Xifaxan® (rifaximin) is a 2-week treatment
Patients can be retreated up to 2 times if symptoms recur1
Xifaxan is a nonsystemic antibiotic1:
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
Xifaxan works by inhibiting1:
Protein synthesis
The growth of bacteria in the gut
Xifaxan is a 2-week treatment1:
One 550-mg tablet 3 times daily
Patients can be retreated up to 2 times if symptoms recur
IMPORTANT SAFETY INFORMATION - XIFAXAN (rifaximin) 550 mg tablets
XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
One 550-mg tablet 3 times daily1
2-week (14 days) treatment1
Can be taken with or without food1
Patients can be retreated up to 2 times if symptoms recur1
IMPORTANT SAFETY INFORMATION - XIFAXAN (rifaximin) 550 mg tablets
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of 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.
Xifaxan® (rifaximin) patients experienced significant improvements in abdominal pain and stool consistency2
2 Pivotal Trials to Evaluate Efficacy PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE2
Xifaxan patients entered TRIAL 1 and 2 with:
>10 years with IBS-D symptoms2
>80% of days with stool urgency2
Moderate abdominal pain2
At study entry, patients (≥18 years of age) met ROME II Criteria* for IBS1
*Rome II Criteria: At least 12 weeks, which need not be consecutive, in the preceding 12 months of abdominal discomfort or pain that has 2 out of 3 features: 1) Relieved with defecation; and/or 2) Onset associated with a change in frequency of stool; and/or 3) Onset associated with a change in form (appearance) of stool.1
Design of TRIAL 1 and 21
double-blinded
treatment
or placebo (n=634)
3 times daily
IBS-D signs
and symptoms
abdominal pain
and stool consistency
Primary endpoint:
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 was defined as a response of “yes or no” to the following weekly Subject Global Assessment (SGA) question: “In regard 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?”1
Composite endpoint:
Patients were responders if they experienced both of the following for
A ≥30% decrease from baseline in abdominal pain
A weekly mean stool consistency score <4 (loose stool)
TRIAL 1 AND 2: PROVEN RELIEF
IN IBS-D SYMPTOMS
Significant relief seen in composite endpoint
A composite endpoint of Trial 1 and 2 defined responders by IBS-related abdominal pain and stool consistency measures1
- Significantly more patients receiving Xifaxan were responders† for abdominal pain and stool consistency in Trials 1 and 2, compared with placebo
- The figure below shows the composite endpoint and individual patient symptoms
†Patients were responders if they experienced both of the following for ≥2 weeks during the month following 2 weeks of treatment1:
- A ≥30% decrease from baseline in abdominal pain
- A weekly mean stool consistency score <4 (loose stool)
Xifaxan patients experienced
significant IMPROVEMENTS in abdominal pain and stool consistency1,2
STOOL CONSISTENCY
P<.05
P=.02
P=.002
STOOL CONSISTENCY
P<.01
P=.02
P=.01
XIFAXAN PATIENTS EXPERIENCED SIGNIFICANT RELIEF
of IBS-D symptoms in BOTH PIVOTAL
CLINICAL trials.1
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 was defined as a response of “yes or no” to the following weekly SGA question: “In regard 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?”1,2
TRIAL 1 AND TRIAL 2 Primary Endpoint:
Adequate Relief of IBS-D Symptoms1,2
TRIAL 1 and 2 most common adverse event1
| Adverse Event |
Xifaxan (n=624) | Placebo (n=634) |
|---|---|---|
| Nausea | 3% | 2% |
IMPORTANT SAFETY INFORMATION - XIFAXAN (rifaximin) 550 mg tablets
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.
Exercise caution when administrating XIFAXAN concomitantly with a P-glycoprotein (P-gp) inhibitor such as cyclosporine. Concomitant administration of drugs that are P-gp inhibitors can substantially increase the systemic exposure to XIFAXAN. In patients with hepatic impairment, a potential additive effect of reduced metabolism and concomitant P-gp inhibitors may further increase the systemic exposure to XIFAXAN.
TRIAL 3 evaluated repeat treatment in adults with IBS-D meeting Rome III‡ criteria for up
- A total of 2579 patients were enrolled to receive open-label Xifaxan for 14 days
- Of 2438 evaluable patients, 1074 (44%) responded to initial treatment and were evaluated for continued response or recurrence of IBS-D symptoms
- A total of 636 patients (59% of responders) had symptom recurrence and were randomized into the double-blind phase of the study
- These patients were scheduled to receive Xifaxan 3 times daily (n=328) or placebo (n=308) for 2 additional 14-day repeat-treatment courses separated by 10 weeks
TRIAL 3 STUDY DESIGN1
treatment
of Xifaxan
responded§
during
for recurrence
responders did not
experience
recurrence of
symptoms
for up to an
follow-up period
had a recurrence
was
recurrent symptoms
were not as severe
as at baseline
did not continue in the trial
with 2 weeks of Xifaxan or placebo
‡ROME III Criteria: Recurrent abdominal pain or discomfort (uncomfortable sensation not described as pain) at least 3 days/month in the last 3 months associated with 2 or more of the following: 1) improvement with defecation; 2) onset associated with a change in frequency of stool; 3) onset associated with a change in form (appearance) of stool.1
§Responders had to experience both of the following during the 4 weeks following treatment:
- ≥30% improvement from baseline in the weekly average abdominal pain score
- ≥50% reduction in number of days in a week with mushy or watery stool
llAbdominal pain or mushy/watery stool consistency for 3 weeks of a rolling 4-week period.1
TRIAL 3: DOUBLE-BLIND PHASE
Repeat treatment provided similar symptom relief of abdominal pain and stool consistency1
TRIAL 3 PRIMARY ENDPOINT RESULTS1
STOOL CONSISTENCY
P<.05
Primary endpoint responders experienced both a ≥30% improvement from baseline in the weekly average abdominal pain score and a ≥50% reduction in the number of days in a week with mushy or watery stool during the 4 weeks after repeat treatment1
- Patients achieved the same endpoint after a second course of treatment, having less severe symptoms than at baseline
Patients who experience a recurrence of symptoms can be retreated up to 2 times with the same regimen1
TRIAL 3 most common adverse events1
| Adverse Event |
Xifaxan (n=328) | Placebo (n=308) |
|---|---|---|
| Nausea | 2% | 1% |
| ALT increased | 2% | 1% |
IMPORTANT SAFETY INFORMATION - XIFAXAN (rifaximin) 550 mg tablets
XIFAXAN may cause fetal harm. Discontinue in nursing mothers after taking into account the importance of the drug to the mother.
