Xifaxan (rifaximin) is a semisynthetic rifamycin derivative and non-systemic gastrointestinal site-specific broad spectrum antibiotic.
Xifaxan is specifically indicated for the treatment of of irritable bowel syndrome with diarrhea (IBS-D) in adults.
Xifaxan is supplied as a tablet for oral administration. The recommended dose is one 550 mg tablet taken orally three times a day for 14 days. Patients who experience a recurrence of symptoms can be retreated up to two times with the same dosage regimen.
The FDA approval of Xifaxan for IBS-D was based on three phase III randomized, multi-center, double-blind, placebo-controlled trials, TARGET-1, -2 and -3.
TARGET-1 and -2
These two trials enrolled a total of 1,258 patients meeting Rome II criteria for IBS who were randomized to receive Xifaxan 550 mg three times a day (n=624) or placebo (n=634) for 14 days and then followed for a 10-week treatment free period. The primary endpoint for both trials was the proportion of patients who achieved adequate relief of IBS signs and symptoms for at least 2 of 4 weeks during the month following 14 days of treatment. Adequate relief of IBS symptoms was experienced by more patients receiving Xifaxan than those receiving placebo during the month following 2 weeks of treatment (SGA-IBS Weekly Results: 41% vs. 31%, p=0.0125; 41% vs. 32%, p=0.0263).
This trial enrolled 2,579 patients who were scheduled to receive an initial 14-day course of open label Xifaxan followed by 4 weeks of treatment-free follow-up. At the end of the follow-up period, patients were assessed for response to treatment. Responders were then followed for recurrence of their IBS-related symptoms of abdominal pain or mushy/watery stool consistency for up to 20 treatment-free weeks. When patients experienced recurrence of their symptoms of abdominal pain or mushy/ watery stool consistency for 3 weeks of a rolling 4-week period, they were randomized into the double-blind, placebo-controlled repeat treatment phase. Of 1,074 patients who responded to open-label Xifaxan, 382 experienced a period of symptom inactivity or decrease that did not require repeat treatment by the time they discontinued, including patients who completed the 22 weeks after initial treatment with Xifaxan. Overall, 1,257 of 2,579 patients (49%) were nonresponders in the open-label phase and per the study protocol were withdrawn from the study. There were 1,074 (44%) of 2,438 evaluable patients who responded to initial treatment with improvement in abdominal pain and stool consistency. The response rate for each IBS symptom during the open-label phase of Trial 3 is similar to the rates seen in Trials 1 and 2. A total of 636 patients subsequently had sign and symptom recurrence and were randomized to the repeat treatment phase. Patients who responded to treatment with Xifaxan 550 mg but experienced recurrent symptoms responded to repeat treatment in the FDA composite endpoint versus placebo.
Adverse effects associated with the use of Xifaxan for IBS-D may include, but are not limited to, the following:
Xifaxan (rifaximin) is a semi-synthetic derivative of rifampin and acts by binding to the betasubunit of bacterial DNA-dependent RNA polymerase blocking one of the steps in transcription. This results in inhibition of bacterial protein synthesis and consequently inhibits the growth of bacteria.
For additional information regarding Xifaxan or IBS-D, please visit https://shared.salix.com/shared/pi/xifaxan-pi.pdf