Omez 10/20/40 10mg. 20mg. 40mg Capsule

OMEZ 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 programme with appropriate antibiotics.
• Treatment of non-steroidal anti-inflammatory drugs (NSAID)-associated gastric and/or duodenal ulcer/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 NSAID treatment.

Children

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

Posology

RECOMMENDED DOSAGES FOR ADULTS

Duodenal ulcer

• 20 mg once daily for two to four 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 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 programme with appropriate antibiotics.

Gastric ulcer and reflux oesophagitis

• 20 mg once daily for four to eight 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 OMEZ at a dosage of 20 mg once daily.

NSAID-associated gastro-duodenal lesions with or without continued NSAID treatment

• 20 mg once daily. In most patients healing occurs within four weeks. For patients who may not be fully healed after the initial course, healing usually occurs during a further four weeks of treatment.

Prevention of NSAID-associated gastro-duodenal lesions and dyspeptic symptoms

• 20 mg once daily.

Symptomatic gastro-oesophageal reflux disease

• 20 mg daily. Patients may respond adequately to 10 mg daily therefore individual dose adjustments should be considered. If symptom control has not been achieved after four weeks of treatment with the prescribed daily dose, further investigation is recommended.

Zollinger-Ellison Syndrome

• 60 mg once daily. The dosage should be adjusted individually and treatment continued as long as it is clinically indicated. With doses above 80 mg daily the dose should be divided and given twice daily. There is very limited experience with the use of OMEZ in children (see Section 4.4).

Severe ulcerative reflux oesophagitis in children from one year and older

Recommended dosages:

• Weight: 10 to 20 kg: 10 mg once daily. If needed increase to 20 mg once daily.
• Weight: > 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 OMEZ in patients with renal and hepatic impairment has not been established (see Section 4.4).

Impaired renal function

• Dose reductions are not necessary in renal impairment.

Impaired hepatic function

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

Method of administration

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

Hypersensitivity to omeprazole or to any of the other ingredients of OMEZ (see Section 6.1).

Safety in pregnancy and lactation has not been established.

OMEZ must not be used concomitantly with nelfinavir or atazanavir (see Section 4.5).

OMEZ should not be administered with St. Johnu2019s Wort (see Section 4.5).

In the presence of any alarm symptom (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 may alleviate symptoms and delay diagnosis.

Hepatic impairment may require a reduction in dose (see Section 4.2).

The long-term safety of OMEZ in patients with renal and/or hepatic impairment has not been established.

There is very limited experience with the use of OMEZ in children. Some children with chronic illnesses may require long-term treatment although it is not recommended.

Co-administration of atazanavir with proton pump inhibitors is not recommended (see Section 4.5).

OMEZ, 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.

OMEZ is a CYP2C19 inhibitor. When starting or ending treatment with omeprazole, the potential for interactions with drugs metabolised through CYP2C19 should be considered. An interaction is observed between clopidogrel and OMEZ (see Section 4.5). The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of OMEZ and clopidogrel should be avoided.

Increased risk of bone fractures: OMEZ, 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 to 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.

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

Subacute cutaneous lupus erythematosus (SCLE): Proton pump inhibitor (PPI) therapy like OMEZ is 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 OMEZ. SCLE after previous treatment with OMEZ 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, OMEZ 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 OMEZ treatment.

Effects related to acid inhibition: During long-term treatment gastric glandular cysts have been reported in increased frequency. These physiological changes result from pronounced inhibition of gastric acid secretion. Decreased gastric acidity increases gastric counts of bacteria normally present in the gastro-intestinal tract. Treatment with OMEZ may lead to an increased risk of gastro-intestinal infections such as Salmonella, Campylobacter, or Clostridium difficile.

Clostridium-difficile-associated diarrhoea: Proton pump inhibitor (PPI) therapy like OMEZ may be associated with an increased risk of Clostridium difficile associated diarrhoea (CDAD), especially in hospitalised patients. This diagnosis should be considered for diarrhoea that does not improve (see Section 4.8). Patients should use the lowest dose and shortest duration of OMEZ therapy appropriate to the condition being treated.

