Sandoz Omeprazole 20 20 mg Capsule

SANDOZ OMEPRAZOLE 20 is indicated in:

Adults:

• Treatment of duodenal ulcer, including prevention of relapse, gastric ulcer, and reflux oesophagitis.
• Long-term management of reflux oesophagitis, and Zollinger-Ellison syndrome.
• Symptomatic relief of heartburn in patients with gastro-oesophageal reflux disease (GORD) and the short-term relief of functional dyspepsia.
• Helicobacter pylori-positive duodenal ulcers, as part of an eradication program with appropriate antibiotics.
• Treatment of non-steroidal anti-inflammatory drugs (NSAIDs)-associated gastric and/or duodenal ulcers and erosions.
• Reduction of the risk to develop gastric and/or duodenal ulcer/erosions, and reduction of the risk of relapse for previously healed gastric and/or duodenal ulcer/erosions in patients on NSAIDs treatment.

Children:

Short-term (up to 3 months) treatment of severe ulcerative reflux oesophagitis resistant to previous medical treatment.

SANDOZ OMEPRAZOLE 20 is recommended to be given in the morning and swallowed whole with a half glass of liquid. The SANDOZ OMEPRAZOLE 20 capsules should not be chewed or crushed.

The recommended dosages for adults are:

Duodenal ulcer: 20 mg once daily for 2 to 4 weeks. In some duodenal ulcer patients refractory to other treatment regimens, 40 mg once daily may be effective.

Prevention of relapse in patients with duodenal ulcer: 10 mg once daily. If necessary, the dose can be increased up to 20 to 40 mg once daily. The above recommended dosage regimens are inclusive of Helicobacter pylori-positive duodenal ulcers as part of the eradication program with appropriate antibiotics.

Gastric ulcer and reflux oesophagitis: 20 mg once daily for 4 to 8 weeks. In some gastric ulcer and reflux oesophagitis patients refractory to other treatment regimens, 40 mg once daily may be effective. For the long-term management of patients with reflux oesophagitis, the recommended dose is 10 mg once daily. If necessary, the dose can be increased to 20 to 40 mg once daily. In patients with severe or symptomatic recurrent reflux oesophagitis treatment can be continued with SANDOZ OMEPRAZOLE 20 at a dosage of 20 mg once daily.

NSAIDs-associated gastroduodenal lesions with or without continued NSAID treatment: 20 mg once daily. In most patients healing occurs within 4 weeks. For patients who may not be fully healed after the initial course, healing usually occurs during a further 4 weeks of treatment.

Prevention of NSAIDs-associated gastroduodenal lesions and dyspeptic symptoms: 20 mg once daily.

Symptomatic gastroesophageal reflux disease: 20 mg once daily. Patients may respond adequately to 10 mg daily, therefore individual dose adjustments should be considered. If symptom control has not been achieved after 4 weeks of treatment with 20 mg daily, further investigation is recommended.

Zollinger-Ellison syndrome: 60 mg once daily. The dosage should be adjusted individually and treatment continued as long as clinically indicated. With doses above 80 mg daily, the dose should be divided and given twice daily.

The recommended dosages for children are: There is very limited experience with the use of SANDOZ OMEPRAZOLE 20 in children (see u201cWARNINGS AND SPECIAL PRECAUTIONSu201d). Severe ulcerative reflux oesophagitis in children from one year and older:

Weight: Dosage:

• 10 to 20 kg: 10 mg once daily. If needed increase to 20 mg once daily.
• uff1e 20 kg: 20 mg once daily. If needed increase to 40 mg once daily.

Special populations

Elderly: Dose reductions are not necessary in elderly patients. The long-term safety of SANDOZ OMEPRAZOLE 20 in patients with renal and/or hepatic impairment has not been established (see u201cWARNINGS AND SPECIAL PRECAUTIONSu201d).

Impaired hepatic function: Bioavailability and plasma half-life of SANDOZ OMEPRAZOLE 20 are increased in patients with impaired hepatic function, therefore a daily dose of 10 to 20 mg is generally sufficient.

Hypersensitivity to omeprazole, substituted benzimidazoles or to any of the excipients listed in section 6.1. Safety in pregnancy and lactation has not been established. SANDOZ OMEPRAZOLE 20 should not be administered with St Johnu2019s Wort (see section 4.5). SANDOZ OMEPRAZOLE 20 must not be used concomitantly with nelfinavir or atazanavir (see section 4.5).

In the presence of any alarm symptoms (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded as treatment with SANDOZ OMEPRAZOLE 20 may alleviate symptoms and delay diagnosis. Co-administration of atazanavir with proton pump inhibitors is not recommended (see section 4.5). Hepatic impairment may require a reduction in dose (see section 4.2). SANDOZ OMEPRAZOLE 20, as all acid-blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypohydria/achlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy.

