For multiple IBS-D symptom relief,
there's XIFAXAN1

In adults with IBS-D

Just 2 weeks of XIFAXAN provided significant relief from both abdominal pain and diarrhea1,2*†

TARGET 1 & 21,2†

*Patients who experience recurrence can be retreated up to 2 times.

P<0.001 represents pooled data.

TARGET 1 and 2 study design1,2

Two identical Phase 3, randomized, double-blind, placebo-controlled trials conducted over a 3-month period. A total of 1258 patients meeting Rome II criteria for IBS were to receive XIFAXAN 550 mg (n=624) or placebo (n=634) 3 times a day for 14 days.

Primary endpoint: Adequate relief of IBS signs and symptoms for at least 2 of 4 weeks during the month following 14 days of treatment, with adequate relief defined as a response of “yes” to the weekly Subject Global Assessment (SGA) question: “In regards to your IBS symptoms, compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptoms? [Yes/No].”

Primary endpoint results: 41% of patients (254 of 624) in the XIFAXAN 550 mg group, 31% of TARGET 1 placebo group (98 of 314, P=0.01), and 32% of TARGET 2 placebo group (103 of 320, P=0.03) experienced adequate relief of IBS signs and symptoms.

Composite endpoint: ≥30% decrease from baseline in abdominal pain, with a weekly mean stool consistency score of <4 (loose stool) for ≥2 weeks during the month following 2 weeks of treatment.

No rescue medication was allowed in these clinical trials2

XIFAXAN provided significant relief of bloating2

Percentage of BLOATING responders based on weekly responses in
TARGET 1 & 22

§P<0.001 represents pooled data.

Key secondary endpoint: The proportion of subjects who achieved adequate relief of IBS-related bloating (ie, responders) for at least 2 of 4 weeks during the month following 14 days of treatment.2

A bloating responder was defined as a patient who responded “yes” to the weekly question:“In regards to your IBS symptom of bloating, compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptom of bloating? [Yes/No].”2||

||Responses were given during the first 4 weeks of the treatment-free period following 2 weeks of active treatment (primary evaluation period).

XIFAXAN provided significant relief of urgency3

Percentage of URGENCY responders based on weekly responses in
TARGET 1 & 2 in a pooled post hoc analysis3

P=0.0003 represents data from pooled post hoc analysis.

Stool frequency (number of bowel movements per day) was assessed as a secondary endpoint, but there was no statistically significant difference between XIFAXAN and placebo.4

  • A bowel movement urgency responder was defined as a patient with a ≥30% decrease from baseline in the percentage of days with urgency for at least 2 of 4 weeks during the month following 14 days of treatment. Urgency was determined based on patient response of “yes” to the daily question: “Have you felt or experienced a sense of urgency today? [Yes/No]”3

Short-term therapy.1# Lasting relief
from abdominal pain and diarrhea.

#Patients who experience recurrence can be retreated up to two times.1

Median of 10 weeks (range of 6 to 24 weeks).1

Just 2 weeks of XIFAXAN provided significant relief from abdominal pain and diarrhea for up to 6 months1#Δ◊

TARGET 31◊

  • Primary endpoint: 38% experienced significant improvement in stool consistency and abdominal pain (n=125/328, P<0.05) vs 31% for placebo (n=97/308)1,5
  • Median time to symptom recurrence was 10 weeks (range of 6 to 24 weeks)
TARGET 3 study design1,5

The primary focus was to assess response to treatment during an 18-week observation phase after initial 4-week follow-up (total of 22 weeks following 2-week treatment). If a patient responded to open-label treatment but later experienced a recurrence, they entered the randomized, double-blind retreatment phase. Randomized patients then received a repeat treatment with either XIFAXAN or placebo.

A responder was defined as a patient experiencing a ≥30% improvement from baseline in the weekly average abdominal pain score (based on daily self-reports) and a ≥50% reduction in the number of days in a week with a daily stool consistency of Bristol Stool Scale type 6 or 7 (mushy or watery) for ≥2 weeks during the month following 2 weeks of treatment.

Recurrence was defined as the return of abdominal pain or lack of stool consistency for 3 weeks of a rolling 4-week period.

Primary endpoint in the double-blind, placebo-controlled portion of the trial was the proportion of patients who were responders to repeat treatment in both IBS-related abdominal pain and stool consistency.

After initial relief, recurring symptoms were less severe than baseline1,5a

Change from baseline in mean daily global IBS symptom score during the first and second repeat treatment double-blind phases. Global daily IBS-D symptoms score is based on a 6-question patient assessment related to bowel movement, urgency, pain, bloating, and severity of symptoms.

aBaseline was defined as study entry into open-label phase.

bStatistically significant difference versus placebo (least squares mean data). Data were analyzed using last observation carried forward methodology.

IBS-D = irritable bowel syndrome with diarrhea

XIFAXAN was given a strong recommendationc to treat global IBS-D symptoms in the 2020 ACG Clinical Guideline on Managing IBS6d

dBased on a moderate quality of evidence6e

  • ACG=American College of Gastroenterology
  • cStrength of recommendation: Strong=Most patients should receive the recommended course of action; Conditional=Many patients should have this recommended course of action, but different choices may be appropriate for some patients.
  • eSummary of quality of evidence:
  • High=The estimate of effect is unlikely to change with new data.
  • Moderate;
  • Low;
  • Very low=Estimate of effect is very uncertain.
INDICATIONS

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

IMPORTANT SAFETY INFORMATION
  • XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
  • Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
  • There is an increased systemic exposure in patients with severe (Child-Pugh Class C) hepatic impairment. Caution should be exercised when administering XIFAXAN to these patients.
  • Caution should be exercised when concomitant use of XIFAXAN and P-glycoprotein (P-gp) and/or OATPs inhibitors is needed. Concomitant administration of cyclosporine, an inhibitor of P-gp and OATPs, significantly increased the systemic exposure of rifaximin. In patients with hepatic impairment, a potential additive effect of reduced metabolism and concomitant P-gp inhibitors may further increase the systemic exposure to rifaximin.
  • In clinical studies, the most common adverse reactions for XIFAXAN were:
    • HE (≥10%): Peripheral edema (15%), nausea (14%), dizziness (13%), fatigue (12%), and ascites (11%)
    • IBS-D (≥2%): Nausea (3%), ALT increased (2%)
  • INR changes have been reported in patients receiving rifaximin and warfarin concomitantly. Monitor INR and prothrombin time. Dose adjustment of warfarin may be required.
  • XIFAXAN may cause fetal harm. Advise pregnant women of the potential risk to a fetus.

To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here for full Prescribing Information.

References: 1. XIFAXAN [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals. 2. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364(1):22-32. 3. Pimentel M, Cash BD, Lacy BE, et al. Assessing the efficacy of rifaximin in diarrhea-predominant irritable bowel syndrome: a post hoc analysis of two phase 3, randomized, placebo controlled trials. Poster presented at: World Congress of Gastroenterology; October 13-18, 2017; Orlando, FL. 4. Data on file. Salix Pharmaceuticals. Bridgewater, NJ. 5. Lembo A, Pimentel M, Rao SS, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2016;151(6):1113-1121. 6. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44.

INDICATIONS

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

IMPORTANT SAFETY INFORMATION
  • XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
  • Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.