Salix's Once–Daily APRISO Demonstrates Long–Term Safety in Patients for Maintenance of Remission from Ulcerative Colitis
CHICAGO, IL, June 2, 2009 – Data was announced today that demonstrated Salix Pharmaceuticals' (NASDAQ:SLXP) APRISO™ (mesalamine)
0.375g extended–release capsules had a favorable safety profile in patients in remission from ulcerative colitis (UC) for up to 24 months. APRISO is approved for use up to six months. The majority of treatment–emergent adverse events were mild or moderate in intensity, and were similar
to what was seen during the 6–month phase 3 trials. The study, which is the first to examine the long–term safety profile of APRISO,
was presented at the Digestive Disease Week (DDW) annual meeting in Chicago, Illinois.
"It is important to provide UC patients with a new treatment option that can be safely used over the long–term," said Dr. Glenn L. Gordon, Medical
Director and President of the Center for Digestive and Liver Diseases, Inc. in Mexico, Missouri. "The favorable long–term safety profile of
APRISO, combined with once–daily dosing, may support its use as first–line therapy for long–term* maintenance of UC remission."
Patients with UC may experience periods of remission (times when the symptoms go away) that can last for months or years. Maintenance therapy refers to
treatment given to patients to enable them to stay in remission, and to maintain their health in a disease–free, or limited–disease, state.
UC is a lifelong disease; therefore, maintenance medications must usually be taken for a prolonged period of time.
The Long–Term Safety Analysis
Safety data for this analysis included 557 patients in remission from UC who were treated with APRISO in a long–term, open–label extension trial, with 250 patients exposed to APRISO for greater than one year, of which 137 patients were exposed for over 18 months. Patients included in this
long–term safety analysis were either new, or had rolled over from two randomized, double–blind, placebo–controlled, phase 3 trials.
The majority of treatment–emergent adverse events were mild or moderate in intensity, and were similar to what was seen during the 6–month
phase 3 trials. Overall, long–term compliance with APRISO was high, with an average compliance of 90 percent in the safety analysis population.
Additional Abstracts Presented at DDW Further Support the Safety and Efficacy of APRISO for the Maintenance of Remission of UC.
Poster #T1202
Two phase 3 studies (n=562) showed that a significantly greater proportion of patients receiving once–daily APRISO (1.5 g) remained relapse–free
after six months of treatment, compared to placebo (79 percent vs. 62 percent [P<0.001]). Further, those treated with APRISO maintained remission
of UC symptoms with noticeable improvement as early as one month after initiation. Also within one month of treatment, the probability of remaining
relapse–free improved in patients treated with APRISO 94 percent (95 percent CI, 0.92–0.96) compared to those in the placebo group
84 percent (95 percent CI, 0.79–0.90).
Poster #T1204
A post hoc analysis of two clinical trials (n=562) revealed that the majority of a sub–population of patients (n=158) who had previously received
corticosteroid therapy to treat UC flares or to maintain UC remission, remained in remission after treatment with APRISO (1.5 g). Of the patients who had previously received corticosteroids, 77 percent of patients treated with APRISO did not experience a relapse, compared to 55 percent of patients
receiving placebo (P=0.006). Further, according to the Kaplan–Meier log–rank statistics, the probability of patients remaining relapse–free
without further corticosteroid treatment was significantly higher in those treated with APRISO, versus placebo. The probability of remaining
relapse–free for the corticosteroid subpopulation was comparable to the entire study population (Poster #T1202). Limiting exposure to
steroids is important for these patients who may require long–term treatment.
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, 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 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%).
Salix acquired rights to market APRISO in the U.S. from Dr. Falk Pharma GmbH of Freiburg, Germany. Mesalamine granules have been approved in Germany since
2001 for the treatment of symptoms related to inflammatory bowel disease. In addition, consistent with the FDA–approved labeling, once–daily
dosing of mesalamine granules is currently approved via the mutual recognition procedure in Austria, Belgium, Denmark, Finland, Greece, Ireland,
Luxemburg, Netherlands, Norway, Portugal, Sweden, Spain and the UK.
About Salix Pharmaceuticals
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, North Carolina, 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.
About Dr. Falk Pharma
Dr. Falk Pharma GmbH one of the most recognized companies worldwide in gastroenterology. Dr. Falk Pharma products are sold in more than 60 countries. The Falk Foundation, which is associated with the Company, provides medical information via international symposia, forums and postgraduate courses. Over the past 40 years the Falk Foundation has sponsored more than 200 symposia in which over 100,000 physicians from 110 countries have come together
to advance knowledge in gastroenterology and hepatology.
Salix also markets XIFAXAN® (rifaximin) tablets 200 mg, OSMOPREP® (sodium phosphate monobasic monohydrate, USP and sodium
phosphate dibasic anhydrous, USP) Tablets, MOVIPREP® (PEG 3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate
and Ascorbic Acid for Oral Solution), VISICOL® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous,
USP) Tablets, 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. METOZOLV™ ODT (metoclopramide), vapreotide acetate and rifaximin for additional indications
are under development.
* Efficacy has not been established beyond 6 months for the maintenance of remission.
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.
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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,
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, 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.