Essium Iv 40 mg Powder for injection

ESSIUM IV is indicated for Gastro-oesophageal Reflux Disease as an alternative where oral therapy is not appropriate and for the shortest possible time. Gastro-oesophageal reflux disease:

• treatment of erosive reflux oesophagitis
• long-term management of patients with healed oesophagitis to prevent relapse
• treatment of severe symptoms of reflux disease.

ESSIUM IV is indicated for the short-term maintenance of haemostasis and prevention of re-bleeding in patients following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers.

Posology

Adults: When oral therapy is possible or appropriate, intravenous therapy with ESSIUM IV should be discontinued and the therapy should be continued orally.

Gastro-oesophageal reflux disease (GORD): Treatment with ESSIUM IV can be given for up to 7 days as part of a full treatment period for the specified indications.

• Erosive reflux oesophagitis: 40 mg once daily. The duration of treatment should be 4 weeks. An additional 4 weeks treatment is recommended for patients in whom the oesophagitis has not healed or who have persistent symptoms.
• Long-term management of patients with healed oesophagitis to prevent relapse and treatment of severe symptoms of reflux disease: 20 mg once daily.
• Maintenance of haemostasis and prevention of rebleeding of gastric or duodenal ulcers: 80 mg administered as bolus infusion over 30 minutes followed by a continuous IV infusion of 8 mg/hour given over 3 days. The parenteral treatment period should be followed by acid-suppression therapy with 40 mg esomeprazole orally once daily for 4 weeks.

Special populations

• Elderly: Dose adjustment is not required in the elderly.
• Renal impairment: Dose adjustment is not required in patients with impaired renal function. Due to limited experience in patients with severe renal insufficiency, such patients should be treated with caution.
• Hepatic impairment: Gastro-oesophageal reflux disease (GORD): Dose adjustment is not required in patients with mild to moderate liver impairment. Severe liver impairment (Child-Pugh class C): Maximum daily dose of 20 mg of ESSIUM IV should not be exceeded. Bleeding ulcers: Dose adjustment is not required in patients with mild to moderate liver impairment. For patients with severe liver impairment, following an initial bolus dose of 80 mg of ESSIUM IV, a continuous IV dose of 4 mg/hour may be sufficient to maintain adequate acid control.
• Paediatric population: ESSIUM IV should not be used in children since no data are available.

Method of administration

For instructions on reconstitution of the medicine before administration, see section 6.6.

Injection: 40 mg dose: The reconstituted solution should be given as an intravenous injection over a period of at least 3 minutes (see section 6.6). 20 mg dose: Half the reconstituted solution should be given as an intravenous injection over a period of approximately 3 minutes (see section 6.6).

Infusion: 40 mg dose: The reconstituted solution should be given as an intravenous infusion over a period of 10 u2013 30 minutes (see section 6.6). 20 mg dose: Half of the reconstituted solution should be given as an intravenous infusion over a period of 10 u2013 30 minutes (see section 6.6).

Continuous infusion (40 mg vial): 80 mg bolus dose: The reconstituted solution containing 80 mg esomeprazole should be given as a continuous intravenous infusion over 30 minutes (see section 6.6). 8 mg/hour dose: The reconstituted solution should be given as a continuous intravenous infusion over a period of 71.5 hours (calculated rate of infusion of 8 mg/hour).

Hypersensitivity to esomeprazole, to substituted benzimidazoles or to any of the excipients listed in section 6.1. ESSIUM IV should not be used concomitantly with nelfinavir and atazanavir (see section 4.5).

In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, hematemesis or melena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with Essium IV may alleviate symptoms and delay diagnosis. Concomitant administration of ESSIUM IV with medicines such as atazanavir and nelfinavir is contraindicated (see section 4.5 and 4.3). Therapeutic medicine monitoring is recommended during concomitant treatment with warfarin.

During treatment with ESSIUM IV serum gastrin increases, in response to the decreased acid secretion.

Gastrointestinal infections: Treatment with proton pump inhibitors may lead to increased risk of gastrointestinal infections such as Salmonella and Campylobacter and possibly also Clostridium difficile in hospitalised patients.

Absorption of vitamin B12: ESSIUM IV may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypoorachlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy.

Hypomagnesaemia: Severe hypomagnesaemia has been reported in patients treated with proton pump inhibitors (PPIs) like ESSIUM IV 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 ESSIUM IV. For patients expected to be on prolonged treatment or who take ESSIUM IV with digoxin or medicinal products that may cause hypomagnesaemia (e.g. diuretics), healthcare professionals should consider measuring magnesium levels before starting ESSIUM IV treatment and periodically during treatment.

Risk of fracture: ESSIUM IV 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.

Subacute cutaneous lupus erythematosus (SCLE): Proton pump inhibitors such as ESSIUM IV 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 Essium IV. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

Combination with other medicines: Co-administration of esomeprazole with atazanavir is not recommended (see section 4.5). Esomeprazole is a CYP2C19 inhibitor. When starting or ending treatment with esomeprazole, the potential for interactions with medicinal products metabolised through CYP2C19 should be considered. An interaction is observed between clopidogrel and esomeprazole (see section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of esomeprazole and clopidogrel should be discouraged.

Interference with laboratory tests: Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, ESSIUM IV 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 as in ESSIUM IV.

