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ETC / RX - Alimentary system drugs - Ameprazol 20, 40

COMPOSITIONS:

Capsules AMEPRAZOL® 20: Each capsule contains: Esomeprazole 20 mg (as Esomeprazole magnesium pellets 8.5% (w/w))

Capsules AMEPRAZOL® 40: Each capsule contains: Esomeprazole 40 mg (as Esomeprazole magnesium pellets 8.5% (w/w))


PHARMACODYNAMICS:

Esomeprazole is the S-isomer of omeprazole and reduces gastric acid secretion through a specific targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. Both the R- and S-isomer of omeprazole have similar pharmacodynamic activity.

Site and mechanism of action

Esomeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the secretory canaliculi of the parietal cell, where it inhibits the enzyme H+K+-ATPase, the acid pump and inhibits both basal and stimulated acid secretion.


PHARMACOKINETICS:

Esomeprazole is rapidly absorbed following oral administration, with peak plasma levels occuring after about 1 to 2 hours. It is acid labile and is administered orally as enteric-coated pellets. The absolute bioavailability is 64% after a single dose of 40 mg and increases to 89% after repeated once-daily administration. For 20 mg esomeprazole the corresponding values are 50% and 68%, respectively.

Food delays and decreases the absorption of esomeprazole, but this does not significantly change its effect on intragastric acidity. Esomeprazole is about 97% bound to plasma proteins.

It is extensively metabolised in the liver by the cytochrome P450 isoenzyme CYP2C19 to hydroxy and desmethyl metabolites, which have no effect on gastric acid secretion. The remainder is metabolised by the cytochrome P450 isoenzyme CYP3A4 to esomeprazole sulfone. With repeated administration, there is a decrease in first-pass metabolism and systemic clearance, probably caused by an inhibition of the CYP2C19 isoenzyme. However, there is no accumulation during once daily administration. The plasma elimination half-life is about 1.3 hours. Almost 80% of an oral dose is eliminated as metabolites in the urine, the remainder in the faeces.


INDICATIONS:

AMEPRAZOL is indicated for:

Gastroesophageal Reflux Disease (GERD)

  • Treatment of erosive reflux oesophagitis
  • Long-term management of patients with healed oesophagitis to prevent relapse
  • Symptomatic treatment of gastro-oesophageal reflux disease (GERD)

In combination with an appropriate antibacterial therapeutic regimen for the eradication of Helicobacter pylori and

  • Healing of Helicobacter pylori associated duodenal ulcer
  • 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.

Prolonged treatment after IV induced prevention of rebleeding of peptic ulcers

Treatment of Zollinger Ellison Syndrome.


ADMINISTRATION AND DOSAGE:

The capsules should be swallowed whole with liquid. The pellets must not be chewed or crushed.

Adults and adolescents from the age of 12 years:

Gastro-Oesophageal Reflux Disease (GERD)

Treatment of erosive reflux oesophagitis: 40 mg once daily for 4 weeks.

An additional 4 weeks treatment is recommended for patients in whom oesophagitis has not healed or who have persistent symptoms.

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

Symptomatic treatment of gastro-oesophageal reflux disease (GERD): 20 mg once daily in patients without oesophagitis. If symptom control has not been achieved after four weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using 20 mg once daily.

In adults, an on demand regimen taking 20 mg once daily, when needed, can be used.

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:

20 mg Esomeprazole with 1 g amoxicillin and 500 mg clarithromycin, all twice daily for 7 days.

Patients requiring continued NSAID therapy

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

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

Prolonged treatment after IV induced prevention of rebleeding of peptic ulcers.

40 mg once daily for 4 weeks after IV induced prevention of rebleeding of peptic ulcers.

Treatment of Zollinger Ellison Syndrome

The recommended initial dosage is Esomeprazole 40 mg twice daily. The dosage should then be individually adjusted. The majority of patients can be controlled on doses between 80 and 160 mg esomeprazole daily. With doses above 80 mg daily, the dose should be divided and given twice-daily.

Children below the age of 12 years:

Esomeprazole should not be used in children younger than 12 years since no data is available.

Impaired renal function:

Dose adjustment is not required in patients with mild to moderate impaired renal function.

Impaired hepatic function:

Dose adjustment is not required in patients with mild to moderate liver impairment. For patients with severe liver impairment, should not be exceeded 20 mg daily.

