Salix Pharmaceuticals Reviews American Association For The Study Of Liver Diseases Annual Meeting
Data Demonstrate Protective Effect and Durability of Rifaximin for Maintenance of Remission of Hepatic Encephalopathy
Data Demonstrate Rifaximin Significantly Improved Critical Flicker Frequency and Time–Weighted CFF Correlated with Overt Hepatic Encephalopathy
BOSTON, MA, November 02, 2009 – Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announces that the 60th Annual Meeting of the American Association
for the Study of Liver Diseases is the venue for two presentations describing the investigation of rifaximin for the maintenance of remission from hepatic encephalopathy. The Liver Meeting® is being held in Boston, Saturday, October 31 – Tuesday, November 3, 2009.
The Protective Role of Rifaximin (550 mg tablet, 1100 mg daily) from Hepatic Encephalopathy Observed in a Double–Blind Placebo–Controlled Study
is Substantiated and Durable Over the Long Term
(Poster Presentation # 305, F. Poordad, et al.)
Dr. Fred Poordad and colleagues presented the results of an analysis of the protective effect and the durability analyses of rifaximin treatment in the
maintenance of remission in hepatic encephalopathy (HE) in an open label maintenance study (OLM). A randomized, double–blind trial (RCT) of 299 subjects demonstrated that rifaximin 550 mg BID significantly reduced the risk of a breakthrough HE episode by 57.9% (p<0.0001) in cirrhotic patients
with a history of two or more overt HE episodes (Conn score equal to or greater than two) within 12 months before study enrollment. Subjects from
the RCT, as well as new subjects (with a history of one or more HE episodes with Conn score equal to or greater than two within 12 months), were
enrolled in the OLM. Patients received 550 mg rifaximin BID and lactulose use was permitted. Breakthrough HE as defined as an increase to a Conn score equal to or more than two; or, if the baseline Conn score was zero, an increase of 1 each in Conn score and asterixis grade. In the OLM 266 patients
had post baseline data (70 rifaximin and 82 placebo patients from the RCT and 114 new patients.) In the OLM rifaximin demonstrated a significantly
protective effect (p<0.0001) compared to prior placebo experience in the time to first HE breakthrough for the 82 placebo patients from the RCT.
Additionally, the estimates of time to first HE breakthrough for the 196 patients new to rifaximin (114 new plus 82 PBO from RCT) were equivalent
to estimates of time for patients who had HE breakthrough in the RCT rifaximin group. 60 rifaximin patients who maintained remission throughout the
RCT were followed in the OLM for up to 680 days of rifaximin therapy with a mean exposure of 482 days.
"Phase 3 study results have clearly demonstrated that rifaximin is effective in the treatment of hepatic encephalopathy (HE)," said Fred Poordad, M.D.,
Chief of Hepatology and Liver Transplantation at the Comprehensive Transplant Center at Cedars–Sinai Medical Center in Los Angeles. "The data
from this particular analysis further substantiate the highly significant protective effect of rifaximin in minimizing breakthrough HE episodes and
show that the effect from rifaximin was durable over the long term for the maintenance of HE remission. These promising results suggest that rifaximin
will be an important addition to the treatment arena of hepatic encephalopathy."
Rifaximin (550 mg, twice daily) Significantly Improved Critical Flicker Frequency and Time–Weighted CFF Correlated with Overt Hepatic Encephalopathy
as Assessed by Conn Score in a Six–Month Study
(Poster Presentation # 306, M.R. Brown, et al.)
Dr. Robert Brown and colleagues presented results of an analysis of the effect of rifaximin treatment on critical flicker frequency (CFF) response and the association between quantitative CFF results and breakthrough overt hepatic encephalopathy (HE) episodes, as assessed by Conn score (CS). This randomized,
double–blind, placebo–controlled trial evaluated rifaximin 550 mg BID for six months in patients (140 rifaximin and 159 placebo)
with history of two or more episodes of HE (Conn score equal or greater than two) within prior six months and were in remission (Conn score 0 or 1) at baseline. 104 patients experienced HE breakthrough episodes and 194 patients maintained remission. CFF was measured at baseline and biweekly during
the study. An area under the curve analysis for CFF over time was normalized by exposure time (time–weighted average or TWA). The correlation
between TWA and the presence or absence of a breakthrough HE episode was analyzed. Mean changes from baseline showed significantly improved
CFF in the rifaximin group compared to placebo (p=0.0320). The difference between the frequency distributions of CFF TWA in breakthrough HE epidoses
versus remission was statistically significant (p<0.0001), with a significant correlation between mean TWA and breakthrough HE episodes (p<0.0001).