Acute Tubulointerstitial Nephritis: Acute Tubulointerstitial Nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. TIN is characterised by an inflammatory reaction within the tubulointerstitial space of the kidney. Acute interstitial inflammatory reactions are associated with damage to the tubulointerstitium, leading to acute kidney injury. TIN may be drug-related, infectious, systemic, autoimmune, genetic, and idiopathic with the most common cause being related to a medication or drug exposure. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decrease renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extrarenal manifestations (e.g., fever rash or arthralgia). Discontinue OMEZ and evaluate patients with suspected acute TIN.

As in all long-term treatments, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.

Excipients: Mannitol: OMEZ contains mannitol which, on rare occasions, may cause hypersensitivity reactions and may have a laxative effect.

Effects of omeprazole on the pharmacokinetics of other active substances

Active substances with pH dependent absorption: The decreased intragastric acidity during treatment with omeprazole might increase or decrease the absorption of active substances with a gastric pH dependent absorption.

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).

Digoxin: Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10 %. Digoxin toxicity has been reported. Caution should be exercised when omeprazole is given at high doses in elderly patients. Therapeutic drug monitoring of digoxin should then be reinforced (see Section 4.4).

Nelfinavir and atazanavir: In case of co-administration with OMEZ, the plasma levels of nelfinavir and atazanavir are decreased. Concomitant administration of OMEZ with nelfinavir is contraindicated (see Section 4.3). Co-administration of OMEZ (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 omeprazole with atazanavir is not recommended. Concomitant administration of OMEZ (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. The co-administration of OMEZ (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg to healthy volunteers resulted in a decrease of approximately 30 % in the atazanavir exposure as compared to atazanavir 300 mg/ritonavir 100 mg once daily.

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: OMEZ 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 OMEZ is given concomitantly.

Cilostazol: Omeprazole given in doses of 40 mg to healthy subjects in a cross-over study, increased Cmax 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 OMEZ treatment and, if a phenytoin dose adjustment is made, monitoring and a further dose adjustment should occur upon ending OMEZ 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 omeprazole may need to be considered.

Effects of other active substances on the pharmacokinetics of omeprazole

Inhibitors of CYP2C19 and/or CYP3A4: Since omeprazole is metabolised by CYP2C19 and CYP3A4, active substances known to inhibit CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole) may lead to increased omeprazole serum levels by decreasing omeprazoleu2019s rate of metabolism. Concomitant voriconazole treatment resulted in more than doubling of the omeprazole exposure. As high doses of omeprazole have been well-tolerated, adjustment of the OMEZ dose is not generally required. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.

Inducers of CYP2C19 and/or CYP3A4: Active substances known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. Johnu2019s Wort may lead to decreased omeprazole serum levels by increasing omeprazoleu2019s rate of metabolism and should not be used concomitantly with OMEZ.

Safety in pregnancy and lactation has not been established (see Section 4.3). Omeprazole is excreted in breast milk.

OMEZ may lead to drowsiness and impaired concentration that may be aggravated by the simultaneous intake of alcohol or other central nervous system depressants. Patients should be advised, particularly at the initiation of therapy, against taking charge of vehicles or 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.

Infections and Infestations

Frequency not known: Clostridium-difficile-associated diarrhoea.

Blood and lymphatic system disorders

Less frequent: Leucopaenia, thrombocytopaenia, agranulocytosis, pancytopaenia.

Immune system disorders

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

Metabolic and nutritional 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, agitation, aggression, insomnia and hallucinations have occurred (predominantly in severely ill patients).

Nervous system disorders

Frequent: Headache (severe enough to cause discontinuation in some patients). Less frequent: Dizziness, somnolence, parasthaesias, taste disturbances.

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 patients), constipation, abdominal pain or colic, nausea, vomiting, flatulence, gastric glandular cysts, fundic gland polyps (benign). Less frequent: Dry mouth, stomatitis, gastrointestinal candidiasis, acid regurgitation and increased gastro-intestinal bacteria. Frequency unknown: microscopic colitis.

Hepato-biliary 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: Skin rash and itching, urticaria, pruritus, photosensitivity, bullous eruption, toxic epidermal necrolysis, Stevens-Johnson syndrome, alopecia, erythema multiforme. Frequency unknown: Subacute cutaneous lupus erythematosus (see Section 4.4).

Musculoskeletal, connective tissue and bone disorders

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

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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

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 medical practitioner/doctor consultation.