AVELOX as effective as multi-dose combination therapy for intra-abdominal infections

Results published in current Annals of Surgery

Schering-Plough Corporation (NYSE: SGP) today reported that monotherapy with the once-daily, broad-spectrum antibiotic AVELOX (moxifloxacin HCl) was as effective and well tolerated as a standard multi-dose combination antibiotic regimen in the treatment of patients with complicated intra-abdominal infections (cIAI), according to results of a study involving 681 patients published in the current issue of the Annals of Surgery.(1) AVELOX, the only marketed fluoroquinolone antibiotic approved by the U.S. Food and Drug Administration (FDA) as monotherapy to treat cIAI, was shown to be effective at eradicating the most common bacteria that cause cIAI, including E. coli and B. fragilis.

In the study, patients who took 400 mg once daily of AVELOX intravenous (I.V.) followed by oral monotherapy achieved similar clinical cure rates (80 percent) at the test-of-cure visit (the primary efficacy endpoint) as patients who took a standard regimen of I.V. piperacillin-tazobactam followed by oral amoxicillin-clavulanate (78 percent).

Importantly, AVELOX demonstrated a significantly higher cure rate of 82 percent – compared to 55 percent for the combination therapy – among patients who acquired their cIAI in a hospital setting (including both mild-to-moderate and more severe hospital-acquired infections). Hospital-acquired infections are often caused by more resistant bacteria than community-acquired infections. Clinical cure rates for patients with community-acquired infections were similar between the two treatment groups.

The incidence of adverse events in the study due to any cause was similar for the two treatment groups, with the majority being mild or moderate in nature. The most common adverse events were nausea, hypokalemia, abdominal pain and constipation. The incidence of drug-related serious adverse events or premature discontinuation due to adverse events was similar for the two treatment groups.

"The results of this study are important because complicated intra-abdominal infections are typically caused by mixed bacteria and require both surgery or drainage of the infection site and broad-spectrum antibiotic therapy for effective treatment," said Mark Malangoni, M.D., lead study investigator and Professor of Surgery at Case Western Reserve University School of Medicine and Surgeon-in-Chief at MetroHealth Medical Center in Cleveland. "AVELOX has demonstrated potent activity against the bacteria most common in these infections and is a safe and effective treatment. It also can be continued as a once-daily tablet, which is convenient for patients."

AVELOX is indicated to treat polymicrobial cIAI infections, including infections caused by mixed aerobic and anaerobic bacteria (bacteria that thrive without oxygen) commonly seen in patients with cIAI.(2,3)

"One fixed dose of AVELOX offers physicians a convenient treatment option with no dose adjustment required as symptoms improve and patients transition from intravenous (hospital-based) to oral therapy," said Joseph S. Solomkin, M.D., Professor in the Department of Surgery and Director of Research of the Division of Trauma/Critical Care at the University of Cincinnati College of Medicine, and a leading expert in the field. "The key benefit of staying with the same agent is the knowledge that the patient responded to it intravenously and can continue with the oral form when they leave the hospital."

Complicated intra-abdominal infections are caused by disease, trauma or surgery in the abdomen that can allow bacteria to leak from the gastrointestinal tract into adjacent tissue. The biggest challenge to effective cIAI treatment is early recognition of the problem; the sooner the infection is diagnosed, the greater the chance that the physician will prescribe an effective treatment.(4)

In the absence of effective cIAI therapy, treatment failure and mortality rates increase. Clinical practice guidelines recommend that antimicrobial therapy should begin as soon as infection is suspected, before an exact diagnosis is confirmed.(5) There are approximately 3.5 million annual cases of cIAI in the United States.(6)

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About the Study
In this prospective, randomized, double-blind, comparative, multicenter clinical trial, 681 patients from 71 sites in the United States, Canada and Israel were randomized to receive either sequential (I.V. followed by oral) AVELOX, 400 mg once daily regardless of route of administration, or I.V. piperacillin–tazobactam, 3.0/0.375 g four times a day, followed by oral amoxicillin–clavulanate, 800/114 mg twice daily. A total of 656 patients were included in the intent-to-treat analysis and of these 379 were found valid to assess efficacy (183 AVELOX/196 piperacillin–tazobactam). Patient baseline medical characteristics were similar for the two treatment groups. The duration of combined I.V./oral treatment in the study was 5–14 days. This study served as the basis for FDA approval of AVELOX for the treatment of cIAIs in November 2005.

