ULCESEP Hard gelatin capsule Ref.[51141] Active ingredients: Omeprazole

Decreased gastric acidity due to any means, including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract.

Treatment with acid-reducing drugs may lead to a slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.

For severely ill children, who require long-term treatment with Ulcesep, and may have borderline levels or body stores of B₁₂, it may be advisable to monitor serum B₁₂ levels during long-term treatment (see section 4.8).

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Due to the decreased intragastric acidity the absorption of ketoconazole or itraconazole may be reduced during omeprazole treatment as it is during treatment with other acid secretion inhibitors.

As Ulcesep is metabolised in the liver through cytochrome P450 it can prolong the elimination of diazepam, phenytoin and warfarin. Monitoring of patients receiving warfarin or phenytoin is recommended and a reduction of warfarin or phenytoin dose may be necessary. However concomitant treatment with Ulcesep 20 mg daily did not change the blood concentration of phenytoin in patients on continuous treatment with phenytoin. Similarly concomitant treatment with Ulcesep 20 mg daily did not change coagulation time in patients on continuous treatment with warfarin.

Plasma concentrations of omeprazole and clarithromycin are increased during concomitant administration. This is considered to be a useful interaction during H. pylori eradication. There is no interaction with metronidazole or amoxicillin. These antimicrobials are used together with omeprazole for eradication of Helicobacter pylori.

There is no evidence of an interaction with phenacetin, theophylline, caffeine, propranolol, metoprolol, ciclosporin, lidocaine, quinidine, estradiol, or antacids. The absorption of Ulcesep is not affected by alcohol or food. There is no evidence of an interaction with piroxicam, diclofenac or naproxen. This is considered useful when patients are required to continue these treatments.

Simultaneous treatment with omeprazole and digoxin in healthy subjects lead to a 10% increase in the bioavailability of digoxin as a consequence of the increased intragastric pH.

Co-administration of omeprazole (40mg once daily) with atazanavir 300 mg/ritonavir 100mg to healthy volunteers resulted in a substantial reduction in atazanavir exposure (approximately 75% decrease in AUC, C_max, and C_min).

Increasing the atazanavir dose to 400mg did not compensate for the impact of omeprazole on atazanavir exposure. PPIs including omeprazole should not be coadministered with atazanavir (see section 4.3)

Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus.

Pregnancy

The analysis of the results from three epidemiological studies has revealed no evidence of adverse events of omeprazole on pregnancy or on the health of the foetus/newborn child. Ulcesep can be used during pregnancy.

Lactation

Omeprazole is excreted in breast milk but is not likely to influence the child when therapeutic doses are used.

No effects are foreseen.

Ulcesep is well tolerated and adverse reactions have generally been mild and reversible. The following have been reported as adverse events in clinical trials or reported from routine use, but in many cases a relationship to treatment with omeprazole has not been established.

The following definitions of frequencies are used: Common >1/100, Uncommon >1/1000 and <1/100, Rare <1/1000.

Common:

Central and peripheral nervous system: Headache

Gastrointestinal: Diarrhoea, constipation, abdominal pain, nausea/vomiting and flatulence

Uncommon:

Central and peripheral nervous system: Dizziness, paraesthesia, light headedness, feeling faint, somnolence, insomnia and vertigo

Hepatic: Increased liver enzymes

Skin: Rash and/or pruritus. urticaria

Other: Malaise

Rare:

Central and peripheral nervous system: Reversible mental confusion, agitation, aggression, depression and hallucinations, predominantly in severely ill patients

Endocrine: Gynaecomastia

Gastrointestinal: Dry mouth, stomatitis and gastrointestinal candidiasis

Haematological: Leukopenia, thrombocytopenia, agranulocytosis and pancytopenia

Hepatic: Encephalopathy in patients with pre existing severe liver disease; hepatitis with or without jaundice, hepatic failure

Musculoskeletal: Arthritic and myalgic symptoms and muscular weakness

Reproductive system and breast disorders: Impotence

Skin: Photosensitivity, bullous eruption, erythema multiforme, StevensJohnson syndrome, toxic epidermal necrolysis (TEN), alopecia

Other: Hypersensitivity reactions e.g. angioedema, fever, broncho spasm, interstitial nephritis and anaphylactic shock. Increased sweating, peripheral oedema, blurred vision, taste disturbance and hyponatraemia

The safety of omeprazole has been assessed in 310 children aged 0 to 16 years with acid related disease and 62 physiologically normal volunteers aged 2 years to 16 years. Omeprazole was generally well tolerated with an adverse event profile resembling that in adults.

In a study of 106 children aged 0-24 months with gastro-oesophageal reflux, treated with omeprazole, 11 patients had moderate elevations of serum liver enzymes (AST, ALT, GGT), but were clinically asymptomatic. In addition, 52 patients had mild to moderate reductions in neutrophil counts, although there was only one case of reduction in WBC.

There are limited long term safety data from 46 children who received maintenance therapy of omeprazole during a clinical study for severe erosive oesophagitis for up to 749 days (see section 5.1). In this group, a retrospective review of patients showed that serum vitamin B12 levels decreased mildly in 18 children during 24 months of the study. In no patient did the level fall below normal limits. Iron deficiency anaemia was reported in 12 patients. Elevations in serum gastrin levels were noted in 20 patients, and 4 children had argyophil (ECL) hyperplasia during this study.

None known.