Salix Pharmaceuticals Previews American College Of Gastroenterology 2009 Annual Scientific Meeting
Data Shows Rifaximin Demonstrated Favorable Long–Term Safety Profile for Maintenance of Remission of Hepatic Encephalopathy
Data Shows Once–Daily APRISO™ Maintained Long–Term UC Remission and Reduced Risk of Adverse Events in Patients Previously Treated with Corticosteroids
RALEIGH, NC, October 26, 2009 – Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced that the 2009 American College of Gastroenterology (ACG)
Annual Scientific Meeting will be the venue for 13 presentations describing the investigation of the Company's bacterial–related disease, inflammatory bowel disease and bowel cleansing product lines. ACG is being held in San Diego, CA October 23–28.
Rifaximin Has a Favorable Long–Term Safety Profile for Maintenance of Remission from Overt Hepatic Encephalopathy
Oral 54, Wed., Oct. 28, 8:30 – 10:15 a.m., Room: Ballroom 20 AB
In an oral presentation, Dr. Muhammad Y. Sheikh and colleagues will present the results of an open–label maintenance extension study from the pivotal
Phase 3, multinational, randomized, double–blind, placebo–controlled study of 299 patients with a history of hepatic encephalopathy
(HE). The results demonstrate the rates and spectrum of adverse events (AEs) were similar in rifaximin–treated patients compared with patients
receiving placebo. Most patients in both treatment arms – rifaximin and placebo – received concomitant lactulose therapy. A total of 336 patients, comprised of the 299 patients who completed the six–month randomized, double–blind, placebo–controlled trial plus 37
new patients, were treated with rifaximin for up to 840 days. Of these, 257 patients were on rifaximin for equal to or greater than six months and
114 patients were on rifaximin for equal to or greater than one year. In the six–month randomized trial, the pattern of adverse events was similar between rifaximin and placebo groups, with adverse events experienced by 80 percent of patients in each group. Fewer patients in the rifaximin
group than the placebo group experienced severe AEs (26% vs 31%), drug–related AEs (19% vs 21%), serious AEs (36% vs 40%) and AEs leading to
discontinuation (21% vs 28%). The safety profile of rifaximin during long–term treatment was similar to that in the six–month randomized
trial.
"The robust data emerging from these studies clearly demonstrate that rifaximin has a very promising long–term safety profile for maintenance of remission from overt hepatic encephalopathy," said Muhammad Y. Sheikh M.D., Associate Professor of Clinical Medicine, University of California San Francisco
(UCSF) and Chief of Gastroenterology at UCSF Fresno. "With the previous data demonstrating rifaximin's durable efficacy in the maintenance of
remission of HE, these results continue to support rifaximin's potential role in the long term management of this disabling complication of cirrhosis.
We believe the availability of rifaximin has the potential to bring a paradigm shift in the management of HE. We have waited for such a pharmacologic
change for more than 30 years. Today's news marks another positive milestone for rifaximin and patients suffering from this serious condition."
Long–Term Maintenance with Mesalamine Granules (1.5 g) in Patients Previously Treated with Corticosteroids is Associated with a Low Incidence of Ulcerative Colitis–Related Adverse Events
Poster 718 Mon, Oct. 26, 12:15 – 2:00 p.m.
Dr. Gary Lichtenstein and colleagues will present results describing the long–term (over 30 months) impact of once–daily mesalamine granules
(MG) (1.5 g) on patients in remission from ulcerative colitis (UC) who were treated with steroids prior to enrollment. Patients were enrolled in two Phase 3, randomized, double–blind, placebo–controlled trials (RCT) and treated for six months with once–daily dosing of 1.5 g granulated
mesalamine and then rolled over into a 24–month open label extension trial (OLT). The results of this long–term trial demonstrate
that the reduced risk of treatment emergent adverse events and UC–related symptoms demonstrated during the two RCT trials (six months) was
sustained over the subsequent OLT (24 months). In the two RCT trials, more MG–treated patients than placebo–treated patients remained relapse–free for six months (79.4 % vs. 63.0%; p<0.001). This highly significant effect also was noted in a subpopulation of 158 patients treated
with steroids prior to enrollment (77% vs. 55%; p<0.004). Seventy four MG–treated patients from the two RCT trials continued MG treatment into the 24–month open label extension trial. The low probability of recurrence of events and symptoms was sustained during the 24–month open label extension trial.
