemia (see section 4.4).

Hypocalcaemia

Hypokalaemia

Nervous system disorders

Headache

Dizziness, or disturbances in vision (blurred vision).

Taste disorders

Paraesthesia

Psychiatric disorders

Sleep disorders

Depression.

Disorientation, confusion hallucinations (and all aggravations of these symptoms in pre-existence)

Eye disorders

Blurred vision

Gastric-intestinal disorders

Upper abdominal pain, diarrhoea, constipation or flatulence

Nausea, vomiting, dry mouth

Microscopic colitis

Hepato-biliary disorders

Increased bilirubin. Liver enzymes increased (transaminases, u03b3 -GT)

Severe hepatocellular damage leading to jaundice with or without hepatic failure.

Skin and subcutaneous tissue disorders

Allergic reactions such as pruritus, and skin rash, urticaria, angioedema and severe skin reactions such as Stevens-Johnson syndrome, erythema multiforme, Lyell syndrome and photosensitivity

Drug reaction with eosinophilia and systemic symptoms (DRESS)

Musculoskeletal connective tissue and bone disorders

Fracture of the hip, wrist or spine (see section 4.4)

Arthralgia, myalgia.

Muscle spasm

Renal and urinary disorders

Interstitial nephritis with possible progression to renal failure

Reproductive system and breast disorders

Gynaecomastia

General disorders and administration site conditions

Asthenia, fatigue and malaise

Body temperature increased, oedema peripheral

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. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u20186.04 Adverse Drug Reaction Reporting formu2019, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/index/8

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