SIGNIFICANT RELIEF OF ABDOMINAL PAIN AND DIARRHEA FOLLOWING A 2-WEEK TREATMENT1,5†

image showing a block chart with a composite endpoint of trials 1 &2 showing improvement in symptoms of abdominal pain and diarrhea vs minor improvement with just placibo. image showing a block chart with a composite endpoint of trials 1 &2 showing improvement in symptoms of abdominal pain with XIFAXAN over placebo image showing a block chart with a composite endpoint of trials 1 &2 showing improvement in symptoms of diarrhea ober placebo

†Targets 1 & 2 Study Design1,5: Two identical, randomized, phase 3, double-blind, placebo-controlled trials were conducted over a 3-month period. A total of 1258 patients meeting Rome II criteria for IBS were randomized to receive XIFAXAN 550 mg 3 times a day (n=624) or placebo (n=634) for 14 days. Primary endpoint: 41% (n=254) of patients in both XIFAXAN 550 mg groups and 31% and 32% (n=201) of patients in the placebo groups experienced adequate relief of IBS signs and symptoms for at least 2 of 4 weeks during the month following 14 days of treatment; P<0.05 vs placebo. Adequate relief was 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].” Composite endpoint: 47% (n=291) of patients in both XIFAXAN 550 mg groups and 39% in Target 1 and 36% in Target 2 (n=237) of patients in the placebo groups experienced a ≥30% decrease from baseline in abdominal pain for ≥2 weeks during the month following 2 weeks of treatment and had a weekly mean stool consistency score of <4 (loose stool) for ≥2 weeks during the month following treatment; P<0.05 for TARGET 1, P<0.01 for TARGET 2.

P<0.001 represents pooled data.1

No rescue medication allowed in clinical trials.1

THE ONLY 2-WEEK TREATMENT PROVEN TO PROVIDE SIGNIFICANT RELIEF FOR UP TO 6 MONTHS5§||#

Image of calendar showing 6 months of duration relief with a study median of 10 weeks for Trial 3 composite endpoint results

#Target 3 Study Design5: XIFAXAN was evaluated in 2438 IBS-D patients. 44% (n=1074) experienced relief from an open-label course of treatment. Relief was defined as experiencing a ≥30% iimprovement 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) compared with baseline. If patients experienced a recurrence of either of their symptoms for 3 weeks of a rolling 4-week period, they entered the randomized, double-blind treatment phase. Randomized patients then received a repeat treatment with either XIFAXAN or placebo. The primary endpoint was the proportion of patients who experienced relief in both symptoms (defined exactly as in the open-label period) during the 4 weeks following repeat treatment.

Recurring symptoms, when reported, were less severe than at first occurrence.5

WELL-ESTABLISHED SAFETY PROFILE5

  • >13 years of therapeutic use; studied in clinical trials across >3300 patients5
  • NOT a controlled substance
  • NOT contraindicated in patients without a gallbladder5
  • No association of pancreatitis was observed in patients taking XIFAXAN in the clinical trials5,6
MINIMAL SIDE EFFECTS AT RATES SIMILAR TO PLACEBO5
Image of chart minimal side effects shown with trials 1,2 & 3.
Constipation was observed in only 0.5% of XIFAXAN patients6

Did not cause any clinically relevant antibiotic resistance after 1 to 3 treatment cycles6

CONVENIENT DOSING THAT DELIVERS
LASTING SYMPTOM RELIEF5§||

Dosing Features5
  • One 550 mg tablet 3 times daily for 2 weeks
  • Can be taken with or without food
  • ||Patients who experience recurrence can be retreated
    up to two times
Image showing a Rx pad with a prescription written for XIFAXAN 550 MG TID 14 days #42

§Range of 6 to 24 weeks; median of 10 weeks.

Image of certificate showing blue ribbon with #1 and the statement that XIFAXAN is the #1 IBS-D medication prescribed by primary care physicians and gastroenterologists.

‡‡ The ICD-10 code and other information provided are for informational purposes only. It is the treating physician’s responsibility to determine the proper diagnosis, treatment and applicable ICD-10 code. Salix Pharmaceuticals does not guarantee coverage or reimbursement for the product.

UP TO 16 MILLION AMERICANS SUFFER WITH IBS-D8,9

IBS IS CLASSIFIED INTO SUBTYPES BASED ON BOWEL HABITS10,11
Image of ven diagram showing the subtypes based on bowel habits 40% IBS-D, IBS-C 35% and the overlap of 23% for IBS-M
Image of icons with percentages next to them tablet icon 47$, heart icon 40% and coffee cup 55%
A symptom-based diagnosis of IBS-D is recommended and reliable11,14

Diagnosis should include:

  • History based on Rome IV criteria10
    • Abdominal pain at least 1 day per week for the last 3 months associated with 2 or more of the following:
      • defecation
      • change in frequency of stool
      • change in form (appearance) of stool
  • Exclusion of alarm features15
    • Symptom onset after age 50
    • Severe or progressively worsening symptoms
    • Unexplained weight loss
    • Nocturnal diarrhea
    • Rectal bleeding
    • Iron-deficiency anemia
    • Family history of colon cancer, celiac disease, or inflammatory bowel disease
  • Physical examination
Image showing Bristol stool scale for Type 1, Type 2, Type 3, Type 4, Type 5, Type 6, Type 7.
In one trial, diagnosis based on symptoms alone was accurate in 98% of patients.16

References: 1. 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. 2. Ringel Y. The gut microbiome in irritable bowel syndrome and other functional bowel disorders. Gastroenterol Clin North Am. 2017;46(1):91-101. 3. Zhong W, Lu X, Shi H, et al. Distinct microbial populations exist in the mucosa-associated microbiota of diarrhea predominant irritable bowel syndrome and ulcerative colitis. J Clin Gastroenterol. 2017;00:1-13. 4. Rivkin A, Rybalov S. Update on the management of diarrhea-predominant irritable bowel syndrome: focus on rifaximin and eluxadoline. Pharmacotherapy. 2016;36(3):300-316. 5. XIFAXAN [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals. 6. Data on file. Salix Pharmaceuticals. Bridgewater, NJ. 7. ICD-10 data. http://www.icd10data.com/. Accessed December 12, 2017. 8. Grundmann O, Yoon SL. Irritable bowel syndrome: epidemiology, diagnosis and treatment: an update for health-care practitioners. J Gastroenterol Hepatol. 2010;25(4):691-699. 9. Quick Facts. United States Census Bureau website. https://www.census.gov/quickfacts/table/PST045215/00. Accessed October 11, 2017. 10. Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150(6):1393-1407. 11. Brandt LJ, Chey WD, Foxx-Orenstein AE, et al; American College of Gastroenterology Task Force on Irritable Bowel Syndrome. An evidence-based systematic review on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104(Suppl 1):S1-S35. 12. Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10(7):712-721. 13. The American Gastroenterological Association. IBS in America: survey highlights physical, social and emotional impact. http://www.multivu.com/players/ English/7634451-aga-ibs-in-america-survey/. Accessed October 11, 2017. 14. Cash BD, Schoenfeld P, Chey WD. The utility of diagnostic tests in irritable bowel syndrome patients: a systemic review. Am J Gastroenterol. 2002;97(11):2812-2819. 15. Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review. JAMA. 2015;313(9):949-958. 16. Vanner SJ, Depew WT, Paterson WG, DaCosta LR, Groll AG, Djurfeldt M. Predictive value of the Rome criteria for diagnosing the irritable bowel syndrome. Am J Gastroenterol. 1999;94(10):2912-2917.

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.

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.