Peptazol 40 40 mg Enteric coated tablets

PEPTAZOL 20 mg, which is available as a different formulation, is indicated for the symptomatic improvement (e.g., heartburn, acid regurgitation, pain on swallowing) and healing of mild gastro-oesophageal reflux disease (GERD).

• for long-term management and prevention of relapse in gastro-oesophageal reflux disease (GERD).
• 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.

PEPTAZOL 40 is indicated for 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, PEPTAZOL 40 used in combination with appropriate antibiotics may be useful.

PEPTAZOL 40 is indicated for the treatment of Zollinger-Ellison syndrome.

Posology

Mild gastro-oesophageal reflux disease (GERD)

The recommended oral dosage is one PEPTAZOL 20 tablet per day. A 4-week period is usually required for healing of mild GERD. 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, recurring symptoms can be controlled using an on-demand regimen of 20 mg once daily when required. A different formulation should be used, as PEPTAZOL 40 cannot be divided.

Duodenal ulcer

The recommended oral dosage is one PEPTAZOL 40 tablet daily in the morning for 2 to 4 weeks. If the duodenal ulcer has been demonstrated to be associated with Helicobacter pylori infection, the use of PEPTAZOL 40, in combination with appropriate antibiotics, may be useful.

Gastric ulcer

The recommended oral dosage is one PEPTAZOL 40 tablet daily in the morning for 4 to 8 weeks. In the case of a suspected gastric ulcer, malignancy of the ulcer should be excluded, as treatment could conceal the symptoms and may delay diagnosis.

Reflux oesophagitis

The recommended oral dosage is one PEPTAZOL 40 tablet daily in the morning 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 PEPTAZOL 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 GERD

For long-term management, a maintenance dose of one PEPTAZOL 20 per day is recommended, increasing to one PEPTAZOL 40 per day if a relapse occurs. After healing of the relapse, the dosage can be reduced to one PEPTAZOL 20 tablet. Experience with long-term administration is limited. A different formulation should be used, as PEPTAZOL 40 cannot be divided.

Special populations

Elderly

No dosage adjustment is necessary in the elderly.

Renal and hepatic impairment

No dosage adjustment is required in the presence of impaired renal function. A daily dose of 20 mg PEPTAZOL should not be exceeded in patients with liver impairment.

Method of administration

For oral use only. PEPTAZOL 40 should be taken in the morning, swallowed whole with a little water either before or during breakfast.

• Hypersensitivity to pantoprazole or to any of the excipients listed in section 6.1.
• Safety and efficacy in children have not been established.
• Severe liver function impairment (see section 4.2, Special Populations section 4.2 and section 4.4).
• Co-administration with atazanavir (see section 4.5).

Possible malignancy

PEPTAZOL 40 is not indicated for mild gastro-intestinal complaints such as dyspepsia. Prior to treatment, the possibility of a malignant gastric ulcer or a malignant disease of the oesophagus should be excluded, as the treatment with PEPTAZOL 40 may alleviate the symptoms of malignant ulcers and can thus delay diagnosis.

Long term treatment

PEPTAZOL 40 is not indicated for long-term management and prevention of relapse in gastro-oesophageal reflux disease. Diagnosis of reflux oesophagitis should be confirmed by endoscopy. In long-term treatment, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.

Influence on vitamin B 12 absorption

PEPTAZOL 40 may reduce the absorption of vitamin B 12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B 12 absorption on long-term therapy or if respective clinical symptoms are observed.

Renal inflammation

PEPTAZOL 40 may increase the risk of subclinical acute or chronic interstitial nephritis associated with proton pump inhibitors (PPIs) leading to chronic renal inflammation and reduced renal function (tubular injury being u201ctubulointerstitial nephritisu201d).

Hepatic impairment

In patients with mild and moderate liver impairment the liver enzymes should be monitored regularly during treatment with pantoprazole, particularly on long-term use. In the case of a rise of the liver enzymes the treatment should be discontinued. PEPTAZOL 40 is contraindicated in patients with severe liver impairment (see section 4.3).

Co-administration with HIV protease inhibitors

Co-administration of PEPTAZOL 40 is contraindicated 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).

Gastrointestinal infections caused by bacteria

Treatment with PEPTAZOL 40 may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter or C. difficile. PEPTAZOL 40 might be expected to increase the counts of bacteria normally present in the upper gastrointestinal tract.

Hypomagnesaemia

Severe hypomagnesaemia has been reported in patients treated with proton pump inhibitors (PPIs), as in PEPTAZOL 40, 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 dysrhythmia can occur, but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia 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), healthcare professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.

Bone fractures

Proton pump inhibitors (PPIs) as in PEPTAZOL 40, 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 u2013 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.

Subacute cutaneous lupus erythematosus (SCLE)

Proton pump inhibitors (PTIs), as in PEPTAZOL 40, 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 PEPTAZOL 40. 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, PEPTAZOL 40 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.

Excipients with known effect

PEPTAZOL 40 contains FD&C Yellow Nu00b05 (tartrazine) which may cause allergic reactions. PEPTAZOL 40 contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially sodium-free.

Medicinal products with pH-dependent absorption pharmacokinetics

PEPTAZOL 40 may reduce or increase the absorption of medicines whose bioavailability is pH-dependent e.g., ketoconazole.

