red in 0.4% of patients. The adverse reactions leading to discontinuation were taste loss, dysentery, weight decrease, anorexia, nausea and nasal passage irritation.
The adverse reaction that occurred at a frequency ≥2% in XIFAXAN-treated patients (n=320) at a higher rate than placebo (n=228) in the two placebo-controlled trials of TD was:
•headache (10% XIFAXAN, 9% placebo)
Hepatic Encephalopathy
The data described below reflect exposure to XIFAXAN in 348 patients, including 265 exposed for 6 months and 202 exposed for more than a year (mean exposure was 364 days). The safety of XIFAXAN 550 mg taken two times a day for reducing the risk of overt hepatic encephalopathy recurrence in adult patients was eva luated in a 6-month placebo-controlled clinical trial (n=140) and in a long term follow-up study (n=280). The population studied had a mean age of 56 (range: 21 to 82) years; approximately 20% of the patients were ≥65 years old, 61% were male, 86% were White, and 4% were Black. Ninety-one percent of patients in the trial were taking lactulose concomitantly. The most common adverse reactions that occurred at an incidence ≥5% and at a higher incidence in XIFAXAN-treated subjects than in the placebo group in the 6-month trial are provided in Table 1.
Table 1: Most Common Adverse Reactions* in HE Trial
reported in ≥5% of Patients Receiving XIFAXAN and at a higher incidence than placebo
Irritable Bowel Syndrome with Diarrhea
The safety of XIFAXAN for the treatment of IBS-D was eva luated in 3 placebo-controlled studies in which 952 patients were randomized to XIFAXAN 550 mg three times a day for 14 days. Across the 3 studies, 96% of patients received at least 14 days of treatment with XIFAXAN. In Trials 1 and 2, 624 patients received only one 14-day treatment. Trial 3 eva luated the safety of XIFAXAN in 328 patients who received 1 open-label treatment and 2 double-blind repeat treatments of 14 days each over a period of up to 46 weeks. The combined population studied had a mean age of 47 (range: 18 to 88) years of whom approximately 11% of the patients were ≥65 years old, 72% were female, 88% were White, 9% were Black and 12% were Hispanic.
The adverse reaction that occurred at a frequency ≥2% in XIFAXAN-treated patients at a higher rate than placebo in Trials 1 and 2 for IBS-D was:
•nausea (3% XIFAXAN, 2% placebo)
The adverse reactions that occurred at a frequency ≥2% in XIFAXAN-treated patients (n=328) at a higher rate than placebo (n=308) in Trial 3 for IBS-D during the double-blind treatment phase were:
•ALT increased (XIFAXAN 2%, placebo 1%)
•nausea (XIFAXAN 2%, placebo 1%)
Less Common Adverse Reactions
The following adverse reactions, presented by body system, were reported in less than 2% of patients in clinical trials of TD and IBS-D and in less than 5% of patients in clinical trials of HE:
Hepatobiliary disorders: Clostridium colitis
Investigations: Increased blood creatine phosphokinase
Musculoskeletal and connective tissue disorders: myalgia
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of XIFAXAN. Because these reactions are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to either their seriousness, frequency of reporting or causal connection to XIFAXAN.
Infections and Infestations
Cases of C. difficile-associated colitis have been reported [see |