Elderly:

Dose adjustment is not required in the elderly.


CONTRAINDICATIONS:

  • Known hypersensitivity to esomeprazole, substituted benzimidazoles or any other constituents of the formulation.
  • Use concomitantly with atazanavir or nelfinavir.

WARNINGS AND PRECAUTIONS:

  • In the presence of any alarm symptom (eg, 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.
  • Due to limited experience in patients with severe renal insufficiency, such patients should be treated with caution.
  • Patients on long-term treatment (particularly those treated for over 1 year) should be kept under regular surveillance.
  • Patients on on-demand treatment should be instructed to contact their physician if their symptoms change in character. When prescribing esomeprazole for on demand therapy, the implications for interactions with other pharmaceuticals, due to fluctuating plasma concentrations of esomeprazole should be considered.
  • 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 eg, cisapride.
  • Pregnancy: For esomeprazole, clinical data on exposed pregnancies are insufficient. Animal studies with esomeprazole do not indicate direct or indirect harmful effects with respect to embryonal/fetal development. Caution should be exercised when prescribing to pregnant women.
  • 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 breastfeeding.

SIDE EFFECTS:

Headache, abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting.

Uncommon: Peripheral oedema, insomnia, dizziness, paraesthesia, somnolence, vertigo, dry mouth, increased liver enzymes, dermatitis, pruritus, rash, urticaria.

Rare: Leukopenia, thrombocytopenia, hypersensitivity reactions (e.g fever, angioedema and anaphylactic reaction or shock), hyponatraemia, agitation, confusion, depression, taste disturbance, blurred vision, bronchospasm, stomatitis, gastrointestinal candidiasis, hepatitis with or without jaundice, alopecia, photosensitivity, arthralgia, myalgia, malaise, increased sweating.

Very rare: Agranulocytosis, pancytopenia, aggression, hallucinations, hepatic failure, encephalopathy in patients with pre-existing liver disease, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), muscular weakness, interstitial nephritis, gynaecomastia.

In case of an unexpected reaction, consult your physician.


INTERACTIONS:

  • The decreased intragastric acidity during treatment with esomeprazole, might increase or decrease the absorption of drugs if the mechanism of absorption is influenced by gastric acidity. The absorption of ketoconazole and itraconazole can decrease during treatment with esomeprazole.
  • Esomeprazole should not be co-administered with atazanavir because it may reduce in atazanavir exposure (decrease in AUC, Cmax and Cmin).
  • In healthy volunteers, concomitant oral administration of esomeprazole and cisapride resulted in increased AUC and prolongation of elimination half-life (T1/2) but no significant increase in peak plasma levels of cisapride.
  • 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.
  • Esomeprazole is metabolised by CYP2C19 and CYP3A4. Concomitant administration of esomeprazole and a CYP3A4 inhibitor, resulted in a doubling of the exposure (AUC) to esomeprazole. Concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP 3A4 may result in more than doubling of the esomeprazole exposure. A dose adjustment of esomeprazole is not regularly required in either of these situations. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.
  • Concomitant administration of esomeprazole to warfarin-treated patients in a clinical trial showed that coagulation times were within the accepted range. Monitoring is recommended when initiating and ending concomitant esomeprazole treatment during treatment with warfarin or other coumarine derivatives.

OVERDOSAGE:

There is very limited experience to date with deliberate overdose. The symptoms described in connection with an oral dose of 280 mg were gastrointestinal symptoms and weakness. Single oral doses of esomeprazole 80 mg were uneventful. No specific antidote is known. Esomeprazole is extensively plasma protein bound and is therefore not readily dialyzable. As in any case of overdose, treatment should be symptomatic and general supportive measures should be utilised.


PRESENTATION:

AMEPRAZOL® 20 :

  • Box of 5 blisters x 6 capsules
  • Box of 10 blisters x 6 capsules

AMEPRAZOL® 40 :

  • Box of 5 blisters x 6 capsules
  • Box of  10 blisters x 6 capsules
  • Box of  2 blisters x 7 capsules
  • Box of  4 blisters x 7 capsules

Storage: Store at temperature from 150C to 250C, in a dry place.

Shelf-life: 24 months from manufacturing date. Do not use after expiry date.