Annals of Long-Term Care

Transcription

1 SUPPLEMENT TO Annals of Long-Term Care PRODUCT BULLETIN This material was prepared by HMP Communications, LLC in collaboration with Salix Pharmaceuticals. DECEMBER 2012 OVERVIEW OF FECAL INCONTINENCE Fecal incontinence (FI) is defined as either the involuntary passage or the inability to control the discharge of fecal matter from the anus. Clinically there are 3 subtypes: (1) passive incontinence the involuntary discharge of stool or gas without awareness; (2) urge incontinence the discharge of fecal matter in spite of attempts to retain bowel contents; and (3) fecal seepage the leakage of stool following otherwise normal evacuation. 1 FI may result from damage to the muscles or nerves in the anus. The damage sometimes occurs during childbirth or it could result from spinal cord injury or other injuries. In some cases the causes of FI are unknown. 2 Although FI affects individuals of all ages, its prevalence is disproportionally greater in the elderly population and long-term care (LTC) residents. Factors in determining the prevalence of FI vary and depend on the clinical setting, the influence of social stigma, the definition of incontinence, and its frequency. 1 The prevalence of FI in the general population is between 9% and 15%, with more than 15 million Americans suffering from it. 3 A study by Rey et al found that 15% of the population 50 years suffers from FI, and an additional 7% will develop FI in the following 10 years. 4 FI is one of the leading causes of entrance into nursing homes. 4 FI is a devastating problem for patients who suffer from this medical condition as well as their families. FI can lead to loss of self-esteem, social isolation, and diminished quality of life. 1,4 The Fecal Incontinence Quality of Life (FIQoL) Scale found that FI can have a significant impact on numerous dimensions of quality of life. FIQoL is a validated disease-specific tool used to quantify the impact of FI on 4 aspects of patients quality of life: Lifestyle, Coping behaviors, Depression or Self-perception, and Please see complete Prescribing Information attached to the Product Bulletin. HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA

2 Figure 1. Spectrum of treatment options of fecal incontinence Conservative Therapies SOLESTA Surgical Therapies Generally safe Low success rates Patients may not wish to proceed to surgery Patients may not be candidates for surgery Non-surgical treatment Office-based procedure No anesthesia required Patients may resume limited physical activity immediately Unlikely to impede future procedures Proven safety and efficacy in clinical trials Invasive High cost Prolonged recovery General anesthetic Potential safety issues SOLESTA is contraindicated in patients with active inflammatory bowel disease, immunodeficiency disorders or ongoing immunosuppressive therapy, previous radiation treatment to the pelvic area, significant mucosal or full thickness rectal prolapse, active proctitis or other infections in the anorectal region, anorectal atresia, tumors, or malformation, rectocele, rectal varices, presence of existing implant (other than SOLESTA) in anorectal region, or allergy to hyaluronic acid-based products. Embarrassment. The FIQoL survey measures quality of life on a 1 to 4 scale in the categories of Lifestyle, Coping, and Embarrassment, and on a 1 to 6 scale for the category of Depression or Self-perception. A study by Rockwood et al found that patients who had FI and completed the 29-item scale scored significantly lower in all 4 categories, indicating a poorer quality of life than a control group of patients who had other gastrointestinal problems. 5 FI is commonly encountered in LTC residents and is associated with significant use of healthcare resources. 6 Most incontinent residents have some combination of cognitive (eg, dementia) and physical impairments (eg, immobility) that preclude residents from getting to the bathroom and/or changing their soiled garments. 6,7 For caregivers in LTC, FI presents challenges. Practice guidelines specify that a resident s soiled garments should be changed and skin cleansed in a timely fashion. 7 Patient immobility, for example, is an added burden for caregivers because more staff time is spent assisting incontinent patients, handling laundry, and incontinence supplies. Furthermore, staff have to devote more time to skin care regimens for patients with FI to help reduce incontinenceassociated dermatitis, prevent incontinence-associated skin breakdown, and promote skin hygiene. 6,7 FI is also associated with a significant economic burden. Data indicate that the average annual total cost for FI is $4,110 per person, and the average cost per patient in the outpatient setting is estimated at $17,166. 1,8 In a long-term facility, the annual cost for a patient with both mixed fecal and urinary incontinence is $9, Total cost of FI is measured based on average annual spending for both medical (eg, physician visits, laboratory testing, surgery, hospitalization, and medication) and nonmedical (eg, transportation to care and routine care) costs. 8 Estimates put the approximate expenditure for adult diapers used to manage FI at $400 million per year. 1 Given the rapidly 2 HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA 19355

