Data Released Today Demonstrate that Mesalamine Granules Maintain Remission in Ulcerative Colitis Patients Who Switch from Another 5–ASA
More Patients Switched to Mesalamine Granules Maintained Remission Versus Placebo (78 percent versus 59 percent)
ORLANDO, FL, October 7, 2008 – Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced
that 1.5 g mesalamine granules once–daily maintained
remission versus placebo in ulcerative colitis (UC) patients who switched from another 5–ASA product (78 percent of relapse–free subjects
vs. 59 percent [P<0.001]). These patients also had a greater probability of remaining relapse free after six months compared to placebo (77 percent
vs. 50 percent [P<0.001] cumulative relapse–free probability)1. Mesalamine granules are being studied as a 5–ASA with both a delayed
and extended release system that delivers mesalamine directly to the colon with minimal systemic exposure and convenient once–daily dosing.
These data were presented today at the American College of Gastroenterology (ACG) 2008 Annual Scientific Meeting in Orlando, Florida.
"It is crucial for remittent ulcerative colitis patients to stay on treatment to prevent relapse, yet these patients often fail or switch 5–ASA therapy
due to non–adherence or lack of efficacy," said study author Gary R. Lichtenstein, MD, Director, Inflammatory Bowel Disease Program, Gastroenterology
Division, Department of Medicine, University of Pennsylvania. "These results coupled with the formulation and convenient once–daily
dosing may improve patient compliance, potentially making it an attractive maintenance therapy for remission of ulcerative colitis (subject to
the FDA's pending review)."
About the Study
Patients (n=487) with documented UC remission (as defined by the revised Sutherland Disease Activity Index) received 1.5 g mesalamine granules (four 375–mg
capsules once daily) or placebo once daily for six months. Patients taking mesalamine granules achieved the following results:
* Overall, nearly 8 out of 10 patients maintained remission of UC after six months (78 percent vs. 59 percent with placebo [P<0.001])
* In a sub–set analysis, 305 patients who switched from a prior 5–ASA had a higher probability of remaining relapse free after six months (77
percent vs. 50 percent [P<0.001])
Additional Mesalamine Granules Abstracts Presented at ACG
Poster 279
Mesalamine granules 1.5 g once–daily were clinically demonstrated to be more effective than placebo in maintaining long–term remission of UC
(79 percent vs. 58 percent of patients were relapse–free at six months [P<0.001]). A larger proportion of mesalamine granules patients showed
a clinically favorable change from baseline in physician–rated disease activity at month six compared with placebo (78 percent vs. 64 percent
[P=0.005]). Patients taking mesalamine granules also had a higher probability of remaining relapse–free at six months (77 percent vs. 56 percent
[P<0.001]). 2
Poster 673
Overall, fewer patients taking mesalamine granules (28 percent) withdrew versus patients who received placebo (43 percent) due to disease relapse (12 percent
vs. 20 percent for placebo) or adverse events (11 percent vs. 16 percent for placebo). For mesalamine granules versus placebo, the most common
adverse events were UC flare (11 percent vs. 24 percent), headache (11 percent vs. 8 percent), and diarrhea (8 percent vs. 7 percent). Incidence
of renal, hepatic, and pancreatic AEs was low and comparable in both the mesalamine granules (6 percent) and placebo (5 percent) groups. The percentage
of patients who experienced serious adverse events was small in both the mesalamine granules (1 percent) and placebo (two percent) groups, and
no event reported in the mesalamine granules group was considered drug–related.3
Poster 682 & Poster 681
An additional study showed that the pharmacokinetic profile and systemic absorption of mesalamine granules was comparable whether administered once–
or twice–daily.4 In addition, the overall systemic absorption of mesalamine granules was low and essentially unaltered by a high–fat
meal eaten before dosing, as seen in a fifth study5. The ability to take mesalamine granules with or without food, along with its once–daily
dosing, may improve patient compliance and treatment success.
"The results of these studies, providing evidence of once–daily mesalamine granules in maintaining remission, are good news for remittent ulcerative
colitis patients," said Bill Forbes, Pharm.D., Salix Vice President, Research & Development, and Chief Development Officer. "Salix is committed
to continually striving to better serve the needs of patients who suffer from this debilitating condition."
About Mesalamine Granules
Salix acquired rights to market mesalamine granules 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, the once–daily dosing label is currently
approved in Austria, Ireland, Netherlands, Portugal, Sweden, UK, and Spain.
Salix is currently seeking regulatory approval of the product in the U.S. Given the product's unique delivery mechanism, Salix intends to develop it for
a variety of treatment options and improved dosing regimens.
About Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory disease of the colon or large intestine. The inflammation usually begins in the rectum and lower colon, but
it may also involve the entire colon. Because the inflammation makes the colon empty frequently, symptoms typically include diarrhea (sometimes accompanied by blood) and often abdominal pain. About five percent of people with ulcerative colitis will develop colorectal cancer.
Patients with ulcerative colitis may experience periods of remission (times when the symptoms go away) that can last for months or years. However, most
patients' symptoms eventually return. Active therapy is treatment given to treat ulcerative colitis symptoms when they are active. Maintenance therapy
refers to treatment given to patients to enable them to stay in remission, to maintain their health in a disease–free, or limited–disease,
state. Maintenance medications must be taken for a prolonged period of time.
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.
Salix 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, COLAZAL® (balsalazide disodium) Capsules 750 mg, 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),
mesalamine granules, balsalazide tablet, vapreotide acetate and rifaximin for additional indications are under development.
1 Lichtenstein GR, et al. Once–daily mesalamine granules effectively maintains remission in patients with ulcerative colitis who switch from different 5–ASA formulations
2 Gordon GL, et al. Once–daily mesalamine granules is effective and safe in maintenance of remission in mild–to–moderate ulcerative colitis
3 Zakko, S, et al. Safety profile of once–daily mesalamine granules as maintenance therapy for mild–to–moderate ulcerative colitis
4 Safdi A, et al. Multiple–dose pharmacokinetics of mesalamine granules, a unique formulation providing delayed and extended release of 5–ASA
5 Safdi A, et al. Minimal effect of a high–fat meal on the pharmacokinetics of once–daily mesalamine granules
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).
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.