s-1743 and Liver-Cirrhosis

Esomeprazole is efficient for acid-dependent diseases of the gastrointestinal tract in patients with chronic hepatitis and hepatic cirrhosis as it can reduce the disease symptoms and cause the epithelization of erosive and ulcerative defects of the mucous coat. The terms of the cicatrisation of erosive and ulcerative defects of the mucous coat of the esophagus, stomach and duodenum are comparable in patients with liver diseases and in the population (without chronic hepatic diseases). The simultaneous application of Nexium and modern hepatotropic drugs does not cause the development of hepatotoxic reactions.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Chronic Disease; Esomeprazole; Female; Gastric Acid; Hepatitis, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Peptic Ulcer

Hepatic encephalopathy (HE) is a serious complication of cirrhosis and is associated with gut dysbiosis. Proton pump inhibitors (PPIs), frequently prescribed to patients with cirrhosis, can contribute to small-bowel bacterial overgrowth. We investigated whether PPI predisposes patients with cirrhosis to HE using a large database of patients.. We performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000), followed up longitudinally from 1998 through 2011. Patients with cirrhosis and an occurrence of HE (n = 1166) were selected as the case cohort and matched to patients without HE (1:1, controls) for sex, enrollment time, end point time, follow-up period, and advanced cirrhosis. Information on prescribed drugs, drug dosage, supply days, and numbers of dispensed pills was extracted from the Taiwan National Health Insurance database. PPI use was defined as more than 30 cumulative defined daily doses (cDDDs); PPI nonuse was defined as 30 cDDDs or fewer. We performed logistic regression analyses to estimate the association between PPI use and the occurrence of HE.. Among patients with cirrhosis and an occurrence of HE, 38% (n = 445) had a history of PPI use before HE occurrence. We observed a relationship between dose of PPI taken and HE risk. The confounder-adjusted odd ratios were 1.41 (95% confidence interval [CI], 1.09-1.84), 1.51 (95% CI, 1.11-2.06), and 3.01 (95% CI, 1.78-5.10) for patients with 30-120 cDDDs, 120-365 cDDDs, and more than 365 cDDDs, respectively, compared with PPI nonusers. All categories of PPIs, except rabeprazole, were associated with an increased risk of HE.. Based on an analysis of data from Taiwan National Health Insurance beneficiaries, we found that use of PPIs in patients with cirrhosis increases the risk for HE; risk increases with dose. It therefore is important for health care providers to carefully consider prolonged PPI use by patients with cirrhosis.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administrative Claims, Healthcare; Adult; Aged; Case-Control Studies; Esomeprazole; Female; Hepatic Encephalopathy; Humans; Incidence; Insurance, Health; Lansoprazole; Liver Cirrhosis; Longitudinal Studies; Male; Middle Aged; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Taiwan

To evaluate the pharmacokinetics and safety of esomeprazole (Nexium), the S-isomer of omeprazole, after repeated oral dosing in patients with hepatic impairment.. Single-centre, open-label one-way study.. Twelve patients (aged 40-60 years) with mild to severe hepatic impairment received once-daily oral esomeprazole 40 mg for 5 days. Serial blood samples were drawn up to 24 h post-dose on day 5 to determine plasma levels of esomeprazole and its metabolites. Pharmacokinetic parameters were compared with an historical control group of 36 gastro-oesophageal reflux disease (GORD) patients (aged 29-58 years) with normal hepatic function.. Esomeprazole was absorbed rapidly (mean maximum plasma concentration (Cmax) 6.1 micromol/l, mean time to Cmax (tmax) 1.9 h) and eliminated rapidly (mean plasma elimination half-life (t1/2) 2.1 h). Elimination of its pharmacologically inactive sulphone and hydroxy metabolites was more gradual. Patients with mild hepatic impairment had area under the plasma concentration-time curve during the dosage interval (AUCtau) and t1/2 values largely within the range of the control group. In patients with moderate hepatic impairment, t1/2 values were similar and AUCtau was slightly higher than in controls, whereas both parameters were increased in patients with severe hepatic impairment. The mean ratios of esomeprazole AUCtau, Cmax and t1/2 values in patients with and without hepatic impairment were 1.8, 1.3 and 1.3, respectively.. The steady-state pharmacokinetics of esomeprazole were not altered substantially by mild or moderate hepatic impairment; however, plasma levels of esomeprazole were elevated in severe cases. Thus, dose adjustment appears unwarranted in mild or moderate hepatic impairment, but may be required in some severely impaired patients. Esomeprazole was tolerated well across the spectrum of hepatic impairment.

Topics: Administration, Oral; Adult; Anti-Ulcer Agents; Case-Control Studies; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Liver Cirrhosis; Male; Middle Aged