"Ulcerative colitis is a chronic disease that requires continuous management and it is critically important to provide patients with a treatment option
that will offer long–term symptom relief," said study author Gary R. Lichtenstein, M.D., Director, Inflammatory Bowel Disease Program, Gastroenterology
Division, Department of Medicine, University of Pennsylvania. "This data further demonstrates that APRISO is a safe and effective option
to maintain remission, even for UC patients who have previously received steroid therapy."
Additional Presentations
RIFAXIMIN
- Poster 747 – Basu, et al. Prevalence of Restless Leg Syndrome in Patients with Functional Bowel Disease in the Community. Mon, Oct. 26, 12:15 – 2:00 p.m.
- Poster 534 – Randall, et al. Rifaximin is Efficacious in the Treatment of Small Intestinal Bacterial Overgrowth. Mon, Oct. 26, 12:15 – 2:00
p.m.
- Oral 17 – Chang, et al. Double–Blind Randomized Controlled Trial of Rifaximin for Small Intestinal Bacterial Overgrowth (SIBO) in Celiac Disease. Mon, Oct. 26, 2:00 – 2:40 p.m., Room: Ballroom 20 CD
- Poster 998 – Neff, et al. Efficacy of Rifaximin in Maintenance of Remission in Patients with Hepatic Encephalopathy. Tues, Oct. 27, 12:15 –
2:00 p.m.
- Poster 1139 – Shafran, et al. Rifaximin Maintenance Therapy for Crohn's Disease. Tues, Oct. 27, 12:15 – 2:00 p.m.
- Poster 1155 – Infantolino, et al. Small Intestinal Bacterial Overgrowth (SIBO) in Patients with Irritable Bowel Syndrome (IBS); A Retrospective
Review of Symptoms Following Treatment. Tues, Oct. 27, 12:15 – 2:00 p.m.
- Poster 1093 – Basu, et al. Rifaximin Salvage Therapy for Metronidazole–Resistant Clostridium difficile Infection – A Prospective
Pilot Trial. Tues, Oct. 27, 12:15 – 2:00 p.m.
- Poster 1074 – Lillo, et al. Rifaximin: A Predisposing Agent to Clostridium difficile? Tues, Oct. 27, 12:15 – 2:00 p.m.
APRISO™
- Poster 717 – Lichtenstein, et al. Effect of Prognostic Factors on Maintenance of Remission from Ulcerative Colitis in Patients Treated with Once–Daily
Mesalamine Granules (1.5 g). Mon, Oct. 26, 12:15 – 2:00 p.m.
MOVIPREP®
- Poster 412 – Cohen, et al. Is a "Good" Colonoscopy Bowel Prep Good Enough? Adenoma Detection Rates from a Randomized Study of Two Colon Cleansing
Formulations. Mon, Oct. 26, 3:30 – 7:00 p.m.
- Poster 759 – Matro, et al. Efficacy and Tolerance of 2L Polyethylene Glycol–electrolyte Solution with Sodium Ascorbate and Ascorbic Acid (PEG) Administered Entirely in the Morning (AM–only) Compared to Split Dose (PM/AM) Administration Prior to Afternoon Colonoscopy. Mon, Oct. 26,
12:15 – 2:00 p.m.
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– producing 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 APRISO™
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, amniosalicylates, 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 greater than 3% of adult patients taking 1.5 g/day of APRISO (versus placebo) were headache (11% vs. 8%), diarrhea
(8% vs. 7%), upper abdominal pain (5% vs 3%), nausea (4% vs 3%), nasopharyngitis (4% vs 3%), influenza and influenza–like illness (4% vs 4%)
and sinusitis (3% vs 3%).
About MOVIPREP®
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 should be used with caution in patients
using concomitant medications that increase the risk of electrolyte abnormalities such as diuretics or angiotensin converting enzyme (ACE)–inhibitors
or in patients with known or suspected hyponatremia. MOVIPREP should also be used with caution in patients with severe ulcerative colitis,
ileus, gastrointestinal obstruction or perforation, gastric retention, toxic colitis, or toxic megacolon. In clinical trials, abdominal distension,
anal discomfort, thirst, nausea and abdominal pain were some of the most common adverse reactions to MOVIPREP administration. Vomiting occurred
less frequently.