3 Figure 2. Over time, the beads adhere to the anal canal. 10 Figure 3. Injection procedure viewed from the prone jackknife position aging population, the severity of the economic burden of FI is only expected to increase. TREATMENT OPTIONS FOR FECAL INCONTINENCE Once FI has been diagnosed, clinicians initially treat FI with conservative therapies to improve symptoms. Conservative therapies include dietary changes, fiber therapy, and antimotility treatment. 9 Whereas these therapies are generally safe, the success rates are low. Biofeedback may also be recommended as an initial treatment option for patients with FI who have not responded to simple dietary modification or medication. 9 Surgical interventions may be the next step in treating patients who do not respond to conservative therapies. Surgical options include anal sphincter repair, sacral nerve stimulation, dynamic graciloplasty, artificial bowel sphincter, and SECCA procedure. 9 Surgical therapies, however, are invasive, expensive, involve general anesthesia, have a prolonged recovery, and have potential safety issues. See Figure 1. SOLESTA AS A TREATMENT OPTION For patients who do not find relief with conservative therapies, SOLESTA provides clinicians with an alternative treatment option that may preclude the need for more invasive surgical procedures. SOLESTA is a sterile, injectable gel that is FDA approved to treat FI in patients 18 years and older for whom other conservative therapies have failed. SOLESTA is a biocompatible bulking agent injected into the submucosal layer of the anal canal. It is a viscous combination of dextranomer microspheres in stabilized hyaluronic acid. 2 The beads provide the framework for fibrin and collagen synthesis, eventually forming durable, tissue-like formations in the anal canal. 10 See Figure 2. SOLESTA is contraindicated in patients with active inflammatory bowel disease, immunodeficiency disorders or ongoing immunosuppressive therapy, previous radiation treatment to the pelvic area, significant mucosal or full thickness rectal prolapse, active proctitis or other infections in the anorectal region, anorectal atresia, tumors, or malformation, rectocele, rectal varices, presence of existing implant (other than SOLESTA) in anorectal region, or allergy to hyaluronic acid-based products. 2 SOLESTA contains a reliable agent with over 10 years of clinical experience. 2,3 More than 50,000 children worldwide with vesicoureteral reflux disease have been treated with Deflux, the same compound contained in SOLESTA. 3 Administration of SOLESTA is minimally invasive, convenient, and office-based or an outpatient procedure with no anesthesia required. The procedure takes approximately 10 minutes. Injections are done via anoscopy. Four 1-mL syringes of SOLESTA are injected into the submucosal tissue 5 mm above the dentate line in a posterior, left-lateral, anterior, right lateral sequence. See Figure 3. Injection into tissue above the dentate line is pain free because there are no nerve endings in this region of the anal canal. Treatment can be done in a doctor s office; patient observation time is about 1 hour and no hospital stay is necessary. 2 SOLESTA has minimal postprocedure impact on patients. SOLESTA is unlikely to impede future procedures. After 1 week, patients are able to resume a normal lifestyle and engage in all physical activities, except anal manipulation. 2 Studies have shown that treatment with SOLESTA led to a reduction of FI episodes, greater control over FI, dependable results without surgery, and a positive impact on quality of life. 2,3,11-13 SOLESTA was also found to be generally safe and HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA

4 Figure 4. Efficacy with SOLESTA was proven over time in 3 clinical studies 2,3,11,12 Responder 50 (%) Pivotal Study 2,3 Open-Label Study 2,11 Proof-of-Concept Study 2, Months Months Months The most common adverse reactions with SOLESTA (incidence >4%) in the clinical study were proctalgia, anorectal hemorrhage, injection site hemorrhage, pyrexia, injection site pain, diarrhea, and anorectal discomfort. effective in the first long-term assessment of FI patients treated with SOLESTA for up to 36 months. Treatment success was defined as a reduction in the number of FI episodes by 50% compared to baseline. The results found that the number of FI episodes declined by 67% at both 12 and 36 months of follow-up and treatment success was achieved in 60% and 59%, respectively at follow-up. All 4 domains of the FIQoL scale improved significantly, compared with baseline. 14 SOLESTA MECHANISM OF ACTION While the exact mechanism of action has not been identified, SOLESTA is thought to work by building or bulking up tissue in the anal area. By narrowing the opening of the anus, the muscles used to prevent waste from escaping may be able to better close down until the patient is ready to empty their bowels. 2 CLINICAL STUDIES OF SOLESTA Results from 3 clinical studies demonstrate that SOLESTA provides a significant reduction in FI episodes, significant improvement in quality of life, and durable long-term reduction in FI. 11,13-15 See Figure 4. PIVOTAL STUDY The efficacy of SOLESTA in the reduction of FI episodes was assessed in an international, multicenter, randomized, double-blind, sham-controlled, 12-month pivotal study of 206 adult patients with FI. Patients aged 18 to 75 years were enrolled if they did not respond to conservative therapy, had a Cleveland Clinic Florida Fecal Incontinence Score (CCFIS) of 10, and had 4 or more solid or liquid FI episodes in the 2 weeks prior to the study. Patients were randomized in a 2:1 ratio to receive SOLESTA (n=136) or sham injection (n=70). The blinded phase (0-6 months) compared SOLESTA treatment with sham injection. At 1 month, all patients with CCFIS 10 were offered a repeat procedure of their original treatment. 2,13 During the open phase (6-12 months), the SOLESTA group continued treatment while the sham injection group was offered SOLESTA, then excluded from further analysis. The primary endpoint was based on the number of incontinence episodes, with response defined as a 50% 4 HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA 19355

5 Figure 5. Significant improvement in quality of life with SOLESTA (P<0.001) FIQoL score improvement* Lifestyle Coping/Behavior Depression/ Self-perception Embarrassment 1 Baseline n=115 6 months n= months n=91 *The Fecal Incontinence Quality of Life (FIQoL) survey measures quality of life attributes on a 1 to 4 scale in the categories of Lifestyle, Coping, and Embarrassment, and on a 1 to 6 scale for the category of Depression/Self-perception. reduction in the number of incontinence episodes at 6 and 12 months, compared with baseline. Treatment met the primary objective if it fulfilled the following 3 criteria 13 : A statistically significant (P<0 05) difference in proportion of responders between the treatment and sham groups at 6 months A lower 95% confidence interval (CI) for the proportion of responders in the active treatment group greater than 35% at 6 months A lower 95% CI of greater than 50% for proportion of patients in the active treatment group with 25% or more reduction in number of episodes at 12 months compared with baseline Secondary endpoints were assessment of change from baseline at 6 and 12 months in number of incontinencefree days, number of FI episodes, CCFIS, and quality of life. Adverse events were also evaluated. 2,13 The results showed a significant reduction of FI response episodes at 6 months in the SOLESTA treatment group, compared with the sham injection group; a 50% or greater reduction in the number of incontinence episodes was noted in 71 patients in the active treatment group (52%) compared with 22 (31%) in the sham treatment group (odds ratio 2 36, 95% CI , P=0.0089). Treatment response in the active treatment group met the primary objective criteria at both 6 and 12 months. There was a significant increase in the number of incontinence-free days at 6 months in the SOLESTA group versus the sham injection (P=0.0156) The median number of incontinence episodes during 2 weeks in the SOLESTA group decreased from 15.0 at baseline to 6.2 at 12 months (P<0.0001) and the mean number of incontinence-free days increased from 4.4 at baseline to 7.9 at 12 months (P<0.0001). Patients CCFIS decreased from 14.3 at baseline to 10.9 at 12 months (P<0.0001). Significant improvement compared with baseline was observed in all 4 categories on the FIQoL scale at 12 months. 2,13 SOLESTA was well tolerated over the 12-month study. The most common adverse events were proctalgia (14%), pyrexia (8%), rectal bleeding (7%), diarrhea (5%), rectal discharge (4%), constipation (2%), anal pruritus (2%), and painful defecation (2%). Two of the treatment-related adverse events were serious 1 prostatic abscess that was resolved after antibiotic treatment and 1 rectal abscess that had to be surgically drained. 2,13 LONG TERM EFFICACY Recently, 36-month follow-up data to the pivotal study were presented at the 2012 American Society of Colon & Rectal Surgeons Annual Scientific Meeting. The results indicated SOLESTA is a safe and effective treatment in controlling FI in a majority of patients in a long-term follow-up out to 36 months. Patients evaluated at 36 months (n=102) experienced a significant (67%) decrease in FI HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA

6 Figure 6. Significant improvement in FIQoL scores over 20 months postoperation * FIQoL score improvement* Lifestyle Coping/Behavior Depression/ Self-perception Embarrassment 1 Preoperation 20 months postoperation n=18 *The Fecal Incontinence Quality of Life (FIQoL) survey measures quality of life attributes on a 1 to 4 scale in the categories of Lifestyle, Coping, and Embarrassment, and on a 1 to 6 scale for the category of Depression/Self-perception. The results demonstrated a significant reduction from baseline in the number of FI episodes in 57.1% of patients at 6 months and 64% of patients at 12 months. episodes (P<0.0001) and treatment success was observed in 59%. Statistically significant increases in quality of life scores were noted in all 4 domains of the FIQoL scale as compared with baseline measures. Adverse events, most of which were mild and self-limited, included proctalgia, mild, minor bleeding, and low-grade fever. 15 OPEN-LABEL STUDY SOLESTA provided a significant reduction in FI episodes and improved quality of life at 6 and 12 months in an openlabel, noncomparative, multicenter, 12-month study of 115 adult patients (aged years) with FI. Patients were enrolled who had previously failed conservative therapy, had a CCFIS score of 5, and had 4 or more FI episodes in the 4 weeks prior to the study. At 1 month, patients still incontinent according to their patient diary, and who experienced no persistent adverse events, were offered treatment. 2,11 The primary endpoint was efficacy based on the assessment of FI episodes and was measured by the proportion of responders at 12 months after the last treatment. Response was defined as a 50% decrease from baseline in the number of FI episodes (28-day patient diary data) of solid or loose stool. Secondary endpoints included change in baseline at 6 and 12 months in CCFIS score and quality of life assessments. Treatment-related adverse events were also evaluated. 2,11 The results demonstrated a significant reduction from baseline in the number of FI episodes in 57.1% of patients (n=101) at 6 months and 64% of patients (n=91) at 12 months. Significant improvements were also shown in CCFIS and FIQoL scores. Improvement from baseline in CCFIS was statistically significant at both 6 months (P<0.001) and 12 months (P<0.001). At 6 months the mean CCFIS was reduced from 13.5 at baseline to 9.2 at 6 months. Similarly, the mean CCFIS was reduced from 13.4 at baseline to 8.7 at 12 months. Statistically significant increases from baseline were observed at 6 and 12 months for all 4 FIQoL domains. 2,11 See Figure 5. The majority of treatment-related adverse events (94%) were mild or moderate, with the vast majority (98.7%) resolving spontaneously or following treatment. The most common adverse events included proctalgia (n=15), pyrexia (n=8), and abdominal complaints (diarrhea and constipation, n=10). Six serious adverse events occurred; 1 case each of perineal abscess, rectovaginal septum abscess, 6 HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA 19355