Omeprazole is a CYP2C19 inhibitor. When starting or ending treatment with SANDOZ OMEPRAZOLE 20, the potential for interactions with medicinal products metabolised through CYP2C19 should be considered. An interaction is observed between clopidogrel and SANDOZ OMEPRAZOLE 20 (see section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of SANDOZ OMEPRAZOLE 20 and clopidogrel should be avoided.

Severe hypomagnesaemia has been reported in patients treated with proton pump inhibitors (PPIs) like SANDOZ OMEPRAZOLE 20 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. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the proton pump inhibitor. For patients expected to be on prolonged treatment or who take SANDOZ OMEPRAZOLE 20 with digoxin or medicinal products that may cause hypomagnesaemia (e.g., diuretics), healthcare professionals should consider measuring magnesium levels before starting SANDOZ OMEPRAZOLE 20 treatment and periodically during treatment.

SANDOZ OMEPRAZOLE, 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.

Acute Tubulointerstitial Nephritis

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue SANDOZ OMEPRAZOLE and evaluate patients with suspected acute TIN.

During long-term treatment, gastric glandular cysts have been reported in increased frequency. These physiological changes result from pronounced inhibition of gastric acid secretion.

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 SANDOZ OMEPRAZOLE 20. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with SANDOZ OMEPRAZOLE 20.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, SANDOZ OMEPRAZOLE 20 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 SANDOZ OMEPRAZOLE 20 treatment.

Treatment with SANDOZ OMEPRAZOLE may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and, in hospitalised patients, possibly also Clostridium difficile (see section 5.1). There is very limited experience with the use of SANDOZ OMEPRAZOLE 20 in children. Some children with chronic illnesses may require long-term treatment although it is not recommended. The long-term safety of SANDOZ OMEPRAZOLE 20 in patients with renal and/or hepatic impairment has not been established. As in all long-term treatments, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.

Sucrose: SANDOZ OMEPRAZOLE 20 contains sucrose. Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take SANDOZ OMEPRAZOLE 20. Sucrose may have an effect on the glycaemic control of patients with diabetes mellitus.

Effects of omeprazole on the pharmacokinetics of other active substances

Active substances with pH dependent absorption

The decreased intragastric acidity during treatment with SANDOZ OMEPRAZOLE 20 might increase or decrease the absorption of active substances with a gastric pH dependent absorption.

Nelfinavir, atazanavir

The plasma levels of nelfinavir and atazanavir are decreased in case of co-administration with SANDOZ OMEPRAZOLE 20. Concomitant administration of SANDOZ OMEPRAZOLE 20 with nelfinavir is contraindicated (see section 4.3). Co-administration of SANDOZ OMEPRAZOLE 20 (40 mg once daily) reduced mean nelfinavir exposure by ca. 40 % and the mean exposure of the pharmacologically active metabolite M8 was reduced by ca. 75 to 90 %. The interaction may also involve CYP2C19 inhibition. Concomitant administration of SANDOZ OMEPRAZOLE 20 with atazanavir is contraindicated (see section 4.3). Concomitant administration of SANDOZ OMEPRAZOLE 20 (40 mg once daily) and atazanavir 300 mg/ritonavir 100 mg to healthy volunteers resulted in a 75 % decrease of the atazanavir exposure. Increasing the atazanavir dose to 400 mg did not compensate for the impact of omeprazole on atazanavir exposure.

Digoxin

Concomitant treatment with SANDOZ OMEPRAZOLE 20 (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10 %. Digoxin toxicity has been rarely reported. Caution should be exercised when SANDOZ OMEPRAZOLE 20 is given at high doses in elderly patients. Therapeutic medicinal monitoring of digoxin should then be reinforced.

Clopidogrel

Results from studies in healthy subjects have shown a pharmacokinetic (PK)/pharmacodynamic (PD) interaction between clopidogrel (300 mg loading dose / 75 mg daily maintenance dose) and omeprazole (80 mg p.o. daily, at the same time as clopidogrel). The exposure to the active metabolite of clopidogrel was decreased by 46 % (Day 1) and 42 % (Day 5) when clopidogrel and omeprazole were administered together. Mean inhibition of platelet aggregation (IPA) was diminished by 47 % (24 hours) and 30 % (Day 5) when clopidogrel and omeprazole were administered together. The consequence of this would be a reduction in the antiplatelet activity of clopidogrel, which may predispose to an increase in cardiovascular events. As a precaution, concomitant use of omeprazole and clopidogrel should be avoided (see section 4.4).

Other active substances

The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced and thus clinical efficacy may be impaired. For posaconazole and erlotinib concomitant use should be avoided.

Active substances metabolised by CYP2C19

SANDOZ OMEPRAZOLE 20 is a moderate inhibitor of CYP2C19, the major omeprazole metabolising enzyme. Thus, the metabolism of concomitant active substances also metabolised by CYP2C19, may be decreased and the systemic exposure to these substances increased. Examples of such medicines are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin. Monitoring of INR is recommended and dosage reductions may be necessary when SANDOZ OMEPRAZOLE 20 is given concomitantly.

