Salix Receives FDA Marketing Approval for Metozolv™ ODT (Orally Disintegrating Tablets) for Relief of Diabetic Gastroparesis and Symptomatic Documented GERD
The First Available Orally Disintegrating Metoclopramide Tablet Designed to Offer Improved Convenience
RALEIGH, NC, September 8, 2009 – Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced
the U.S. Food and Drug Administration (FDA) has granted
marketing approval for METOZOLV™ ODT (metoclopramide HCl) 5mg and 10mg orally disintegrating tablets. METOZOLV ODT is indicated for the relief of symptoms in adults associated with acute and recurrent diabetic gastroparesis and for the treatment of short–term therapy (4–12
weeks) for adults with symptomatic documented gastroesophageal reflux disease (GERD) who fail to respond to conventional therapyi.
"METOZOLV ODT is the first available treatment for both diabetic gastroparesis and symptomatic documented GERD that offers physicians and patients the similar safety and efficacy of metoclopramide with the added convenience of an orally disintegrating tablet formulation," said Ronnie Fass, MD, FACP, FACG and Professor of Internal Medicine at the University of Arizona. "Patients with diabetic gastroparesis and symptomatic documented GERD may have trouble adhering to treatment because of difficulty swallowing, the need for treatment when they do not have water available, or the need for a portable
way to take medication. METOZOLV ODT, which rapidly* melts on the tongue, gives these patients a new choice that may be more convenient than traditional
metoclopramide tablets."
"The addition of METOZOLV ODT to Salix's expanding GI–specialty product portfolio provides physicians and patients an innovative treatment choice
that may offer improved convenience over traditional metoclopramide therapy," said Bill Forbes, Pharm.D., Senior Vice President, Research and Development,
Chief Development Officer, Salix Pharmaceuticals. "Diabetic gastroparesis and symptomatic documented GERD are growing health issues among adults
in the United States.ii,iii,iv Bringing METOZOLV ODT – the first commercially available orally disintegrating form of metoclopramide for the relief
of diabetic gastroparesis and symptomatic gastroesophageal reflux to market – demonstrates Salix's commitment to meeting the unmet GI treatment
needs of physicians and patients. We anticipate METOZOLV ODT should be available for physicians and patients during November 2009."
About METOZOLV™ ODT (metoclopramide HCl) 5mg and 10mg Orally Disintegrating Tablets
Salix acquired the world–wide marketing rights for the orally disintegrating formulation of metoclopramide from Wilmington Pharmaceuticals in September
2007. Salix has entered into a separate agreement with Catalent Pharma Solutions to supply METOZOLV ODT, which incorporates Catalent's Zydis,
the fastest disintegrating oral tablet availablev. METOZOLV ODT has patent protection until 2017, and additional patent protection pending that, if
issued, could provide patent protection until 2025.
Important Safety Information
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 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. 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. METOZOLV ODT should be used with caution in patients showing acute dystonic reactions, drug–induced
Parkinsonism, or other extrapyramidal symptoms; neuroleptic malignant syndrome; with a prior history of depression; hypertension; congestive heart failure and
ventricular arrhythmia. Patients may experience withdrawal symptoms 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.
About Metoclopramide
Metoclopramide is a potent dopamine receptor antagonist that promotes gastric emptying and functions as an antiemetic. It is indicated for diabetic gastroparesis
and for relief of symptomatic documented gastroesophageal reflux disease (GERD). Prior to the approval of METOZOLV ODT, metoclopramide was available in intravenous (IV), intramuscular (IM) and oral tablet formulations. The U.S. market for tablet formulation metoclopramide in 2008 was
6.4 million prescriptions equating to 511 million total tablets.vi Metoclopramide has been available in the United States since 1980 and has published
clinical data regarding the safety and efficacy as an antiemetic dating back to the 1960svii.
About Diabetic Gastroparesis
Gastroparesis is estimated to affect up to five million people in the United States, with females being at higher risk than males.ii Diabetes, a rapidly
growing health concern in the United Statesii, is the second leading cause of gastroparesis, affecting 29 percent of patients with gastroparesis
or 1.45 million people in the country.viii Gastroparesis in people with diabetes can lead to poor glucose control and complications of diabetes.v Diabetic
gastroparesis, also called delayed gastric emptying, is a disorder in which the stomach takes too long to empty its contents. Normally, the stomach
contracts to move food down into the small intestine for digestion. The vagus nerve controls the movement of food from the stomach through the
digestive tract. Gastroparesis occurs when the vagus nerve is damaged and the muscles of the stomach and intestines do not work normally. Food then
moves slowly or stops moving through the digestive tract. If food stays in the stomach too long it can cause infection due to bacterial overgrowth.
Food can form into bezoars, or solid lumps, causing pain, nausea and blockages in the GI tract. Gastroparesis may also result in impaired glucose
control. Symptoms include nausea, vomiting, bloating, early satiety, decreased appetite, heartburn and abdominal pain. Risk factors include diabetes,
obesity, narcotics use, and Parkinson's disease.ii
About Symptomatic Documented Gastroesophageal Reflux Disease (GERD)
Studies suggest that approximately one–third of the U.S. population or approximately 100 million people have gastroesophageal reflux disease (GERD)ix.
Refractory GERD is a term used to describe a condition in which patients continue to have symptoms of GERD despite standard Proton Pump Inhibitor
(PPI) therapy or initial treatment attempts. Twenty percent of patients with refractory GERD or 20 million people in the United States continue to experience
unmanageable reflux symptoms despite twice daily PPI therapy.x Certain conditions can make a person more susceptible to GERD, including pregnancy,
which lowers pressure in lower esophageal sphincter, and scleroderma, diseases that weaken the esophageal muscles. For many patients, GERD
can be treated with lifestyle changes and medications, while others may require additional pharmaceutical or surgical intervention. Direct and indirect
costs of GERD total $10 billion per year in the United States.ii
About Salix Pharmaceuticals
Salix Pharmaceuticals, Ltd., headquartered in Morrisville, 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 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, APRISO™ (mesalamine) extended–release capsules 0.375 g., 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.
# # #
*METOZOLV ODT disintegrates on the tongue in a median of 53.5 seconds (mean ± standard deviation, 76.8 ± 110.6 seconds).i
iMETOZOLV™ ODT (metoclopramide) Prescribing Information
iiCDC diabetes program data and trends. http://www.cdc.gov/diabetes/statistics/prev/national/figpersons.htm. Accessed September 30, 2009
iiiHasler WL. Gastroparesis–current concepts and considerations. Medscape J Med. 2008;10:16.
viEverhart, J. Gastroesophageal Reflux Disease. The Burden of Digestive Diseases. 2009; 14:69–72.
vCatalent – Zydis Fast Dissolve Technology. http://www.catalent.com/drug/oral/zydis/. Accessed February 25, 2009.
viWolters Kluwer Source® Pharmaceutical Audit Suite (PHAST), September 2008
viiUS Food and Drug Administration. Overview. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=REGLAN. Accessed February 19, 2009.
viiiHasler WL. Gastroparesis–current concepts and considerations. Medscape J Med. 2008;10:16.
ixInternational Foundation for Functional Gastrointestinal Disorders. The Prevalence and Impact of Gastroesophageal Reflux Disease. http://www.aboutgerd.org/site/about–gerd/characteristics/prevalence. Accessed February 25, 2009.
xNoar and Noar. Surg Endosc. 2008 [Epub ahead of print].
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.