About Complicated Intra-Abdominal Infections (cIAI)
Complicated intra-abdominal infections arise from the hollow organs of the peritoneal cavity, including the stomach, small and large bowel, appendix and biliary system. Types of cIAI include appendicitis with perforation or abscess, intra-abdominal abscess or peritonitis (diffuse inflammation of peritoneum lining the abdominal wall and bowel), perforations of the stomach or bowel, and surgical site infections related to previous intra-abdominal surgery. Generally, cIAI are acquired when the integrity of the gastrointestinal (GI) tract is affected as a result of previous surgery, intrinsic disease or trauma. The leakage of bacteria from within the GI tract into adjacent tissues results in infection. In the case of post-surgical infections, cIAI are caused by nosocomial bacteria specific to the surgical site and to the specific hospital and unit.

About AVELOX
AVELOX, available in tablet and I.V. formulations, was developed by Bayer Pharmaceuticals Corporation and is marketed in the United States by Schering-Plough. AVELOX offers patients a once-daily dosing regimen that does not require dosage adjustment when switching from I.V. to oral therapy. AVELOX patients suffering from renal impairment do not need to have their dosage adjusted.

AVELOX is approved for use in adult patients (18 years of age and older) for the treatment of: Acute Bacterial Sinusitis (ABS) caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis; Acute Bacterial Exacerbations of Chronic Bronchitis (ABECB) caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus or Moraxella catarrhalis; Community Acquired Pneumonia (CAP) caused by Streptococcus pneumoniae (including multi-drug resistant strains*), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae or Chlamydia pneumoniae; Uncomplicated Skin and Skin Structure Infections (uSSSI) caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes; Complicated Skin and Skin Structure Infections (cSSSI) caused by methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Enterobacter cloacae; and Complicated Intra-Abdominal Infections (cIAI) including polymicrobial infections such as abscesses caused by Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron or Peptostreptococcus species.

*MDRSP, Multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP (Penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following antibiotic classes: penicillin (MIC greater than or equal to 2 mcg/mL), second generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

SAFETY INFORMATION about AVELOX
AVELOX is generally well tolerated, with adverse events being similar to standard therapy. The most common side effects caused by AVELOX, which are usually mild, include dizziness, nausea and diarrhea. Patients should be careful about driving or operating machinery until they are sure that AVELOX is not causing dizziness. Patients should inform a health care professional of other side effects. Patients who have ever had an allergic reaction to AVELOX or any of the other group of antibiotics known as "quinolones" should avoid taking AVELOX. Patients who have been diagnosed with an abnormal heartbeat such as an arrhythmia or are using certain medications used to treat an abnormal heartbeat should avoid taking AVELOX.

AVELOX is not for use during pregnancy or nursing, as the effects on the unborn child or nursing infant are unknown. AVELOX is not for children under the age of 18 years. Convulsions have been reported in patients receiving quinolone antibiotics. Patients should be sure to let their physician know if they have a history of convulsions. Many antacids and multivitamins may interfere with the absorption of AVELOX and may prevent it from working properly. Patients should take AVELOX either 4 hours before or 8 hours after taking these products. Please see full prescribing information for AVELOX available at www.AVELOXUSA.com.

About Schering-Plough Corporation Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 32,000 people around the world. The company is based in Kenilworth, N.J., and its Web site is www.schering-plough.com.

SCHERING-PLOUGH DISCLOSURE NOTICE: This press release contains certain "forward-looking statements" within the meaning of the Securities Litigation Reform Act of 1995, including statements related to the potential market for AVELOX. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough's forward-looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition and the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Item 1A. Risk Factors in the Company's 2005 10-K.

References
1. Malangoni MA, et al. Randomized Controlled Trial of Moxifloxacin Compared with Piperacillin–Tazobactam and Amoxicillin–Clavulanate for the Treatment of Complicated Intra-Abdominal Infections. Annals of Surgery 2006;244:204-211.
2. Golan Y, McDermott LA, Jacobus NV, et al. Emergence of fluoroquinolone resistance among Bacteroides species. Journal of Antimicrobial Chemotherapy 2003;52:208-13.
3. Edmiston CE, Krepel CJ, Seabrook GR, et al. In vitro activities of moxifloxacin against 900 aerobic and anaerobic surgical isolates from patients with intra-abdominal and diabetic foot infections. Antimicrobial Agents and Chemotherapy 2004;48:1012-6.
4. Solomkin JS, et al. Guidelines for the Selection of Anti-infective Agents for Complicated Intra-abdominal Infections. Clinical Infectious Diseases, 2003;37:997-1005.
5. Ibid.
6. The Hospital Antibiotic Market Guide by AMR/Arlington Medical Resources, Inc.; MAT June 2004. (Intra-abdominal Infection cases based on Bayer HealthCare customized definition.)


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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