Pantoprazole 40 Mg Tablets

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

The recommended once daily dose of PANTOPRAZOLE 40 mg PD should be taken in the morning.

Duodenal ulcer
The recommended oral dose is 40 mg of PANTOPRAZOLE PD once daily. The total treatment with intravenous and oral 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 PD used in combination with appropriate antibiotics may be useful.

Gastric ulcer
The recommended oral dose is 40 mg of PANTOPRAZOLE PD 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 PD 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 PD. Therefore, the dose 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 PD per day. A 4-week period is usually required for healing of mild GORD. If this is not sufficient, healing will usually be achieved within a further 4 weeks.

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

Special populations
Elderly patients
No dosage adjustment is necessary in 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 of PANTOPRAZOLE PD should not be exceeded in patients with mild to moderately severe liver impairment (see sections 5.2 and 4.4).

Method of administration
For oral use. PANTOPRAZOLE 40 mg PD should be swallowed whole with a little water either before or during breakfast.

• hypersensitivity to pantoprazole or to any of the ingredients of PANTOPRAZOLE 40 mg PD (see section 6.1)
• safety and efficacy in children has not been established
• severely impaired liver function (see section 4.4)
• co-administration with atazanavir (see section 4.5).

The daily dose of PANTOPRAZOLE 40 mg PD should not be exceeded in elderly patients or those with impaired renal function.

Co-administration with anticoagulants
The response to anticoagulants such as 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 PANTOPRAZOLE 40 mg PD is initiated, discontinued or taken irregularly. Changes in absorption should be observed when medicines whose absorption is pH-dependent, e.g. ketoconazole, are taken concomitantly.

Gastric malignancy
Prior to treatment, or in the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia or melaena), the possibility of malignancy of gastric ulcer or a malignant disease of the oesophagus should be excluded, as the treatment with PANTOPRAZOLE 40 mg PD may alleviate the symptoms of malignant ulcers and can thus delay diagnosis.

Diagnosis of reflux oesophagitis
Diagnosis of reflux oesophagitis should be confirmed by endoscopy.

Clostridium difficile associated diarrhoea (CDAD)
PANTOPRAZOLE 40 mg PD may be associated with an increased risk of Clostridium difficile associated diarrhoea (CDAD). A diagnosis of CDAD should be considered for patients taking PANTOPRAZOLE 40 mg PD who develop diarrhoea that does not improve. Patients should use the lowest dose and shortest duration of PANTOPRAZOLE 40 mg PD therapy appropriate to the condition being treated.

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 especially in hospitalised patients. Pantoprazole, like all proton pump inhibitors (PPIs), might be expected to increase the counts of bacteria normally present in the upper gastrointestinal tract. This diagnosis should be considered for diarrhoea that does not improve (see section 4.8).

Hypomagnesaemia
Severe hypomagnesaemia has been rarely reported in patients treated with proton pump inhibitors (PPIs) like PANTOPRAZOLE 40 mg PD 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 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
The use of PANTOPRAZOLE 40 mg PD may be associated with an increased risk of bone fractures in the hip, wrist or spine. This effect has been reported mostly in people taking high doses, on long-term treatment, and in those who were 50 years and older or in presence of other recognised risk factors. It is not clear if PANTOPRAZOLE 40 mg PD is the actual cause of an increased risk of bone fractures. 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.

Hepatic impairment
In patients with severe liver impairment the liver enzymes should be monitored regularly during treatment with PANTOPRAZOLE 40 mg PD, particularly on long-term use. In the case of a rise of the liver enzymes PANTOPRAZOLE 40 mg PD should be discontinued.

Mild gastro-intestinal complaints
PANTOPRAZOLE 40 mg PD is not indicated for mild gastro-intestinal complaints such as nervous dyspepsia.

Vitamin B12 absorption
Daily treatment with acid-blocking medicines including PANTOPRAZOLE 40 mg PD over a long period of time (e.g. longer than 3 years) may lead to malabsorption of vitamin B12 caused by hypo- or achlorhydria. Cases of vitamin B12 deficiency under acid-blocking therapy have been reported. This should be considered when respective clinical symptoms are observed.

Co-administration with HIV protease inhibitors
Co-administration of PANTOPRAZOLE 40 mg PD 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.