"The Critical Flicker Frequency (CFF) test measures eye and brain function during visual stimulation and is known to be impaired (lower Hz) in patients
with hepatic encephalopathy (HE)," said Robert S. Brown, Jr., M.D., M.P.H., Frank Cardile Professor of Medicine at the Columbia University College of Physicians and Surgeons and Chief, Division of Abdominal Organ Transplantation, New York–Presbyterian Hospital, New York. "The CFF test independently
predicted breakthrough HE occurrences which underscores the utility of quantitative CFF results in predicting and managing breakthrough overt
HE. The study results demonstrate rifaximin therapy significantly improved CFF performance versus placebo and could be used prophylactically to
prevent breakthrough HE."
About Hepatic Encephalopathy
Hepatic encephalopathy (HE) is a neurological disorder caused by chronic liver failure resulting in cognitive, psychiatric, and motor impairments.1 The
condition encompasses a wide spectrum of often reversible neuropsychiatric abnormalities caused by the inability of the liver to remove toxic products
in the gut, most notably ammonia produced by bacteria.2 When toxins reach the central nervous system, this condition can result in symptoms ranging
in severity from mild cerebral function deficits to coma and characterized by disruption in sleep patterns, changes in personality and intellectual
capacity, high blood ammonia levels, altered neuromuscular activity and electroencephalogram (EEG) abnormalities.3,4
About XIFAXAN® (rifaximin)
Rifaximin is a gut–selective antibiotic with negligible systemic absorption (<0.4%) and broad–spectrum activity in vitro against both gram–positive
and gram–negative pathogens. Rifaximin has a similar tolerability profile to that of placebo.
Rifaximin tablets 200 mg, which Salix markets in the United States under the trade name XIFAXAN® (rifaximin) tablets 200 mg, currently is
approved for the treatment of patients, 12 years of age or older, with travelers' diarrhea caused by non–invasive strains of Escherichia
coli. XIFAXAN (rifaximin) is a gut–selective antibiotic with negligible systemic absorption (<0.4%) and broad–spectrum activity
in vitro against both gram–positive and gram–negative pathogens. Rifaximin has a similar tolerability profile to that of placebo and has activity against the most common TD pathogens. XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. XIFAXAN should be discontinued if diarrhea symptoms get worse or persist more than
24–48 hours and alternative antibiotic therapy should be considered. In clinical trials, XIFAXAN was generally well tolerated. The most common
side effects (vs. placebo) were flatulence 11.3% (versus 19.7%), headache 9.7% (versus 9.2%), abdominal pain 7.2% (versus 10.1 %) and rectal tenesmus
7.2% (versus 8.8%).
About Salix Pharmaceuticals
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, NC, develops and markets prescription pharmaceutical products for the treatment of gastrointestinal
diseases. Salix's strategy is to in–license late–stage or marketed proprietary therapeutic drugs, complete with any required development
and regulatory submission of these products, and market them through the Company's gastroenterology specialty sales and marketing team.
Salix also markets OSMOPREP® (sodium phosphate monobasic monohydrate, USP and sodium phosphate dibasic anhydrous, USP) Tablets, VISICOL®
(sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets, METOZOLVTM ODT (metoclopramide HCl), PEPCID® (famotidine) for Oral Suspension, Oral Suspension DIURIL® (Chlorothiazide), AZASAN® Azathioprine
Tablets, USP, 75/100 mg, ANUSOL–HC® 2.5% (Hydrocortisone Cream, USP), ANUSOL–HC® 25 mg Suppository (Hydrocortisone
Acetate), PROCTOCORT® Cream (Hydrocortisone Cream, USP) 1% and PROCTOCORT® Suppository (Hydrocortisone Acetate Rectal Suppositories) 30 mg. Crofelemer, budesonide foam and rifaximin for additional indications are under development.
For full prescribing information, including BOXED WARNINGS for VISICOL, OSMOPREP and METOZOLV, on Salix products, including BOXED WARNINGS for OSMOPREP, VISICOL and METOZOLV, please visit www.salix.com. Salix trades on the NASDAQ Global Select Market under the ticker symbol "SLXP".
For more information, please visit our Web site at www.salix.com or contact the Company at 919-862-1000. Information on our Web site is not incorporated into our SEC filings.
