Gender

The AUC and Cmax values were slightly higher (13%) in females than in males at steady state. Dosage adjustment based on gender is not necessary.

Hepatic Insufficiency

The steady state pharmacokinetics of esomeprazole obtained after administration of 40 mg once daily to 4 patients each with mild (Child Pugh Class A), moderate (Child Pugh Class B), and severe (Child Pugh Class C) liver insufficiency were compared to those obtained in 36 male and female GERD patients with normal liver function. In patients with mild and moderate hepatic insufficiency, the AUCs were within the range that could be expected in patients with normal liver function. In patients with severe hepatic insufficiency the AUCs were 2 to 3 times higher than in the patients with normal liver function. No dosage adjustment is recommended for patients with mild to moderate hepatic insufficiency (Child Pugh Classes A and B). However, in patients with severe hepatic insufficiency (Child Pugh Class C) a dose of 20 mg once daily should not be exceeded [see Dosage and Administration (2)].

Renal Insufficiency

The pharmacokinetics of NEXIUM in patients with renal impairment are not expected to be altered relative to healthy volunteers as less than 1% of esomeprazole is excreted unchanged in urine.

Other pharmacokinetic observations

Coadministration of oral contraceptives, diazepam, phenytoin, or quinidine did not seem to change the pharmacokinetic profile of esomeprazole.

Studies eva luating concomitant administration of esomeprazole and either naproxen (non-selective NSAID) or rofecoxib (COX-2 selective NSAID) did not identify any clinically relevant changes in the pharmacokinetic profiles of esomeprazole or these NSAIDs.

12.4 Microbiology
NEXIUM, amoxicillin, and clarithromycin triple therapy has been shown to be active against most strains of Helicobacter pylori (H. pylori) in vitro and in clinical infections as described in the Clinical Studies (14) and Indications and Usage (1) sections.

Helicobacter pylori: Susceptibility testing of H.pylori isolates was performed for amoxicillin and clarithromycin using agar dilution methodology, and minimum inhibitory concentrations (MICs) were determined.

Pretreatment Resistance: Clarithromycin pretreatment resistance rate (MIC ≥ 1 mcg/mL) to H.pylori was 15% (66/445) at baseline in all treatment groups combined. A total of > 99% (394/395) of patients had H. pylori isolates that were considered to be susceptible (MIC ≤ 0.25 mcg/mL) to amoxicillin at baseline. One patient had a baseline H. pylori isolate with an amoxicillin MIC = 0.5 mcg/mL.

Clarithromycin Susceptibility Test Results and Clinical/Bacteriologic Outcomes: The baseline H. pylori clarithromycin susceptibility results and the H. pylori eradication results at the Day 38 visit are shown in the table below:

Table 7

Clarithromycin S