Subacute cutaneous lupus erythematosus (SCLE)
Proton pump inhibitors are associated with very infrequent cases of Subacute cutaneous lupus erythematosus (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 provider should consider stopping PANTOPRAZOLE 40 mg PD. 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, PANTOPRAZOLE 40 mg PD treatment should be stopped for at least 5 days before CgA measurements. 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.

Combination therapy
In the case of combination therapy, the summaries of product characteristics of the respective medicines should be observed.

Information on excipients of PANTOPRAZOLE 40 mg PD: PANTOPRAZOLE 40 mg PD contains mannitol. Patients with rare hereditary conditions of fructose intolerance should not take PANTOPRAZOLE 40 mg PD. PANTOPRAZOLE 40 mg PD contains sodium. To be taken into consideration in patients on a sodium controlled diet.

Concomitant intake of food has no influence on the bioavailability. PANTOPRAZOLE 40 mg PD may reduce or increase the absorption of medicines whose bioavailability is pH-dependent, e.g. ketoconazole, itraconazole, posaconazole and other medicines like erlotinib.

HIV protease inhibitors
It has been shown that atazanivir 300 mg/ritonavir 100 mg with a proton pump inhibitors (PPIs) to healthy volunteers resulted in a substantial reduction in the bioavailability of atazanivir. The absorption of atazanavir is pH-dependent. Therefore PPIs, including pantoprazole should not be co-administered with atazanavir (see section 4.3). 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 40 mg PD dose of 20 mg per day should not be exceeded. Dosage of the HIV protease inhibitor may need to be adjusted.

Coumarin anticoagulants (phenprocoumon or warfarin)
The response to anticoagulants such as warfarin, phenprocoumon and acenocoumarol may be affected by any concomitant medicine. 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. It is therefore good practice to monitor the patient with additional PT (prothrombin time) /INR (international normalised ratio) determinations when PANTOPRAZOLE 40 mg PD is initiated, discontinued or taken irregularly.

Methotrexate
Concomitant use of high-dose methotrexate (e.g. 300 mg) and proton pump inhibitors including PANTOPRAZOLE 40 mg PD 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.

Inhibitors of 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 40 mg PD, or those with hepatic impairment.

Enzyme inducers affecting CYP2C19 and CYP3A4
Enzyme inducers affecting CYP2C19 and CYP3A4, such as rifampicin and St Johnu00b4s wort (Hypericum perforatum), may reduce the plasma concentrations of PPIs that are metabolized through these enzyme systems.

Other interactions studies:
The active ingredient of PANTOPRAZOLE 40 mg PD is metabolised in the liver via the cytochrome P450 enzyme system. An interaction of PANTOPRAZOLE 40 mg PD 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. 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.

Safety in pregnancy and during lactation has not been established.

Pregnancy
Animal studies have shown reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of PANTOPRAZOLE 40 mg PD during pregnancy.

Breastfeeding
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, breastfeeding while on PANTOPRAZOLE 40 mg PD is not recommended.

Fertility
There was no evidence of impaired fertility following the administration of pantoprazole in animal studies. There is no data on fertility in humans with PANTOPRAZOLE 40 mg PD.

PANTOPRAZOLE 40 mg PD may have a minor or moderate influence on the ability to drive. PANTOPRAZOLE 40 mg PD may affect the ability to drive in that adverse 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 adverse drug reactions (ADRs).

Tabulated list of adverse effects

*Post marketing adverse events.

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 professionals are asked to report any suspected adverse reactions to SAHPRA via the online service for adverse drug reaction reporting by following the link: https://www.sahpra.org.za/document/adverse-drug-reactions-and-quality-problem-reporting-form/ https://www.sahpra.org.za/Publications/Index/8. An email can be sent directly to the company, [email protected], to ensure safety of the product.

Signs and symptoms:
There are no known symptoms of overdosage in man. Systemic exposure with up to 240 mg administered intravenously over 2 minutes was well tolerated.

Management of overdose:
As pantoprazole is extensively protein bound, it is not readily dialysable. No specific therapeutic recommendation can be made in cases of overdosage with clinical signs of intoxication. Treatment is symptomatic and supportive.