In the treatment of Helicobacter pylori (H. pylori) infection and duodenal ulcer disease Previous macrolide exposure puts your H. pylori treatment success at risk Choose PYLERA® Capsules plus omeprazole Previous macrolide exposure increases the risk of clarithromycin resistance1,2 • ACG* Guidelines recommend an OBMT† treatment as first-line therapy3 PYLERA® Capsules plus omeprazole is an OBMT-based treatment regimen that does not contain macrolides4 “The first course of therapy offers the greatest likelihood of eradicating H. pylori infection”3 • Failure to eradicate results in regrowth of H. pylori up to pretreatment levels5 *ACG = American College of Gastroenterology. † OBMT = omeprazole, bismuth, metronidazole, tetracycline. INDICATION • PYLERA® Capsules (bismuth subcitrate potassium, metronidazole, and tetracycline hydrochloride), in combination with omeprazole, are indicated for the treatment of patients with Helicobacter pylori (H. pylori) infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori • The eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence • To reduce the development of drug-resistant bacteria and maintain the effectiveness of PYLERA® and other antibacterial drugs, PYLERA® should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria • When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy Please see Important Safety Information on page 3 and back. Please see accompanying full US Prescribing Information. Previous macrolide exposure changes the Prior macrolide exposure increases the risk of clarithromycin resistance1,2 • 61.2% of the US population has been exposed to at least one course of macrolide antibiotics during the last 9 years6 • In one study, 92% of patients who had a clarithromycin-resistant H. pylori strain had been treated with a macrolide antibiotic in the past 10 years2 11-fold increase 80% 80% The Likelihood of ClarithromycinResistant H. pylori Infection Increases With Multiple Macrolide Courses Prescribed Before Diagnosis*2 Adapted from McMahon et al. Ann Intern Med; 2003. *P<.001. 70% 60% 7-fold increase 50% 50% 40% 4-fold increase Up to 28% 30% 20% 10% 0% 7% 0 1-2 3-4 Previous courses of macrolides ≥5 Data from a retrospective cohort analysis of the relationship between previous antimicrobial use and antimicrobial resistance in H. pylori infections, based on data collected from 1998 to 2002 in 125 Alaskan native adults with culture-confirmed H. pylori infection. Forty-five percent of patients in this study had hemorrhagic or superficial ulcerations of the gastric mucosa, 3% had duodenal ulcers, and 6% had gastric ulcers. Previous antibiotic use was determined from computerized records of antimicrobial courses prescribed in the 10 years before diagnosis. The antimicrobial susceptibility of H. pylori isolates was determined using agar dilution.2 • ACG Guidelines recommend asking patients if they have previously used a macrolide for any reason, such as for the treatment of upper respiratory infection2,3 “Clinicians may want to reconsider the use of traditional triple therapy in patients with previous macrolide exposure.”1 —Chey WD. Gastroenterol Hepatol; 2009 2 References: 1. Chey WD. Selecting a therapeutic regimen and optimizing outcomes. Gastroenterol Hepatol. 2009;5(4)(suppl 13):7-8. http://www.clinicaladvances.com/article_pdfs/gh-article-200904-sup13.pdf. Accessed September 20, 2011. 2. McMahon BJ, Hennessy TW, Bensler JM, et al. The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections. Ann Intern Med. 2003;139(6):463-469. 3. Chey WD, Wong BCY; Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology Guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808-1825. 4. PYLERA® [package insert]. Birmingham, AL: Axcan Pharma US, Inc.; 2011. 5. Vakil N. Management of refractory H. pylori infection. Gastroenterol Hepatol. 2009;5(4)(suppl 13):10-11. http://www.clinicaladvances.com/article_pdfs/gh-article-200904-sup13.pdf. Accessed September 20, 2011. 6. IMS Health, 2011. 7. Graham DY, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut. 2010;59(8):1143-1153. 8. Sasaki M, Ogasawara N, Utsumi K, et al. Changes in 12-year first-line eradication rate of Helicobacter pylori based on triple therapy with proton pump inhibitor, amoxicillin and clarithromycin. J Clin Biochem Nutr. 2010;47(1):53-58. 9. Laine L, Hunt R, El-Zimaity H, Nguyen B, Osato M, Spénard J. Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial. Am J Gastroenterol. 2003;98(3):562-567. 