Cilostazol

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 active metabolites by 29 % and 69 % respectively.

Phenytoin

Monitoring phenytoin plasma concentration is recommended during the first two weeks after initiating SANDOZ OMEPRAZOLE 20 treatment and, if a phenytoin dose adjustment is made, monitoring and a further dose adjustment should occur upon ending SANDOZ OMEPRAZOLE 20 treatment.

There may be interactions with other medicines that are also metabolised via the cytochrome P450 enzyme system.

Unknown mechanism

Saquinavir

Concomitant administration of omeprazole with saquinavir/ritonavir resulted in increased plasma levels up to approximately 70 % for saquinavir. Caution is advised with concomitant use of saquinavir/ritonavir.

Tacrolimus

Concomitant administration of omeprazole has been reported to increase the serum levels of tacrolimus. A reinforced monitoring of tacrolimus concentrations as well as renal function (creatinine clearance) should be performed, and dosage of tacrolimus adjusted if needed.

Methotrexate

When given together with proton pump inhibitors, methotrexate levels have been reported to increase in some patients. In high-dose methotrexate administration a temporary withdrawal of SANDOZ OMEPRAZOLE 20 may need to be considered.

Safety in pregnancy and lactation has not been established (see u201cCONTRAINDICATIONSu201d). SANDOZ OMEPRAZOLE 20 is excreted in breast milk.

SANDOZ OMEPRAZOLE 20 may lead to drowsiness and impaired concentration that may be aggravated by the simultaneous intake of alcohol or other central nervous system depressant agents. Patients should be advised, particularly at the initiation of therapy, against driving of vehicles or operating machinery or performing potentially hazardous tasks where loss of concentration could lead to accidents.

Summary of the safety profile

The most frequent undesirable effects are headache, abdominal pain, constipation, diarrhoea, flatulence and nausea/vomiting.

Blood and lymphatic system disorders

Less frequent: Pancytopenia, thrombocytopenia, agranulocytosis, leucopenia

Immune system disorders

Less frequent: Hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock

Metabolism and nutrition disorders

Less frequent: Hyponatraemia

Frequency unknown: Hypomagnesaemia Severe hypomagnesaemia may result in hypocalcaemia. Hypomagnesaemia may also be associated with hypokalaemia.

Psychiatric disorders

Less frequent: Confusion, aggression, hallucinations, insomnia and parasthaesias have occurred, predominantly in severely ill patients, agitation

Nervous system disorders

Frequent: Headache (severe enough to require discontinuation of therapy in some cases)

Less frequent: Taste disturbances, paraesthaesia, dizziness and somnolence

Eye Disorders

Less frequent: Blurred vision

Ear and labyrinth disorders

Less Frequent: Vertigo

Respiratory, thoracic and mediastinal disorders

Less frequent: Bronchospasm

Gastrointestinal disorders

Frequent: Diarrhoea (severe enough to require discontinuation of therapy in some cases), constipation, nausea, vomiting, flatulence, abdominal pain or colic, fundic gland polyps (benign)

Less frequent: Dry mouth, stomatitis, gastrointestinal candidiasis, acid regurgitation and increased gastrointestinal bacteria

Frequency unknown: Microscopic colitis

Hepatobiliary disorders

Less frequent: Increased liver enzymes, hepatitis with or without jaundice, hepatic failure, encephalopathy in patients with pre-existing liver disease.

Skin and subcutaneous tissue disorders

Less frequent: Photosensitivity, bullous eruption, erythema multiforme, pruritus dermatitis, skin rash and itching, urticaria, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, alopecia

Frequency unknown: Subacute cutaneous lupus erythematosus (see section 4.4)

Musculoskeletal and connective tissue disorders

Less frequent: Asthenia, arthralgia, myalgia, fracture of the hip, wrist or spine, muscular weakness

Renal and urinary disorders

Less frequent: Interstitial nephritis (may progress to acute kidney injury and/or chronic renal failure and symptoms of interstitial nephritis may persist even when treatment with PPI is terminated).

Reproductive system and breast disorders

Less frequent: Gynaecomastia

General disorders and administration site conditions

Less frequent: Increased sweating, peripheral oedema, malaise

There is limited information available on the effects of overdoses of omeprazole in humans. In the literature, doses of up to 560 mg have been described, and occasional reports have been received when single oral doses have reached up to 2400 mg omeprazole (120 times the usual recommended clinical dose). Blurred vision, diaphoresis, flushing, headache, malaise, nausea, vomiting, dizziness, abdominal pain, diarrhoea and tachycardia have been reported. Also apathy, depression and confusion have been described in single cases. There is no specific antidote for overdose with omeprazole. Treatment is symptomatic and supportive. Due to extensive protein binding, omeprazole is not readily dialysable. Patients in whom overdose is confirmed or suspected should be referred for a consultation with a medical practitioner/doctor.