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 on Salix products, please visit www.salix.com or
contact the Company at 919–862–1000.
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
in 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).
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,
bowel perforation, toxic megacolon, gastric bypass or stapling surgery, or hypomotility syndrome. Use with caution in patients with impaired renal
function, patients with a history of seizures or at higher risk of seizure, patients with higher risk of cardiac arrhythmias, known or suspected electrolyte
disturbances (such as dehydration), or people taking drugs that affect electrolyte levels. Patients with electrolyte abnormalities such as
hypernatremia, hyperphosphatemia, hypokalemia, or hypocalcemia should have their electrolytes corrected before treatment with OSMOPREP.
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 for OSMOPREP including BOXED WARNING, please click here.
Important Safety Information about XIFAXAN 550 mg
XIFAXAN® 550 mg is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients ≥18 years of age. In the trials of XIFAXAN for HE, 91% of the patients were using lactulose concomitantly. XIFAXAN has not been studied in patients with MELD scores >25, and only 8.6% of patients in the controlled trial had MELD scores over 19. There is increased systemic exposure in patients with more severe hepatic dysfunction. Therefore, caution should be exercised when administering XIFAXAN to patients with severe hepatic impairment (Child-Pugh C).
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 nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon which may lead to overgrowth of C difficile. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C difficile may need to be discontinued.
The most common adverse reactions occurring in >8% of patients in the clinical study were edema peripheral (15%), nausea (14%), dizziness (13%), fatigue (12%), ascites (11%), muscle spasms (9%), pruritus (9%), and abdominal pain (9%).
For complete Prescribing Information, please click here.
Important Safety Information about METOZOLV ODT
Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible.
The risk of developing tardive dyskinesia increases with the duration of treatment and the total cumulative dose.
Metoclopramide therapy should be discontinued in patients who develop signs or symptoms of tardive dyskinesia.
There is no known treatment for tardive dyskinesia. In some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped.
Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia.
METOZOLV® ODT
(metoclopramide HCl) is indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal
reflux disease (GERD) who fail to respond to conventional therapy and for the relief of symptoms associated with acute and
recurrent diabetic gastroparesis (diabetic gastric stasis) in adults. Therapy should not exceed 12 weeks in duration. Take on
an empty stomach up to four times daily, at least 30 minutes before eating and at bedtime.
METOZOLV ODT is contraindicated in patients with intestinal obstruction, hemorrhage, or perforation; pheochromocytoma;
known sensitivity or intolerance to metoclopramide; epilepsy; or are receiving concomitant medications with extrapyramidal reactions.
Extrapyramidal symptoms (EPS), manifested primarily as acute dystonic reactions, occur in approximately 1 in 500 patients treated with the
usual adult dosages of 30 to 40 mg/day of metoclopramide. These usually are seen during the first 24 to 48 hours of treatment with metoclopramide,
occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at higher doses.
Drug-induced Parkinsonism can occur during metoclopramide therapy, more commonly within the first 6 months after beginning treatment,
but also after longer periods. Patients with a history of Parkinson’s disease should be given metoclopramide cautiously, if at all,
since such patients can experience exacerbation of Parkinsonian symptoms when taking metoclopramide.
There have been rare reports of an uncommon but potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) associated
with metoclopramide. Clinical manifestations of NMS include hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability.
The management of NMS should include immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy.
Depression associated with metoclopramide use has occurred in patients with and without a history of depression.
For those patients with a prior history of depression, metoclopramide should only be given if the expected benefits outweigh the potential risks.
In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, caution should be exercised
when metoclopramide is used in patients with hypertension. Any rapid rise in blood pressure associated with METOZOLV ODT use should result in immediate
cessation of metoclopramide use in those patients.
Since metoclopramide produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing
fluid retention and volume overload. If these side effects occur at any time in any patients during metoclopramide therapy, the drug should be discontinued.
Adverse reactions, especially those involving the nervous system, may occur after stopping the use of METOZOLV ODT.
In clinical studies, the most frequently reported adverse events (≥2% occurrence) were headache, nausea, fatigue, somnolence, and vomiting.
Full Prescribing Information for METOZOLV ODT, including BOXED WARNING.