Peprazom/Peprazom IV Special Precautions

In the presence of any alarm symptom (eg, significant unintentional weight loss, recurrent vomiting, dysphagia, hematemesis or melena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with esomeprazole may alleviate symptoms and delay diagnosis.
Patients on long-term treatment (particularly those treated for >1 year) should be kept under regular surveillance.
Patients on on-demand treatment should be instructed to contact the physician if 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.
Peprazom contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take Peprazom. It also contains parahydroxybenzoates, which may cause allergic reactions (possibly delayed).
Treatment with proton-pump inhibitors may lead to slightly increased risk of gastrointestinal infections eg, Salmonella and Campylobacter.
Co-administration of esomeprazole with atazanavir is not recommended. If the combination of atazanavir with a proton-pump inhibitor is judged unavoidable, close clinical monitoring is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir; esomeprazole 20 mg should not be exceeded.
Peprazom IV: Hypomagnesemia: Severe hypomagnesemia has been reported in patients treated with PPIs like esomeprazole for at least 3 months, and in most cases for a year. Serious manifestations of hypomagnesemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesemia improved after magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesemia (e.g. diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.
Risk of hip, wrist and spine fracture: Omeprazole as well as esomeprazole act as inhibitors of CYP2C19. 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.
In healthy volunteers, concomitant oral administration of 40 mg esomeprazole and cisapride resulted in a 32% increase in area under the plasma concentration-time curve (AUC) and a 31% prolongation of elimination half-life (te2) but no significant increase in peak plasma levels of cisapride. The slightly prolonged QTc Interval observed after administration of cisapride alone, was not further prolonged when cisapride was given in combination with esomeprazole.
Esomeprazole has been shown to have no clinically relevant effects on the pharmacokinetics of amoxicillin or quinidine.
No in vivo interaction studies have been performed with the high dose iv regimen (80mg+80mg/h). The effect of esomeprazole on drugs metabolised by CYP2C19 may be inure pronounced during this regimen, and patients should be monitored closely for adverse effects, during the 3-day i.v. treatment period.
In a crossover clinical study, clopidogrel (300 mg loading dose followed by 75 mg/day) alone and with omeprazole (80 mg at the same time as clopidogrel) were administered for 5 days. 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. In another study it was shown that administering clopidogrel and omeprazole at different times did not prevent their Interaction that is likely to be driven by the inhibitory effect of omeprazole on CYP2C19. Inconsistent data on the clinical implications of this PK/PD interaction in terms of major cardiovascular events have been reported from observational and clinical studies.
Unknown mechanism: When given together with PPIs, methotrexate levels have been reported to increase in some patients. In high-dose methotrexate administration, a temporary withdrawal of esomeprazole may need to be considered.
Effects of other drugs on the pharmacokinetics of esomeprazole: Esomeprazole is metabolised by CYP2C19 and CYP3A4. Concomitant oral administration of esomeprazole and a CYP3A4 inhibitor. clarithromycin (500 mg b.i.d.), 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. The CYP2C19 and CYP3A4 inhibitor voriconazole increased omeprazole AUC, by 280%. 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.
Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's wort) may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.
Effects on the Ability to Drive or Operate Machinery: No effects have been observed.