Effects of other medicinal products on esomeprazole: Medicines which inhibit CYP2C19 and/or CYP3A4: Esomeprazole is metabolised by CYP2C19 and CYP3A4. Concomitant administration of ESSIUM IV and a CYP3A4 inhibitor, clarithromycin (500 mg twice daily), resulted in a doubling of the exposure (AUC) to esomeprazole. Concomitant administration of ESSIUM IV and a combined inhibitor of CYP2C19 and CYP3A4, e.g. voriconazole, may result in more than doubling of esomeprazole exposure. However, dose adjustment of ESSIUM IV is not required in either of these situations. In patients with severe hepatic impairment, and if long-term treatment is indicated, dose adjustment should be considered.

Medicines which induce CYP2C19 and/or CYP3A4: Medicines known to induce CYP2C19 or CYP3A4 or both, such as St Johnu2019s wort and rifampicin, may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

Effects of other medicinal products on esomeprazole: The decreased intragastric acidity during treatment with ESSIUM IV, might increase or decrease the absorption of medicines if the mechanism of absorption is influenced by gastric acidity. In common with the use of other inhibitors of acid secretion or antacids, the absorption of ketoconazole, itraconazole and erlotinib can decrease while the absorption of medicines such as digoxin can increase during treatment with ESSIUM IV. Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10 % (up to 30 % in 2 out of 10 subjects). Digoxin toxicity has been reported. Caution should be exercised when ESSIUM IV is given at high doses in elderly patients. Therapeutic monitoring of digoxin levels should be done.

ESSIUM IV inhibits CYP2C19, the major esomeprazole metabolising enzyme. Concomitant administration of 30 mg Esomeprazole as in ESSIUM IV resulted in a 45 % decrease in clearance of the CYP2C19 substrate diazepam. This interaction is unlikely to be of clinical relevance. Concomitant administration of 40 mg Esomeprazole as in ESSIUM IV resulted in a 13 % increase in trough plasma levels of phenytoin in epileptic patients; dose adjustment was not required in this study. From post marketed use cases of elevated International Normalised Ratio (INR) of clinical significance have been reported during concomitant treatment with warfarin. Close monitoring is recommended when warfarin or other coumarine derivatives is co-administered with ESSIUM IV at initiation of treatment, during the treatment and ending the treatment.

Omeprazole as well as esomeprazole act as inhibitors of CYP2C19. Omeprazole given in doses of 40 mg to healthy subjects in a cross-over study, increased C max and AUC for cilostazol by 18 % and 26 % respectively, and one of its metabolites by 29 % and 69 % respectively. In healthy volunteers, concomitant administration of 40 mg Esomeprazole as in ESSIUM IV resulted in a 32 % increase in area under the plasma concentration-time curve (AUC) and a 31 % prolongation of elimination half-life (t 1/2) but no significant increase in peak plasma levels of cisapride. This interaction did not alter the influence of cisapride on cardiac electrophysiology.

When given together with proton pump inhibitors, methotrexate levels have been reported to increase in some patients by up to three fold. In high-dose methotrexate administration a temporary withdrawal of esomeprazole may need to be considered. Omeprazole has been reported to interact with some antiretroviral medicines. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral medicines. Other possible interaction mechanisms are via CYP2C19. For some antiretroviral medicines, such as atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole and concomitant administration is not recommended. For other antiretroviral medicines, such as saquinavir, increased serum levels have been reported of 80-100 %. There are also some antiretroviral medicines for which unchanged serum levels have been reported when given with omeprazole. Close monitoring or dose alteration is recommended.

Concomitant administration with esomeprazole and antiretroviral medicines such as atazanavir and nelfinavir is not recommended. ESSIUM IV substantially decreases the concentration of atazanavir and nelfinavir. Co-administration of esomeprazole (40 mg once daily) reduced mean nelfinavir exposure by approximately 40 % and the mean exposure of the pharmacological active metabolite was reduced by approximately 75-90 %. Tipranavir may decrease the concentration of ESSIUM IV. Co-administration is not recommended. However, if used concurrently, the dose of ESSIUM IV should be increased. ESSIUM IV has been shown to have no clinically relevant effects on the pharmacokinetics of amoxicillin or quinidine. Studies evaluating concomitant administration of Esomeprazole as in ESSIUM IV and either naproxen (non-selective NSAID) or rofecoxib (COX-2-selective NSAID) did not identify any clinically relevant interaction.

Pregnancy: Limited clinical data on exposed pregnancies are available. A moderate amount of data on pregnant women (between 300 u2013 1000 pregnancy outcomes) indicated no malformative or foeto/neonatal toxicity of Esomeprazole as in ESSIUM IV. However, caution should be exercised when prescribing ESSIUM IV to pregnant women.

Breastfeeding: It is not known whether ESSIUM IV is excreted in human breast milk. No studies in lactating women have been performed. Therefore, ESSIUM IV should not be used during breastfeeding.

ESSIUM IV may cause dizziness and blurred vision, thereby affecting the ability to drive or use machinery.

Summary of the safety profile: Headache, abdominal pain, diarrhoea and nausea are among those adverse reactions that have been frequently reported.

Tabulated list of adverse reactions: The following adverse drug reactions have been identified.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. 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

No specific antidote is known. ESSIUM IV is extensively plasma protein bound and is therefore not readily dialysable. As in any case of overdose, treatment should be symptomatic and general supportive measures should be utilised.