Medicines metabolised in the liver via cytochrome P450 enzyme system

The active ingredient of PEPTAZOL 40 is metabolised in the liver via cytochrome P450 enzyme system. An interaction of PEPTAZOL 40 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, diazepam, theophylline, digoxin, oral contraceptives, phenytoin, nifedipine, carbamazepine, diclofenac, naproxen, piroxicam, metoprolol, glibenclamide, ethanol and caffeine.

Warfarin or phenprocoumon

Concomitant administration of warfarin or phenprocoumon has no influence on its effect on coagulation factors. However, the response to anticoagulants such as warfarin may be affected by any concomitant medications. Monitoring the patient with additional PT (prothrombin time)/INR (international normalised ratio) determinations when PEPTAZOL 40 is initiated, discontinued, or taken irregularly is advised.

HIV protease inhibitors

Co-administration of PEPTAZOL 40 is contraindicated 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 4.4). 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.

Methotrexate

Concomitant use of high dose methotrexate (e.g. 300 mg) and proton-pump inhibitors, as in PEPTAZOL 40, 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.

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 PEPTAZOL 40, or those with hepatic impairment.

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

Antacids

There were no interactions with concomitantly administered antacids.

Antibiotics

Interaction studies have also been performed by concomitantly administering pantoprazole with the respective antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically relevant interactions were found.

Pregnancy

Safety in pregnancy has not been established. A moderate amount of data on pregnant women indicates no malformative or foeto/neonatal toxicity of pantoprazole. Animal studies have shown reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of PEPTAZOL 40 during pregnancy.

Breastfeeding

Safety in lactation has not been established. Animal studies have shown 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.

Fertility

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

PEPTAZOL 40 may influence the ability to drive and to use machinery. Possible side effects (see section 4.8), such as dizziness and disturbances in vision e.g. blurred vision may occur. It is not always possible to predict to what extent PEPTAZOL 40 may interfere with the daily activities of a patient. Patients should ensure that they do not engage in the above activities until they are aware of the measure to which PEPTAZOL 40 affects them.

a. Summary of the safety profile

Approximately 5 % of patients can be expected to experience adverse drug reactions (ADRs). The most frequent reported ADRs are diarrhoea and headache, both occurring in approximately 1 % of patients.

b. Tabulated summary of adverse reactions

System Organ Class Frequency Adverse reactions

Blood and lymphatic system disorders Less frequent Leukopenia, thrombocytopenia, agranulocytosis, pancytopenia

Immune system disorders Less frequent Anaphylactic reactions including anaphylactic shock, allergic reactions such as skin rash, pruritus, and angioedema.

Metabolism and nutrition disorders Less frequent Hyperlipidaemias and lipid increases (triglycerides, cholesterol), weight changes

Frequency unknown Hyponatraemia, hypomagnesaemia (see section 4.4), hypocalcaemia in association with hypomagnesaemia, hypokalaemia

Psychiatric disorders Less frequent Sleep disorders, depression (and all aggravations), disorientation (and all aggravations)

Frequency unknown Hallucination, confusion (especially in predisposed patients, as well as the aggravation of these symptoms in case of pre-existence)

Nervous system disorders Frequent Headache

Less frequent Dizziness, taste disorders

Eye disorders Less frequent Disturbances in vision (blurred vision)

Gastrointestinal disorders Frequent Upper abdominal pain, diarrhoea, nausea, constipation, flatulence, vomiting, dry mouth, Fundic gland polyps (benign)

Frequency unknown Microscopic colitis

Hepato-biliary disorders Less frequent Increase in liver enzymes (transaminases, u03b3 - GT), severe hepatocellular damage leading to jaundice with or without hepatic failure, bilirubin increased

Skin and subcutaneous tissue disorders Less frequent Urticaria, rash, pruritis, severe skin reactions such as Stevens-Johnson syndrome, erythema multiforme and Lyell-syndrome, photosensitivity

Frequency unknown Subacute cutaneous lupus erythematosus (see section 4.4)

Musculoskeletal, connective tissue and bone disorders Less frequent Myalgia subsiding after termination of therapy, arthralgia. Fracture of the hip, wrist or spine (see section 4.4)

Frequency unknown Muscle spasm as a consequence of electrolyte disturbances

Renal and urinary disorders Less frequent Interstitial nephritis (with possible progression to renal failure)

Reproductive system and breast disorders Less frequent Gynaecomastia

General disorders and administrative site conditions Less frequent Increased body temperature and peripheral oedema, both subsiding after termination of treatment

c. Description of selected adverse reactions

Renal effects

The renal effect of proton pump inhibitors (PPIs) may progress to renal failure as it is not necessarily reversed when treatment is discontinued. There is an increased risk of subclinical acute or chronic interstitial nephritis associated with proton pump inhibitors (PPIs) leading to chronic renal inflammation and reduced renal function (tubular injury being u201ctubulointerstitial nephritisu201d). Acute tubulointerstitial nephritis is characterised by an inflammatory reaction within the tubulointerstitial space of the kidney. Acute interstitial inflammatory reactions are associated with damage to the tubulointerstitial, leading to acute kidney injury. Interstitial nephritis may lead to renal failure.

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 u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8. In addition, side-effects can also be reported to [email protected].

There are no known symptoms of overdosage in humans. No specific recommendation can be made in cases of overdosage. Treatment is symptomatic and supportive. As pantoprazole is extensively protein bound, it is not readily dialysable.