The most common adverse reactions for XIFAXAN in IBS-D were nausea (3%) and increased ALT (2%).
TOLERABILITY PROFILE1
Adverse events in ≥2% of patients receiving Xifaxan, at a higher rate than placebo
| TRIAL 1 and 2 most common adverse event1 | ||
| Adverse Event | Xifaxan (n=624) | Placebo (n=634) |
| Nausea | 3% | 2% |
| TRIAL 3 most common adverse events1 | ||
| Adverse Event | Xifaxan (n=328) | Placebo (n=308) |
| Nausea | 2% | 1% |
| ALT increased | 2% | 1% |
Abbreviation: ALT = alanine transaminase
Additional safety information about Xifaxan:
In clinical trials, constipation was observed
Xifaxan did not cause any clinically relevant antibiotic resistance after 1 to 3 treatment cycles3
- Clostridium difficile-associated diarrhea (CDAD) has been reported with use of 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
Exercise caution when administrating Xifaxan concomitantly with a P-glycoprotein (P-gp) inhibitor such as cyclosporine1
Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis1
Activate a Xifaxan Instant Savings Card
¶ Eligibility Criteria, Terms and Conditions: This offer is only valid for patients with commercial insurance, including commercially insured patients without coverage for Xifaxan. Patients without commercial insurance are not eligible. Commercially insured patients with coverage for Xifaxan will receive savings to reduce their copay to $0. Commercially insured patients without coverage for Xifaxan will receive savings off of retail price to reduce the out-of-pocket cost to as little as $50. The maximum benefit is $1000. Patient is responsible for all additional costs and expenses after application of the maximum benefits. This savings card can be used up to 12 times before the expiration date. This offer is not valid for any person eligible for reimbursement of prescriptions, in whole or in part, by Medicaid, Medicare (including Medicare Advantage and Part D Plans), or any other federal or state funded healthcare programs (including VA, DOD, Tricare, CHAMPUS and any state prescription drug programs). This offer is only good in the USA at participating retail pharmacies. This offer cannot be redeemed at other locations, including government-subsidized clinics or facilities. This offer is not valid where otherwise prohibited, taxed, or otherwise restricted. Patient is responsible for reporting receipt of co-pay assistance to any insurer, health plan, or other third party who pays for or reimburses any part of the prescription filled using the co-pay card, as may be required. This offer cannot be combined with other offers. This card has no cash value. No other purchase is necessary. This offer is nontransferable. No substitutions are permitted. This card is not health insurance. You understand and agree to comply with the terms and conditions of this offer as set forth above. Offer expires December 31, 2016. Salix Pharmaceuticals reserves the right to rescind, revoke, or amend this offer at any time without notice.
If you have patients who need assistance with their copay for Xifaxan, please direct them to call 1-866-XIFAXAN (943-2926)
- Xifaxan [prescribing information]. Raleigh, NC: Salix Pharmaceuticals; 2015.
- 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.
- Data on file. Raleigh, NC: Salix Pharmaceuticals; 2015.
XIFI.0100.USA.15
Salix Pharmaceuticals
8510 Colonnade Center Drive, Raleigh, NC 27615
The Xifaxan 550 mg product and the Xifaxan trademark are licensed by Alfa Wassermann S.p.A. to Salix Pharmaceuticals or its affiliates.
This MPR Prescribing Alert is produced as a basic reminder of important information for healthcare professionals. Readers are advised to consult manufacturers and specialists if questions arise about specific products, treatments, or diseases. The publisher and editors do not assume liability for any errors or omissions. MPR and MPR Prescribing Alert are registered trademarks of Haymarket Media, Inc.
© 2016 Haymarket Media, Inc.
INDICATION
XIFAXAN (rifaximin)
IMPORTANT SAFETY INFORMATION - XIFAXAN (rifaximin) 550 mg tablets
- XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, any of the 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 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.
- Exercise caution when administrating XIFAXAN concomitantly with a P-glycoprotein (P-gp) inhibitor such as cyclosporine. Concomitant administration of drugs that are P-gp inhibitors can substantially increase the systemic exposure to XIFAXAN. In patients with hepatic impairment, a potential additive effect of reduced metabolism and concomitant P-gp inhibitors may further increase the systemic exposure to XIFAXAN.
- XIFAXAN may cause fetal harm. Discontinue in nursing mothers after taking into account the importance of the drug to the mother.
- The most common adverse reactions for XIFAXAN in IBS-D were nausea (3%) and increased ALT (2%).
- Click here for full Prescribing Information