The first solution is preferable for a number of reasons. In fact, the concomitant use of two drugs increases costs and the

possibility of side effects. At the present time, a direct comparison between lactulose and rifaximin in prevention of HE is available only for patients with cirrhosis submitted to TIPS; in this group Selleckchem BMN673 both agents failed to prevent HE efficiently.4 However, these results may not be extendable to other categories of patients at risk of HE. The recent trial by Bass et al. was not designed to compare rifaximin to lactulose but included patients who had essentially failed lactulose.6 This is because all patients had to have at least 2 HE episodes in the 6 months while compliant on lactulose. In addition, during the study, lactulose was dispensed according to guidelines which ensured that they were taking it as prescribed. Because <10% of patients were not on lactulose, the confidence Vorinostat nmr interval for rifaximin in this subgroup was wide and did not reach significance. On the other hand, break-through HE episodes occurred in 22.1% of patients in the rifaximin arm, and in 45.9% of the placebo group. Similarly, HE-related hospitalisation was reported in

13.6% of rifaximin compared to 22.6% of placebo group. Thus, the second choice, adding rifaximin to lactulose seems to maintain HE remission in a larger number of patients when compared to lactulose therapy alone.6 This approach could increase possible side effects and reduce adherence. The Bass study did not show a significant effect of rifaximin (P = 0.21) in patients with MELD score >19, probably due to the low numbers of patients enrolled. medchemexpress Thus the question whether or not patients with a MELD score >19 will benefit from use of rifaximin remains undetermined.

Clinically significant drug interactions are not significant with rifaximin. Rifaximin undergoes efflux through P-glycoprotein and does not have significant interactions with other substrates for the P-glycoprotein such as digoxin. In addition no significant interactions with the bile-salt export pump were observed in vitro. Even at concentrations of 200 ng/mL, rifaximin did not inhibit the major cytochrome P450 and in vitro, the ability to induce cytochrome P450 3A4 was half that of rifampin. Clinically, the dose of 200 mg three times daily did not alter the pharmacokinetics of oral midazolam or oral Ortho-cyclen whereas the 550 mg three times daily dose for 7-14 days only slightly (10%) reduced midazolam exposure. In contrast previous exposure to midazolam reduced area under the curve of oral midazolam by 95%. Thus, based on in vitro and in vivo data, no dose adjustment is recommended when rifaximin is coadministered with other drugs.10 Selection of resistant mutants, especially when an antibiotic therapy is needed life-long, is a valid concern. This risk is probably low.14 Encouragingly, the resistant bacteria disappear after a 5 day course but there are no long-term data at this time.