ESOSTAD Capsule

For:

- Gastro-oesophageal Reflux Disease (GORD): Treatment of erosive reflux oesophagitis; long-term management of patients with healed oesophagitis to prevent relapse; symptomatic treatment of gastroesophageal reflux disease (GORD).

- In combination with an appropriate antibacterial therapeutic regimen for the eradication of Helicobacter pylori, healing of Helicobacter pylori associated duodenal ulcer and prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcers.

- Patients requiring continued NSAID therapy: Healing of gastric ulcers associated with NSAID therapy; prevention of gastric and duodenal ulcers associated with NSAID therapy, in patients at risk.

- Treatment of Zollinger-Ellison syndrome.

Dosage and Administration

Administration

Esostad should be swallowed whole with some water. The capsules should not be chewed or crushed.

Dosage

Adults and adolescents from the age of 12 years

Gastro-oesophageal reflux disease (GORD):

- Treatment of erosive reflux oesophagitis: 20mg once daily for 4 weeks. An additional 4 weeks treatment is recommended for patients in whom oesophagitis has not healed or who have persisted symptoms.

- Long-term management of patients with healed oesophagitis to prevent relapse: 20mg once daily.

- Symptomatic treatment of gastro-oesophageal reflux disease (GORD): 20mg once daily in patients without oesophagitis. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using 20mg once daily. In adults, an on-demand regimen taking 20mg once daily, when needed, can be used. In NSAID treated patients at risk of developing gastric and duodenal ulcers, subsequent symptom control using an on-demand regimen is not recommended.

Adults

In combination with an appropriate antibacterial therapeutic regimen for the eradication of Helicobacter pylori and healing of Helicobacter pylori associated duodenal ulcer and prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcers: 20mg esomeprazole with 1g amoxicillin and 500mg clarithromycin, all trice daily for 7 days.

Patients requiring continued NSAID therapy:

- Healing of gastric ulcers associated with NSAID therapy: The usual dose is 20mg once daily. The treatment duration is 4-8weeks.

- Prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk: 20mg daily.

Treatment of Zollinger-Ellison syndrome:

The recommended initial dosage is esomeprazole 40mg twice daily. The dosage should then be individually adjusted and treatment continues as long as clinically indicated. Based on the clinical data available, the majority of patients can be controlled on doses between 80-160mg esomeprazole daily. With doses above 80mg daily, the dose should be divided and given twice-daily.

Children below the age of 12 years: Esomeprazole capsule should not be used in children younger than 12 years since no data is available.

(See the package insert about the details below.)

Impaired renal function

Impaired hepatic function

Elderly

- Known hypersensitivity to esomeprazole, substituted benzimidazoles or any other constituents of the formulation.

- Pregnancy in the first trimester.

Common

- General: Headache, vertigo, skin rashed.

- Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea, constipation, flatulence, dry mouth.

Uncommon

-General: Fatigue, insomnia, rash, pruritus, abnormal vision.

Rare

- General: Fever, increased sweating, peripheral oedema, photosensitivity, hypersensitivity reactions (e.g. urticaria, angioedema, bronchospasm and anaphylactic reaction/shock).

- Central nervous system: Agitation, depression reversible confusion, hallucinations.

- Haematological: Agranulocytosis, leukopenia, thrombocytopenia.

- Hepatic: Increased liver enzymes, hepatitis, jaundice, impaired hepatic function.

- Gastrointestinal: Taste disturbance.

- Musculoskeletal: Arthralgia, myalgia.

- Urinary: Interstitial nephritis.

- Skin: Bullous eruption, Stevens-Johnson syndrome, toxic epidermal necrolysis, dermatitis.

- By decreasing gastric acidity, proton pump inhibitors may increases the risk of gastrointestinal infections.

Medicinal products with pH dependent absorption

- The absorption of ketoconazole and itraconazole can decrease during treatment with esomeprazole.

- Co-administration of omeprazole (40mg once daily) with atazanavir 300mg/ritonavir 100mg to healthy volunteers resulted in a substantial reduction in atazanavir exposure.

Drugs metabolised by CYP2C19

- Esomeprazole is a CYP2C19 inhibitor. When starting or ending treatment with esomeprazole, the potential for interactions with drugs metabolised through CYP2C19 should be considered. Am interaction is observed between clopidogrel and omeprazole. The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of esomeprazole and clopidogrel should be discouraged.

- When esomeprazole is combined with drugs metabolised by CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin etc., the plasma concentrations of these drugs may be increased and a dose reduction could be needed. It is recommended to monitor the plasma concentration of phenytoin when treatment with esomeprazole is introduced or withdrawn.

- Concomitant administration of 40mg esomeprazole to warfarin-treated patients in a clinical significance have been reported during concomitant treatment.

Pregnancy

There are no adequate and controlled studies to date using esomeprazole in pregnant women, and the drug should be used during pregnancy only when clearly needed.

Lactation

It is not known whether esomeprazole is excreted in human breast milk. No studies in lactating women have been performed. Therefore esomeprazole should not be used during breast-feeding.

- 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 with esomeprazole may alleviate symptoms and delay diagnosis.

- PPIs, especially if used in high doses and over long duration (> 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 PPIs 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.

- When prescribing esomeprazole for eradication of Helicobacter pylori, possible drug interactions for all components in the triple therapy should be considered. Clarithromycin is a potent inhibitor of CYP3A4 and hence contraindications and interactions for clarithromycin should be considered when the triple therapy is used in patients concurrently taking other drugs metabolised via CYP3A4 such as cisapride.

- Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients with PPIs for at least 3 months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPI with medications such as digoxin or drugs that may cause hypomagnesemia (e.g. diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.

- Decreased gastric acidity due to any means including PPIs, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with PPIs may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.

Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell.

Esomeprazole is the S-isomer of omeprazole that are protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20-40mg and leads to inhibition of gastric acid secretion.