The use of NSAIDs may be associated with acute renal failure in patients with severe hepato-cirrhosis. These patients frequently also have concomitant coagulopathy related to inadequate synthesis of clotting factors. Antiplatelet effects associated with naproxen could further increase risk of severe bleeding in these patients.
Section 4.5
Clopidogrel paragraph - percentages and wording updated
Drugs with gastric pH-dependent absorption
Paragraph text updated to read:
The gastric acid suppression during treatment with esomeprazole and other PPIs might decrease or increase the absorption of drugs with a gastric pH dependent absorption. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, itraconazole, posaconazole and erlotinib can decrease while the absorption of drugs such as digoxin can increase during treatment with esomeprazole. Concomitant use with posaconazole and erlotinib should be avoided. Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10% (up to 30% in two out of ten subjects).
Paragraph inserted after “Dose adjustment of esomprazole is not required in any of these cases.”
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.
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.
Section 5.1
Text added to Other effects related to acid inhibition paragraph
Also chromogranin A (CgA) increases due to decreased gastric acidity.
New paragraph added before “Clinical efficacy and safety” paragraph
Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.
Second paragraph from end of section text updated
Section 5.2
Naproxen
Text – "not recommended” replaced with “contraindicated”
Esomeprazole:
Following text deleted
Therefore, a maximum of 20 mg daily should not be exceeded in patients with severe hepatic impairment.
Section 10
Date of revision changed to 9th September 2011
