Pantoloc Range 20 mg/40 mg Tablets

PANTOLOC u00ae IV is indicated for intravenous administration to patients who cannot be treated orally. PANTOLOC u00ae 40 and PANTOLOC u00ae IV are 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, PANTOLOC u00ae 40 or PANTOLOC u00ae IV used in combination with appropriate antibiotics may be useful. PANTOLOC u00ae 40 and PANTOLOC u00ae IV are indicated for the treatment of Zollinger-Ellison Syndrome. PANTOLOC 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. PANTOLOC u00ae 20 is indicated for long-term management and prevention of relapse in gastro-oesophageal reflux disease. PANTOLOC 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.

PANTOLOC u00ae 20 and PANTOLOC u00ae 40 should be swallowed whole with a little water either before or during breakfast. PANTOLOC u00ae IV is indicated for intravenous administration to patients who cannot be treated orally. A ready-to-use solution is prepared by injecting 10 ml of physiological sodium chloride (0.9%) solution into the vial containing the dry substance. PANTOLOC u00ae IV may be used intravenously for up to 7 days. After preparation the solution in physiological sodium chloride solution and 5% glucose must be used within 12 hours and any unused portion discarded after 12 hours. The solution may be administered directly or it may be further diluted by mixing with 100 ml physiological sodium chloride solution or 5% glucose ONLY. The medicine should be administered intravenously over 2 - 15 minutes.

As soon as oral therapy is possible, treatment should be replaced with the same oral dose (PANTOLOC u00ae 40 tablets) in compliance with the approved dosage regimen.

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

Gastric ulcer
The recommended oral or IV dose is 40 mg PANTOLOC 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 or IV dose is 40 mg PANTOLOC 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 PANTOLOC u00ae 40 or 2 vials of PANTOLOC u00ae IV). 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. In case rapid acid control is required, a starting dose of 2 x 80 mg PANTOLOC u00ae IV is sufficient to manage a decrease of acid output into the target range (<10 mmol/h) within one hour in the majority of patients. Transition from PANTOLOC u00ae IV to the oral formulation PANTOLOC u00ae 40 should be performed as soon as it is clinically justified.

Long-term treatment
Long-term treatment with PANTOLOC u00ae IV is currently not indicated as there is insufficient clinical data.

Mild gastro-oesophageal reflux disease
The recommended oral dose is 20 mg PANTOLOC 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 PANTOLOC u00ae 20 tablet per day is recommended, increasing to 40 mg PANTOLOC u00ae per day if a relapse occurs. After healing of the relapse, the dose can be reduced to 20 mg PANTOLOC 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 PANTOLOC u00ae 20 tablet per day.

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 PANTOLOC u00ae should not be exceeded in patients with mild to moderate liver impairment (see Section 5.2 and Section 4.4).

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

PANTOLOC u00ae IV is for intravenous route only and must not be given by any other route. PANTOLOC 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 PANTOLOC u00ae should not be exceeded in elderly patients or in those with impaired renal function.

Clostridium difficile - associated diarrhoea
Published observational studies suggest that proton pump inhibitor therapy, like PANTOLOC 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 AND Section 4.4).

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 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, as 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 PANTOLOC u00ae 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 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
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 - 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.

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 PANTOLOC 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, PANTOLOC 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.

PANTOLOC u00ae contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially u2018sodium-freeu2019.

Mannitol in excipients
Patients with the rare hereditary condition of mannitol intolerance should not take PANTOLOC u00ae.

Hepatic impairment
In patients with mild to moderate liver impairment, the liver enzymes should be monitored regularly during treatment with 40 mg PANTOLOC u00ae, particularly on long-term use. In the case of a rise of the liver enzymes, the treatment should be discontinued (see section 4.2).

Use of PANTOLOC 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. PANTOLOC u00ae is not indicated for mild gastro-intestinal complaints such as nervous dyspepsia. In the presence of any alarming symptoms (e.g., significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or malaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with PANTOLOC u00ae may alleviate symptoms and delay diagnosis. Daily treatment with any acid-blocking medicines including PANTOLOC u00ae over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin caused by hypo- or achlorhydria. Cases of cyanocobalamin 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 PANTOLOC u00ae is metabolised in the liver via the cytochrome P450 enzyme system. An interaction of PANTOLOC 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.

Coumarin anticoagulants
However, the response to anticoagulants such as warfarin, phenprocoumon and acenocoumarol 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 PANTOLOC u00ae is initiated, discontinued or taken irregularly. Due to long lasting inhibition of gastric acid secretion PANTOLOC 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, nelfinavir; due to significant reduction in their bioavailability (see Contraindications, 4.3).

There were no interactions with concomitantly administered antacids.

Safety in pregnancy and during lactation has not been established.

PANTOLOC u00ae may have an influence on the ability to drive and use machines and the individual patientu2019s response must be assessed.

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 MEDRA System 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
Injection site thrombophlebitis u2020 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.

u2020 Applicable to pantoprazole 40 mg I.V. only

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.