1National Institute on Alcoholism and Alcohol Abuse of the National Institutes of Health. Hepatic Encephalopathy. September 29, 2004. Available at: http://pubs.niaaa.nih.gov/publications/arh27–3/240–246.htm
2Blei AT, Co'rdoba J and The Practice Parameters Committee of the American College of Gastroenterology. Hepatic Encephalopathy. Practice Guidelines. Vol.
96, No. 7, 2001.
3IBID
4Abou–Assi S. Vlahcevic ZR. Hepatic encephalopathy. Metabolic consequence of cirrhosis often is reversible. Postgraduate Medicine. 109(2):52–4,
57–60, 63–5 passim, 2001 Feb.
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APRISO™ is a locally-acting aminosalicylate indicated for the maintenance of remission of ulcerative colitis in patients 18 years and older.
APRISO is contraindicated in patients with hypersensitivity to salicylates, aminosalicylates, or to any of the components of APRISO capsules.
The recommended dose of APRISO is four 0.375 g capsules once daily in the morning (1.5 g/day) with or without food. Because dissolution of the coating of APRISO
granules depends on pH, APRISO should not be coadministered with antacids. Patients with phenylketonuria should be aware that APRISO contains aspartame,
equivalent to 0.56 mg of phenylalanine. In two well-controlled clinical trials, the most common treatment-related adverse events occurring in at least 3%
of adult patients taking 1.5 g/day of APRISO were headache (11% vs. 8% for placebo), diarrhea (8% vs. 7% for placebo), upper abdominal pain (5% vs 3% for placebo),
nausea (4% vs 3% for placebo), nasopharyngitis (4% vs 3% for placebo), influenza and influenza-like illness (4% vs 4% for placebo) and sinusitis (3% vs 3% for placebo).
For complete Prescribing Information, please click here.
MoviPrep® (PEG-3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution) is indicated for cleansing of the
colon as a preparation for colonoscopy in adults 18 years of age or older. MoviPrep is contraindicated in patients who have had a severe hypersensitivity reaction
to any of its components. MoviPrep should be used with caution in patients using concomitant medications that increase the risk of electrolyte abnormalities, in patients with known or suspected hyponatremia,
severe ulcerative colitis, ileus, gastrointestinal obstruction or perforation, gastric retention, toxic colitis, toxic megacolon, or glucose-6-phosphate dehydrogenase deficiency. In clinical trials, abdominal
distention, anal discomfort, thirst, nausea, and abdominal pain were the most common adverse reactions to MoviPrep administration. MoviPrep contains a maximum of 2.33 mg of phenylalanine per treatment.
Consult with your physician to see if this product is right for you.
For complete Prescribing Information, please click here.
Important Safety Information about OsmoPrep
There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior
to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long–term dialysis. While some
cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with
increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using
medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers
[ARBs], and possibly nonsteroidal anti–inflammatory drugs [NSAIDs]).
It is important to use the dose and dosing regimen as recommended (PM/AM split dose).
Please see accompanying brief summary of Prescribing Information for OsmoPrep, including
BOXED WARNINGS.
OsmoPrep® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets are indicated for cleansing
of the colon as a preparation for colonoscopy in adults 18 years of age or older. Considerable caution should be advised before OsmoPrep is used in
patients with severe renal insufficiency, congestive heart failure, ascites, unstable angina, gastric retention, ileus, severe chronic constipation,
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OsmoPrep is contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients, and in patients with
biopsy–proven acute phosphate nephropathy. In clinical trials, the most commonly reported adverse reactions (reporting frequency >3%) were
abdominal bloating, nausea, abdominal pain, and vomiting. It is recommended that patients receiving OsmoPrep be advised to adequately hydrate before,
during, and after the use of OsmoPrep.
For complete Prescribing Information, please click here.
SAFETY CONSIDERATIONS
Xifaxan® (rifaximin) Tablets are indicated for the treatment of patients (≥12 years of age) with travelers’ diarrhea caused by noninvasive strains of
Escherichia coli. Xifaxan should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. Xifaxan should be
discontinued if diarrhea symptoms get worse or persist more than 24-48 hours and alternative antibiotic therapy should be considered. Escherichia coli has been shown to develop resistance to rifaximin in vitro. However, the clinical significance of such an effect has not been studied.
In clinical trials, Xifaxan was generally well tolerated. The most common side effects (vs. placebo) were flatulence 11.3% (vs. 19.7%), headache 9.7% (vs. 9.2%), abdominal pain 7.2% (vs. 10.1%), rectal tenesmus 7.2%
(vs. 8.8%), defecation urgency 5.9% (vs. 9.2%) and nausea 5.3% (vs. 8.3%).
For complete Prescribing Information, please click here.