7 rectal abscess, concurrent rectal prolapse, proctalgia, and rectal hemorrhage. 11 QUALITY OF LIFE STUDY A study by Schwandner et al analyzed the safety and functional outcome of SOLESTA in 21 patients (aged years) with passive FI who had failed conservative treatment. Patients were followed up to 4 weeks to assess postoperative healing. Patients were followed up at 3, 12, and 24 months postoperatively to evaluate functional outcome, continence, and quality of life. Long-term outcomes were assessed after a mean follow-up of 20 months (range months). 14 The primary endpoints were quality of life assessed by the FIQoL scale and generic EQ-5D Visual Analogue Scale (VAS). Change in incontinence status was also analyzed using the Wexner incontinence score. The results showed FIQoL scores over 20 months postoperation improved significantly. See Figure 6. Significant improvement was also seen in EQ-5D VAS; the score increased from 46.9 at preoperation to 60.3 at 20 months postoperation (P<.05). Wexner incontinence score decreased from 16.8 to Quality of life was maintained 20 months after injection. At 3 and 20 months after injection 55.6% of patients showed improvement in FIQoL scores. Functional outcomes related to symptoms at 3 and 20 months after injection showed 66.7% and 55.6% of patients had a reduction in incontinence episodes, 61.1% and 55.6% of patients had a reduction in soiling, and 38.9% and 27.8% of patients had improvement in fecal urgency, respectively. 14 SAFETY AND TOLERABILITY OF SOLESTA Overall, 96% of the 203 SOLESTA treatment-related adverse events in the Pivotal study were of mild to moderate intensity, and 97% of the events required no intervention or required medical or simple non-invasive interventions, including application of local pressure, silicon ointment, water irrigation, and warm baths. The most common adverse reactions with SOLESTA (incidence >4%) in the clinical study were proctalgia, anorectal hemorrhage, injection site hemorrhage, pyrexia, injection site pain, diarrhea, and anorectal discomfort. See Table 1. Most of the SOLESTA-related adverse events occurred shortly after treatment, and the median duration of events was 1 week. Three adverse events assessed as related to SOLESTA, or 1.3% of the treatment-related adverse events, were deemed serious by the investigators. These 3 serious adverse events occurred in 3 patients, including one case of an E. coli bacteremia, and 2 cases of rectal abscesses (one event per patient). 2 Table 1. Adverse event profile through 18 months 2 Adverse event Number of events Percentage of patients Proctalgia % Injection site hemorrhage % Rectal hemorrhage % Pyrexia % Injection site pain % Diarrhea % Anal hemorrhage 9 4.1% Anorectal discomfort 8 4.1% FACILITATING REIMBURSEMENT FOR SOLESTA In order to help healthcare providers receive reimbursement for SOLESTA, it is recommended that they use the SOLESTA Reimbursement Helpline ( ) as their initial point of contact. The Helpline has a 3-step process for clinicians: 1. Complete the SOLESTA Patient Enrollment Form 2. Have patients fill out the SOLESTA Reimbursement Helpline Patient Authorization Form 3. Fax both signed forms to Helpline at In a 36-month follow-up of the Pivotal Study, treatment with SOLESTA showed long-term success in reducing the frequency of FI episodes. HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA

8 IMPORTANT SAFETY INFORMATION SOLESTA (hyaluronic acid/dextranomer) is contraindicated in patients with active inflammatory bowel disease, immunodeficiency disorders or ongoing immunosuppressive therapy, previous radiation treatment to the pelvic area, significant mucosal or full thickness rectal prolapse, active anorectal conditions (including abscess, fissures, sepsis, bleeding, proctitis, or other infections), anorectal atresia, tumors, or malformation, rectocele, rectal varices, presence of existing implant (other than SOLESTA) in anorectal region, or allergy to hyaluronic acid-based products. SOLESTA must not be injected intravascularly as injection of SOLESTA into blood vessels may cause vascular occlusion. Injection in the midline of the anterior wall of the rectum should be avoided in men with an enlarged prostate. SOLESTA should only be administered by physicians experienced in performing anorectal procedures and who have successfully completed a comprehensive training and certification program on the SOLESTA injection procedure. The most common adverse reactions with SOLESTA (incidence >4%) in the clinical study were proctalgia, anorectal hemorrhage, injection site hemorrhage, pyrexia, injection site pain, diarrhea, and anorectal discomfort. Please please see complete Prescribing Information for SOLESTA at * Safety information presented in the Package Insert only includes data up to 18 months. n Solesta is under license from and manufactured by Q-Med AB for Salix Pharmaceuticals, Inc. Solesta is a registered trademark of Q-Med AB. 8 HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA 19355