10. O’Morain C, Borody T, Farley A, et al. Efficacy and safety of single-triple capsules of bismuth biskalcitrate, metronidazole and tetracycline, given with omeprazole, for the eradication of Helicobacter pylori: an international multicentre study. Aliment Pharmacol Ther. 2003;17(3):415-420. 11. Malfertheiner P, Bazzoli F, Delchier J-C, et al, for the Pylera Study Group. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet. 2011;377(9769):905-913. 12. Pavičić MJAMP, Namavar F, Verboom T, van Winkelhoff AJ, de Graaff J. In vitro susceptibility of Helicobacter pylori to several antimicrobial combinations. Antimicrob Agents Chemother. 1993;37(5):1184-1186. 13. Van Caekenberghe DL, Breyssens J. In vitro synergistic activity between bismuth subcitrate and various antimicrobial agents against Campylobacter pyloridis (C. pylori). Antimicrob Agents Chemother. 1987;31(9):1429-1430. perspective on first-line treatment of H. pylori Increasing clarithromycin resistance often leads to treatment failure3,7 • Clarithromycin resistance is one of the main causes of treatment failure and declining eradication rates7 100% The Relationship Between Clarithromycin Resistance and Eradication Rates Over a Decade8 80% 91.2% 80.2% 76.0% 60% 40% 26.7% 23.5% 20% 0% 69.0% 34.4% 8.7% 1995-2000 2001-2003 Year 2004-2006 2007-2008 Eradication rate after clarithromycin-based triple therapy (n=709) Primary resistance to clarithromycin (n=453) Data from a retrospective investigation of the H. pylori eradication rate and primary resistance to clarithromycin from January 1995 to December 2008 in 750 patients in Japan. Patients were eligible if they had been diagnosed with H. pylori infection by at least 1 positive result from culture test, microscopy, or I3C-urea breath test. Over 34% of patients in this study had gastric ulcer, 25.1% had duodenal ulcer, and 7.6% had gastroduodenal ulcer. Patients had received a clarithromycin-based triple therapy consisting of a proton pump inhibitor (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg bid), amoxicillin (750 mg bid), and clarithromycin (200 mg or 400 mg bid).8 The goal of first-line therapy is to achieve ≥90% eradication.7 IMPORTANT SAFETY INFORMATION: DRUG INTERACTIONS Drug interactions exist with PYLERA®. Please refer to the full US Prescribing Information for complete details. • Methoxyflurane: Risk of fatal renal toxicity; do not co-administer • Disulfiram: Psychotic reactions can occur; do not take concurrently or within the last 2 weeks of disulfiram • Alcohol: Abdominal cramps, nausea, vomiting, headaches, and flushing can occur; do not consume during therapy and for at least 3 days afterwards • Oral Contraceptives: Decreased efficacy possibly resulting in pregnancy; use a different or additional form of contraception • Anticoagulants: Potentiation of the anticoagulant effect; prothrombin time, international normalized ratio (lNR), or other suitable anticoagulation tests should be closely monitored • Lithium: Increased lithium serum concentrations; measure serum lithium and serum creatinine concentrations during therapy • Antacids, Multivitamins, or Dairy Products: Decreased absorption of PYLERA®; do not take concomitantly Please see additional Important Safety Information on back. Please see accompanying full US Prescribing Information. 3 Exposure to Macrolide Antibiotics by State 61.2% of the US population has been exposed to at least one course of macrolide antibiotics during the last 9 years Previous macrolide exposure rates by state: percentage of population exposed to macrolide antibiotics from 2002–2011* AK 41.5% WA 41.7% MT 54.5% OR 40.4% MN 48.0% ID 48.2% WY 66.2% NV 45.7% UT 48.8% CA 44.7% AZ 48.2% VT 59.3% ND 61.3% IL 59.4% KS 72.2% OK 70.2% NM 49.2% MO 74.3% HI 35.0% IN 76.4% OH 74.2% WV 85.4% MA 59.3% VA 62.0% CT 60.0% 64.0% NJ 71.9% DE DC 70.9% 47.4% MD 59.6% NC 74.1% TN 81.3% AR 83.6% NH 61.0% RI PA 65.7% KY 85.6% SC 89.8% MS 85.1% TX 62.6% NY 69.7% MI 63.7% IA 75.9% NE 57.9% CO 43.7% WI 49.0% SD 65.4% ME 63.9% AL 81.5% GA 64.1% LA 78.9% 30-40% FL 64.9% 40-50% 50-60% 60-70% 70-80% *Projected population of patients based on data collected from October 2002 to September 2011, combined with the 2010 census. Reference: IMS Health, 2011. 