9 REFERENCES 1. Rao SS. Diagnosis and management of fecal incontinence. American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol. 2004;99(8): SOLESTA [package insert]. Raleigh, NC: Salix Pharmaceuticals, Inc; Data on file. Salix Pharmaceuticals Inc. 4. Rey E, Choung RS, Schleck CD, Zinsmeister AR, Locke GR 3rd, Talley NJ. Onset and risk factors for fecal incontinence in a US community. Am J Gastroenterol. 2010;105(2): Rockwood TH, Church JM, Fleshman JW, et al. Fecal Incontinence Quality of Life Scale: quality of life instrument for patients with fecal incontinence. Dis Colon Rectum. 2000;43(1): Leung FW, Schnelle JF. Urinary and fecal incontinence in nursing home residents. Gastroenterol Clin North Am. 2008;37(3): Al Samarrai NR, Uman GC, Al-Samarrai T, Alessi CA. Introducing a new incontinence management system for nursing home residents. J Am Med Dir Assoc. 2007;8(4): Xu X, Menees SB, Zochowski MK, Fenner DE. Economic cost of fecal incontinence. Dis Colon Rectum. 2012;55(5): Tjandra JJ, Dykes SL, Kumar RR, et al. Practice parameters for the treatment of fecal incontinence. Dis Colon Rectum. 2007;50(10): Stenberg A, Larsson E, Lackgren G. Endoscopic treatment with dextranomer-hyaluronic acid for vesicoureteral reflux: histological findings. J Urol. 2003;169(3): Dodi G, Jongen, J, de la Portilla F, Raval M, Altomare DF, Lehur PA. An open-label, noncomparative, multicenter study to evaluate efficacy and safety of NASHA/ Dx Gel as a bulking agent for the treatment of fecal incontinence. Gastroenterol Res Pract. 2010;2010: Danielson J, Karlbom U, Sonesson AC, Wester T, Graf W. Submucosal injection of stabilized nonanimal hyaluronic acid with dextranomer: a new treatment option for fecal incontinence. Dis Colon Rectum. 2009;52(6): Graf W, Mellgren A, Matzel KE, Hull T, Johasson, Berstein M. Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: randomized, sham-controlled trial. Lancet. 2011;377(9770): Schwandner O, Brunner M, Dieti O. Quality of life and functional results of submucosal injection therapy using dextranomer hyaluronic acid for fecal incontinence. Surg Innov. 2011;18(2): Mellgren A, Pollack J, Hull T, Berstein M, Matzel K, Graf W. Long-term efficacy of NASHA/DX Injection Therapy (SOLESTA ) for the treatment of fecal incontinence. Presented at: The American Society of Colon & Rectal Surgeons Annual Scientific Meeting. June 2-6, San Antonio, Texas. S46. HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA

10 Please see complete attached Prescribing Information. For more information, please visit Publisher s Note: This publication is not intended to serve as an endorsement of the product by the publisher or the editor of Annals of Long-Term Care. Clinical judgment must guide each professional in weighing the benefits of treatment against the risks. Consult full Prescribing Information before prescribing. To download an electronic version please visit MCOSOL 12/19 10 HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA 19355

11 Publishing Staff Director of Medical Communications Lisa A. Tomaszewski, PhD Senior Project Manager Eileen Koutnik-Fotopoulos Assistant Project Editor Kerri Fitzgerald Projects Intern Danielle Seltzer Creative Director Vic Geanopulos Art Director Alana Balboni Business Staff Vice President & Group Publisher Christopher Ciraulo National Accounts Manager Jessica Bammann National Accounts Manager Rebecca Leone Classified/Reprint Sales Associate Joseph Miller Circulation Manager Bonnie Shannon HMP Communications Holdings, LLC Chief Executive Officer Jeff Hennessy Chief Financial Officer Dan Rice Senior Vice President Anthony Mancini Director of E-Media and IT Tim Shaw Senior Manager, IT Ken Roberts HMP Communications, LLC President Bill Norton Controller Meredith Cymbor-Jones 2012, HMP Communications, LLC (HMP). All rights reserved. Reproduction in whole or in part prohibited. Opinions expressed by authors, contributors, and advertisers are their own and not necessarily those of HMP Communications, the editorial staff, or any member of the editorial advisory board. HMP Communications is not responsible for accuracy of dosages given in articles printed herein. The appearance of advertisements in this journal is not a warranty, endorsement or approval of the products or services advertised or of their effectiveness, quality or safety. HMP Communications disclaims responsibility for any injury to persons or property resulting from any ideas or products referred to in the articles or advertisements. Content may not be reproduced in any form without written permission. Rights, permission, reprint, and translation information is available at: HMP Communications, LLC (HMP) is the authoritative source for comprehensive information and education servicing healthcare professionals. HMP s products include peer-reviewed and nonpeer-reviewed medical journals, national tradeshows and conferences, online programs and customized clinical programs. HMP is a wholly owned subsidiary of HMP Communications Holdings LLC. Discover more about HMP s products and services at: HMP Communications., LLC HMP Communications, LLC 83 General Warren Blvd., Suite 100 Malvern, PA

12 Click here to view complete Prescribing Information, LLC 2012, HMP Communications, LLC (HMP). All rights reserved. Reproduction in whole or in part prohibited