80-90% Exposure to Macrolide Antibiotics by State Percentage of population exposed to 3–4 courses and ≥5 courses of macrolide antibiotics from 2009–2011* Courses of antibiotics Courses of antibiotics Courses of antibiotics State 3–4 ≥5 State 3–4 ≥5 1.6% Kentucky 8.5% 3.0% Ohio 6.9% 2.3% 6.6% 2.0% Louisiana 6.6% 2.0% Oklahoma 5.2% 1.4% 2.1% 0.6% Maine 5.4% 1.7% Oregon 2.6% 0.7% 4.6% 1.4% Pennsylvania 6.5% 2.3% State 3–4 ≥5 United States 5.0% Alabama Alaska Arizona 3.0% 0.8% Maryland Arkansas 7.4% 2.3% Massachusetts 5.2% 1.7% Rhode Island 6.1% 2.2% California 3.2% 1.0% Michigan 4.9% 1.6% South Carolina 7.0% 2.1% Colorado 2.7% 0.8% Minnesota 3.2% 1.0% South Dakota 5.6% 1.9% Connecticut 5.6% 1.8% Mississippi 7.3% 2.3% Tennessee 7.5% 2.5% Delaware 6.7% 2.2% Missouri 6.0% 2.0% Texas 4.5% 1.2% District of Columbia 2.6% 0.8% Montana 3.7% 1.1% Utah 3.2% 1.0% Florida 4.0% 1.1% Nebraska 4.0% 1.2% Vermont 4.9% 1.6% 2.9% 0.9% Virginia 5.1% 1.6% Georgia 5.0% 1.5% Nevada Hawaii 2.0% 0.6% New Hampshire 4.9% 1.5% Washington 2.8% 0.8% Idaho 3.2% 0.9% New Jersey 7.3% 2.5% West Virginia 9.1% 3.6% Illinois 5.1% 1.7% New Mexico 3.7% 1.1% Wisconsin 3.4% 1.0% Indiana 6.0% 1.9% New York 6.2% 2.1% Wyoming 5.6% 1.8% Iowa 6.0% 2.0% North Carolina 5.7% 1.6% Kansas 6.1% 2.0% North Dakota 5.7% 1.9% Axcan Pharma US, Inc., a subsidiary of Aptalis Pharma Inc. 22 Inverness Center Parkway Birmingham, Alabama 35242 USA Tel (800) 472-2634 Fax (205) 991-8426 www.aptalispharma.com *Projected population of patients based on data collected from January 1, 2009, to September 30, 2011. Reference: Data on file, Adheris study, Aptalis Pharma US, Inc.; 2011. 11/11 PY150-1111A ©2011 Axcan Pharma US, Inc. PYLERA is a registered trademark used under license by Axcan Pharma US, Inc. In the treatment of Helicobacter pylori (H. pylori) infection and duodenal ulcer disease PYLERA® Capsules plus omeprazole—the #1 prescribed branded OBMT therapy6 An OBMT-based treatment regimen that does not contain macrolides4 • Up to 93% eradication after 10 days of treatment9-11 • Up to 90% eradication in the presence of clarithromycin resistance9 • Generally well tolerated4 Innovative 3-in-1 Capsule • PYLERA® Capsules contain a unique form of bismuth (bismuth subcitrate potassium) that has demonstrated synergism with both metronidazole and tetracycline, as seen in vitro12,13 Generically available? No Yes No* PYLERA® component 140 mg bismuth subcitrate potassium 125 mg metronidazole 125 mg tetracycline *Each course of PYLERA® therapy provides 375 mg tetracycline. Available generic solid oral dosage forms are either 250 mg or 500 mg, which either undermedicate or overmedicate. Dispense: 120 capsules 3 PYLERA Capsules taken 4 times a day for 10 days, after meals and at bedtime Dispense: 20 capsu les 1 omepra zole 20-mg ca psule tak en with PYL ERA twic e a day, afte r mornin g and even ing meals IMPORTANT SAFETY INFORMATION: CONTRAINDICATIONS • Patients with renal impairment • Patients with known hypersensitivity to product components ADVERSE REACTIONS The most frequently reported adverse reactions (≥5%) during clinical trials were: • Abnormal feces • Nausea • Diarrhea • Headache WARNINGS AND PRECAUTIONS • Fetal Toxicity: Advise pregnant women of the risk for permanent discoloration of teeth with tetracycline if used during the second or third trimester • Maternal Toxicity: Risk of hepatotoxicity in pregnant women with high doses of intravenous tetracycline also resulting in stillborn or premature birth • Central and Peripheral Nervous System Effects: Encephalopathy and peripheral neuropathy with metronidazole, pseudotumor cerebri with tetracycline and neurotoxicity with bismuth-containing products; monitor patients with CNS conditions closely and discontinue promptly if abnormal neurologic signs develop • Development of Superinfection: If superinfection occurs, discontinue PYLERA® and institute appropriate therapy • Photosensitivity: Avoid exposure to sun and sun lamps USE IN SPECIFIC POPULATIONS • Nursing Mothers: Discontinue drug or nursing, taking into consideration the importance of the drug to the mother • Pediatric Use: Tetracycline may cause permanent discoloration of the teeth. Enamel hypoplasia has also been reported. Do not use in children less than 8 years of age Please see additional Important Safety Information on page 3. Please see accompanying full US Prescribing Information. Axcan Pharma US, Inc., a subsidiary of Aptalis Pharma Inc. 22 Inverness Center Parkway Birmingham, Alabama 35242 USA Tel (800) 472-2634 Fax (205) 991-8426 www.aptalispharma.com 11/11 PY150-1111 ©2011 Axcan Pharma US, Inc. PYLERA is a registered trademark used under license by Axcan Pharma US, Inc.
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